Journal of the American College of Cardiology
Editor-in-Chief’s Top Picks From 2016: Part Two
Author + information
- Published online February 20, 2017.
Author Information
- Valentin Fuster, MD, PhD
Abstract
Each week, I record audio summaries for every article in JACC, as well as an issue summary. While this process has been incredibly time-consuming, I have become quite familiar with every paper that we publish. Thus, I personally select papers (both original investigations and review articles) from 15 distinct specialties each year for your review. In addition to my personal choices, I have included manuscripts that have been the most accessed or downloaded on our websites, as well as those selected by the JACC Editorial Board members. In order to present the full breadth of this important research in a consumable fashion, we will present these manuscripts in this issue of JACC.
Part One included the sections: Basic & Translational Research, Cardiac Failure, Cardiomyopathies/Myocardial & Pericardial Diseases, Congenital Heart Disease, Coronary Disease & Interventions, and CVD Prevention & Health Promotion.
Part Two includes the sections: CV Medicine & Society, Hypertension, Imaging, Metabolic & Lipid Disorders, Rhythm Disorders, Valvular Heart Disease, and Vascular Medicine (1–84).
CV Medicine & Society
Association Between Presence of a Cardiac Intensivist and Mortality in an Adult Cardiac Care Unit
S.J. Na, et al.
Background
Dedicated intensive care unit (ICU) physician staffing is associated with a reduction in ICU mortality rates in general medical and surgical ICUs. However, limited data are available on the role of a cardiac intensivist in the cardiac intensive care unit (CICU).
Objectives
This study investigated the association of cardiac intensivist–directed care with clinical outcomes in adult patients admitted to the CICU.
Methods
This study analyzed 2,431 patients admitted to the CICU at Samsung Medical Center in Seoul, South Korea, from January 2012 to December 2015. In January 2013 the CICU was changed from a low-intensity staffing model to a high-intensity staffing model managed by a dedicated cardiac intensivist. Eligible patients were divided into either a low-intensity management group (n = 616) or a high-intensity management group (n = 1,815). One-to-many (1:N) propensity score matching with variable matching ratios was also performed. The primary outcome was death in the CICU.
Results
Death in the CICU occurred in 55 patients (8.9%) in the low-intensity group versus 74 patients (4.1%) in the high-intensity group (p < 0.001). Of 135 patients who underwent extracorporeal membrane oxygenation, the CICU mortality rate in the high-intensity group was also lower than that in the low-intensity group (54.5% vs. 22.5%; p = 0.001). On propensity score matching, high-intensity staffing was found associated with a lower CICU mortality rate in the matched cohort of patients (7.5% vs. 3.7%; adjusted odds ratio: 0.53; 95% confidence interval: 0.32 to 0.86; p = 0.010). In overall and propensity-matched patients, there were no substantive differences in either median length of CICU stay or readmission rates between the 2 groups.
Conclusions
The presence of a dedicated cardiac intensivist was associated with a reduction in CICU mortality rates in patients with cardiovascular disease who required critical care (1).
The Changing Landscape of Randomized Clinical Trials in Cardiovascular Disease
W.S. Jones, et al.
Large randomized clinical trials in cardiovascular disease have proliferated over the past 3 decades, with results that have influenced every aspect of cardiology practice. Despite these advances, there remains a substantial need for more high-quality evidence to inform cardiovascular clinical practice, given the increasing prevalence of cardiovascular disease around the world. Traditional clinical trials are increasingly challenging due to rising costs, increasing complexity and length, and burdensome institutional and regulatory requirements. This review will examine the current landscape of cardiovascular clinical trials in the United States, highlight recently conducted registry-based clinical trials, and discuss the potential attributes of the recently launched pragmatic clinical trial by the Patient-Centered Outcomes Research Institute’s National Patient-Centered Clinical Research Network, called the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing the Benefits and Long-term Effectiveness) trial (2).
The Essential Role of Educator Development: 10 Years of the ACC Emerging Faculty Program
A.J. Auseon, et al.
The American College of Cardiology Emerging Faculty program was developed in 2005 to promote a systematic approach to “educate the educators” through training and mentorship. A primary focus of the program is the biennial Teaching Skills Workshop, which has had 130 participants since its inception and is focused on the concepts of effective adult learning, curriculum design, and optimization of presentation skills. A survey of participants (80 respondents of 130 total participants) found that the majority stated that participation in the program had a large impact on their ability to apply instructional design principles (49%) and present in face-to-face settings (47%), and it had a moderately large to large positive impact on their personal careers. Thus, the Emerging Faculty program combines several elements of the College’s strategic plan in a single program that provides member value to early career professionals and sustained benefit for the cardiovascular community and patients (3).
The Importance of Global Health Experiences in the Development of New Cardiologists
M. Abdalla, et al.
As the global burden of cardiovascular disease continues to increase worldwide, nurturing the development of early-career cardiologists interested in global health is essential to create a cadre of providers with the skill set to prevent and treat cardiovascular diseases in international settings. As such, interest in global health has increased among cardiology trainees and early-career cardiologists over the past decade. International clinical and research experiences abroad present an additional opportunity for growth and development beyond traditional cardiovascular training. We describe the American College of Cardiology International Cardiovascular Exchange Database, a new resource for cardiologists interested in pursuing short-term clinical exchange opportunities abroad, and report some of the benefits and challenges of global health cardiovascular training in both resource-limited and resource-abundant settings (4).
The Supply and Demand of the Cardiovascular Workforce: Striking the Right Balance
A. Narang, et al.
As the burden of cardiovascular disease in the United States continues to increase, uncertainty remains on how well-equipped the cardiovascular workforce is to meet the challenges that lie ahead. In a time when health care is rapidly shifting, numerous factors affect the supply and demand of the cardiovascular workforce. This Council Commentary critically examines several factors that influence the cardiovascular workforce. These include current workforce demographics and projections, evolving health care and practice environments, and the increasing burden of cardiovascular disease. Finally, we propose 3 strategies to optimize the workforce. These focus on cardiovascular disease prevention, the effective utilization of the cardiovascular care team, and alterations to the training pathway for cardiologists (5).
Hypertension
Diastolic Blood Pressure, Subclinical Myocardial Damage, and Cardiac Events: Implications for Blood Pressure Control
J.W. McEvoy, et al.
Background
The optimal systolic blood pressure (SBP) treatment goal is in question, with SPRINT (Systolic Blood Pressure Intervention Trial) suggesting benefit for 120 mm Hg. However, achieving an SBP this low may reduce diastolic blood pressure (DBP) to levels that could compromise myocardial perfusion.
Objectives
This study sought to examine the independent association of DBP with myocardial damage (using high-sensitivity cardiac troponin-T [hs-cTnT]) and with coronary heart disease (CHD), stroke, or death over 21 years.
Methods
The authors studied 11,565 adults from the ARIC (Atherosclerosis Risk In Communities) cohort, analyzing DBP and hs-cTnT associations as well as prospective associations between DBP and events.
Results
Mean baseline age was 57 years, 57% of patients were female, and 25% were black. Compared with persons who had DBP between 80 to 89 mm Hg at baseline (ARIC visit 2), the adjusted odds ratio of having hs-cTnT ≥14 ng/l at that visit was 2.2 and 1.5 in those with DBP <60 mm Hg and 60 to 69 mm Hg, respectively. Low DBP at baseline was also independently associated with progressive myocardial damage on the basis of estimated annual change in hs-cTnT over the 6 years between ARIC visits 2 and 4. In addition, compared with a DBP of 80 to 89 mm Hg, a DBP <60 mm Hg was associated with incident CHD and mortality, but not with stroke. The DBP and incident CHD association was strongest with baseline hs-cTnT ≥14 ng/l (p value for interaction <0.001). Associations of low DBP with prevalent hs-cTnT and incident CHD were most pronounced among patients with baseline SBP ≥120 mm Hg.
Conclusions
Particularly among adults with an SBP ≥120 mm Hg, and thus elevated pulse pressure, low DBP was associated with subclinical myocardial damage and CHD events. When titrating treatment to SBP <140 mm Hg, it may be prudent to ensure that DBP levels do not fall below 70 mm Hg, and particularly not below 60 mm Hg (6).
Generalizability of SPRINT Results to the U.S. Adult Population
A.P. Bress, et al.
Background
In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP goal of <140 mm Hg.
Objectives
The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized.
Methods
We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age ≥50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m2, 10-year CVD risk ≥15%, or age ≥75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m2, or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with ≥1 class of antihypertensive medication identified through a pill bottle review.
Results
Overall, 7.6% (95% confidence interval [CI]: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension.
Conclusions
A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT (7).
Morning Home Blood Pressure Is a Strong Predictor of Coronary Artery Disease: The HONEST Study
K. Kario, et al.
Background
Few studies have evaluated out-of-office blood pressure (BP) measurements as predictors of coronary artery disease (CAD) events.
Objectives
The aim of this study was to determine morning home blood pressure (HBP) as a predictor of CAD events.
Methods
Using data from the HONEST (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure) study, we investigated the relationship between morning HBP and incidence of stroke and CAD events.
Results
In 21,591 treated hypertensive patients (mean age 64.9 years; mean follow-up 2.02 years), 127 stroke events (2.92 per 1,000 patient-years), and 121 CAD events (2.78 per 1,000 patient-years) occurred. The incidence of stroke events was significantly higher in patients with morning home systolic blood pressure (HSBP) ≥145 mm Hg compared with <125 mm Hg, and in patients with clinic systolic blood pressure (CSBP) ≥150 mm Hg compared with <130 mm Hg. Hazard ratios (HRs) were 6.01 (95% confidence interval [CI]: 2.85 to 12.68) between patients with morning HSBP ≥155 mm Hg and those with morning HSBP <125 mm Hg and 5.82 (95% CI: 3.17 to 10.67) between patients with CSBP ≥160 mm Hg and those with CSBP <130 mm Hg; morning HSBP predicted stroke events similarly to CSBP. Incidence of CAD events was significantly higher in patients with morning HSBP ≥145 mm Hg compared with <125 mm Hg and in patients with CSBP ≥160 mm Hg compared with <130 mm Hg. The HR for morning HSBP ≥155 mm Hg was 6.24 (95% CI: 2.82 to 13.84) and for CSBP ≥160 mm Hg was 3.51 (95% CI: 1.71 to 7.20); therefore, compared with morning HSBP, CSBP may underestimate CAD risk. Goodness-of-fit analysis showed that morning HSBP predicted CAD events more strongly than CSBP.
Conclusions
Morning HBP is a strong predictor of future CAD and stroke events, and may be superior to clinic BP in this regard. There does not appear to be a J-curve in the relationship between morning HBP and stroke or CAD events. (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure Study [HONEST]; UMIN000002567) (8).
Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention
N.R. Cook, et al.
Background
The relationship between lower sodium intake and total mortality remains controversial.
Objectives
This study examined the relationship between well-characterized measures of sodium intake estimated from urinary sodium excretion and long-term mortality.
Methods
Two trials, phase I (1987 to 1990), over 18 months, and phase II (1990 to 1995), over 36 months, were undertaken in TOHP (Trials of Hypertension Prevention), which implemented sodium reduction interventions. The studies included multiple 24-h urine samples collected from pre-hypertensive adults 30 to 54 years of age during the trials. Post-trial deaths were ascertained over a median 24 years, using the National Death Index. The associations between mortality and the randomized interventions as well as with average sodium intake were examined.
Results
Among 744 phase I and 2,382 phase II participants randomized to sodium reduction or control, 251 deaths occurred, representing a nonsignificant 15% lower risk in the active intervention (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.66 to 1.09; p = 0.19). Among 2,974 participants not assigned to an active sodium intervention, 272 deaths occurred. There was a direct linear association between average sodium intake and mortality, with an HR of 0.75, 0.95, and 1.00 (references) and 1.07 (p trend = 0.30) for <2,300, 2,300 to <3,600, 3,600 to <4,800, and ≥4,800 mg/24 h, respectively; and with an HR of 1.12 per 1,000 mg/24 h (95% CI: 1.00 to 1.26; p = 0.05). There was no evidence of a J-shaped or nonlinear relationship. The HR per unit increase in sodium/potassium ratio was 1.13 (95% CI: 1.01 to 1.27; p = 0.04).
Conclusions
We found an increased risk of mortality for high-sodium intake and a direct relationship with total mortality, even at the lowest levels of sodium intake. These results are consistent with a benefit of reduced sodium and sodium/potassium intake on total mortality over a 20-year period (9).
The Cardiovascular Risk of White-Coat Hypertension
S.S. Franklin, et al.
Background
The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood.
Objectives
Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects.
Methods
European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as ≥3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age- and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects.
Results
In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low- and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort- and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age ≥60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044).
Conclusions
WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age- and risk-adjusted normotensive control subjects (10).
Imaging
1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study
P.S. Douglas, et al.
Background
Coronary computed tomographic angiography (CTA) plus estimation of fractional flow reserve using CTA (FFRCT) safely and effectively guides initial care over 90 days in patients with stable chest pain. Longer-term outcomes are unknown.
Objectives
The study sought to determine the 1-year clinical, economic, and quality-of-life (QOL) outcomes of using FFRCT instead of usual care.
Methods
Consecutive patients with stable, new onset chest pain were managed by either usual testing (n = 287) or CTA (n = 297) with selective FFRCT (submitted in 201, analyzed in 177); 581 of 584 (99.5%) completed 1-year follow-up. Endpoints were adjudicated major adverse cardiac events (MACE) (death, myocardial infarction, unplanned revascularization), total medical costs, and QOL.
Results
Patients averaged 61 years of age with a mean 49% pre-test probability of coronary artery disease. At 1 year, MACE events were infrequent, with 2 in each arm of the planned invasive group and 1 in the planned noninvasive cohort (usual care strategy). In the planned invasive stratum, mean costs were 33% lower with CTA and selective FFRCT ($8,127 vs. $12,145 usual care; p < 0.0001); in the planned noninvasive stratum, mean costs did not differ when using an FFRCT cost weight of zero ($3,049 FFRCT vs. $2,579; p = 0.82), but were higher when using an FFRCT cost weight equal to CTA. QOL scores improved overall at 1 year (p < 0.001), with similar improvements in both groups, apart from the 5-item EuroQOL scale scores in the noninvasive stratum (mean change of 0.12 for FFRCT vs. 0.07 for usual care; p = 0.02).
