Circulation Editors’ Picks

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HomeCirculationVol. 128, No. 13Circulation Editors’ Picks Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculation Editors’ PicksMost Read Articles on the Topic of Valvular Heart Disease The Editors The Editors Search for more papers by this author Originally published24 Sep 2013https://doi.org/10.1161/CIRCULATIONAHA.113.005947Circulation. 2013;128:e195–e200Increased Risk of Left Heart Valve Regurgitation Associated With Benfluorex Use in Patients With Diabetes Mellitus: A Multicenter StudySummary—The aim of this population-based multicenter study was to compare the frequency of left heart valve regurgitations diagnosed by echocardiography in prospectively included diabetic patients who had taken benfluorex for at least 3 months and in matched diabetic control subjects (matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease) without previous exposure to the drug. We found a significant increase in the frequency of mild or greater left heart valve regurgitations among patients treated with benfluorex compared with propensity-matched control subjects (31% vs. 13%;P<0.001). Exposure to benfluorex was associated with a >3-fold increase in the risk of mild or greater left heart valve regurgitations. Furthermore, the risk of benfluorex-induced regurgitations was more important for the aortic valve compared with the mitral valve. Finally, the higher frequency of left heart valve regurgitations among benfluorex-treated patients compared with control subjects was due mainly to an increased frequency of mild regurgitations. The natural history of benfluorex-induced valve abnormalities needs further research.Conclusions—Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.1Comprehensive Annular and Subvalvular Repair of Chronic Ischemic Mitral Regurgitation Improves Long-Term Results With the Least Ventricular RemodelingSummary—Chronic ischemic mitral regurgitation (MR) remains one of the most complex and unresolved aspects in the management of ischemic heart disease. Restrictive annuloplasty, combined with coronary revascularization, is currently the most commonly performed surgical procedure to treat chronic ischemic MR. However, the variable results, the potentially induced mitral stenosis, and the high rate of MR recurrence after this strategy create the need for a new approach that involves the subvalvular mitral valve apparatus. We previously demonstrated the efficacy of mitral valve leaflet chordal cutting in reducing chronic ischemic MR and left ventricular remodeling in an experimental model along with clinical applications. Chordal cutting, by decreasing the apical leaflet tenting, improves coaptation and decreases MR. Because the leaflet tethering is applied at both annular and papillary muscle levels, we conducted an experimental ovine study using our model of chronic ischemic MR to evaluate the potential benefit of associating undersized ring annuloplasty with chordal cutting versus each technique alone. Our results seem to demonstrate that cutting the secondary chordae associated with undersized annuloplasty in the chronic post–myocardial infarction setting improves the long-term results, with almost a disappearance of ischemic MR along with a regression of chronic left ventricular remodeling. We believe that this physiological therapeutic approach will have the potential to improve mitral valve repair results in the chronic ischemic MR setting and will provide an opportunity in the near future for a more tailored personal approach of mitral valve repair in the case of ischemic MR.Conclusions—Comprehensive annular and subvalvular repair improves long-term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up.2Coronary Artery Bypass Surgery With or Without Mitral Valve Annuloplasty in Moderate Functional Ischemic Mitral Regurgitation: Final Results of the Randomized Ischemic Mitral Evaluation (RIME) TrialSummary—The role of mitral valve repair (MVR) during coronary artery bypass grafting (CABG) in patients with moderate ischemic mitral regurgitation is uncertain. We randomized 73 patients referred for CABG with moderate ischemic mitral regurgitation and an ejection fraction >30% to receive either CABG plus MVR (34 patients) or CABG only (39 patients). At 1 year, patients in the CABG plus MVR group had a significantly greater improvement in functional capacity as measured by peak oxygen consumption, and greater left ventricular reverse remodeling as measured by the left ventricular end-systolic volume index, reduction in mitral regurgitation severity, and B-type natriuretic peptide levels, compared with the CABG-only group. However, operation duration, blood transfusion, intubation duration, and hospital stay duration were greater in the CABG plus MVR group. There