Author + information
- Received October 10, 2013
- Revision received December 19, 2013
- Accepted January 7, 2014
- Published online May 20, 2014.
- Shahbudin H. Rahimtoola, MB, FRCP, DSc (Hon)∗ ()
- Griffith Center, Division of Cardiovascular Medicine, Department of Medicine, LAC+USC Medical Center, Keck School of Medicine at University of Southern California, Los Angeles, California
- ↵∗Reprint requests and correspondence:
Dr. Shahbudin. H. Rahimtoola, University of Southern California, 1200 N. State Street/ Old Gen Hosp Room 3221, Los Angeles, California 90033.
- aortic stenosis
- infective endocarditis
- mitral regurgitation
- mitral stenosis
- mitral valve repair
- prosthetic heart valve
- transcatheter valve therapy
Guidelines on Valvular Heart Disease
A European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (1)
Comment: A total of 46 pages and 241 references. Of the 66 recommendations, none had Level of Evidence: A. There were 28 Class I recommendations with Level of Evidence: B in 6 and C in 22. There were 31 Class IIa recommendations with Level of Evidence: B in 1 and C in 30. There are 7 Class IIb recommendations; all were with Level of Evidence: C.
1. North Western Adelaide Health Study. This study evaluated changes over a time period of 4 years in 204 randomly selected subjects age 63 ± 6 years who had aortic sclerosis (ASc) (2). The authors demonstrated: 1) progression occurs in the majority of the normal aging population; 2) the importance of the nitric oxide signaling cascade in disease development; and 3) provided additional data linking angiotensin-converting enzyme inhibitor/angiotensin II receptors with the retardation of ASc.
2. Study of aortic stenosis (AS)/ASc and aortic atherosclerosis. Position emission and computed tomography was performed using 18F-sodium fluoride and 18F-fluorodeoxyglucose (18F-FDG) in 101 patients with calcific aortic valve disease from Scotland (3). The results showed that AS/ASc are distinctly different processes from aortic atherosclerosis and skeletal bone formation. In AS/ASc, active calcification was more pronounced and inflammation was less prominent than in aortic atherosclerosis. In AS, endothelial nitric oxide synthase uncoupling is markedly increased, and the pathophysiological processes are locally determined and regulated in the valve itself.
Comment: This study complements an earlier study (4). The accompanying editorial points out that both calcific aortic valve disease and aortic atherosclerosis are very common in the older population and that a correlation does not necessarily imply a cause-and-effect relationship (5).
3. Genetics associations with valvular calcifications and AS. One single-nucleotide polymorphism (SNP) in the lipoprotein (a) [Lp(a)] locus (LPA, rs10455872) reached genome-wide significance for the presence of aortic valve calcification (odds ratio [OR] per allele 2.05, p = 9.0 × 10−10). This finding was replicated in additional white European, African-American, and Hispanic-American cohorts (6). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic valve calcification, “supporting a causal role for Lp(a).” The authors concluded: “We have identified a SNP in the LPA locus that is significantly correlated with aortic-valve calcification. Our findings implicate genetic variation at the LPA locus, through elevated plasma Lp(a) levels, in the development of aortic-valve disease.”
Comment: The accompanying editorial by Dorn (7) is excellent. It emphasizes that the frequency of the LPA gene variant is 0.03. Thus, 5 or 6 persons in 100 carry this risk allele, whereas calcification of the aortic valve occurs commonly.
4. Role of osteogenic progenitor cells in calcific AS. Blood from patients with mild-to-moderate AS (n = 17), severe calcific AS (n = 26), severe AS/severe coronary artery disease (CAD) (n = 33), and controls (n = 22) were examined (8). Patients with severe AS showed a higher number of endothelial progenitor cells (EPC) with osteoblastic phenotype (OCN) than did controls. Immunofluorescence showed colocalization of nuclear factor kappa-B and OCN in diseased and normal valves. CD34+/OCN+ cells were abundant in the endothelial and deeper layers of calcific AS. The authors concluded EPC-OCN may play a significant role in the pathogenesis and as markers of prognostication of calcific AS.
B Assessment of severe AS
1. Criteria for severe AS: mean aortic valve gradient (AVG) is problematic; aortic valve area (AVA) ≤1.0 cm2 is reliable. In an “elderly” community, in Olmsted County, Minnesota, which represents the “community practice” of the Mayo Clinic “whose personnel perform all cardiology services.” There were 360 residents who had AS diagnosed by echocardiography from 1988 to 1997 (9); 96 of them had severe AS (AVA <1.0 cm2), but 67% had a mean aortic valve gradient (AVG) of <40 mm Hg, and in 32%, the mean AVG was <30 mm Hg and left ventricular ejection fraction (LVEF) was ≥0.50. The reasons for not performing aortic valve replacement (AVR) included low gradient in 57%, symptoms judged equivocal in 43%, comorbidities 37%, patient refusal of surgery in 20%, and physician choice in 20%. In patients who did not have surgery, the survival was worse for those with AVA <1.0 cm2 (Fig. 1). AVR was ultimately performed in 131 patients, who comprised only 45% of those with AVA <1.0 cm2, which reduced mortality (hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.39 to 0.94, p = 0.02) and heart failure (HR: 0.29, 95% CI: 0.13 to 0.64, p < 0.01).