Conclusions
In patients with stable chest pain and planned invasive coronary angiography, care guided by CTA and selective FFRCT was associated with equivalent clinical outcomes and QOL, and lower costs, compared with usual care over 1-year follow-up. (The PLATFORM Study: Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts [PLATFORM]; NCT01943903) (11).
A Simple Disease-Guided Approach to Personalize ACC/AHA-Recommended Statin Allocation in Elderly People: The BioImage Study
M.B. Mortensen, et al.
Background
The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend primary prevention with statins for individuals with ≥7.5% 10-year risk for atherosclerotic cardiovascular disease (ASCVD). Everyone living long enough will become eligible for risk-based statin therapy due to age alone.
Objectives
This study sought to personalize ACC/AHA risk-based statin eligibility using noninvasive assessment of subclinical atherosclerosis.
Methods
In 5,805 BioImage participants without known ASCVD at baseline, those with ≥7.5% 10-year ASCVD risk were down-classified from statin eligible to ineligible if imaging revealed no coronary artery calcium (CAC) or carotid plaque burden (cPB). Intermediate-risk individuals were up-classified from optional to clear statin eligibility if CAC was ≥100 (or equivalent cPB).
Results
At a median follow-up of 2.7 years, 91 patients had coronary heart disease and 138 had experienced a cardiovascular disease event. Mean age of the participants was 69 years, and 86% qualified for ACC/AHA risk-based statin therapy, with high sensitivity (96%) but low specificity (15%). CAC or cPB scores of 0 were common (32% and 23%, respectively) and were associated with low event rates. With CAC-guided reclassification, specificity for coronary heart disease events improved 22% (p < 0.0001) without any significant loss in sensitivity, yielding a binary net reclassification index (NRI) of 0.20 (p < 0.0001). With cPB-guided reclassification, specificity improved 16% (p < 0.0001) with a minor loss in sensitivity (7%), yielding an NRI of 0.09 (p = 0.001). For cardiovascular disease events, the NRI was 0.14 (CAC-guided) and 0.06 (cPB-guided). The positive NRIs were driven primarily by down-classifying the large subpopulation with CAC = 0 or cPB = 0.
Conclusions
Withholding statins in individuals without CAC or carotid plaque could spare a significant proportion of elderly people from taking a pill that would benefit only a few. This individualized disease-guided approach is simple and easy to implement in routine clinical practice (12).
Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis: The MyoRacer-Trial
P. Lurz, et al.
Background
Data suggest that T1 and T2 mapping have excellent diagnostic accuracy in patients with suspected myocarditis. However, the true diagnostic performance of comprehensive cardiac magnetic resonance (CMR) mapping versus endomyocardial biopsy (EMB) has not been determined.
Objectives
This study assessed the performance of CMR imaging, including T1 and T2 mapping, compared with EMB in an unselected, consecutive patient cohort with suspected myocarditis. It also examined the potential role of CMR field strength by comparing 1.5-T versus 3.0-T imaging.
Methods
Patients underwent biventricular EMB, cardiac catheterization (for exclusion of coronary artery disease), and CMR imaging on 1.5- and 3-T scanners. The CMR protocol included current standard Lake Louise criteria (LLC) for myocarditis as well as native T1, calculation of extracellular volume fraction (ECV), and T2 mapping (only on 1.5-T). Patients were divided into 2 groups according to symptom duration (acute: ≤14 days vs. chronic: >14 days).
Results
A total of 129 patients underwent 1.5-T imaging. In patients with acute symptoms, native T1 yielded the best diagnostic performance as defined by the area under the curve (AUC) of receiver-operating curves (0.82) followed by T2 (0.81), ECV (0.75), and LLC (0.56). In patients with chronic symptoms, only T2 mapping yielded an acceptable AUC (0.77). On 3.0-T, AUCs of native T1, ECV, and LLC were comparable to 1.5-T with no significant differences.
Conclusions
In patients with acute symptoms, mapping techniques provide a useful tool for confirming or rejecting the diagnosis of myocarditis and are superior to the LLC. However, only T2 mapping has acceptable diagnostic performance in patients with chronic symptoms. (Magnetic Resonance Imaging in Myocarditis [MyoRacer]; NCT02177630) (13).
Computed Tomography and Cardiac Magnetic Resonance in Ischemic Heart Disease
M.R. Dweck, et al.
Ischemic heart disease is a complex disease process caused by the development of coronary atherosclerosis, with downstream effects on the left ventricular myocardium. It is characterized by a long preclinical phase, abrupt development of myocardial infarction, and more chronic disease states such as stable angina and ischemic cardiomyopathy. Recent advances in computed tomography (CT) and cardiac magnetic resonance (CMR) now allow detailed imaging of each of these different phases of the disease, potentially allowing ischemic heart disease to be tracked during a patient’s lifetime. In particular, CT has emerged as the noninvasive modality of choice for imaging the coronary arteries, whereas CMR offers detailed assessments of myocardial perfusion, viability, and function. The clinical utility of these techniques is increasingly being supported by robust randomized controlled trial data, although the widespread adoption of cardiac CT and CMR will require further evidence of clinical efficacy and cost effectiveness (14).
Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study
A. Dedic, et al.
Background
It is uncertain whether a diagnostic strategy supplemented by early coronary computed tomography angiography (CCTA) is superior to contemporary standard optimal care (SOC) encompassing high-sensitivity troponin assays (hs-troponins) for patients suspected of acute coronary syndrome (ACS) in the emergency department (ED).
Objectives
This study assessed whether a diagnostic strategy supplemented by early CCTA improves clinical effectiveness compared with contemporary SOC.
Methods
In a prospective, open-label, multicenter, randomized trial, we enrolled patients presenting with symptoms suggestive of an ACS at the ED of 5 community and 2 university hospitals in the Netherlands. Exclusion criteria included the need for urgent cardiac catheterization and history of ACS or coronary revascularization. The primary endpoint was the number of patients identified with significant coronary artery disease requiring revascularization within 30 days.
Results
The study population consisted of 500 patients, of whom 236 (47%) were women (mean age 54 ± 10 years). There was no difference in the primary endpoint (22 [9%] patients underwent coronary revascularization within 30 days in the CCTA group and 17 [7%] in the SOC group [p = 0.40]). Discharge from the ED was not more frequent after CCTA (65% vs. 59%, p = 0.16), and length of stay was similar (6.3 h in both groups; p = 0.80). The CCTA group had lower direct medical costs (€337 vs. €511, p < 0.01) and less outpatient testing after the index ED visit (10 [4%] vs. 26 [10%], p < 0.01). There was no difference in incidence of undetected ACS.
Conclusions
CCTA, applied early in the work-up of suspected ACS, is safe and associated with less outpatient testing and lower costs. However, in the era of hs-troponins, CCTA does not identify more patients with significant CAD requiring coronary revascularization, shorten hospital stay, or allow for more direct discharge from the ED. (Better Evaluation of Acute Chest Pain with Computed Tomography Angiography [BEACON]; NCT01413282) (15).
Diagnostic Strategies for the Evaluation of Chest Pain: Clinical Implications From SCOT-HEART and PROMISE
C.B. Fordyce, et al.
SCOT-HEART (Scottish COmputed Tomography of the HEART) and PROMISE (PROspective Multicenter Imaging Study for Evaluation of chest pain) represent the 2 largest and most comprehensive cardiovascular imaging outcome trials in patients with stable chest pain and provide significant insights into patient diagnosis, management, and outcomes. These trials are particularly timely, given the well-recognized knowledge gaps and widespread use of noninvasive imaging. The overall goal of this review is to distill the data generated from these 2 pivotal trials to better inform the practicing clinician in the selection of noninvasive testing for stable chest pain. Similarities and differences between SCOT-HEART and PROMISE are highlighted, and clinical and practical implications are discussed. Both trials show that coronary computed tomography angiography should have a greater role in the diagnostic pathway of patients with stable chest pain (16).
Femoral and Carotid Subclinical Atherosclerosis Association With Risk Factors and Coronary Calcium: The AWHS Study
M. Laclaustra, et al.
Background
Early subclinical atherosclerosis has been mainly researched in carotid arteries. The potential value of femoral arteries for improving the predictive capacity of traditional risk factors is an understudied area.
Objectives
This study sought to evaluate the association of subclinical carotid and femoral plaques with risk factors and coronary artery calcium score (CACS) in middle-aged men.
Methods
Participants (n = 1,423) of the AWHS (Aragon Workers’ Health Study), a study designed to assess cardiovascular risk and subclinical atherosclerosis in a cohort of middle-aged men (40 to 59 years of age), underwent carotid and femoral ultrasound plus noncontrast coronary computed tomography. Subclinical atherosclerosis was defined as the presence of any plaque in carotid or femoral arteries and/or CACS ≥1. Logistic regression models were used to estimate the prevalence of atherosclerosis adjusted for risk factors and age, to evaluate the association of atherosclerosis with risk factors, and to calculate areas under the receiver-operating characteristic curves for the presence of positive CACS.
Results
Subclinical atherosclerosis was found in 72% of participants. Plaques were most common in femoral arteries (54%), followed by coronary calcification (38%) and carotid plaques (34%). Association of atherosclerosis with risk factors was stronger in femoral arteries than carotid or coronary arteries. The area under the receiver-operating characteristic curve for prediction of positive CACS increased from 0.665 when considering only risk factors (dyslipidemia, current smoking, hypertension, diabetes, and age) to 0.719 when adding femoral and carotid plaques (p < 0.001). In this model, the femoral odds ratio (2.58) exceeded the carotid odds ratio (1.80) for prediction of positive CACS.
Conclusions
Subclinical atherosclerosis was highly prevalent in this middle-aged male cohort. Association with risk factors and positive CACS was stronger in femoral than carotid arteries. Screening for femoral plaques may be an appealing strategy for improving cardiovascular risk scales and predicting coronary disease (17).
Implantable Electronic Cardiac Devices and Compatibility With Magnetic Resonance Imaging
J.D. Miller, et al.
There is a growing population of patients with implanted electronic cardiac devices and a concomitant increase in the use of magnetic resonance (MR). There are theoretical safety risks posed to such devices by MR. However, there are now considerable laboratory data and clinical experience demonstrating safety in this setting, assuming appropriate device selection and patient monitoring. Herein, we review these data and our safety protocol and the new generation of devices that have been prospectively designed and tested to be safe for MR scanning, assuming certain conditions are met (i.e., devices that are MR-conditional). We also argue that the available data do not support a complete transition to implantation of MR-conditional devices (18).
Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study
J.M. Fernández-Alvira, et al.
Background
Leucocyte telomere length (LTL) shortening is associated with cardiovascular ischemic events and mortality in humans, but data on its association with subclinical atherosclerosis are scarce. Whether the incidence and severity of subclinical atherosclerosis are associated with the abundance of critically short telomeres, a major trigger of cellular senescence, remains unknown.
Objectives
The authors conducted a cross-sectional exploration of the association between subclinical atherosclerosis burden and both average LTL and the abundance of short telomeres (%LTL<3 kb).
Methods
Telomere length was assessed by high-throughput quantitative fluorescence in situ hybridization in circulating leukocytes from 1,459 volunteers without established cardiovascular disease (58% men, 40 to 54 years of age) from the PESA (Progression of Early Subclinical Atherosclerosis) study. Subclinical atherosclerosis was evaluated by coronary artery calcium scan and 2-dimensional/3-dimensional ultrasound in different aortic territories. Statistical significance of differences among multiple covariates was assessed with linear regression models. Independent associations of telomere parameters with plaque presence were evaluated using general linear models.
Results
In men and women, age was inversely associated with LTL (Pearson’s r = −0.127, p < 0.001) and directly with %LTL<3 kb (Pearson’s r = 0.085; p = 0.001). Short LTL reached statistical significance as a determinant of total and femoral plaque in men, but not in women. However, this association was not sustained after adjustment for age or additional adjustment for cardiovascular risk factors. No significant independent association was found between %LTL<3 kb and plaque burden. Serum-oxidized low-density lipoprotein levels were directly associated with %LTL<3 kb in men (p = 0.008) and women (p < 0.001).
Conclusions
In a cross-sectional study of a middle-aged population, average LTL and short telomere load are not significant independent determinants of subclinical atherosclerosis. Longitudinal follow-up of PESA participants will assess long-term associations between telomere length and progression of subclinical atherosclerosis (19).
Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease
M.C. Williams, et al.
Background
In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA).
Objectives
The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes.
Methods
In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records.
Results
Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621).
Conclusions
In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590) (20).
Metabolic & LIPID Disorders
A Test in Context: Hemoglobin A1c and Cardiovascular Disease
M.O. Gore, et al.
Measurement of glycated hemoglobin (HbA1c), the most widely accepted indicator of long-term glycemic exposure, is central for the diagnosis and management of diabetes mellitus. Levels of HbA1c track epidemiologically with diabetic complications, and glycemic control, as reflected by HbA1c reduction, results in decreased risk of microvascular complications, including diabetic kidney disease, neuropathy, and retinopathy. The relationship between HbA1c reduction and cardiovascular disease prevention in patients with diabetes is more complex, with data from large randomized trials published over the past decade providing clear evidence that lowering of HbA1c per se is an inadequate marker for a therapeutic regimen’s impact on cardiovascular outcomes and patient survival. Recent revisions in professional society guidelines moved away from uniform recommendations and toward a more nuanced, patient-centered approach to HbA1c therapeutic targets. The context and key evidence underpinning these recent changes are discussed in this paper, alongside a brief overview of HbA1c contemporary assays and their limitations (21).
Atrial Fibrillation and Thromboembolism in Patients With Chronic Kidney Disease
Y.C. Lau, et al.