was also a trend towards higher complication rates in the CABG plus MVR group, although this was not statistically significant. Deaths at 30 days and 1 year were similar in both groups, as was the incidence of hospitalization for heart failure. The results of this study support the addition of MVR to CABG in patients with moderate ischemic mitral regurgitation undergoing CABG, but the benefits of the combined procedure must be balanced against a possible increased risk of morbidity in the perioperative period. The impact of the benefits reported in this study on longer term clinical outcomes remains to be defined.Conclusions—Adding mitral annuloplasty to CABG in patients with moderate ischemic MR may improve functional capacity, left ventricular reverse remodeling, MR severity, and B-type natriuretic peptide levels, compared with CABG alone. The impact of these benefits on longer term clinical outcomes remains to be defined.3Transcatheter Aortic Valve Replacement for Degenerative Bioprosthetic Surgical Valves: Results From the Global Valve-in-Valve RegistrySummary—In the last decade, bioprosthetic valves have been used more commonly during surgical valve replacements; it is estimated that in subsequent years, many patients will suffer from failed surgical bioprostheses. The Global Valve-in-Valve Registry, which includes in the present analysis 202 patients from 38 centers, is the first large, comprehensive evaluation of transcatheter aortic valve replacement with the use of either Edwards SAPIEN (Edwards Lifesciences, Irvine, CA) or CoreValve (Medtronic, Minneapolis, MN) devices for failed surgically inserted aortic bioprostheses, including 1-year clinical and echocardiographic analyses. According to the registry, the valve-in-valve approach is effective and relatively safe. Improvement in patient functional capacity was clear: 84.1% of treated patients were classified as New York Heart Association class I/II early after the procedure. Clinical and hemodynamic results are maintained in 1-year follow-up. Thirty-day mortality and stroke rates (8.4% and 2%, respectively) are comparable to those in other transcatheter aortic valve replacement cohorts. An efficacy concern involved moderately elevated postprocedural gradients, with predictors in multivariate analysis that include the degree of bioprosthesis stenosis and treatment with an Edwards SAPIEN inside a small bioprosthesis. Safety concerns included ostial coronary obstruction (3.5%) and device malposition (15.3%) resulting in relatively high rates of a need for implantation of another transcatheter aortic valve replacement device (8.4%) and retrieval of a CoreValve (8.9%). Operators of valve-in-valve procedures should be skilled in handling device malposition and related technical maneuvers, if needed. The possible impact on cardiac surgery practice includes referral of patients with failed bioprostheses who are at very high surgical risk to valve-in-valve and selection of valve class during surgery (mechanical versus biological), in favor of the use of bioprostheses.Conclusions—The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.4Moderate Aortic Enlargement and Bicuspid Aortic Valve Are Associated With Aortic Dissection in Turner Syndrome: Report of the International Turner Syndrome Aortic Dissection RegistrySummary—Aortic dissection and rupture occurs in young women with Turner syndrome. Although this observation is reiterated in case reports, the rarity of its occurrence has limited the availability of information about the natural history and the clinical picture of aortic dissection in Turner syndrome. We estimated that it would require 50 000 patient-years in a prospective longitudinal study to accumulate data similar to the data obtained from the 20 cases we describe from the International Turner Syndrome Aortic Dissection registry. We show that aortic dissection can occur in individuals with Turner syndrome who have no other documented cardiovascular problems. Pregnancy was associated with 1 of 19 subjects in the International Turner Syndrome Aortic Dissection registry, which is 10 times more common than in the general TS population. Bicuspid aortic valve occurred in 95% of the subjects, but it also occurs commonly in those without aortic dissection. We found that aortic dissection in Turner syndrome occurs at a significantly smaller aortic size than in other genetically triggered aortopathies. Data from 5 individuals with serial echocardiographic measurements obtained before their aortic dissection indicates that a stable ascending aortic size over time may not be a reassuring finding. We conclude that an ascending aortic size index >2.5 cm/m2 is a significant risk factor for aortic dissection in those with Turner syndrome.Conclusions—Aortic dissection in Turner syndrome occurs in young individuals