Comment: There are 3 problems: 1) In this age group, a large majority of patients with severe AS (AVA index ≤0.6 cm2/m2) had a mean AVG <40 mm Hg (10) as in this study. One criteria of severe AS that is used is mean AVG >40 mm Hg, which is being interpreted to indicate that a mean AVG ≤40 mm Hg is not severe AS, as was also common in this study (9). It is best if the criteria of >40 mm Hg is discarded. Alternatively, it needs to be emphasized that mean AVG >40 mm Hg may indicate severe AS, but its specificity and positive predictive value are not known. However, in a study of 636 patients, mean AVG ≥50 mm Hg was documented to be specific, and the positive predictive value for severe AS was ≥90% (11). Moreover, it is best to rely on calculated AVA; 2) symptoms were not attributed to AS; and 3) physician choice.
C Prognosis of severe AS
1. Aortic valve area index (AVAI) by echocardiographic/Doppler is a predictor of event-free survival. In 103 consecutive asymptomatic patients, age 72 ± 11 years, those with AVAI of <0.6 cm2/m2 versus those with AVAI ≥0.6 cm2/m2 had 3-year event-free survival of 41% versus 86%, respectively, p < 0.01 (12). Actuarial total mortality data were not presented.
2. Energy loss index (ELI) is also a predictor of event-free survival but is controversial for total mortality. Data from the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study of 1,563 patients with AS who were initially asymptomatic showed that ELI <0.6 cm2/m2 “provided additional prognostic information to that derived from conventional measures of AS severity” (13). In patients with ELI <0.6 cm2/m2, the incidence of aortic valve events was 3 times greater over 5 to 6 years than in those with larger ELI. Overall survival was said to also be better; however, their Figure 1B shows that at 6 years, overall survival in the 2 groups was virtually identical.
Comment: ELI may be useful in patients with a small aortic root (<2.6 cm) and when the grading of severity is inconsistent between AVA and mean gradient. In the latter instance, it may be more prudent to proceed to careful and complete cardiac catheterization and angiography by skilled and experienced cardiologists.
3. Charlson comorbidity index. Two hundred thirty-nine patients, age >60 years, from the Australian Department of Veterans Affairs, were enrolled from 1988 to 1994 and followed until 2008 (14). During the follow-up, 132 patients developed severe AS (AVA <1.0 cm2 or mean AVG >40 mm Hg). At 10 years, the survival of those with severe AS with conservative management versus AVR was 5 ± 3% versus 50 ± 5% (p < 0.001). The independent predictors of all-cause mortality included age-adjusted Charlson comorbidity index (HR: 1.24, 95% CI: 1.15 to 1.34, p < 0.001); left ventricular (LV) dysfunction (HR: 1.36, 95% CI: 1.09 to 1.71), p < 0.01; AVR (HR: 0.40, 95% CI: 0.28 to 0.58), p < 0.001.
Comment: The Charlson comorbidity index needs to be an additive feature to the EuroSCORE or Society of Thoracic Surgeons (STS) score in evaluating outcome in AS, and therefore, also in clinical decision making for AVR.
4. Prognostic value of myocardial fibrosis. Myocardial fibrosis was evaluated from biopsy specimens obtained from the interventricular septum at the time of AVR in 99 patients (15). The relative volume of myocardial muscle and fibrous tissue was determined by point counting using a 10 × 10 grid at a total magnification of 100×. The fibrosis index (FI) was calculated by dividing the sum of the fibrotic areas by that of the total tissue area, expressed as a percentage: no or mild fibrosis (FI <20%; group 1), moderate fibrosis (FI 20% to 50%; group 2), or severe fibrosis (FI >50%; group 3). The fibrous tissue mass index (FTMI) was estimated as FI × LV mass index/100 (g/m2). There was a positive correlation between FTMI and LV size and functional class, and a negative correlation with LVEF. Hospital mortality was 3%. Patients were followed for 6.2 ± 2 years; those in group 3 had the lowest survival (Fig. 2). The fibrosis and structural alterations occurred predominantly in the subendocardial layers and was followed by progression to all layers of the myocardium. Patients with “significant coronary artery disease” were excluded.
Comment: The initial location of the fibrosis is in the subendocardium, and the subsequent progression suggests fibrosis may be related to myocardial ischemia as the result of associated CAD and/or LV hypertrophy. Also, as discussed later in the text, see the results of surgical aortic valve replacement (S:AVR) and probably may affect results of transcatheter valve treatment. There is a need for uniform measurement and quantification of the amount of fibrosis from gadolinium-enhanced images of magnetic resonance imaging (MRI).
D Management of AS
1. Aortic balloon valvuloplasty (ABV): poor results. Nine hundred patients were evaluated from April 2007 to May 2011; 595 (66.1%) were assigned to the medical/ABV group, of whom 354 had ABV and 241 had only medical therapy (16). In the medical/ABV group, the 30-day mortality was 10.1%; 3- and 12-month mortality was 20% and 45%, respectively, as evaluated from their figure. In the medical/ABV group, the causes of death were cardiac, noncardiac, and unknown in 38.9%, 28.1%, and 32.8%, respectively.