A bidirectional relationship exists between atrial fibrillation (AF) and chronic renal disease. Patients with AF have a higher incidence of renal dysfunction, and the latter predisposes to incident AF. The coexistence of both conditions results in a higher risk for thromboembolic-related adverse events but a paradoxical increased hemorrhagic risk. Oral anticoagulants (both vitamin K antagonists [VKAs] and non-VKA oral anticoagulants [NOACs]) have been demonstrated to be effective in mild to moderate renal dysfunction. Patients with severe renal impairment were excluded from the non-VKA oral anticoagulant trials, so limited data are available. In end-stage renal failure, the net clinical benefit of VKAs in dialysis-dependent patients remains uncertain, although some evidence suggests that such patients may do well with high-quality anticoagulation control. Risk stratification and careful follow-up of such patients are necessary to ensure a net clinical benefit from thromboprophylaxis (22).
Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up
L. Perez de Isla, et al.
Background
Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on attainment of treatment targets; large registries that reflect real-life clinical practice can uniquely provide this information.
Objectives
We sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry.
Methods
The SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT).
Results
The study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals.
Conclusions
Despite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals (23).
Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia
A.V. Khera, et al.
Background
Approximately 7% of American adults have severe hypercholesterolemia (untreated low-density lipoprotein [LDL] cholesterol ≥190 mg/dl), which may be due to familial hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in FH mutation carriers may confer coronary artery disease (CAD) risk beyond that captured by a single LDL cholesterol measurement.
Objectives
This study assessed the prevalence of an FH mutation among those with severe hypercholesterolemia and determined whether CAD risk varies according to mutation status beyond the observed LDL cholesterol level.
Methods
Three genes causative for FH (LDLR, APOB, and PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD case subjects, 8,577 CAD-free control subjects) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database.
Results
Among 20,485 CAD-free control and prospective cohort participants, 1,386 (6.7%) had LDL cholesterol ≥190 mg/dl; of these, only 24 (1.7%) carried an FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers than noncarriers. Compared with a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had a 6-fold higher risk for CAD (odds ratio: 6.0; 95% confidence interval: 5.2 to 6.9), whereas those with both LDL cholesterol ≥190 mg/dl and an FH mutation demonstrated a 22-fold increased risk (odds ratio: 22.3; 95% confidence interval: 10.7 to 53.2). In an analysis of participants with serial lipid measurements over many years, FH mutation carriers had higher cumulative exposure to LDL cholesterol than noncarriers.
Conclusions
Among participants with LDL cholesterol ≥190 mg/dl, gene sequencing identified an FH mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers had substantially increased risk for CAD (24).
Incretin-Based Therapy for Diabetes: What a Cardiologist Needs to Know
G. Waldrop, et al.
Incretin-based therapies are effective glucose-lowering drugs that have an increasing role in the treatment of type 2 diabetes because of their efficacy, safety, and ease of use. Both glucagon-like peptide–1 receptor agonists and dipeptidyl peptidase–4 inhibitors are commonly used for glycemic control as adjuncts to metformin, other oral antiglycemic agents, or insulin. Glucagon-like peptide–1 receptor agonists may have additional effects, such as weight loss, that may be advantageous in obese patients. There is a large body of evidence from randomized controlled clinical trials supporting the cardiovascular safety of dipeptidyl peptidase–4 inhibitors and some glucagon-like peptide–1 receptor agonists, at least in the short term. However, concerns have been raised, particularly regarding their safety in patients with heart failure. In this review, the authors provide a brief but practical evidence-based analysis of the use of incretin-based agents in patients with diabetes, their efficacy, and cardiovascular safety (25).
Reduced Cardiac Index Is Not the Dominant Driver of Renal Dysfunction in Heart Failure
J.S. Hanberg, et al.
Background
It is widely believed that a reduced cardiac index (CI) is a significant contributor to renal dysfunction in patients with heart failure (HF). However, recent data have challenged this paradigm.
Objectives
This study sought to determine the relationship between CI and renal function in a multicenter population of HF patients undergoing pulmonary artery catheterization (PAC).
Methods
Patients undergoing PAC in either the randomized or registry portions of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial were included (n = 575). We evaluated associations between CI and renal function across multiple subgroups and assessed for nonlinear, threshold, and longitudinal relationships.
Results
There was a weak but significant inverse correlation between CI and estimated glomerular filtration rate (eGFR), such that higher CI was paradoxically associated with worse eGFR (r = −0.12; p = 0.02). CI was not associated with blood urea nitrogen (BUN) or the BUN to creatinine ratio. Similarly, no associations were observed between CI and better renal function across multiple subgroups defined by indications for PAC or hemodynamic, laboratory, or demographic parameters. A nonlinear or threshold effect could not be identified. In patients with serial assessments of renal function and CI, we were unable to find within-subject associations between change in CI and eGFR using linear mixed modeling. Neither CI nor change in CI was lower in patients developing worsening renal function (p ≥ 0.28).
Conclusions
These results reinforce evidence that reduced CI is not the primary driver for renal dysfunction in patients hospitalized for HF, irrespective of the degree of CI impairment or patient subgroup analyzed (26).
Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial
S.A. Murphy, et al.
Background
Intensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin.
Objectives
This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy.
Methods
All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis.
Results
Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005).
Conclusions
Lipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878) (27).
Statin-Associated Side Effects
P.D. Thompson, et al.
Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are “statin-associated symptoms” because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy (28).
Statins in Familial Hypercholesterolemia: Consequences for Coronary Artery Disease and All-Cause Mortality
J. Besseling, et al.
Background
A statin-induced reduction of coronary artery disease (CAD) events and mortality has not been adequately quantified in patients with heterozygous familial hypercholesterolemia (FH).
Objectives
This study estimated the relative risk reduction for CAD and mortality by statins in heterozygous FH patients.
Methods
The authors included all adult heterozygous FH patients, identified by the Dutch screening program for FH between 1994 and 2013, who were free of CAD at baseline. Hospital, pharmacy, and mortality records between 1995 and 2015 were linked to these patients. The primary outcome was the composite of myocardial infarction, coronary revascularization, and death from any cause. The effect of statins (time-varying) was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, and antihypertensive and antidiabetic medication. The authors applied inverse-probability-for-treatment weighting (IPTW) to account for differences at baseline between statin users and never-users.
Results
The authors obtained medical records of 2,447 patients, of whom 888 were excluded on the basis of age <18 years or previous CAD. Simvastatin 40 mg and atorvastatin 40 mg accounted for 23.1% and 22.8% of all prescriptions, respectively. Statin users (n = 1,041) experienced 89 CAD events and 17 deaths during 11,674 person-years of follow-up versus statin never-users (n = 518), who had 22 CAD events and 9 deaths during 4,892 person-years (combined rates 8.8 vs. 5.3 per 1,000 person-years, respectively; p < 0.001). After applying IPTW and adjusting for other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.56 (95% confidence interval: 0.33 to 0.96).
Conclusions
In patients with heterozygous FH, moderate- to high-intensity statin therapy lowered the risk for CAD and mortality by 44%. This is essential information in all cost-effectiveness studies of this disorder, such as when evaluating reimbursement of new lipid-lowering therapies (29).
Rhythm Disorders
A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I
L. Calò, et al.
Background
Risk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS).
Objectives
This study sought to analyze the usefulness of electrocardiographic parameters as markers of sudden cardiac death (SCD) in BrS.
Methods
This study analyzed data from 347 consecutive patients (78.4% male; mean age 45 ± 13.1 years) with spontaneous type 1 BrS by ECG parameters but with no history of cardiac arrest (including 91.1% asymptomatic at presentation, 5.2% with a history of atrial fibrillation [AF], and 4% with a history of arrhythmic syncope). Electrocardiographic characteristics at the first clinic visit were analyzed to predict ventricular fibrillation (VF)/SCD during follow-up.
Results
During the follow-up (48 ± 38 months), 276 (79.5%) patients remained asymptomatic, 39 (11.2%) developed syncope, and 32 (9.2%) developed VF/SCD. Patients who developed VF/SCD had a lower prevalence of SCN5A gene mutations (p = 0.009) and a higher prevalence of positive electrophysiological study results (p < 0.0001), a family history of SCD (p = 0.03), and AF (p < 0.0001). The most powerful marker for VF/SCD was a significant S-wave (≥0.1 mV and/or ≥40 ms) in lead I. In the multivariate analysis, the duration of S-wave in lead I ≥40 ms (hazard ratio: 39.1) and AF (hazard ratio: 3.7) were independent predictors of VF/SCD during follow-up. Electroanatomic mapping in 12 patients showed an endocardial activation time significantly longer in patients with an S-wave in lead I, mostly because of a significant delay in the anterolateral right ventricular outflow tract.
Conclusions
The presence of a wide and/or large S-wave in lead I was a powerful predictor of life-threatening ventricular arrhythmias in patients with BrS and no history of cardiac arrest at presentation. However, the prognostic value of a significant S-wave in lead I should be confirmed by larger studies and by an independent confirmation cohort of healthy subjects (30).
A Tale of 2 Diseases: The History of Long-QT Syndrome and Brugada Syndrome
O. Havakuk, et al.
The Brugada syndrome (BrS) and long-QT syndrome (LQTS) present as congenital or acquired disorders with diagnostic electrocardiograms (ST-segment elevation and prolonged QT interval, respectively) and increased risk for malignant arrhythmias. Our understanding of the 2 disease forms (congenital vs. acquired) differs. A female patient on quinidine for atrial fibrillation who develops ventricular fibrillation is diagnosed with “acquired LQTS” and is discharged with no therapy other than instructions to avoid QT-prolonging medications. In contrast, an asymptomatic male patient who develops a Brugada electrocardiogram on flecainide is diagnosed with “asymptomatic BrS” and could be referred for an electrophysiological evaluation that could result in defibrillator implantation. The typical patient undergoing defibrillator implantation for BrS is asymptomatic but has a Brugada electrocardiogram provoked by a drug. The authors describe how the histories of LQTS and BrS went through the same stages, but in different sequences, leading to different conclusions (31).
Acute Kidney Injury in Asians With Atrial Fibrillation Treated With Dabigatran or Warfarin
Y.-H. Chan, et al.
Background
Whether dabigatran is associated with a lower risk of acute kidney injury (AKI) in patients with nonvalvular atrial fibrillation (NVAF) remains unknown.
Objectives
The authors compared the risk of AKI in Asians with NVAF who were prescribed dabigatran versus warfarin.
Methods
The authors analyzed patients enrolled in the Taiwan nationwide retrospective cohort study from June 1, 2012, to December 31, 2013. Dabigatran and warfarin were taken by 7,702 and 7,885 NVAF patients without a history of chronic kidney disease (CKD) and 2,256 and 2,089 NVAF patients with a history of CKD, respectively. A propensity-score weighted method was used to balance covariates across study groups.
Results
A total of 6,762 (88%) and 940 (12%) CKD-free patients and 2,025 (90%) and 231 (10%) CKD patients took dabigatran 110 mg and 150 mg twice daily, respectively. Dabigatran was associated with a lower risk of AKI than warfarin for either the CKD-free (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.49 to 0.77; p < 0.001) or CKD (HR: 0.56; 95% CI: 0.46 to 0.69; p < 0.001) cohort. As the increment in CHA2DS2-VASc score (a risk score based on congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, aged 65 to 74 years, and female sex) increased from 0/1 to 6+ points, the incidence of AKI for the dabigatran group was relatively stable (1.87% to 2.91% per year for the CKD-free cohort; 7.31% to 13.15% per year for the CKD cohort) but increased obviously for patients taking warfarin for either CKD-free (2.00% to 6.16% per year) or CKD cohorts (6.82 to 26.03% per year). The warfarin group had a significantly higher annual risk of AKI than the dabigatran group for those with a high CHA2DS2-VASc score (≥4 for the CKD-free cohort and ≥3 for the CKD cohort). Subgroup analysis revealed that among dabigatran users, those taking either low-dose or standard-dose dabigatran, those with a warfarin-naïve or warfarin-experienced history, those with or without diabetes, and those with CHA2DS2-VASc ≥4 or HAS-BLED ≥3 (risk score based on hypertension, abnormal renal and liver function, stroke, prior major bleeding, labile international normalized ratios, age 65 years or older, drugs or alcohol usage history) all had a lower risk of AKI than those taking warfarin.
Conclusions
Among Asians with NVAF, dabigatran is associated with a lower risk of AKI than warfarin (32).
Alcohol and Atrial Fibrillation: A Sobering Review
A. Voskoboinik, et al.
Alcohol is popular in Western culture, supported by a perception that modest intake is cardioprotective. However, excessive drinking has detrimental implications for cardiovascular disease. Atrial fibrillation (AF) following an alcohol binge or the “holiday heart syndrome” is well characterized. However, more modest levels of alcohol intake on a regular basis may also increase the risk of AF. The pathophysiological mechanisms responsible for the relationship between alcohol and AF may include direct toxicity and alcohol’s contribution to obesity, sleep-disordered breathing, and hypertension. We aim to provide a comprehensive review of the epidemiology and pathophysiology by which alcohol may be responsible for AF and determine whether alcohol abstinence is required for patients with AF (33).
Bariatric Surgery and the Risk of New-Onset Atrial Fibrillation in Swedish Obese Subjects
S. Jamaly, et al.
Background
Obesity is a risk factor for atrial fibrillation, which in turn is associated with stroke, heart failure, and increased all-cause mortality.
Objectives
The authors investigated whether weight loss through bariatric surgery may reduce the risk of new-onset atrial fibrillation.
Methods
SOS (Swedish Obese Subjects) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary healthcare centers in Sweden. The cohort was recruited between 1987 and 2001. Among 4,021 obese individuals with sinus rhythm and no history of atrial fibrillation, 2,000 underwent bariatric surgery (surgery group), and 2,021 matched obese control subjects received usual care (control group). The outcome, first-time atrial fibrillation, was ascertained by crosschecking the SOS database with the Swedish National Patient Register on inpatient and outpatient diagnosis codes.