at smaller aortic diameters than in the general population or other forms of genetically triggered aortopathy. The absence of aortic valve or other cardiac malformations appears to markedly reduce the risk of aortic dissection However, aortic dissection can occur in Turner syndrome without cardiac malformations or hypertension. Individuals with Turner syndrome who are >18 years of age with an ascending aortic size index >2.5 cm/m2 should be considered for an aortic operation to prevent aortic dissection.5Long-Term Survival After Aortic Valve Replacement Among High-Risk Elderly Patients in the United States: Insights From the Society of Thoracic Surgeons Adult Cardiac Surgery Database, 1991 to 2007Summary—We used the Society of Thoracic Surgeons database to examine long-term survival among 145 911 aortic valve replacement patients ≥65 years of age. In-hospital complications and long-term survival were stratified by age, Society of Thoracic Surgeons perioperative risk of mortality, and several comorbidities. We found that long-term survival after surgical aortic valve replacement in the elderly is excellent, although patients with a high Society of Thoracic Surgeons perioperative risk of mortality and those with certain comorbidities (lung disease and renal failure, particularly dialysis-dependent renal failure) carry a particularly poor long-term prognosis. Although the current Society of Thoracic Surgeons perioperative risk of mortality calculator provides reasonable differentiation of long-term survival, a model calibrated to the prediction of long-term risk would be expected to add accuracy. We believe our study is significant in that it examines an area in which there are limited data, namely contemporary long-term outcomes after aortic valve replacement in older individuals. We believe that our findings may improve long-term outcomes for this elderly population by helping to establish best practices in operative and perioperative care.Conclusion—Long-term survival after surgical aortic valve replacement in the elderly is excellent, although patients with a high Society of Thoracic Surgeons perioperative risk of mortality and those with certain comorbidities carry a particularly poor long-term prognosis.6Determinants and Prognostic Significance of Exercise Pulmonary Hypertension in Asymptomatic Severe Aortic StenosisSummary—The management and timing of surgery in asymptomatic patients with severe aortic stenosis remain matters of concern. The risks of aortic valve surgery and late complications of prosthesis in such patients need to be balanced against the possible prevention of sudden death and lowering of cardiac mortality. Hence, early elective surgery could be proposed only to well-selected patients considered at high risk of poor outcome. In the present study, 105 consecutive asymptomatic patients with severe aortic stenosis underwent comprehensive resting and exercise stress echocardiography to evaluate the presence of pulmonary hypertension (PHT). The results showed that 55% of asymptomatic patients may develop exercise PHT. Patients with exercise PHT had significantly lower cardiac event-free survival and a markedly higher rate of death than those without exercise PHT. In addition, exercise PHT was associated with poorer outcome independently of demographic and resting echocardiographic data and exercise-induced changes in mean transaortic pressure gradient. Beyond both resting aortic stenosis severity and systolic pulmonary arterial pressure, the assessment of the presence of exercise PHT provided important incremental predictive value. Even in patients with markedly elevated aortic jet velocity, those with exercise PHT depicted a higher risk of reduced cardiac event-free survival. These results strongly support the use of exercise stress echocardiography in the management of asymptomatic severe aortic stenosis. Early elective aortic valve surgery to prevent irreversible left ventricular myocardial damage, diastolic dysfunction, and symptoms could be advised in patients developing exercise PHT. In contrast, asymptomatic patients with no exercise PHT may be conservatively followed up.Conclusions—In asymptomatic patients with severe aortic stenosis, the main determinants of Ex-PHT are male sex, resting systolic pulmonary arterial pressure, and exercise parameters of diastolic burden. Moreover, Ex-PHT is associated with a 2-fold increased risk of cardiac events. These results strongly support the use of exercise stress echocardiography in asymptomatic aortic stenosis.7Influence of Mitral Regurgitation Repair on Survival in the Surgical Treatment for Ischemic Heart Failure TrialSummary—Chronic ischemic mitral regurgitation (MR) is associated with heart failure and increased mortality. The optimal treatment strategy for ischemic MR remains