Comment: The data on outcomes in the medical/ABV subgroup are similar to 7 previously published studies of outcomes with ABV (17–23): 4 studies comprising 1, 480 patients showed the hospital/30-day mortality was 9.9% (17–19,23); 1 study showed 6-month mortality was 50% (22); 4 studies showed 1-year mortality ranged from 25% to 45% (17,18,20,21); 3 studies showed the 2-year mortality was 40% to 65% (18,20,21); and 2 studies showed 2-year event-free survival was 19% and 25% (18,21).
2. S:AVR: excellent results. From October 1991 to July 2010, 3,923 patients had AVR for AS: 1,637 (42%) had AVR alone, 2,286 (58%) patients had AVR + coronary artery bypass grafting (CABG) (24). Their ages were 75 ± 8.1 years versus 70 ± 11 years, respectively. In the AVR + CABG group versus the AVR-alone group, hospital mortality was 2.4% versus 1.3%, and survival at 1, 5, and 10 years was 91% versus 94%, 83% versus 90%, and 43% versus 59%, respectively. There are a large amount of data that are comprehensive, and the authors presented survival in the overall group and in the propensity-matched patients. Ten-year survival in propensity-matched patients showed the 10-year survival of isolated AS and AS + CAD was similar at 55% and 50%, respectively. Within the isolated AS group, matched patients had a lower survival than unmatched patients with few comorbidities: 55% versus 70%; AS + CAD–matched patients had a better survival than unmatched patients with myocardial damage and many comorbidities: 50% versus 36% (Fig. 3). The authors also concluded: “Patients with severe AS and CAD risk factors should undergo early diagnostics and should have AVR + CABG before ischemic myocardial damage occurs.”
Comment: The question is how early is early enough? In this or similar age groups, the incidence of associated CAD is up to 60% (25); in this study, it was 58%. I have suggested that in the asymptomatic patient with severe AS, diagnostic coronary contrast angiography followed by AVR may be very valuable in managing patients in this age group (25) if: 1) The operative mortality for subsequent AVR alone at an institution is ≤1% to 2% and for AVR + CABG is ≤2% to 4%. In the present study, it was 1.3% and 2.4%, respectively; 2) The stented bioprosthesis that is inserted has a documented low rate of structural valve deterioration (SVD) out to 20 years (please also see the data on the Charlson comorbidity index  and on myocardial fibrosis in the preceding text ; and 3) It would be important and clinically valuable if the study had described the outcomes up to 10 years of the 741 patients who were asymptomatic at baseline and also that of patients who had received 19-mm prosthetic heart valves.
3. Low rate of complications of noncardiac surgery (NCS) in patients with severe AS. In this study, 244 patients with severe AS undergoing NCS were matched to 976 who had no AS (26). Severe AS was defined as AVA <1.0 cm2, and patients had a variety of NCS. Outcomes were evaluated at 30 days after NCS for mortality, post-operative myocardial infarction (MI), heart failure, and stroke compared with those with no AS. In the asymptomatic AS group (n = 172), the difference in each of the complications was not significantly different compared with the no-AS group. In the symptomatic severe AS group (n = 72), the incidence of post-operative MI was 5.6% versus 1.4% in the no-AS group, p = 0.009, but the incidence of the other complications was not significant; however, the incidence of a combination of 30-day mortality and post-operative MI was higher: 8.3% versus 2.7%, p = 0.007. The authors stated, “The heightened anesthetic management in patients with severe AS is extremely relevant to current surgical practice and represents the norm rather than the exception.”
Comment: Previously, 3 studies with a combined total of 97 patients had similar findings (27–29). The National Hospital Discharge Survey from 1996 to 2002 showed that 5,149 patients with a diagnosis of AS had undergone NCS and were matched with 10,284 controls (30). There was no significantly increased risk of death in AS versus controls, and the risk of perioperative MI was 3.86% versus 2.03%, p < 0.001, with an OR of 1.55, 95% CI: 1.27 to 1.90, p < 0.001 (30). Several of the studies emphasized careful monitoring during anesthesia induction and the procedure, and prevention of hypotension. Consideration should be given to monitoring during NCS with the use of right-heart balloon catheter and intra-arterial pressure.
E Combined AS and aortic regurgitation is associated with a higher event rate
Seventy consecutive asymptomatic patients (21 women, age 52 ± 17 years, normal LVEF ≥0.55) had “at least moderate AS” and “at least moderate [aortic regurgitation (AR)]” (31). At a median follow-up of 8.9 years, 50 patients developed an indication for AVR, 43 had AVR, and 33 of the 43 developed symptoms. Event-free survival for the entire patient population at 1, 2, 3, 4, and 6 years was 82 ± 5%, 62 ± 6%, 49 ± 6%, 33 ± 6%, and 19 ± 5%, respectively. There were no cardiac deaths.
Comment: The high event rate supports close follow-up of these patients.
F Discrete subaortic stenosis in adults
1. Natural history: slow progression. Data are from 149 patients at 4 centers (32). Longitudinal follow-up data were available for 149 patients, age 20 years (interquartile range [IQR]: 18 to 34 years), 48% male Forty percent had associated congenital heart defects; the baseline LV outflow tract (LVOT) gradient was 32.3 ± 17 mm Hg, which increased by 0.8 ± 0.1 mm Hg/year. Presence of a congenital heart defect was associated with faster progression (p = 0.005), mild AR was common, but did not significantly progress over time (p = 0.701). The median intervention-free survival was 16 years; the mean age at discrete subaortic stenosis (DSS) surgery was 35.1 ± 14 years. Independent predictors for intervention were LVOT gradient ≥50 mm Hg, LVOT gradient progression, and moderate-to-severe AR.