Results
During a median follow-up of 19 years, first time atrial fibrillation occurred in 247 patients (12.4%) in the surgical group, and in 340 (16.8%) control subjects. The risk of developing atrial fibrillation was 29% lower in the surgery group versus the control group (hazard ratio: 0.71; 95% confidence interval: 0.60 to 0.83; p < 0.001). Younger individuals benefited more from surgical intervention than those who were older (p value for interaction 0.001). Also, those with a high diastolic blood pressure benefitted more from surgery than did those with a low diastolic blood pressure (p for interaction = 0.028).
Conclusions
Compared with usual care, weight loss through bariatric surgery reduced the risk of atrial fibrillation among persons being treated for severe obesity. The risk reduction was more apparent in younger people and in those with higher blood pressure (34).
Causes of Death in Anticoagulated Patients With Atrial Fibrillation
A. Gómez-Outes, et al.
Background
Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population.
Objectives
The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF.
Methods
The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies.
Results
71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings.
Conclusions
In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF (35).
Clinical Inferences of Cardiovascular Implantable Electronic Device Analysis at Autopsy
S.K. Sinha, et al.
Background
Cardiovascular implantable electronic device (CIED) removal and interrogation are recommended at autopsy in suspected cases of sudden cardiac death, but data on the role of nonselective post-mortem CIED (pacemaker or defibrillator) analysis in this setting are lacking.
Objectives
This study undertook an institutional registry analysis to determine the utility of systematic routine CIED removal, interrogation, and analysis at autopsy.
Methods
From May 19, 2009, to May 18, 2015, autopsy subjects with a CIED at a Johns Hopkins University medical institution (Baltimore, Maryland) underwent CIED removal and interrogation by an electrophysiologist for clinical alerts. The CIED was then submitted for technical analysis by the manufacturer. The CIED interrogation, the manufacturer’s technical analysis, and the final autopsy report were all cataloged in the Johns Hopkins Post-mortem CIED Registry.
Results
A total of 2,025 autopsies were performed; 84 subjects had CIEDs removed and analyzed. These devices included 37 pacemakers and 47 defibrillators. Overall, 43 subjects had died suddenly, and 41 had not died suddenly. Significant clinical alerts (sustained tachyarrhythmias or an elevated fluid index value) were seen in 62.8% cases of sudden deaths. In the nonsudden death cohort, 19.5% displayed a significant clinical alert. Significant association of CIED alerts were noted when comparing sudden deaths versus nonsudden deaths (p < 0.001), defibrillators versus pacemakers (p < 0.005), and cardiac versus noncardiac causes of death (p < 0.001). Manufacturer analyses revealed a case of premature pacemaker battery depletion, as well as a hard reset in a defibrillator as a result of cold exposure.
Conclusions
Post-mortem CIED analysis was clinically useful in assisting with determination of the timing, mechanism, and cause of death in the majority of sudden deaths and in almost 20% of nonsudden deaths. The authors advocate CIED removal with analysis as an important diagnostic tool in all autopsies and to assist manufacturers in identifying potentially fatal device failures (36).
Clinically Significant Pocket Hematoma Increases Long-Term Risk of Device Infection: BRUISE CONTROL INFECTION Study
V. Essebag, et al.
Background
The BRUISE CONTROL trial (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial) demonstrated that a strategy of continued warfarin during cardiac implantable electronic device surgery was safe and reduced the incidence of clinically significant pocket hematoma (CSH). CSH was defined as a post-procedure hematoma requiring further surgery and/or resulting in prolongation of hospitalization of at least 24 h, and/or requiring interruption of anticoagulation. Previous studies have inconsistently associated hematoma with the subsequent development of device infection; reasons include the retrospective nature of many studies, lack of endpoint adjudication, and differing subjective definitions of hematoma.
Objectives
The BRUISE CONTROL INFECTION (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial Extended Follow-Up for Infection) prospectively examined the association between CSH and subsequent device infection.
Methods
The study included 659 patients with a primary outcome of device-related infection requiring hospitalization, defined as 1 or more of the following: pocket infection; endocarditis; and bloodstream infection. Outcomes were verified by a blinded adjudication committee. Multivariable analysis was performed to identify predictors of infection.
Results
The overall 1-year device-related infection rate was 2.4% (16 of 659). Infection occurred in 11% of patients (7 of 66) with previous CSH and in 1.5% (9 of 593) without CSH. CSH was the only independent predictor and was associated with a >7-fold increased risk of infection (hazard ratio: 7.7; 95% confidence interval: 2.9 to 20.5; p < 0.0001). Empiric antibiotics upon development of hematoma did not reduce long-term infection risk.
Conclusions
CSH is associated with a significantly increased risk of infection requiring hospitalization within 1 year following cardiac implantable electronic device surgery. Strategies aimed at reducing hematomas may decrease the long-term risk of infection. (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial [BRUISE CONTROL]; NCT00800137) (37).
Implantable Cardioverter-Defibrillators at End of Battery Life: Opportunities for Risk (Re)-Stratification in ICD Recipients
F.M. Merchant, et al.
Although implantable cardioverter-defibrillators (ICDs) are frequently viewed as a lifelong commitment in that patients are routinely scheduled for generator exchange (GE) at end of battery life, several considerations should prompt a reevaluation of risks and benefits before GE. Compared with initial ICD implant, patients receiving replacement devices are older, and have more comorbidities and shorter life expectancy, all of which may limit the benefit of ICD therapy following GE. Additionally, GE is associated with significant complications, including infection, which may increase the risk of mortality. In this paper, we review recent data regarding opportunities for risk stratification before GE, with a particular focus on those with improved left ventricular function and those who have not experienced ICD therapies during the first battery life. We also provide a broader perspective on ICD therapy, focusing on how decisions regarding GE may affect goals of care at the end of life (38).
Left Atrial Appendage Isolation in Patients With Longstanding Persistent AF Undergoing Catheter Ablation: BELIEF Trial
L. Di Biase, et al.
Background
Longstanding persistent (LSP) atrial fibrillation (AF) is the most challenging type of AF. In addition to pulmonary vein isolation, substrate modification and triggers ablation have been reported to improve freedom from AF in patients with LSPAF.
Objectives
This study sought to assess whether the empirical electrical isolation of the left atrial appendage (LAA) could improve success at follow-up.
Methods
This was an open-label, randomized study assessing the effectiveness of empirical electrical left atrial appendage isolation for the treatment of LSPAF. Patients were randomly assigned to undergo empirical electrical left atrial appendage isolation along with extensive ablation (group 1; n = 85) or extensive ablation alone (group 2; n = 88). Recurrence of atrial arrhythmias was the primary endpoint. Secondary endpoints included cardiac-related hospitalization, all-cause mortality, and stroke at follow-up.
Results
Major clinical characteristics were not different between the 2 groups. At 12-month follow-up, 48 (56%) patients in group 1 and 25 (28%) in group 2 were recurrence free after a single procedure (unadjusted hazard ratio [HR] for recurrence with standard ablation: 1.92; 95% confidence interval [CI]: 1.3 to 2.9; log-rank p = 0.001). After adjusting for age, sex, and left atrial size, standard ablation was predictive of recurrence (HR: 2.22; 95% CI: 1.29 to 3.81; p = 0.004). During repeat procedures, empirical electrical left atrial appendage isolation was performed in all patients. After an average of 1.3 procedures, cumulative success at 24-month follow-up was reported in 65 (76%) in group 1 and in 49 (56%) in group 2 (unadjusted HR: 2.24; 95% CI: 1.3 to 3.8; log-rank p = 0.003).
Conclusions
This randomized study showed that both after a single procedure and after redo procedures in patients with LSPAF, empirical electrical isolation of the LAA improved long-term freedom from atrial arrhythmias without increasing complications. (Effect of Empirical Left Atrial Appendage Isolation on Long-term Procedure Outcome in Patients With Persistent or Longstanding Persistent Atrial Fibrillation Undergoing Catheter Ablation [BELIEF]; NCT01362738) (39).
Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers
S. Kumar, et al.
Background
Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain.
Objectives
This study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic significance of the index cardiac phenotype.
Methods
The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined.
Results
The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death.
Conclusions
LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted (40).
Long-Term Clinical Outcomes of Subcutaneous Versus Transvenous Implantable Defibrillator Therapy
T.F. Brouwer, et al.
Background
Transvenous implantable cardioverter-defibrillators (TV-ICDs) improve survival in patients at risk for sudden cardiac death, but complications remain an important drawback. The subcutaneous ICD (S-ICD) was developed to overcome lead-related complications. Comparison of clinical outcomes of both device types in previous studies was hampered by dissimilar patient characteristics.
Objectives
This retrospective study compares long-term clinical outcomes of S-ICD and TV-ICD therapy in a propensity-matched cohort.
Methods
The authors analyzed 1,160 patients who underwent S-ICD or TV-ICD implantation in 2 high-volume hospitals in the Netherlands. Propensity matching for 16 baseline characteristics, including diagnosis, yielded 140 matched pairs. Clinical outcomes were device-related complications requiring surgical intervention, appropriate and inappropriate ICD therapy, and were reported as 5-year Kaplan-Meier rate estimates.
Results
All 16 baseline characteristics were balanced in the matched cohort of 140 patients with S-ICDs and 140 patients with TV-ICDs (median age 41 years [interquartile range: 30 to 52 years] and 40% women). The complication rate was 13.7% in the S-ICD group versus 18.0% in the TV-ICD group (p = 0.80). The infection rate was 4.1% versus 3.6% in the TV-ICD groups (p = 0.36). Lead complications were lower in the S-ICD arm compared with the TV-ICD arm, 0.8% versus 11.5%, respectively (p = 0.03). S-ICD patients had more nonlead-related complications than TV-ICD patients, 9.9% versus 2.2%, respectively (p = 0.047). Appropriate ICD intervention (antitachycardia pacing and shocks) occurred more often in the TV-ICD group (hazard ratio [HR]: 2.42; p = 0.01). The incidence of appropriate (TV-ICD HR: 1.46; p = 0.36) and inappropriate shocks (TV-ICD HR: 0.85; p = 0.64) was similar.
Conclusions
The complication rate in patients implanted with an S-ICD or TV-ICD was similar, but their nature differed. The S-ICD reduced lead-related complications significantly, at the cost of nonlead-related complications. Rates of appropriate and inappropriate shocks were similar between the 2 groups (41).
Long-Term Trends in Newly Diagnosed Brugada Syndrome: Implications for Risk Stratification
R. Casado-Arroyo, et al.
Background
A proband of Brugada syndrome (BrS) is the first patient diagnosed in a family. There are no data regarding this specific, high-risk population.
Objectives
This study sought to investigate the Brugada probands diagnosed from 1986 through the next 28 years.
Methods
We included 447 probands belonging to families with a diagnostic type 1 electrocardiogram Brugada pattern. The database was divided into 2 periods: the first period identified patients who were part of the initial cohort that became the consensus document on BrS in 2002 (early group); the second period reflected patients first diagnosed from 2003 to January 2014 (latter group).
Results
There were 165 probands in the early group and 282 in the latter group. Aborted sudden death as the first manifestation of the disease occurred in 12.1% of the early group versus 4.6% of the latter group (p = 0.005). Inducibility during programmed electrical stimulation was achieved in 34.4% and 19.2% of patients, respectively (p < 0.001). A spontaneous type 1 electrocardiogram pattern at diagnosis was present in 50.3% early versus 26.2% latter patients (p = 0.0002). Early group patients had a higher probability of a recurrent arrhythmia during follow-up (19%) than those of the latter group (5%) (p = 0.007). The clinical suspicion and use of a sodium-channel blocker to unmask BrS has allowed earlier diagnoses in many patients.
Conclusions
Since being first described, the presentation of BrS has changed. There has been a decrease in aborted sudden cardiac death as the first manifestation of the disease among patients who were more recently diagnosed. These variations in initial presentation have important clinical consequences. In this setting, the value of inducibility to stratify individuals with BrS has changed (42).
Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF
K.E. Chan, et al.
Nonvitamin K-dependent oral anticoagulant agents (NOACs) are currently recommended for patients with atrial fibrillation at risk for stroke. As a group, NOACs significantly reduce stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with warfarin. All NOACs are dependent on the kidney for elimination, such that patients with creatinine clearance <25 ml/min were excluded from all the pivotal phase 3 NOAC trials. It therefore remains unclear how or if NOACs should be prescribed to patients with advanced chronic kidney disease and those on dialysis. The authors review the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <30 ml/min) and those on dialysis. The authors frame the evidence in terms of risk versus benefit to bring greater clarity to NOAC-related major bleeding and efficacy at preventing stroke specifically in patients with creatinine clearance <30 ml/min (43).
Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes
P.J. Schwartz, et al.
Drug-induced long QT syndrome (diLQTS) and congenital LQTS (cLQTS) share many features, and both syndromes can result in life-threatening torsades de pointes (TdP). Our understanding of their mechanistic and genetic similarities has led to their improved clinical management. However, our inability to prevent diLQTS has resulted in removal of many medicines from the market and from development. Genetic and clinical risk factors for diLQTS and TdP are well known and raise the possibility of TdP prevention. Clinical decision support systems (CDSS) can scan the patient’s electronic health records for clinical risk factors predictive of diLQTS and warn when a drug that can cause TdP is prescribed. CDSS have reduced prescriptions of QT-prolonging drugs, but these relatively small changes lack the power to reduce TdP. The growing genetic evidence linking diLQTS to cLQTS suggests that prevention of TdP in the future may require inclusion of both genetic and clinical predictors into CDSS (44).
QRS Duration or QRS Morphology: What Really Matters in Cardiac Resynchronization Therapy?
J.E. Poole, et al.