controversial. European practice guidelines recommend mitral valve repair in patients with severe or even moderate ischemic MR and an ejection fraction >30% who are undergoing coronary artery bypass grafting (CABG), even though retrospective analyses using propensity score matching showed no survival benefit of adding mitral valve repair to CABG. The need to add mitral valve repair in patients with an indication for CABG becomes even less clear when left ventricular dysfunction is more severe. The Surgical Treatment for Ischemic Heart Failure (STICH) trial randomized 1212 patients with severe left ventricular dysfunction (ejection fraction <35%) and coronary artery disease amenable to CABG to intensive medical therapy alone or in association with CABG. The decision to repair the mitral valve was left to the operating surgeon. Survival in the medically treated cohort depended strongly on MR grade at baseline, with mortality hazard being increased twice in patients with moderate to severe MR compared with patients with no MR. In patients with mild MR, CABG was associated with improved survival. In patients with moderate to severe MR, adding mitral valve repair to CABG tended to improve survival compared with CABG alone or medical therapy alone. Unfortunately, the decision to repair the valve was not randomized; therefore, even though risk adjustment actually accentuated the difference of survival in favor of adding mitral valve repair, a randomized trial is required to confirm our findings.Conclusions—Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone, a prospective randomized trial is necessary to confirm the validity of these observations.8Effects of Phosphodiesterase Type 5 Inhibition on Systemic and Pulmonary Hemodynamics and Ventricular Function in Patients With Severe Symptomatic Aortic StenosisSummary—Pressure overload resulting from aortic stenosis causes maladaptive ventricular and vascular remodeling that has deleterious consequences. Patients often present when compensatory mechanisms have been exhausted with advanced heart failure and abnormal hemodynamics characterized by pulmonary venous congestion, pulmonary hypertension, and afterload mismatch. These patients are either inoperable or at increased risk for surgery. Other patients have valve replacement before this clinical decompensation, but their outcomes are worse if there is associated hypertrophic ventricular remodeling and diastolic dysfunction. Existing experimental and clinical studies raise the interesting possibility that phosphodiesterase type 5 inhibition may both favorably alter abnormal hemodynamics and retard or reverse maladaptive remodeling in patients with aortic stenosis. Here, we show that a single dose of a phosphodiesterase type 5 inhibitor is safe in patients with severe symptomatic aortic stenosis and is associated with acute improvements in pulmonary and systemic hemodynamics, resulting in biventricular unloading. Importantly, these data suggest that afterload is not necessarily fixed in patients with aortic stenosis and that reducing vascular afterload may improve hemodynamics in these patients. If it is demonstrated that these hemodynamic benefits can be sustained, perhaps adjunctive medical therapy with phosphodiesterase type 5 inhibition in symptomatic patients with advanced heart failure could serve as a stabilizing bridge to definitive therapy with valve replacement with less risk than a balloon valvuloplasty. Our findings support the need for longer-term studies to evaluate the role of phosphodiesterase type 5 inhibition as adjunctive medical therapy in patients with aortic stenosis to address these clinical needs.Conclusions—This study shows for the first time that a single dose of a phosphodiesterase type 5 inhibitor is safe and well tolerated in patients with severe aortic stenosis and is associated with improvements in pulmonary and systemic hemodynamics resulting in biventricular unloading. These findings support the need for longer-term studies to evaluate the role of phosphodiesterase type 5 inhibition as adjunctive medical therapy in patients with aortic stenosis.9Type 2 Diabetes Mellitus Is Associated With Faster Degeneration of Bioprosthetic Valve: Results From a Propensity Score–Matched Italian Multicenter StudySummary—Biological prostheses are increasingly implanted to treat disparate cardiac valve diseases. Postoperative structural valve degeneration represents the most relevant drawback of such artificial valves, sometimes leading to substantial leaflet tissue derangement, clinical deterioration and ultimately, reoperation. The causes and pathogenetic mechanisms of artificial valve structural impairment are not yet fully understood. Atherosclerosis-related risk factors have been suggested recently, through analysis of postoperative outcome in limited