2. High incidence of reoperation. Data are from 313 patients at 4 centers (33). The patients’ age was 20.2 years (IQR: 18.4 to 31.0 years), 52% were male, and median follow-up was 12.9 years (IQR: 6.2 to 20.1 years). There was 1 operative death from heart failure. There were 10 late deaths; 20-year survival was 97%. Eighty patients (25.6%) underwent at least 1 reoperation for recurrent DSS, and 19 required a third operation (1.76% per patient year). Mean time from initial operation to reoperation was 12.0 ± 7.6 years. Predictors for reoperation include female sex (HR: 1.53, 95% CI: 1.02 to 2.30) and progression of LVOT obstruction (HR: 1.45, 95% CI: 1.31 to 1.62). Additional myectomy did not reduce the risk for reoperation, but increased the risk of complete heart block requiring pacemaker implantation (8.1% vs. 1.7%, p = 0.005).
G Heyde’s syndrome
1. Beneficial effects in Heyde’s syndrome after AVR for severe AS. Bleeding in Heyde’s syndrome is attributed to intestinal angiodysplasia. A retrospective study identified 57 patients who underwent AVR for severe AS who had intestinal angiodysplasia and gastrointestinal (GI) bleeding (34). The patients were age 74 ± 10 years, and AVA was 0.7 ± 0.3 cm2. The number of documented episodes of GI bleeding was 4 ± 6 (range 1 to 27), the mean number of bleeds per patient-year was 12. Melena, the most common symptom/sign, was present in 53%. Intestinal angiodysplasia was located in the right colon in 28%, jejunum 25%, and right colon, plus another GI tract location in 21%. CABG was also performed in 32%. There were 2 operative deaths, none since 1987. The 1- and 5-year survival were 93% and 59%, respectively. At follow-up of 4.4 years (range 0.1 to 15 years), 45 patients (79%) had no further bleeding. In 12 (21%) patients, the bleeding episodes were reduced from 4.7 ± 7 to 1.9 ± 2 patients per year.
Comment: From Heyde’s initial clinical observation in 1958 to 2012, studies have described the syndrome’s fundamental biological mechanism (35). Of 3.8 million patients discharged from public hospitals in Ireland, the incidence of GI bleeding in patients with AS was 0.9% (36).
Bicuspid Aortic Valve
A Cardiac MRI is better than 2-dimensional transthoracic echocardiography for diagnosis of bicuspid aortic valve
Of 1,203 patients who had an aortic valve operation, 218 had both pre-operative 2-dimensional transthoracic echocardiography (2D TTE) and cardiac MRI (cMRI); bicuspid aortic valve (BAV) was confirmed in 123 patients (37). Of these 123 patients, 2D TTE confirmed BAV in 76 (62%), misidentified 12 (10%) as tricuspid valve, and was nondiagnostic in 35 (28%). In the same 123 patients, cMRI confirmed BAV in 115 (93%), misidentified 5 (4%) as tricuspid valve, and was nondiagnostic in 3 (2%). The difference in identifying BAV by 2D TTE versus cMRI was significant (p < 0.001). In the entire cohort of 218 patients, 2D TTE was diagnostic for valve morphology in 155 (71%), and cMRI was diagnostic in 212 (97%), p < 0.001.
Excellent 20-year results of catheter balloon commissurotomy for restenosis after previous surgical mitral commissurotomy
One hundred sixty-three patients had catheter balloon commissurotomy (CBC) (called percutaneous mitral commissurotomy) as a result of bicommissural fusion for restenosis after surgical commissurotomy (38). Good immediate result (valve area ≥1.5 cm2 and mitral regurgitation [MR] ≤2/4) was obtained in 135 (83%). In those with a good immediate result, the 20-year results were mortality of 17%, repeat CBC in 18%, survival without surgery was 33.2 ± 5.5%, and good functional result (cardiovascular survival and New York Heart Association [NYHA] functional class [FC] I/II) was 17.9 ± 4.7% (Fig. 4).
B Progressively increasing significant tricuspid regurgitation on long-term follow-up after successful CBC for severe MS
A prospective study of 299 patients showed that after successful CBC, tricuspid regurgitation (TR) regressed (39). However, 56 patients developed significant TR (grade ≥3 on echocardiography/Doppler) during follow-up (median 12 years, IQR: 8.0 to 18 years). The increase was time dependent; at 8, 12, and 18 years after CBC, significant TR was present in 9.4%, 19.8%, and 35.2%, respectively. Atrial fibrillation (A Fib), TR grade ≥2 before CBC, and mitral valve restenosis were important factors for de novo development of late TR.