The beneficial effects of cardiac resynchronization therapy (CRT) have been well established in large, randomized trials. Despite the documented success of this treatment strategy, a significant proportion of patients with heart failure do not achieve the desired response. The aim of this review was to delineate factors contributing to a successful CRT response, emphasizing the interrelated roles of QRS morphology and QRS interval duration. More data are available on QRS duration, as this factor has been used as an enrollment criterion in clinical trials. Response to CRT seems to increase as the QRS duration becomes longer, with greatest benefit in QRS duration ≥150 ms. Recent data have placed more emphasis on QRS morphology, demonstrating variability in clinical response between patients with left bundle branch block, non–left bundle branch block, and right bundle branch block morphology. Notably, myocardial scarring and cardiac dimensions, among other variables, may alter heterogeneity in ventricular activation. Understanding the electrophysiological underpinnings of the QRS complex has become important not only to predict response but also to facilitate the patient-specific delivery of resynchronization therapy (45).
Safety and Efficacy of the Subcutaneous Implantable Defibrillator
G.F. Lewis, et al.
Multiple randomized, multicenter trials have established the role of the implantable cardioverter-defibrillator (ICD) in the treatment and prevention of sudden cardiac death. However, transvenous ICD leads have significant short- and long-term complications, offsetting some of the benefit of this therapy. This has led to the development of the entirely subcutaneous ICD. This system is safe and effective, avoiding the need for intravascular leads. It is best suited for patients at low risk for pacing and increased risk for transvenous lead complications. Ongoing randomized and long-term registries will help identify the optimal role of this device in clinical practice (46).
Thromboembolic, Bleeding, and Mortality Risks of Rivaroxaban and Dabigatran in Asians With Nonvalvular Atrial Fibrillation
Y.-H. Chan, et al.
Background
It is unclear whether the non–vitamin K antagonist oral anticoagulant agents rivaroxaban and dabigatran are superior to warfarin for efficacy and safety outcomes in Asians with nonvalvular atrial fibrillation (NVAF).
Objectives
The aim of this study was to compare the risk for thromboembolic events, bleeding, and mortality associated with rivaroxaban and dabigatran versus warfarin in Asians with NVAF.
Methods
A nationwide retrospective cohort study was conducted of consecutive patients with NVAF taking rivaroxaban (n = 3,916), dabigatran (n = 5,921), or warfarin (n = 5,251) using data collected from the Taiwan National Health Insurance Research Database between February 1, 2013 and December 31, 2013. The propensity score weighting method was used to balance covariates across study groups. Patients were followed until the first occurrence of any study outcome or the study end date (December 31, 2013).
Results
A total of 3,425 (87%) and 5,301 (90%) patients were taking low-dose rivaroxaban (10 to 15 mg once daily) and dabigatran (110 mg twice daily), respectively. Compared with warfarin, both rivaroxaban and dabigatran significantly decreased the risk for ischemic stroke or systemic embolism (p = 0.0004 and p = 0.0006, respectively), intracranial hemorrhage (p = 0.0007 and p = 0.0005, respectively), and all-cause mortality (p < 0.0001 and p < 0.0001, respectively) during the short follow-up period. In comparing the 2 non–vitamin K antagonist oral anticoagulant agents with each other, no differences were found regarding risk for ischemic stroke or systemic embolism, intracranial hemorrhage, myocardial infarction, or mortality. Rivaroxaban carried a significantly higher risk for hospitalization for gastrointestinal bleeding than dabigatran (p = 0.0416), but on-treatment analysis showed that the risk for hospitalized gastrointestinal bleeding was similar between the 2 drugs (p = 0.5783).
Conclusions
In real-world practice among Asians with NVAF, both rivaroxaban and dabigatran were associated with reduced risk for ischemic stroke or systemic embolism, intracranial hemorrhage, and all-cause mortality without significantly increased risk for acute myocardial infarction or hospitalization for gastrointestinal bleeding compared with warfarin (47).
Valvular Heart Disease
3-Year Outcomes in High-Risk Patients Who Underwent Surgical or Transcatheter Aortic Valve Replacement
G.M. Deeb, et al.
Background
In patients with severe aortic stenosis at increased risk for surgery, self-expanding transcatheter aortic valve replacement (TAVR) is associated with improved 2-year survival compared with surgery.
Objectives
This study sought to determine whether this clinical benefit was sustained over time.
Methods
Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were randomized 1:1 to TAVR or open surgical valve replacement (SAVR). Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure.
Results
A total of 797 patients underwent randomization at 45 U.S. centers; 750 patients underwent an attempted procedure. Three-year all-cause mortality or stroke was significantly lower in TAVR patients (37.3% vs. 46.7% in SAVR; p = 0.006). Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients, including all-cause mortality (32.9% vs. 39.1%, respectively; p = 0.068), all stroke (12.6% vs. 19.0%, respectively; p = 0.034), and major adverse cardiovascular or cerebrovascular events (40.2% vs. 47.9%, respectively; p = 0.025). At 3 years aortic valve hemodynamics were better with TAVR patients (mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR; p < 0.001), although moderate or severe residual aortic regurgitation was higher in TAVR patients (6.8% vs. 0.0% in SAVR; p < 0.001). There was no clinical evidence of valve thrombosis in either group.
Conclusions
Patients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery. Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902) (48).
Anticoagulation During Pregnancy: Evolving Strategies With a Focus on Mechanical Valves
L. Alshawabkeh, et al.
Pregnancy is associated with a hypercoagulable state. Women requiring anticoagulation need careful attention throughout pregnancy and the post-partum period. The choice of anticoagulant therapy, the degree of monitoring, and the therapeutic target should be modulated by balancing the risks and the benefits to the mother and fetus. Many of the available anticoagulant agents may be used safely in pregnancy, but they are disadvantaged by competing efficacy and risks to the mother and fetus. For example, vitamin K antagonists are the most efficacious for preventing mechanical valve thrombosis, but they pose risks to the fetus. Collaborative research that collects patient-level data will help clinicians navigate the intricate process of anticoagulation in pregnancy. Development of anticoagulant agents that are homogeneous, efficacious, safe to the fetus, and not affected by physiological perturbations of pregnancy will have tremendous effect on the outcomes of pregnancy in women who require anticoagulation (49).
Aortic Valve Sparing in Different Aortic Valve and Aortic Root Conditions
T.E. David
The development of aortic valve-sparing operations (reimplantation of the aortic valve and remodeling of the aortic root) expanded the surgical armamentarium for treating patients with aortic root dilation caused by a variety of disorders. Young adults with aortic root aneurysms associated with genetic syndromes are ideal candidates for reimplantation of the aortic valve, and the long-term results have been excellent. Incompetent bicuspid aortic valves with dilated aortic annuli are also satisfactorily treated with the same type of operation. Older patients with ascending aortic aneurysm and aortic insufficiency secondary to dilated sinotubular junction and a normal aortic annulus can be treated with remodeling of the aortic root or with reimplantation of the aortic valve. The first procedure is simpler, and both procedures are likely equally effective. As with any heart valve-preserving procedure, patient selection and surgical expertise are keys to successful and durable repairs (50).
Association of B-Type Natriuretic Peptide With Survival in Patients With Degenerative Mitral Regurgitation
M.-A. Clavel, et al.
Background
Studies suggesting that B-type natriuretic peptide (BNP) may predict outcomes of mitral regurgitation (MR) are plagued by small size, inconsistent etiologies, and lack of accounting for shifting normal BNP ranges with age and sex.
Objectives
This study assessed the effect of BNP activation on mortality in a large, multicenter cohort of patients with degenerative MR.
Methods
In 1,331 patients with degenerative MR, BNP was prospectively measured at diagnosis and expressed as BNPratio (ratio to upper limit of normal for age, sex, and assay). Initial surgical management was performed within 3 months of diagnosis in 561 patents.
Results
The cohort had a mean age of 64 ± 15 years, was 66% male, and had a mean ejection fraction 64 ± 9%, mean regurgitant volume 67 ± 31 ml, and low mean Charlson comorbidity index of 1.09 ± 1.76. Median BNPratio was 1.01 (25th and 75th percentiles: 0.42 to 2.36). Overall, BNPratio was a powerful, independent predictor of mortality (hazard ratio: 1.33 [95% confidence interval: 1.15 to 1.54]; p < 0.0001), whereas absolute BNP was not (p = 0.43). In patients who were initially treated medically (n = 770; 58%), BNPratio was a powerful, independent, and incremental predictor of mortality after diagnosis (hazard ratio: 1.61 [95% confidence interval: 1.34 to 1.93]; p < 0.0001). Higher BNP activation was associated with higher mortality (p < 0.0001). All subgroups, particularly severe MR, incurred similar excess mortality with BNP activation. After initial surgical treatment (n = 561, 42%) BNP activation did not impose excess long-term mortality (p = 0.23).
Conclusions
In patients with degenerative MR, BNPratio is a powerful, independent, and incremental predictor of long-term mortality under medical management. BNPratio should be incorporated into the routine clinical assessment of patients with degenerative MR (51).
Cerebral Embolism During Transcatheter Aortic Valve Replacement: The BRAVO-3 MRI Study
E. Van Belle, et al.
Background
Cerebral embolization is a frequent complication after transcatheter aortic valve replacement (TAVR). We hypothesized that cerebral embolization may be reduced by anticoagulation with bivalirudin during TAVR.
Objectives
This study sought to determine the proportion of patients with new cerebral embolus after TAVR and to investigate whether parenteral procedural anticoagulation strategies affect cerebral embolization.
Methods
The BRAVO (Effect of Bivalirudin on Aortic Valve Intervention Outcomes)-3 randomized trial compared bivalirudin with unfractionated heparin in patients undergoing transfemoral TAVR. A prospective cerebral magnetic resonance imaging (MRI) substudy was conducted in 4 sites; 60 patients were imaged with brain MRI after TAVR. Primary endpoint was proportion of patients with new cerebral emboli on MRI. Secondary endpoints included quantitative MRI analyses of cerebral lesions and neurological outcomes at 48 h and 30 days.
Results
Patients were randomized to bivalirudin (n = 29) versus heparin (n = 31). The proportion of patients with new cerebral emboli on MRI did not differ between bivalirudin and heparin groups (65.5% vs. 58.1%; p = 0.55). Groups were similar for median number of emboli per patient (1 [interquartile range (IQR): 0 to 3] vs. 1 [IQR: 0 to 1]; p = 0.08), total volume of emboli (45 [IQR: 0 to 175] mm3 vs. 33 [IQR: 0 to 133] mm3; p = 0.86), or proportion of patients with a clinical neurological deficit at 48 h or 30 days. All patients who presented clinically with stroke had evidence of new emboli on MRI.
Conclusions
This study documented cerebral embolization in nearly two-thirds of patients during contemporary TAVR. There were no significant differences in cerebral embolization for bivalirudin versus heparin anticoagulation during TAVR. (Open-Label, Randomized Trial in Patients Undergoing TAVR to Determine Safety and Efficacy of Bivalrudin vs. UFH [BRAVO-2/3]; NCT01651780) (52).
High-Risk Cardiac Disease in Pregnancy: Part II
U. Elkayam, et al.
Heart disease continues to be the leading cause of nonobstetric maternal morbidity and mortality. Early diagnosis and appropriate care can lead to prevention of complications and improvement of pregnancy outcome. This paper continues the review and provides recommendations for the approach to high-risk cardiovascular conditions during gestation (53).
Long-Term Outcomes in Patients With Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction
A. Mentias, et al.
Background
Chronic severe aortic regurgitation (AR) imposes significant volume and pressure overload on the left ventricle (LV), but such patients typically remain in an asymptomatic state for a very long time.
Objectives
This study sought to examine long-term outcomes in a contemporary group of patients with grade III+ chronic AR and preserved left ventricular ejection fraction (LVEF) and the value of aortic valve (AV) surgery on long-term survival. We also wanted to reassess the threshold of LV dimension, beyond which mortality significantly increases.
Methods
The authors studied 1,417 such patients (mean 54 ± 16 years of age, 75% men) seen between 2002 and 2010. Clinical data were obtained and Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality.
Results
Mean STS score was 5.5% ± 8%, and mean LVEF was 57 ± 4%, whereas 1,228 patients (87%) were asymptomatic, and 93 patients (7%) had indexed LV end-systolic dimension (iLVESD) ≥2.5 cm/m2. At 6.6 ± 3 years, 933 patients (66%) underwent AV surgery (36% isolated AV surgery, 16% concomitant coronary bypass, and 58% aortic replacement), and 262 patients (19%) died. In-hospital postoperative mortality was 2% (0.6% in isolated AV surgery). On multivariate Cox survival analysis, compared to the group of iLVESD <2.5 cm/m2 and no AV surgery, the 2 groups of iLVESD <2.5 cm/m2 with AV surgery and iLVESD ≥2.5 cm/m2 with AV surgery were associated with improved survival (hazard ratios: 0.62 and 0.42, respectively; both p < 0.01). Survival of patients who underwent AV surgery was similar to that of an age- and sex-matched U.S. population with 96% of deaths occurring in those with iLVESD <2.5 cm/m2.
Conclusions
At a high-volume experienced center, patients with grade III or greater AR and preserved LVEF demonstrated significantly improved long-term survival following AV surgery. The risk of death significantly increased at a lower LV dimension threshold than previously described (54).
Mitral Regurgitation in Patients With Hypertrophic Obstructive Cardiomyopathy: Implications for Concomitant Valve Procedures
J.H. Hong, et al.
Background
Incidence and outcome of mitral valve (MV) surgery are unknown in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing extended transaortic septal myectomy.
Objectives
This study sought to define indications and suitable operative strategy for mitral regurgitation (MR) in patients with HOCM.
Methods
A total of 2,107 septal myectomy operations performed in adults from January 1993 to May 2014 at Mayo Clinic in Rochester, Minnesota, were retrospectively reviewed. Patients with prior MV operation and apical hypertrophic cardiomyopathy were excluded. Overall, 2,004 operations were performed in 1,993 patients.