patient experiences, to play a role in postimplantation bioprosthetic failure. This multicenter retrospective study sought to investigate specifically the early and long-term influence of type 2 diabetes mellitus in terms of composite outcome in patients undergoing bioprosthetic heart valve implantation in the aortic or mitral position. Propensity score analysis enabled a 1:1 match in 2226 diabetic and nondiabetic subjects among 6184 patients submitted to cardiac valve replacement with biological valves during a 21-year period. In this study, type 2 diabetes mellitus was shown to be an independent predictor of unfavorable outcome, either in terms of reduced life expectancy or in terms of structural bioprosthetic valve degeneration, with the insulin-treated subjects showing the most unfavorable postoperative results. Furthermore, diabetes mellitus was shown to negatively affect postoperative tissue valve performance, irrespective of other associated cardiovascular risk factors. Additional studies are needed to disclose the pathogenetic mechanisms by which such a metabolic disorder may affect the structural integrity of tissue valves and to investigate methods to reduce such an adverse event. Meanwhile, strict clinical surveillance is advised on the basis of the currently witnessed higher rate of structural valve degeneration in diabetic patients submitted to cardiac valve replacement with a biological prosthesis.Conclusions—Patients with type 2 diabetes mellitus undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.10Clinical Implications of Electrocardiographic Left Ventricular Strain and Hypertrophy in Asymptomatic Patients With Aortic Stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis StudySummary—This is the first study to examine the predictive value of ECG left ventricular strain and hypertrophy during watchful waiting in asymptomatic patients with aortic stenosis. In analyses of 1533 patients with asymptomatic mild to moderate aortic stenosis (aortic peak flow velocity ≥2.5 and ≤4.0 m/s) included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, cardiovascular event rates were considerably higher in those with ECG left ventricular strain or hypertrophy. Despite similar aortic stenosis severity (aortic peak flow velocity ≥3.0 m/s), annual risks of heart failure were ≈1.4% and 0.4% in those with and without ECG strain, respectively. The presence of ECG left ventricular strain and hypertrophy remained significantly associated with poor prognosis also when adjusted by aortic valve area index and mean aortic gradient or when the analyses were updated with annual reexaminations. Thus, low-cost and easily accessible ECG left ventricular strain and hypertrophy data provide valuable tools for risk stratification in patients with aortic stenosis. Whether ECG strain identifies those whose prognosis would be improved by earlier aortic valve replacement merits further study. Finally, treatment with low-dose simvastatin does not influence the progression of ECG left ventricular hypertrophy or strain.Conclusions—ECG left ventricular strain and left ventricular hypertrophy were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis.11Health-Related Quality of Life After Transcatheter Aortic Valve Replacement in Inoperable Patients With Severe Aortic StenosisSummary—Many patients with severe aortic stenosis do not undergo surgical valve replacement because of prohibitive operative risk. In a cohort of such patients, the Placement of Aortic Transcatheter Valves (PARTNER) trial recently showed that transcatheter aortic valve replacement increased 12-month survival by an absolute margin of 20% but was associated with increased risks of vascular complications and stroke compared with standard therapy, which included balloon aortic valvuloplasty in the majority of subjects. In this trial, quality of life was assessed prospectively with the Kansas City Cardiomyopathy Questionnaire and the Short Form-12 General Health Survey. We found that the overall summary score of the Kansas City Cardiomyopathy Questionnaire, the primary quality-of-life end point, improved 20 to 30 points on a 100-point scale 1, 6, and 12 months after transcatheter aortic valve replacement, whereas the improvement in the control group was 10 to 12 points at 1 and 6 months and only 4 points at 12 months. Similar patterns were observed for the other quality-of-life measures. Thus, during the first year after intervention, quality of life was substantially better in the transcatheter aortic valve replacement group than in the control group in this clinical trial population.Conclusions—Among inoperable patients with severe aortic stenosis, compared with standard care, transcatheter aortic valve replacement resulted in significant improvements in health-related quality of life that were maintained