A Resuscitant from sudden death: triad of bileaflet mitral valve prolapse in women, ST–T-wave changes on electrocardiogram, and frequent complex ventricular ectopic activity
Twenty-four of 1,200 patients in the Mayo Clinic Long QT Syndrome/Genetic Heart Rhythm Clinic had idiopathic out-of-hospital cardiac arrest (i.e., negative for ischemia, cardiomyopathy, and channelopathy) (40). All had implantable cardioverter-defibrillators (ICDs). Out-of-hospital cardiac arrest had occurred in 22 (92%). Ten of 24 (42%) had bileaflet mitral valve prolapse (MVP), and comparing these patients to those with normal mitral valves, the incidence in women was 90% versus 50% (p = 0.04), and had a higher incidence of biphasic or inverted waves 77.8% versus 29% (p = 0.04). On Holter monitoring, they had a higher prevalence of: 1) ventricular bigeminy: 100% versus 10%, (p < 0.0001); 2) ventricular tachycardia: 78% versus 10% (p = 0.006); and 3) premature ventricular contractions originating from the outflow tract alternating with the papillary muscle or fascicular region: 78% versus 28%, (p = 0.02) (Fig. 5). Over a median follow-up of 1.8 years (range 0.1 to 11.9 years) after ICD placement, 13 of 24 (54%) patients received appropriate ICD shocks for ventricular fibrillation. Only bileaflet MVP was associated with ventricular fibrillation requiring ICD therapy (p = 0.028).
Comment: Very important data. It should be emphasized that no patient of the 24 idiopathic out-of-hospital cardiac arrests had prolapse of only 1 leaflet.
B Longitudinal outcomes of mitral valve repair in patients ≥65 years of age
Data are presented from the STS database in 14,604 patients who had mitral valve repair (MVrep) from 1991 to 2007 (41). Patients were age 73.3 ± 5.5 years, LVEF was 0.54 ± 0.13, 55.8% were female, and 8.4% were non-Caucasians. Operative mortality was 2.59%, and follow-up was 5.9 ± 3.9 years (range 1 to 18 years). The 10-year actuarial survival was 57.4%. The 10-year actuarial rates of mitral reoperation, heart failure, bleeding, and stroke were 6.2%, 30.1%, 15.3%, and 16.4%, respectively.
Comment: Interesting data. Those data that were important and clinically valuable, but were not presented, included: 1) the number of patients who had mitral valve replacement (MVR) during the same time period; 2) the confidence intervals of survival and of events; 3) the incidence and severity of recurrent MR, which is likely to be underestimated by evaluating the reoperation rate; and 4) the mortality and incidence of heart failure were “high.” Therefore, there is a need to document the extent and intensity of medical treatment on follow-up and at baseline, the incidence of associated CAD based on findings from coronary arteriography, risk factors for CAD, the incidence of moderate and severe MR, the frequency and severity of renal dysfunction, and the causes of death (please also see late outcomes of MVrep in the following text).
C MVP with a near 100% MVrep rate
From 2002 to 2010, MVrep was performed by a single surgeon in 744 consecutive patients; 1 patient had to be converted to MVR (42). Patients were age 58 ± 13 years (range 12 to 90 years), 21% were ≥70 years of age, LVEF was 0.55 ± 0.09, 12% were in NYHA FC III/IV, and MR was moderately severe in 6.5% and severe in 93.5%. Thirty-day mortality was 0.9%. One- and 5-year survival was 99.2 ± 0.3% and 97.4 ± 0.8%, respectively. Seventy percent had late follow-up echocardiography at a follow-up time of 1.5 ± 1.1 years (range 7 to 2,527 days) that showed recurrent ≥2+ MR at 7 years of 9%.
D Late (20-year) outcomes of MVrep
From 1985 to 2004, all 840 patients who had MVrep for “degenerative” MR were reported (43). Their median age was 60 years (IQR: 50 to 68 years), and NYHA FC was I, II, III, and IV in 15.1%, 36.7%, 36.8%, and 11.3%, respectively. LVEF ≥0.60 occurred in 60.1%, severe MR in 95%, and moderate MR in 5%. STS risk score was 1.5% (95% CI: 0.3% to 5.5%). Thirty-day mortality was 4 of 840 (<0.5%). Follow-up times ranged from 0 to 26 years, median was 10.4 years (IQR: 7.4 to 13.7 years). Clinical follow-up was complete in 98.4% of patients. Echocardiographic follow-up extended from 0 to 26 years (median 10.3 years, IQR: 7.5 to 13.3 years) and was complete in 94.9%. By echocardiography/Doppler, valve function was evaluated and data were presented at 5 to 10 years, 10 to 15 years, 15 to 20 years, and >20 years in 97%, 94%, 90%, and 76% of patients, respectively. Outcomes at 10 and 20 years are shown in Table 1.
Comment: Very impressive follow-up data that are comprehensive. Excellent outcomes. Note: The low STS risk score and 52% of patients were in NYHA FC I and II.
E Late outcomes after double-orifice MVrep combined with ring annuloplasty
The edge-to-edge (E-to-E) procedure produces a double-orifice mitral valve. From 1993 to 2000, 174 patients with severe degenerative MR had E-to-E plus ring annuloplasty (44). They comprised 24.5% of patients who had MVrep during this time period. They were age 52 ± 18 years, 71% of patients were in NYHA FC I/II, and A fib was present in 17.2%. Follow-up was 11.5 ± 2.53 years (range 1.1 to 17.6 years) and was complete in 169 (97.1%), 55 patients had an echocardiogram at the authors’ institution, and 114 patients within the previous 6 months by the referring local cardiologist. MR was due to anterior, posterior, and bileaflet prolapse in 20.6%, 5.7%, and 73.5%, respectively. There were no hospital deaths, actuarial survival at 14 years was 86.9 ± 3.37, and freedom from cardiac death was 95.8 ± 1.54%. Freedom of reoperation was 89.6 ± 2.51%. Mitral stenosis requiring reoperation was detected in 1 patient (0.6%). Mitral valve area was 3.2 ± 0.4 cm2, and MR was absent in 24.8%, mild in 49.1%, moderate in 12.4%, and moderate to severe in 3.5%. Recurrence of MR ≥3+ occurred at a median of 8.2 years (IQR: 2.8 to 10.7 years); the only predictor of recurrence of MR ≥3+ was residual MR greater than mild at hospital discharge. The incidence of NYHA FC I, II, and III was 66.2%, 28.9%, and 4.7%, respectively (p = 0.0001 compared with pre-operative values).