Results
Pre-operative MR was grade ≥3 (of 4) in 1,152 operations (57.5%). Systolic anterior motion of mitral leaflets caused the MR in most patients. However, intrinsic MV disease was identified pre-operatively in 99 patients, all of whom had MV surgery (with septal myectomy). In 1,905 operations, no intrinsic MV disease was identified pre-operatively; in 1,830 (96.1%), septal myectomy was performed without a direct MV procedure. For 75 patients, intrinsic MV disease discovered intraoperatively led to concomitant MV repair (86.7%) or replacement (13.3%). After isolated septal myectomy, the percentage of patients with MR grade ≥3 decreased from 54.3% to 1.7% (p = 0.001) on early post-operative echocardiography. Among 174 patients with concomitant MV surgery, late survival was superior with MV repair (n = 133 [76.4%]) versus replacement (10-year survival: 80.0% vs. 55.2%; p = 0.002).
Conclusions
In most patients with HOCM, MR related to systolic anterior motion of the MV is relieved through adequate myectomy. Concomitant MV surgery is rarely necessary unless intrinsic MV disease is present. When MV procedures are required, repair is preferred because of improved survival compared with replacement (55).
Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve
J.P. Dal-Bianco, et al.
Background
In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition.
Objectives
The aim of this study was to explore the clinically relevant situation of tethering and MI, testing the hypothesis that ischemic milieu modifies mitral valve adaptation.
Methods
Twenty-three adult sheep were examined. Under cardiopulmonary bypass, the papillary muscle tips in 6 sheep were retracted apically to replicate tethering, short of producing MR (tethered alone). Papillary muscle retraction was combined with apical MI created by coronary ligation in another 6 sheep (tethered plus MI), and left ventricular remodeling was limited by external constraint in 5 additional sheep (left ventricular constraint). Six sham-operated sheep were control subjects. Diastolic mitral valve surface area was quantified by 3-dimensional echocardiography at baseline and after 58 ± 5 days, followed by histopathology and flow cytometry of excised leaflets.
Results
Tethered plus MI leaflets were markedly thicker than tethered-alone valves and sham control subjects. Leaflet area also increased significantly. Endothelial-to-mesenchymal transition, detected as α-smooth muscle actin-positive endothelial cells, significantly exceeded that in tethered-alone and control valves. Transforming growth factor-β, matrix metalloproteinase expression, and cellular proliferation were markedly increased. Uniquely, tethering plus MI showed endothelial activation with vascular adhesion molecule expression, neovascularization, and cells positive for CD45, considered a hematopoietic cell marker. Tethered plus MI findings were comparable with external ventricular constraint.
Conclusions
MI altered leaflet adaptation, including a profibrotic increase in valvular cell activation, CD45-positive cells, and matrix turnover. Understanding cellular and molecular mechanisms underlying leaflet adaptation and fibrosis could yield new therapeutic opportunities for reducing ischemic MR (56).
Natural History, Diagnostic Approaches, and Therapeutic Strategies for Patients With Asymptomatic Severe Aortic Stenosis
P. Généreux, et al.
Aortic stenosis (AS) is one of the most common valvular diseases encountered in clinical practice. Current guidelines recommend aortic valve replacement (AVR) when the aortic valve is severely stenotic and the patient is symptomatic; however, a substantial proportion of patients with severe AS are asymptomatic at the time of first diagnosis. Although specific morphological valve features, exercise testing, stress imaging, and biomarkers can help to identify patients with asymptomatic severe AS who may benefit from early AVR, the optimal management of these patients remains uncertain and controversial. The current report presents a comprehensive review of the natural history and the diagnostic evaluation of asymptomatic patients with severe AS, and is followed by a meta-analysis from reported studies comparing an early AVR strategy to active surveillance, with an emphasis on the level of evidence substantiating the current guideline recommendations. Finally, perspectives on directions for future investigation are discussed (57).
Outcomes in Moderate Mixed Aortic Valve Disease: Is it Time for a Paradigm Shift?
A.C. Egbe, et al.
Background
A direct comparison of outcomes between moderate mixed aortic valve disease (MAVD) and isolated aortic stenosis (AS) or aortic regurgitation (AR) has not been performed, making evidence-based recommendations difficult in patients with MAVD.
Objectives
This study sought to determine adverse event (AE) occurrence (the primary endpoint), defined as New York Heart Association functional class III/IV symptoms, aortic valve replacement, or cardiac death, and to compare AE rates between MAVD and isolated AS or AR.
Methods
Asymptomatic patients were identified with moderate MAVD and an ejection fraction ≥50% and were followed at Mayo Clinic from 1994 to 2013. Moderate MAVD was defined as a combination of moderate AS and moderate AR. Age- and sex-matched control groups were selected with isolated moderate AR (n = 117), moderate AS (n = 117), or severe AS (n = 117).
Results
At 9.1 ± 4.2 years of follow-up, patients with moderate MAVD (n = 251) had a mean age of 63 ± 11 years, 73% were male, and 38% had bicuspid valve. AE occurred in 193 (77%) patients in this group, including symptom development (69%), aortic valve replacement (67%), and cardiac death (4%). Predictors of AE were older age (hazard ratio [HR]: 1.71 per decade; 95% confidence interval [CI]: 1.38 to 1.97 per decade; p = 0.001), and relative wall thickness >0.42 (HR: 2.01; 95% CI: 1.86 to 2.33; p = 0.002). AE rates were similar in the MAVD and severe AS group (71% vs. 68% at 5 years; p = 0.49), but were significantly higher compared with the moderate AS and AR groups.
Conclusions
MAVD patients had outcomes comparable to those with severe AS, and preserved ejection fraction and should be monitored closely for symptoms (58).
Papillary Muscle Approximation Versus Restrictive Annuloplasty Alone for Severe Ischemic Mitral Regurgitation
F. Nappi, et al.
Background
Guidelines recommend surgery for patients with severe ischemic mitral regurgitation (MR). Nonrandomized studies suggest that subvalvular repair is associated with longer survival, but randomized studies are lacking.
Objectives
This study sought to investigate the benefit of papillary muscle surgery on long-term clinical outcomes of patients with ischemic MR.
Methods
Ninety-six patients with severe ischemic MR were randomized to either undersizing restrictive mitral annuloplasty (RA) or papillary muscle approximation with undersizing restrictive mitral annuloplasty (PMA) associated with complete surgical myocardial revascularization. The primary endpoint was change in left ventricular end-diastolic diameter (LVEDD) after 5 years, measured as the absolute difference from baseline, which was evaluated by paired Student t tests. Secondary endpoints included changes in echocardiographic parameters, overall mortality, the composite cardiac endpoint (major adverse cardiac and cerebrovascular events [MACCE]), and quality of life (QOL) during the 5-year follow-up.
Results
At 5 years, mean LVEDD was 56.5 ± 5.7 mm with PMA versus 60.6 ± 4.6 mm with RA (mean change from baseline −5.8 ± 4.1 mm and −0.2 ± 2.3 mm, respectively; p < 0.001). Ejection fraction was 44.1 ± 6% in the PMA group versus 39.9 ± 3.9% in the RA group (mean change from baseline 8.8 ± 5.9% and 2.5 ± 4.3%, respectively; p < 0.001). There was no statistically significant difference in mortality at 5 years, but freedom from MACCE favored PMA in the last year of follow-up. PMA significantly reduced tenting height, tenting area, and interpapillary distance soon after surgery and for the long-term, and significantly lowered moderate-to-severe MR recurrence. No differences were found in QOL measures.
Conclusions
Compared with RA only, PMA exerted a long-term beneficial effect on left ventricular remodeling and more effectively restored the mitral valve geometric configuration in ischemic MR, which improved long-term cardiac outcomes, but did not produce differences in overall mortality and QOL (59).
Predictors of Early Cerebrovascular Events in Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
V. Auffret, et al.
Background
Identifying transcatheter aortic valve replacement (TAVR) patients at high risk for cerebrovascular events (CVE) is of major clinical relevance. However, predictors have varied across studies.
Objectives
The purpose of this study was to analyze the predictors of 30-day CVE post-TAVR.
Methods
A systematic review of studies that reported the incidence of CVE post-TAVR while providing raw data for predictors of interest was performed. Data on study, patient, and procedural characteristics were extracted. Crude risk ratios (RRs) and 95% confidence intervals for each predictor were calculated.
Results
Sixty-four studies involving 72,318 patients (2,385 patients with a CVE within 30 days post-TAVR) were analyzed. Incidence of CVE ranged from 1% to 11% (median 4%) without significant differences between single and multicenter studies, or according to CVE adjudication availability. The summary RRs indicated lower risk for men (RR: 0.82; p = 0.02) and higher risk for patients with chronic kidney disease (RR: 1.29; p = 0.03) and with new-onset atrial fibrillation post-TAVR (RR: 1.85; p = 0.005), and for procedures performed within the first half of center experience (RR: 1.55; p = 0.003). The use of balloon post-dilation tended to be associated with a higher risk of CVE (RR: 1.43; p = 0.07). Valve type (balloon-expandable vs. self-expandable, p = 0.26) and approach (transfemoral vs. nontransfemoral, p = 0.81) did not predict CVE.
Conclusions
Female sex, chronic kidney disease, enrollment date, and new-onset atrial fibrillation were predictors of CVE post-TAVR. This study provides effect estimates to identify high-risk TAVR patients for early CVE, providing possible guidance for tailored preventive strategies (60).
Prosthetic Heart Valve Thrombosis
G.D. Dangas, et al.
Although surgery was the mainstay of treatment for valvular heart disease, transcatheter valve therapies have grown exponentially over the past decade. Two types of artificial heart valve exist: mechanical heart valves (MHV), which are implanted surgically, and bioprosthetic heart valves (BHV), which can be implanted via a surgical or transcatheter approach. Whereas long-term anticoagulation is required to prevent thromboembolism after MHV replacement, its value in patients receiving BHVs is uncertain. Patients undergoing transcatheter BHV replacement are at risk for thromboembolism in the first few months, and recent data suggest that the risk continues thereafter. BHV thrombosis provides a substrate for subsequent thromboembolism and may identify a reversible cause of prosthesis dysfunction. Hereafter, the authors: 1) review the data on prosthetic valve thrombosis; 2) discuss the pathophysiological mechanisms that may lead to valve thrombus formation; and 3) provide perspective on the implications of these findings in the era of transcatheter valve replacement (61).
Serial Changes in Cognitive Function Following Transcatheter Aortic Valve Replacement
V. Auffret, et al.
Background
Data regarding the mid- to long-term cognitive trajectory of transcatheter aortic valve (TAVR) recipients are scarce.
Objectives
Changes in global cognition and specific cognitive domains up to 1 year post-TAVR were evaluated.
Methods
Fifty-one patients (median age 80.0 [interquartile range: 72.0 to 85.0] years; 37% women) underwent TAVR and prospective assessment of cognitive function using the Montreal Cognitive Assessment (MoCA) at baseline, short-term (30 days), and 1 year post-TAVR. Processing speed and executive cognitive functions were further evaluated with the digit-symbol substitution test (DSST), Trail Making Tests (TMT), and verbal fluency tests at the same time points. Cognitive decline (CD) was determined by changes in mean scores and as a rate using practice-corrected reliable change index (RCI).
Results
The baseline mean total MoCA score was 22.71 ± 3.84. Twenty patients (39.2%) were considered cognitively impaired using a cutoff of <23 of 30 points. Mean total MoCA score improved at short-term post-TAVR and remained stable at 1 year (p = 0.022). On the basis of the RCI of total MoCA score, 4 patients (7.8%) presented with short-term CD, which persisted at 1 year in 1 patient (2.0%). Four patients (7.8%) exhibited cognitive improvement at 1 year, increasing to 15% among those with baseline cognitive impairment. No significant changes were observed over time in the mean DSST, TMT, and verbal fluency test scores. On the basis of the RCI, 10 of 40 patients (25%) presented with a reduction in performance of at least 1 test at 30 days that persisted at 1 year in 4 patients (10%).
Conclusions
TAVR was associated with global improvement in cognitive status, more pronounced among those with cognitive impairment pre-TAVR. However, early decline in some complex cognitive functions was observed in one-quarter of TAVR recipients, persisting at 1 year in 10% of patients (62).
Strain Echocardiography and Functional Capacity in Asymptomatic Primary Mitral Regurgitation With Preserved Ejection Fraction
A. Mentias, et al.
Background
The potential additive utility of baseline resting left ventricular global longitudinal strain (LV-GLS) and exercise stress testing in risk stratification of patients with significant mitral regurgitation (MR) has not been studied.
Objectives
The goal of this study was to determine whether resting LV-GLS and exercise testing provide incremental prognostic utility in asymptomatic patients with ≥3+ primary MR and preserved left ventricular ejection fraction.
Methods
Between 2000 and 2011, resting and exercise echocardiography data, Society of Thoracic Surgeons (STS) scores, and death were recorded in 737 patients (mean age 58 ± 13 years; 68% men).
Results
Coronary artery disease and flail leaflet were seen in 10% and 28% of patients, respectively. STS score, resting left ventricular ejection fraction, mitral effective regurgitant orifice, resting right ventricular systolic pressure (RVSP), exercise metabolic equivalents (METs), and percentage of age-/sex-predicted METs were 1.5 ± 1%, 62 ± 2%, 0.45 ± 0.2 cm2, 31 ± 12 mm Hg, 9.8 ± 3, and 115 ± 27, respectively. Median LV-GLS was –21.7%. Within 3 months (interquartile range: 1 to 15 months), 65% underwent mitral valve surgery. At 8.3 ± 3 years, 64 (9%) patients died (0% 30-day post-operative deaths). On multivariable Cox survival analysis, higher STS score (hazard ratio [HR]: 1.14), more abnormal resting LV-GLS (HR: 1.60), higher baseline RVSP (HR: 1.35), and lower percentage of age-/sex-predicted METs (HR: 1.13) were associated with higher mortality, whereas mitral valve surgery (HR: 0.82) was associated with improved survival (all p < 0.01). Addition of predicted METs and resting LV-GLS to STS, resting RVSP, left ventricular end-systolic dimension, and mitral effective regurgitant orifice increased the C-statistic for longer-term mortality from 0.61 to 0.69 and 0.78, respectively (all p < 0.01). On quadratic spline analysis, the risk of death progressively increased as resting LV-GLS worsened below –21%.
