Editor-in-Chief’s Top Picks From 2016: Part Two

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).

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).

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 A_1c and Cardiovascular Disease

M.O. Gore, et al.

Measurement of glycated hemoglobin (HbA_1c), the most widely accepted indicator of long-term glycemic exposure, is central for the diagnosis and management of diabetes mellitus. Levels of HbA_1c track epidemiologically with diabetic complications, and glycemic control, as reflected by HbA_1c reduction, results in decreased risk of microvascular complications, including diabetic kidney disease, neuropathy, and retinopathy. The relationship between HbA_1c 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 HbA_1c 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 HbA_1c therapeutic targets. The context and key evidence underpinning these recent changes are discussed in this paper, alongside a brief overview of HbA_1c 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

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

Implantable Cardioverter-Defibrillators at End of Battery Life: Opportunities for Risk (Re)-Stratification in ICD Recipients

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

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

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).

Footnotes

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.

American College of Cardiology Foundation

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Abstract

CV Medicine & Society

Association Between Presence of a Cardiac Intensivist and Mortality in an Adult Cardiac Care Unit

Background

Objectives

Methods

Results

Conclusions

The Changing Landscape of Randomized Clinical Trials in Cardiovascular Disease

The Essential Role of Educator Development: 10 Years of the ACC Emerging Faculty Program

The Importance of Global Health Experiences in the Development of New Cardiologists

The Supply and Demand of the Cardiovascular Workforce: Striking the Right Balance

Hypertension

Diastolic Blood Pressure, Subclinical Myocardial Damage, and Cardiac Events: Implications for Blood Pressure Control

Background

Objectives

Methods

Results

Conclusions

Generalizability of SPRINT Results to the U.S. Adult Population

Background

Objectives

Methods

Results

Conclusions

Morning Home Blood Pressure Is a Strong Predictor of Coronary Artery Disease: The HONEST Study

Background

Objectives

Methods

Results

Conclusions

Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention

Background

Objectives

Methods

Results

Conclusions

The Cardiovascular Risk of White-Coat Hypertension

Background

Objectives

Methods

Results

Conclusions

Imaging

1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study

Background

Objectives

Methods

Results

Conclusions

A Simple Disease-Guided Approach to Personalize ACC/AHA-Recommended Statin Allocation in Elderly People: The BioImage Study

Background

Objectives

Methods

Results

Conclusions

Comprehensive Cardiac Magnetic Resonance Imaging in Patients With Suspected Myocarditis: The MyoRacer-Trial

Background

Objectives

Methods

Results

Conclusions

Computed Tomography and Cardiac Magnetic Resonance in Ischemic Heart Disease

Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study

Background

Objectives

Methods

Results

Conclusions

Diagnostic Strategies for the Evaluation of Chest Pain: Clinical Implications From SCOT-HEART and PROMISE

Femoral and Carotid Subclinical Atherosclerosis Association With Risk Factors and Coronary Calcium: The AWHS Study

Background

Objectives

Methods

Results

Conclusions

Implantable Electronic Cardiac Devices and Compatibility With Magnetic Resonance Imaging

1-Year Outcomes of FFR_CT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study

A Test in Context: Hemoglobin A_1c and Cardiovascular Disease