A Persistent positive blood cultures at 48 to 72 h after initiation of antibiotic treatment for left-sided infective endocarditis is associated with increased in-hospital mortality
Of 256 patients with positive blood cultures, 89 (35%) had persistent positive blood cultures at 24 to 72 hours, which was associated with a doubling of in-hospital mortality (OR: 2.1, 95% CI: 1.2 to 3.6) (45). Other independent predictors of in-hospital mortality were staphylococcal infection (OR: 3.3), renal failure (OR: 2.9), heart failure (OR: 2.8), and age (OR: 1.026).
Comment: Forty-three percent of the 99 patients with prosthetic valve endocarditis had positive blood cultures at 48 to 72 h compared with 29% of patients with native valve endocarditis. About 90% of patients with Streptococcus viridans infection had negative blood cultures at 48 to 72 h.
B Neurological complications of infective endocarditis: most embolic events occur during the first 7 days of antibiotic therapy
Data are from a prospective multicenter study from 8 centers in Spain from 1984 to 2009. Of 1,345 consecutive episodes of left-sided infective endocarditis, 340 (25.3%) had ≥1 neurological complication (46). Ischemic events were the most frequent of these complications and occurred in 192 of 340 (56%) patients. Overall mortality was 30%; neurological complications accounted for 45% of the deaths. Antibiotic therapy reduced the neurological complications by 33% to 75%. Importantly, 163 of 192 (85%) ischemic events while on antibiotic therapy occurred in 133 of 163 (82%) patients. Of these, ischemic events occurred ≤7 days of starting antibiotic therapy. Surgery was performed in only 523 of 710 (39%) of those in whom it was indicated.
C The addition of 18F-FDG positron emission tomography/computed tomography to echocardiography improves the diagnosis of prosthetic heart valve endocarditis
Seventy-two patients suspected of prosthetic heart valve (PHV) endocarditis (PVE) were prospectively studied (47), 36 (50%) of whom exhibited abnormal FDG uptake around the site of the PHV. The sensitivity, specificity, positive predictive value, negative predictive value, and global accuracy of FDG uptake were 73%, 80%, 85%, 67%, and 76%, respectively. Adding abnormal FDG uptake around the PHV increased the sensitivity of the modified Duke criteria at admission from 70% to 97%, p = 0.0008; the result was due to a significant reduction (p < 0.0001) in the number of possible PVE cases from 40 (56%) to 23 (32%).
Comment: The accurate diagnosis of PVE is clinically very important but can be problematic. Cardiac positron emission tomography/computed tomography could become a very useful additional diagnostic test.
Transcatheter Valve Therapy
A Updated standardized endpoint definitions for transcatheter aortic valve implantation (48)
B Histopathology of embolic debris captured during aortic transcatheter valve therapy
Forty patients underwent aortic transcatheter valve therapy (TVT) with use of a dual-filter–based embolic protection device (Montage Dual Filter System, Claret Medical, Santa Rosa, California) (49). The debris had 7 different histopathologic characteristics (Table 2). There were different types of thrombus (Fig. 6).
Comment: An important study.
C TVT for SVD of bioprosthetic PHV: data from the Global Valve-in-Valve Registry
Data are from 202 patients in 38 cardiac centers, age 77.7 ± 10.4 years, 52.5% male. They had received a CoreValve (n = 124) (Medtronic, Minneapolis, Minnesota) or Edwards Sapien valve (n = 78) (Edwards Lifesciences, Irvine, California) for TVT (50). The mode of failure of the bioprosthesis was stenosis in 42%, regurgitation in 34%, and stenosis plus regurgitation in 24%. Procedural success rate was 93.1%; adverse outcomes included device malposition in 15.3% and ostial coronary obstruction in 3.5%. Stroke rate was 2%, AR grade ≥2+ occurred in 5%, and the mean AVG was 15.9 ± 8.6 mm Hg. Thirty-day and 1-year mortality rates were 8.4% and 14.2%, respectively. Pre-procedure, 94.2% were in NYHA FC III/IV. At 1 year, 49% and 35.1% were in NYHA FC I and II, respectively.
Comment: An important direction of TVT with impressive early results. A review documented outcomes of this procedure in detail (51). It is still a very early stage of this procedure; inappropriate conclusions that may result in changes in clinical practice should be avoided.
D Women have better short- and long-term survival with TVT
Consecutive 641 patients undergoing aortic TVT in 2 centers in Canada were evaluated (52); 329 (51.3%) were women, and 312 were men. Balloon-expandable valves were used in 97% with a transapical approach in 51.7% in men and 38.1 % of women. Porcelain aorta was present in 29.2% of the women and 12.0% of the men, p < 0.001. Women had more major vascular complications (12.4% versus 5.4%, p = 0.0003) and needed more blood transfusions (9.5% versus 3.6%, p = 0.005), but had a lower 30-day mortality. The survival in women versus men was 82.7% versus 72.5% at 1 year, and 72.1% versus 61.7% at 2 years, p = 0.007.