Conclusions
Reduced exercise capacity and worsening resting LV-GLS were associated with mortality, providing additive prognostic utility (63).
The Mitral Valve in Obstructive Hypertrophic Cardiomyopathy: A Test in Context
M.V. Sherrid, et al.
Mitral valve abnormalities were not part of modern pathological and clinical descriptions of hypertrophic cardiomyopathy in the 1950s, which focused on left ventricular (LV) hypertrophy and myocyte fiber disarray. Although systolic anterior motion (SAM) of the mitral valve was discovered as the cause of LV outflow tract obstruction in the M-mode echocardiography era, in the 1990s structural abnormalities of the mitral valve became appreciated as contributing to SAM pathophysiology. Hypertrophic cardiomyopathy mitral malformations have been identified at all levels. They occur in the leaflets, usually elongating them, and also in the submitral apparatus, with a wide array of malformations of the papillary muscles and chordae, that can be detected by transthoracic and transesophageal echocardiography and by cardiac magnetic resonance. Because they participate fundamentally in the predisposition to SAM, they have increasingly been repaired surgically. This review critically assesses imaging and measurement of mitral abnormalities and discusses their surgical relief (64).
Transcatheter Aortic Valve Replacement 2016: A Modern-Day “Through the Looking-Glass” Adventure
T.P. Vahl, et al.
Transcatheter aortic valve replacement (TAVR) has become a safe and effective therapy for patients with severe aortic stenosis (AS). In recent trials, the hemodynamic performance and clinical outcomes of the latest generation of TAVR devices demonstrated at least parity with surgical outcomes in patients of similar risk. Many initial obstacles with TAVR have largely been overcome, including frequent access site complications and concerns about strokes and paravalvular leaks. Using a multidisciplinary heart team approach, patient selection, procedural planning, and device implantation have been refined and optimized such that clinical outcomes are generally predictable and reproducible. Future research will focus on the durability of TAVR devices, further enhancements in clinical outcomes, and adjunctive therapies. On the basis of initial results from ongoing clinical trials, the indication for TAVR will likely expand to lower-risk patients. This review provides an overview of recent progress in this field, and highlights future opportunities and directions (65).
Transcatheter Aortic Valve Thrombosis: Incidence, Predisposing Factors, and Clinical Implications
N.C. Hansson, et al.
Background
There are limited data on the incidence, clinical implications, and predisposing factors of transcatheter heart valve (THV) thrombosis following transcatheter aortic valve replacement (TAVR).
Objectives
The authors assessed the incidence, potential predictors, and clinical implications of THV thrombosis as determined by contrast-enhanced multidetector computed tomography (MDCT) after TAVR.
Methods
Among 460 consecutive patients who underwent TAVR with the Edwards Sapien XT or Sapien 3 (Edwards Lifesciences, Irvine, California) THV, 405 (88%) underwent MDCT in addition to transthoracic and transesophageal echocardiography 1 to 3 months post-TAVR. MDCT scans were evaluated for hypoattenuated leaflet thickening that indicated THV thrombosis.
Results
MDCT verified THV thrombosis in 28 of 405 (7%) patients. A total of 23 patients had subclinical THV thrombosis, whereas 5 (18%) patients experienced clinically overt obstructive THV thrombosis. THV thrombosis risk did not differ among different generations of THVs (8% vs. 6%; p = 0.42). The risk of THV thrombosis in patients who did not receive warfarin was higher compared with patients who received warfarin (10.7% vs. 1.8%; risk ratio [RR]: 6.09; 95% confidence interval [CI]: 1.86 to 19.84). A larger THV was associated with an increased risk of THV thrombosis (p = 0.03). In multivariable analysis, a 29-mm THV (RR: 2.89; 95% CI: 1.44 to 5.80) and no post-TAVR warfarin treatment (RR: 5.46; 95% CI: 1.68 to 17.7) independently predicted THV thrombosis. Treatment with warfarin effectively reverted THV thrombosis and normalized THV function in 85% of patients as documented by follow-up transesophageal echocardiography and MDCT.
Conclusions
Incidence of THV thrombosis in this large study was 7%. A larger THV size may predispose to THV thrombosis, whereas treatment with warfarin appears to have a protective effect. Although often subclinical, THV thrombosis may have important clinical implications (66).
Transcatheter Pulmonary Valve Replacement Reduces Tricuspid Regurgitation in Patients With Right Ventricular Volume/Pressure Overload
T.K. Jones, et al.
Background
Tricuspid regurgitation (TR) is a common and important comorbidity in patients with postoperative right ventricular outflow tract (RVOT) obstruction or pulmonary regurgitation (PR). Transcatheter pulmonary valve replacement (TPVR) has become a useful tool in the management of postoperative RVOT obstruction and PR, but it is unknown whether relief of the right ventricular volume and/or pressure overload by TPVR will have a beneficial effect on TR, as is often seen with surgical pulmonary valve replacement.
Objectives
This study sought to assess the prevalence of and factors associated with significant TR in patients undergoing TPVR for RVOT obstruction or PR.
Methods
Data were combined from 3 prospective multicenter trials of patients referred for TPVR. Follow-up data through 5 years post-implantation were analyzed.
Results
Of 300 patients studied, 77 (25.6%) had moderate or severe TR at baseline. After TPVR, TR severity was improved in 65% of those patients, and more than one-half had mild TR or less TR at discharge. Of 13 patients with severe TR pre-implantation, only 1 had severe TR at 1-year follow-up and beyond. Moderate or severe baseline TR was associated with shorter freedom from RVOT reintervention after TPVR.
Conclusions
In this prospective multicenter study of post-operative patients with RVOT obstruction and/or PR, TR was common. In patients with significant baseline TR, TPVR resulted in clinically relevant acute reductions in TR that persisted over at least 5 years of follow-up. These observations support the application of TPVR therapy in patients with RVOT obstruction or PR who are anatomically suitable, even in the setting of significant concomitant TR (67).
Transcatheter Therapies for Treating Tricuspid Regurgitation
J. Rodés-Cabau, et al.
Tricuspid valve (TV) disease has been relatively neglected, despite the known association between severe tricuspid regurgitation (TR) and mortality. Few patients undergo isolated tricuspid surgery, which remains associated with high in-hospital mortality rates, particularly in patients with prior left-sided valve surgery. Patients with severe TR are often managed medically for years before TV repair or replacement. Current guidelines recommend TV repair in the presence of a dilated tricuspid annulus at the time of a left-sided valve surgical intervention, even if regurgitation is mild. This proposed algorithm aims to prevent the inevitable progression to severe TR and the need for a second surgical intervention. Recently, novel transcatheter treatment options were developed for treating patients with severe TR and right heart failure with prohibitive surgical risk. Here we describe currently available transcatheter treatment options for severe TR implanted at different levels: the junction between vena cavae and right atrium; the tricuspid annulus; or between TV leaflets, improving coaptation (68).
Treatment of Chronic Functional Mitral Valve Regurgitation With a Percutaneous Annuloplasty System
G. Nickenig, et al.
Background
Current surgical and medical treatment options for functional mitral regurgitation (FMR) are limited and additional interventional approaches are required.
Objectives
This study sought to report the safety and performance data from the feasibility study with a novel direct annuloplasty system.
Methods
Seventy-one patients with moderate to severe FMR (mean 67.7 ± 11.3 years of age, left ventricular [LV] ejection fraction 34.0 ± 8.3%), on stable medical heart failure medication were prospectively enrolled.
Results
Device success rate was 70.4% (n = 50 of 71). No intraprocedural death occurred. In patients receiving implants, 4 patients (8.9%) experienced cardiac tamponade. Thirty-day (n = 45) and 6-month (n = 41) rates for all-cause mortality, stroke, and myocardial infarction were 4.4%, 4.4%, and 0.0% and 12.2%, 4.9%, and 0%, respectively. At 6 months, nonurgent mitral surgery was performed in 1 patient (2.4%) and nonurgent percutaneous repair in 7 patients (17.1%). Echocardiographic core analysis after 6 months showed mitral regurgitation reduction in 50% of treated patients by a mean of 1.3 grades. Concerning mitral valve (MV) annular geometry, we found significant reduction of anterior-posterior (–0.31 ± 0.4 cm) and septal-lateral dimensions (–0.21 ± 0.3 cm), a decreased MV-tenting area (–0.57 ± 1.1 cm2) and increase in MV coaptation length (0.13 ± 0.2 cm). Transthoracic echocardiography indicated reverse LV remodeling with reduction of LV end-diastolic diameter (–0.20 ± 0.4 mm) and volume (–22 ± 39 ml). Treatment was associated with significant improvement in 6-min walking distances (56.5 ± 92.0 m) and improvements in New York Heart Association functional class III/IV at 6 months from 53.3% to 23.3%.
Conclusions
Percutaneous direct annuloplasty is feasible and safe in high-risk FMR patients. This treatment initiates LV reverse remodeling, and provides clinical improvement during 6 months after treatment. (Mitralign Percutaneous Annuloplasty First in Man Study; NCT01852149) (69).
Valve-Sparing Root Replacement Compared With Composite Valve Graft Procedures in Patients With Aortic Root Dilation
M. Ouzounian, et al.
Background
Although aortic valve-sparing (AVS) operations are established alternatives to composite valve graft (CVG) procedures for patients with aortic root aneurysms, comparative long-term outcomes are lacking.
Objectives
This study sought to compare the results of patients undergoing AVS procedures with those undergoing CVG operations.
Methods
From 1990 to 2010, a total of 616 patients age <70 years and without aortic stenosis underwent elective aortic root surgery (AVS, n = 253; CVG with a bioprosthesis [bio-CVG], n = 180; CVG with a mechanical prosthesis [m-CVG], n = 183). A propensity score was used as a covariate to adjust for unbalanced variables in group comparisons. Mean age was 46 ± 14 years, 83.3% were male, and mean follow-up was 9.8 ± 5.3 years.
Results
Patients undergoing AVS had higher rates of Marfan syndrome and lower rates of bicuspid aortic valve than those undergoing bio-CVG or m-CVG procedures. In-hospital mortality (0.3%) and stroke rate (1.3%) were similar among groups. After adjusting for clinical covariates, both bio-CVG and m-CVG procedures were associated with increased long-term major adverse valve-related events compared with patients undergoing AVS (hazard ratio [HR]: 3.4, p = 0.005; and HR: 5.2, p < 0.001, respectively). They were also associated with increased cardiac mortality (HR: 7.0, p = 0.001; and HR: 6.4, p = 0.003). Furthermore, bio-CVG procedures were associated with increased risk of reoperations (HR: 6.9; p = 0.003), and m-CVG procedures were associated with increased risk of anticoagulant-related hemorrhage (HR: 5.6; p = 0.008) compared with AVS procedures.
Conclusions
This comparative study showed that AVS procedures were associated with reduced cardiac mortality and valve-related complications when compared with bio-CVG and m-CVG. AVS is the treatment of choice for young patients with aortic root aneurysm and normal or near-normal aortic cusps (70).
Vascular Medicine
Acute Ischemic Stroke Intervention
P. Khandelwal, et al.
Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States (71).
Acute Pulmonary Embolism: With an Emphasis on an Interventional Approach
W.A. Jaber, et al.
Compared with recent advances in treatment of serious cardiovascular diseases, such as myocardial infarction and stroke, the treatment and outcome of acute pulmonary embolism (PE) have remained relatively unchanged over the last few decades. This has prompted several experts to call for the formation of multidisciplinary PE response teams with a more proactive approach to the treatment of PE. In the current document, we discuss the formation of such teams and describe the available treatment options beyond anticoagulation, with a focus on the interventional approach. Acknowledging the paucity of data to support widespread adoption of such techniques, we call for the collection of outcomes data in multicenter registries and support for randomized trials to evaluate interventional treatments in patients with high-risk PE (72).
Aortic Dissection in Patients With Genetically Mediated Aneurysms: Incidence and Predictors in the GenTAC Registry
J.W. Weinsaft, et al.
Background
Aortic dissection (AoD) is a serious complication of thoracic aortic aneurysm (TAA). Relative risk for AoD in relation to TAA etiology, incidence, and pattern after prophylactic TAA surgery are poorly understood.
Objectives
This study sought to determine the incidence, pattern, and relative risk for AoD among patients with genetically associated TAA.
Methods
The population included adult GenTAC participants without AoD at baseline. Standardized core laboratory tests classified TAA etiology and measured aortic size. Follow-up was performed for AoD.
Results
Bicuspid aortic valve (BAV) (39%) and Marfan syndrome (MFS) (22%) were the leading diagnoses in the studied GenTAC participants (n = 1,991). AoD occurred in 1.6% over 3.6 ± 2.0 years; 61% of AoD occurred in patients with MFS. Cumulative AoD incidence was 6-fold higher among patients with MFS (4.5%) versus others (0.7%; p < 0.001). MFS event rates were similarly elevated versus those in patients with BAV (0.3%; p < 0.001). AoD originated in the distal arch or descending aorta in 71%; 52% of affected patients, including 68% with MFS, had previously undergone aortic grafting. In patients with proximal aortic surgery, distal aortic size (descending thoracic, abdominal aorta) was larger among patients with AoD versus those without AoD (both p < 0.05), whereas the ascending aorta size was similar. Conversely, in patients without previous surgery, aortic root size was greater in patients with subsequent AoD (p < 0.05), whereas distal aortic segments were of similar size. MFS (odds ratio: 7.42; 95% confidence interval: 3.43 to 16.82; p < 0.001) and maximal aortic size (1.86 per cm; 95% confidence interval: 1.26 to 2.67; p = 0.001) were independently associated with AoD. Only 4 of 31 (13%) patients with AoD had pre-dissection images that fulfilled size criteria for prophylactic TAA surgery at a subsequent AoD site.