for at least 1 year.12Arterial Pulse Wave Dynamics After Percutaneous Aortic Valve Replacement: Fall in Coronary Diastolic Suction With Increasing Heart Rate as a Basis for Angina Symptoms in Aortic StenosisSummary—Using the new technique of percutaneous aortic valve replacement in combination with wave intensity analysis, we have identified abnormalities in coronary physiology that are rapidly restored to normal after valve implantation. In addition to being of mechanistic interest, quantification of coronary physiological reserve and in particular its paradoxical reversal may offer a potential way of assessing the severity of aortic stenosis in the presence of comorbidities that may mimic or obscure anginal symptoms. Although currently it is possible to do this analysis only with offline analysis tools, the computational processing requirements are minimal and easily automatable, making online analysis a realistic vision for the future.Conclusions—In aortic stenosis, the coronary physiological reserve is impaired. Instead of increasing when heart rate rises, the coronary diastolic suction wave decreases. Immediately after percutaneous aortic valve replacement (PAVR), physiological reserve returns to a normal positive pattern. This may explain how aortic stenosis can induce anginal symptoms and their prompt relief after PAVR.13Diabetes Mellitus Worsens Diastolic Left Ventricular Dysfunction in Aortic Stenosis Through Altered Myocardial Structure and Cardiomyocyte StiffnessSummary—In aging populations, diabetes mellitus (DM) and aortic stenosis (AS) are becoming frequent comorbidities. Studies looking at the interaction between DM and AS investigated mainly the progression of sclerocalcific valvular dysfunction. In heart failure (HF), DM raises diastolic left ventricular (LV) stiffness, which adversely affects morbidity and mortality. The DM-related rise in diastolic LV stiffness was observed both in HF with reduced ejection fraction and in HF with normal ejection fraction. In HF with reduced ejection fraction, DM affected myocardial stiffness through excessive fibrosis and arteriolar or capillary deposition of advanced glycation end products, whereas in HF with normal ejection fraction, DM increased myocardial stiffness through elevation of cardiomyocyte resting tension (Fpassive). The present clinical study extended these observations on DM-related worsening of diastolic LV stiffness to symptomatic AS and confirmed a similar increase in diastolic LV stiffness in patients suffering from both AS and DM. This increase was evident from higher LV end-diastolic pressure at comparable LV end-diastolic volume index. Furthermore, the increase in diastolic LV stiffness was shown to result from all 3 aforementioned mechanisms, namely excessive fibrosis, intramyocardial vascular advanced glycation end product deposition, and elevated cardiomyocyte Fpassive. The latter could be attributed to hypophosphorylation of the stiff isoform of the cytoskeletal protein titin, which is largely responsible for cardiomyocyte Fpassive. The observed increase in diastolic LV stiffness in patients suffering from both AS and DM could predispose them to earlier development of heart failure symptoms and an earlier need for aortic valve replacement.Conclusions—Worse diastolic LV dysfunction in AS-DM predisposes to heart failure and results from more myocardial fibrosis, more intramyocardial vascular advanced glycation end product deposition, and higher cardiomyocyte Fpassive, which was related to hypophosphorylation of the N2B titin isoform.14Aortic Valve Replacement in the Elderly: Determinants of Late OutcomeSummary—To identify patient factors related to increased longevity and to assess the potential impact of valve type on overall survival, we analyzed late outcomes of 2890 consecutive patients aged ≥70 years who had aortic valve replacement (AVR). Our findings may help clinicians in 2 ways. First, we found that several comorbid conditions (eg, renal failure, immunosuppression, concomitant coronary artery disease, history of myocardial infarction, or stroke) were associated with reduced late survival after AVR. These factors, in general, are not modifiable. But the finding that advanced New York Heart Association class predicted poorer late survival emphasizes the importance of not delaying operation unnecessarily in elderly patients. Delaying surgical referral until symptoms progress will not only result in a higher early mortality but will also decrease the likelihood of a satisfactory long-term survival. Second, our data show no important difference in outcome of patients by type of prosthesis. Our data are reassuring in that there is no survival penalty for use of bioprostheses in elderly patients. In addition, our findings demonstrate that the structural deterioration of aortic biop