A Immediate effects of reduction of MR by mitral clip on LV remodeling and loading conditions
Thirty-three patients, age 78 ± 10 years, with functional (45%), degenerative (48%), or mixed (6%) MR (53), were studied acutely while still under anesthesia immediately before and after placement of the MitraClip (Abbott Vascular, Santa Clara, California). Standard right-heart catheterization and LV catheterization using a conduction catheter were performed, which allowed obtaining continuous measurements of the LV pressure and volume, and allowed measurement/calculation of LV afterload, pre-load, end-diastolic and end-systolic stress, contractility, myocardial energetics, and hemodynamics. The authors summarized their findings as: “1) Reduction of MR by TVT results in an acute increase of LV afterload and reduction of preload. A significant increase in forward cardiac output and decrease of pulmonary pressures indicates the increase in afterload is outweighed by end-diastolic unloading; 2) Despite a decline in LVEF, LV contractility is not significantly affected; 3) LV total mechanical energy remains unchanged and therefore myocardial oxygen consumption is not expected to increase; and 4) The beneficial hemodynamic changes with preserved LV contractility reverses LV remodeling by reducing end-diastolic volume. At 3 months, NYHA functional class and LV dilatation were improved.”
Comment: Sophisticated and excellent study.
Prosthetic Heart Valve
A STS clinical practice guidelines: executive summary
Comment: These guidelines (54) present the viewpoint of the STS with regard to the surgical aspects of heart valves and of the ascending aorta, and include recommendations of the surgical aspects of aortic root, ascending aortic dissection, ascending aorta, and aortic arch.
The STS guidelines have 83 Class I recommendations, of which 6 (7.2%) are based on Level of Evidence: A. Moreover, 2 of the recent randomized trials that have been cited have significant problems (55,56). Of the 145 recommendations, the Level of Evidence was C in 62%.
B Anticoagulation of older patients receiving AVR with bioprosthetic valves: is aspirin alone adequate?
Data are from 25,656 patients age ≥65 years in the 2004 to 2006 STS database (57), their median age was 77 years (IQR: 72 to 81 years), 39.4% were women. A total of 13,458 (52.5%) patients had a prior history of ≥1 risk factor for early thromboembolism at hospital discharge: A fib in 41.1%, thromboembolism in13.6%, or LVEF <0.30 in 4.8%. At hospital discharge, 12,457 (48.6%) received aspirin only (group A), 2,999 (11.7%) received warfarin only (group B), and 5,972 (23.3%) received aspirin plus warfarin (group C). The 3-month incidence of death in these 3 groups was 3.0%, 4.0%, and 3.1%, respectively, and of bleeding was 1.0%, 1.4%, and 2.8%, respectively.
Comment: The answer is yes unless there is an associated comorbid condition for which there is a widely accepted indication for warfarin therapy. There is a very recent randomized trial indicating benefit regarding improved graft patency with use of aspirin + clopidogrel in patients undergoing off-pump CABG (58,59). Should we apply this finding to patients undergoing AVR + CABG? I believe the answer is also yes at the present time.
C Previous CABG does not increase mortality or morbidity of reoperative valve surgery
A total of 1,093 consecutive patients underwent reoperative cardiac surgery between 2000 and 2010 (60), of whom 363 had isolated reoperative valve surgery. Their age was 62 ± 16 years; 38.8% were female; the time from previous surgery was 8.6 ± 7.8 years, and 15% of reoperative surgery occurred within 1 year of the initial operation. In group A patients (n = 133), the previous surgery had included CABG; in group B (n = 230), patients had not had previous CABG. In group A patients, 94% had patent grafts. Operative mortality was 4.1%. In propensity-matched patients, there was no statistically significant difference between the 2 groups for mortality or morbidity. Group A patients had a lower 5-year survival rate than group B patients, but in propensity-matched patients, the difference was not statistically significant. Multivariate predictors of decreased survival were severe pulmonary hypertension (OR: 2.76), diabetes mellitus (OR: 2.01), NYHA FC III or IV (OR 1.69), logistic EuroSCORE (OR: 1.04), and peripheral vascular disease (OR: 0.55).
D Outcomes of David valve-sparing aortic root replacement is similar in those with bi- and tricuspid aortic valves
Two hundred thirty-three patients (BAV in 27%, Marfan syndrome in 40%) underwent Tirone David’s valve-sparing aortic root replacement from 1993 to 2009 (61). Survival at 5 and 10 years was 98.7 ± 0.7% and 93.5 ± 5.1%. At 5 and 10 years, there was no statistically significant difference between patients with bi- and tricuspid aortic valves in survival, reoperation, SVD, or any other functional or clinical endpoints, including those with associated connective tissue disorder.