Conclusions
Among patients with genetically associated TAA, MFS augments risk for AoD even after TAA grafting. Although increased aortic size is a risk factor for subsequent AoD, events typically occur below established thresholds for prophylactic TAA repair (73).
Changing Pathology of the Thoracic Aorta From Acute to Chronic Dissection: Literature Review and Insights
S. Peterss, et al.
We review current knowledge regarding the natural transition of aortic dissection from acute to chronic stages. As this is not well understood, we also bring to bear new data from our institution. Type A dissection rarely transitions naturally into the chronic state; consequently, information is limited. Type B dissections are routinely treated medically and indeed undergo substantial changes during their temporal course. General patterns include: 1) the aorta dilates and, absent surgical intervention, aortic enlargement may cause mortality; 2) continued false lumen patency, particularly with an only partially thrombosed false lumen, increases aortic growth, whereas calcium-channel blockers affect aortic dilation favorably; 3) aortic dilation manifests a temporal dynamic, with early rapid growth and deceleration during transition; 4) the intimal flap dynamically changes over time via thickening, straightening, and loss of mobility; and 5) temporal remodeling, on the cellular level, initially shows a high grade of wall destruction; subsequently, significant fibrosis ensues (74).
Endovascular Repair Compared With Medical Management of Patients With Uncomplicated Type B Acute Aortic Dissection
Y.-L. Qin, et al.
Background
Thoracic endovascular aortic repair (TEVAR) has been used in patients with uncomplicated type B acute aortic dissection (B-AAD) to reduce late morbidity and mortality. The outcomes of comparisons between TEVAR and best medical treatment (BMT) on patients with uncomplicated type B-AAD are inconsistent in the published reports.
Objectives
This study sought to further clarify the early and long-term (11-year) outcomes of TEVAR in patients with uncomplicated type B-AAD compared with those with BMT treatment.
Methods
Between February 2003 and August 2014, 338 patients with uncomplicated type B-AAD were retrospectively identified in 3 tertiary medical centers. Information about baseline characteristics was collected from medical records. Images were retrieved from the imaging archiving system, and the thrombosis status of the false lumen and extent of the dissection were evaluated via computed tomography angiography. Early and late outcomes were recorded and analyzed.
Results
TEVAR procedures were performed on 184 patients (TEVAR group) and BMT for 154 patients (BMT group). Early events and 30-day mortality were not significantly different between the 2 groups. Patients receiving BMT had significantly higher aortic-related adverse events compared with those in the TEVAR group (p = 0.025). All-cause mortality with TEVAR was significantly lower than that of BMT (p = 0.01).
Conclusions
This study confirmed the feasibility of TEVAR for uncomplicated type B aortic dissection in the acute setting with fewer aortic-related adverse events and a lower mortality rate compared with BMT (75).
Management of Pulmonary Embolism: An Update
S.V. Konstantinides, et al.
Pulmonary embolism (PE) remains a major contributor to global disease burden. Risk-adapted treatment and follow-up contributes to a favorable outcome. Age-adjusted cutoff levels increase D-dimer specificity and may decrease overuse of imaging procedures and overdiagnosis of PE. Primary systemic fibrinolysis has an unfavorable risk–benefit ratio in intermediate-risk PE; catheter-directed techniques are an option for patients with hemodynamic decompensation and high bleeding risk. New oral anticoagulant agents are effective and safe alternatives to standard anticoagulation regimens. Recent trial data do not support insertion of cava filters in patients who can receive anticoagulant treatments. Remaining areas of uncertainty include the therapeutic implications of subsegmental PE, the optimal diagnostic approach to the pregnant patient with suspected PE, and the efficacy and safety of new oral anticoagulant agents in patients with cancer. Campaigns to increase awareness combined with strategies to implement guideline recommendations will be crucial steps towards further optimizing management of acute PE (76).
Nonsyndromic Thoracic Aortic Aneurysm and Dissection: Outcomes With Marfan Syndrome Versus Bicuspid Aortic Valve Aneurysm
A.G. Sherrah, et al.
Background
Genetic aortopathy (GA) underlies thoracic aortic aneurysms (TAA) in younger adults. Comparative survival and predictors of outcomes in nonsyndromic TAA (NS-TAA) are incompletely defined compared to Marfan syndrome (MFS) and bicuspid aortic valve (BAV).
Objectives
The study sought to compare survival and clinical outcomes for individuals with NS-TAA, MFS, and BAV.
Methods
From 1988 to 2014, all patients presenting with GA 16 to 60 years of age were enrolled in a prospective study of clinical outcomes. Risk factors for death and aortic dissection were identified by Cox proportional hazards modeling and a mortality risk score developed.
Results
Diagnosis of GA was made for 760 patients (age 36.9 ± 13.6 years, 26.8% female; NS-TAA, n = 311; MFS, n = 221; BAV, n = 228). MFS patients were younger than NS-TAA and BAV. Presentation with aortic dissection was more common for NS-TAA than MFS or BAV. The 687 patients surviving >30 days after presentation were followed for a median of 7 years. Calculated 10-year mortality was 7.8% for NS-TAA, 8.7% for MFS, and 3.5% for BAV (NS-TAA and MFS vs. BAV p <0.05). Factors associated with all-cause mortality were MFS (p = 0.04), age at presentation, and family history of dissection.
Conclusions
Clinical outcomes for MFS and NS-TAA are similar but worse than BAV. Independent predictors of mortality, including family history of aortic dissection and age, can be included in an Aortopathy Mortality Risk Score to predict survival. Management of NS-TAA, including surgical intervention, should be similar to that of MFS (77).
Outcomes of Endovascular Repair of Ascending Aortic Dissection in Patients Unsuitable for Direct Surgical Repair
Z. Li, et al.
Background
Stent grafting is a therapeutic option for patients who are unable to undergo urgent surgical repair of ascending aortic dissections. However, follow-up regarding outcomes is limited.
Objectives
This study reports mid-term outcomes with endovascular repair for ascending aortic dissections in patients deemed high risk for open repair.
Methods
Between May 1, 2009 and January 31, 2011, 15 ascending aortic dissection patients (ages 45 to 78 years) ineligible for direct surgical repair underwent endovascular repair (1 acute dissection, 7 subacute dissections, and 7 chronic dissections) and were closely followed up for a median of 72 months (range 61 to 81 months).
Results
The mean interval between aortic dissection onset and treatment was 25.5 (range 6 to 353) days. Technical success was achieved in all patients. No major morbidity or deaths occurred perioperatively. During the follow-up period, there were no deaths, 8 complications occurred, and there were 4 reinterventions. A new dissection in the aortic arch was treated with a branched endograft. One patient developed retrograde aortic dissection and a left ventricular pseudoaneurysm was successfully treated with open surgery. One cardiovascular ischemia was treated with stenting and 1 supraventricular tachycardia was treated with radiofrequency ablation. Other morbidities included perigraft endoleak, a bird-beak sign, a temporary pericardial effusion, and a left kidney atrophy. Significant enlargements of true lumens and shrinkage of false lumens and overall thoracic aorta were observed at 12 months. No significant changes were detected subsequently. Minimal impact on aortic valve function was recorded over time.
Conclusions
Our results with the novel endovascular procedure appear acceptable. Additional evidence and studies with larger sample size and longer follow-up are needed to support the durability of this new technique (78).
Peripheral Artery Disease: Evolving Role of Exercise, Medical Therapy, and Endovascular Options
J.W. Olin, et al.
The prevalence of peripheral artery disease (PAD) continues to increase worldwide. It is important to identify patients with PAD because of the increased risk of myocardial infarction, stroke, and cardiovascular death and impaired quality of life because of a profound limitation in exercise performance and the potential to develop critical limb ischemia. Despite effective therapies to lower the cardiovascular risk and prevent progression to critical limb ischemia, patients with PAD continue to be under-recognized and undertreated. The management of PAD patients should include an exercise program, guideline-based medical therapy to lower the cardiovascular risk, and, when revascularization is indicated, an “endovascular first” approach. The indications and strategic choices for endovascular revascularization will vary depending on the clinical severity of the PAD and the anatomic distribution of the disease. In this review, we discuss an evidence-based approach to the management of patients with PAD (79).
Recent Endovascular Stroke Trials and Their Impact on Stroke Systems of Care
M. Mokin, et al.
Five recently published randomized trials of endovascular therapy versus medical management, including intravenous thrombolysis, demonstrated strong positive data in support of intra-arterial thrombectomy procedures. The American Heart Association/American Stroke Association released a focused update of the 2013 guidelines on the early management of acute ischemic strokes to specifically incorporate the findings of the 5 “positive” trials. In this review, we examine the key results of those trials and the principal changes in the updated guidelines. We discuss the ongoing and future changes in stroke systems of care, with an emphasis on the role of pre-hospital stroke triage, interhospital transfer, and the 2 main levels of stroke center certification (primary and comprehensive) (80).
Risk of Aortic Dissection in the Moderately Dilated Ascending Aorta
J.B. Kim, et al.
Background
Recent studies have demonstrated that many patients with acute type A aortic dissection (AD) have aortic diameters of <55 mm at presentation, prompting discussion of lowering the prophylactic surgical guidelines. However, risk of dissection at these smaller diameters is poorly defined.
Objectives
The purpose of this study is to understand the risk of AD in moderately dilated ascending aortas using a large echocardiographic data set.
Methods
Using an institutional echocardiography database, we identified 4,654 nonsyndromic adults (age: 68.6 ± 13.1 years; 1,003 women) with maximal ascending aortic diameters of 40 to 55 mm. We performed competing risk analysis to determine the independent risk factors of AD or aortic rupture.
Results
Five hundred eighty-six individuals (12.6%) had bicuspid aortic valves (BAVs). During follow-up (14,431.5 patient-years), AD and rupture occurred in 13 and 1 patients, respectively, which demonstrated a linearized incidence of AD and/or rupture of 0.1% per patient-year. Elective ascending aortic repair was performed in 176 individuals. On multivariable analyses, independent predictors of AD and/or rupture were age (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.01 to 1.12; p = 0.024) and baseline aortic diameters (HR: 1.20; 95% CI: 1.05 to 1.36; p = 0.006). The presence of a BAV was not a significant factor (HR: 0.94; 95% CI: 0.10 to 8.40; p = 0.95). Estimated risks of AD and/or rupture within 5 years were 0.4%, 1.1%, and 2.9% at baseline aortic diameters of 45, 50, and 55 mm, respectively.
Conclusions
Risks of AD and/or rupture were significantly correlated with the aortic diameter and age in patients with moderately dilated ascending aortas. However, the risks were low for diameters <5.0 cm when timely elective aortic repair was performed, regardless of the morphology of the aortic valve (81).
Systematic Search for Present and Potential Portals of Entry for Infective Endocarditis
F. Delahaye, et al.
Background
Looking for and treating the portal of entry (POE) of infective endocarditis (IE) is important, but published research on this topic is nonexistent.
Objectives
The goal of this study was to systematically search for the POEs of present and potentially new episodes of IEs.
Methods
Patients were systematically seen by a stomatologist, an ear, nose, and throat specialist, and a urologist; women were systematically seen by a gynecologist; patients were seen by a dermatologist when there were cutaneous and/or mucous lesions. Colonoscopy and gastroscopy were performed if the microorganism came from the gastrointestinal tract in patients ≥50 years of age and in those with familial histories of colonic polyposis. Treatment of the POE was systematically considered.
Results
The POEs of the present IE episodes were identified in 74% of the 318 included patients. The most frequent POE was cutaneous (40% of identified POEs). It was mainly (62% of cutaneous POEs) associated with health care and with intravenous drug use. The second most frequent POE was oral or dental (29%). A dental infectious focus was more often involved (59% of oral or dental POEs) than a dental procedure (12%). POEs were gastrointestinal in 23% of patients. Colonic polyps were found in one-half of the patients and colorectal adenocarcinomas in 14%. Performance was good regarding the search for an oral or dental or a colonic potential POE, which were found in 53% and 40% of patients, respectively.
Conclusions
Our search for the POEs of present IEs was often successful, as was searching for an oral or dental or a gastrointestinal POE of a new IE episode. We advise the systematic performance of stomatologic examinations in patients with IE and performance of colonoscopy in patients ≥50 years of age or at high risk for colorectal cancer (82).
Treatment of Venous Thromboembolism With New Anticoagulant Agents
C. Becattini, et al.
Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE (83).
Trends in the Management and Outcomes of Acute Pulmonary Embolism: Analysis From the RIETE Registry
D. Jiménez, et al.
Background
Despite advances in hospital management in recent years, it is not clear whether mortality after acute pulmonary embolism (PE) has decreased over time.
Objectives
This study describes the trends in the management and outcomes of acute symptomatic PE.
Methods
We identified adults with acute PE enrolled in the registry between 2001 and 2013. We assessed temporal trends in length of hospital stay and use of pharmacological and interventional therapies. Using multivariable regression, we examined temporal trends in risk-adjusted rates of all-cause and PE-related death to 30 days after diagnosis.
Results
Among 23,858 patients with PE, mean length of stay decreased from 13.6 to 9.3 days over time (32% relative reduction, p < 0.001). For initial treatment, use of low-molecular-weight heparin increased from 77% to 84%, whereas the use of unfractionated heparin decreased from 22% to 8.4% (p < 0.001 for trend for all comparisons). Thrombolytic therapy use increased from 0.7% to 1.0% (p = 0.07 for trend) and surgical embolectomy use doubled from 0.3% to 0.6% (p < 0.01 for trend). Risk-adjusted rates of all-cause mortality decreased from 6.6% in the first period (2001 to 2005) to 4.9% in the last period (2010 to 2013) (p = 0.02 for trend). Rates of PE-related mortality decreased over time, with a risk-adjusted rate of 3.3% in 2001 to 2005 and 1.8% in 2010 to 2013 (p < 0.01 for trend).
Conclusions
In a large international registry of patients with PE, improvements in length of stay and changes in the initial treatment were accompanied by a reduction in short-term all-cause and PE-specific mortality (84).
- American College of Cardiology Foundation
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