E Long-term survival after S:AVR among the high-risk “elderly” from the STS database 1991 to 2007
Data on 103,500 Medicare-linked S:AVR patients from 1999 to 2007 are presented (62). Patients were categorized by procedure type (AVR, AVR + CABG) and age (65 to 69, 70 to 79, and ≥80 years). Operative mortality of AVR (n = 43,809) and of AVR + CABG (n = 59,691) were 3.9% and 5.0%, respectively. For patients in the 65 to 69, 70 to 79, and ≥80 years of age groups, the median survival after AVR was 12.8, 9.2, and 6.2 years, respectively, and for AVR + CABG was 10.4, 8.2, and 5.9 years, respectively. Median survival was also presented by categorization to several high-risk groups. Severe lung disease and renal failure were each associated with a ≥50% reduction in median survival among all age groups. The survival is said to be “excellent” and was matching that of a “similarly aged U.S. population.”
Comment: These data are important. However, data that are clinically valuable, but not presented, included: 1) operative mortality in the 3 subgroups characterized by age: 2) IQR of the median survival; 3) survival curves do not present, either in the text or figures, the CIs and numbers of patients at risk; and 4) data that match the survival to that of the U.S. population. Note also that 1 criterion of renal failure in the STS database (creatinine >2.0 mg/l) does not precisely delineate the extent of renal dysfunction.
Dr. Rahimtoola has received honoraria for educational lectures from the American College of Cardiology Foundation, American College of Physicians, University of California Los Angeles, University of California Irvine, Cornell University, Creighton University, Thomas Jefferson University, Cedars-Sinai Medical Center, Harvard Medical School, University of Wisconsin, University of Hawaii, Cardiologists Association of Hong Kong, China, University of California Fresno, University of Arizona, Tucson Medical Center, ATS, St. Jude Medical, Carbomedics, Edwards Lifesciences, Merck & Co., and Pfizer.
This review includes articles published from July 2012 through June 2013, with 2 exceptions.
- Received October 10, 2013.
- Revision received December 19, 2013.
- Accepted January 7, 2014.
- American College of Cardiology Foundation
- The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS),
- Vahanian A.,
- Alfieri O.,
- Andreotti F.,
- et al.
- Sverdlov A.L.,
- Ngo D.T.M.,
- Chan W.P.A.,
- et al.
- Dweck M.R.,
- Khaw H.J.,
- Sng G.K.Z.,
- et al.
- Miller J.D.,
- Chu Y.,
- Brooks R.M.,
- Richenbacher W.E.,
- Pena-Silva R.,
- Heistad D.D.
- Rahimtoola S.H.
- Gössl M.,
- Khosla S.,
- Zhang X.,
- et al.
- Minners J.,
- Allgeier M.,
- Gohlke-Barwolf C.,
- Kienzle R.P.,
- Neumann F.J.,
- Jander K.
- Griffith M.J.,
- Carey C.,
- Coltast D.J.,
- Jenkins B.S.,
- Webb-Peploe M.M.
- Bahlmann E.,
- Gerdts E.,
- Cramariuc D.,
- et al.
- O’Neill W.W.
- (1991) Percutaneous balloon aortic valvuloplasty. Acute and 30-day follow-up results in 674 patients from the NHLBI Balloon Valvuloplasty Registry. Circulation 84:2383–2397.
- Otto C.M.,
- Mickel M.C.,
- Kennedy J.W.,
- et al.
- Lieberman E.B.,
- Bashore T.M.,
- Hermiller J.B.,
- et al.
- Ben-Dor I.,
- Pichard A.D.,
- Satler L.F.,
- et al.
- Don C.W.,
- Witzlse C.,
- Cueddu R.J.,
- et al.
- Beach J.M.,
- Mihalgevic T.,
- Svensson L.G.,
- et al.
- Rahimtoola S.H.
- Agarwal S.,
- Rajamanickam A.,
- Bajaj N.S.,
- et al.
- Zilberszac R.,
- Gabriel H.,
- Schemper M.,
- et al.
- van der Linde D.,
- Takkenberg J.J.M.,
- Rizopoulos D.,
- et al.
- van der Linde D.,
- Roos-Hesselink J.W.,
- Rizopoulos D.,
- et al.
- Bouleti C.,
- Jung B.,
- Himbert D.,
- et al.
- Lee S.-P.,
- Kim H.-K.,
- Kim K.-H.,
- et al.
- Sriram C.S.,
- Syed F.F.,
- Ferguson M.F.,
- et al.
- David T.E.,
- Armstrong S.,
- McCrindle B.W.,
- Manlhiot C.
- López J.,
- Sovilla T.,
- Vilacusta I.,
- et al.
- García-Cabrera E.,
- Fernández-Hidalgo N.,
- Almirante B.,
- et al.
- Saby L.,
- Laas O.,
- Habib G.,
- et al.
- Kappetein A.P.,
- Head S.J.,
- Généreux P.,
- et al.
- Van Mieghem N.M.,
- Schipper M.E.I.,
- Ladich E.,
- et al.
- Dvir D.,
- Webb J.,
- Brecker S.,
- et al.
- Humphries K.H.,
- Toggweiler S.,
- Rodés-Cabau J.,
- et al.
- Gaemperli O.,
- Biaggi P.,
- Gugelmann R.,
- et al.
- Rahimtoola S.H.
- Rahimtoola S.H.
- Brennan J.M.,
- Edwards F.H.,
- Zhao Y.,
- et al.
- Mannacio V.A.,
- Tommaso L.D.,
- Antignan A.,
- De Amicis V.,
- Vosa C.
- Elefteriades J.A.,
- Meier P.
- Brennan J.M.,
- Edwards F.H.,
- Zhao Y.,
- et al.