Age-Related Outcomes After Transcatheter Mitral Valve Repair in Patients With Heart Failure: Analysis From COAPT

ObjectivesThe aim of this study was to assess the impact of age on outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial.BackgroundIn the COAPT trial, TEER with the MitraClip device in patients with heart failure (HF) and moderate to severe or severe secondary mitral regurgitation (SMR) reduced the risk for HF hospitalization (HFH) and all-cause mortality compared with maximally tolerated guideline-directed medical therapy (GDMT) alone. There are limited data regarding the effectiveness of MitraClip therapy in elderly patients.MethodsPatients (n = 614) were grouped by median age at randomization (74 years) and by MitraClip treatment vs GDMT alone. The primary endpoint was the 2-year rate of death or HFH assessed by multivariable Cox regression.ResultsDeath or HFH within 2 years occurred less frequently after treatment with the MitraClip vs GDMT alone in patients <74 years of age (37.3% vs 64.5%; adjusted HR: 0.41; 95% CI: 0.29-0.59) and ≥74 years of age (51.7% vs 69.6%; adjusted HR: 0.58; 95% CI: 0.42-0.81) (P_int = 0.17). Mortality was also consistently reduced with MitraClip treatment in young and elderly patients (P_int = 0.42). In contrast, elderly patients treated with the MitraClip vs GDMT alone tended to have a lesser reduction of HFH than younger patients (P_int = 0.03). Younger and older patients had similar improvements in quality of life after treatment with the MitraClip compared with GDMT alone.ConclusionsIn the COAPT trial, MitraClip treatment of moderate to severe and severe SMR reduced the composite risk for death or HFH and improved survival and quality of life regardless of age. As such, young and elderly patients with HF and severe SMR benefit from TEER, although elderly patients may not have as great a benefit from the MitraClip device in reducing HFH.     

3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure

BackgroundIn the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone.ObjectivesThis study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit.MethodsThis study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months.ResultsThe annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p < 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006).ConclusionsAmong patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079)     

NYHA Functional Classification and Outcomes After Transcatheter Mitral Valve Repair in Heart Failure: The COAPT Trial

ObjectivesThe aim of this study was to evaluate the outcomes of MitraClip implantation versus guideline-directed medical therapy (GDMT) in patients with secondary mitral regurgitation (SMR) according to baseline functional status as assessed by the widely used New York Heart Association (NYHA) functional classification.BackgroundPatients with heart failure (HF) and impaired functional status at baseline have poor prognosis. Whether the effects of transcatheter repair of secondary SMR in patients with HF are influenced by baseline functional status is unknown.MethodsIn the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, patients with HF with moderate to severe or severe SMR who remained symptomatic despite maximally tolerated GDMT were randomized to MitraClip implantation versus GDMT alone. Outcomes were evaluated according to baseline functional status as assessed using the NYHA functional classification. The primary endpoint of interest was the rate of death or HF-related hospitalization (HFH) at 2 years in time-to-first-event analyses.ResultsAmong 613 randomized patients, 240 were in NYHA functional class II (39.2%), 322 were in NYHA functional class III (52.5%), and 51 were in ambulatory NYHA functional class IV (8.3%). Rates of death or HFH were progressively higher with increasing NYHA functional class. Compared with GDMT alone, MitraClip implantation resulted in lower 2-year rates of death or HFH consistently in patients in NYHA functional class II (39.7% vs. 63.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.37 to 0.77), NYHA functional class III (46.6% vs. 65.5%; HR: 0.60; 95% CI: 0.45 to 0.82), and NYHA functional class IV (66.7% vs. 85.2%; HR: 0.55; 95% CI: 0.28 to 1.10; p_interaction = 0.86). Greater improvements in quality of life at 2 years were observed in patients treated with the MitraClip compared with GDMT irrespective of baseline functional status.ConclusionsThe NYHA functional classification provides prognostic utility in patients with HF and moderate to severe or severe SMR. In the COAPT trial, the benefits of MitraClip implantation were consistent in patients with better or worse functional status as assessed by NYHA functional class. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079)     

Right Ventricular–Pulmonary Arterial Coupling in Patients With HF Secondary MR: Analysis From the COAPT Trial

ObjectivesThe aim of this study was to determine the prognostic impact of right ventricular (RV)–pulmonary arterial (PA) coupling in patients with heart failure (HF) with severe secondary mitral regurgitation (SMR) enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.BackgroundRV contractile function and PA pressures influence outcomes in patients with SMR, but the impact of RV-PA coupling in patients randomized to transcatheter edge-to-edge repair (TEER) vs guideline-directed medical therapy (GDMT) is unknown.MethodsRV-PA coupling was assessed by the ratio of RV free wall longitudinal strain derived from speckle-tracking echocardiography and noninvasively measured RV systolic pressure. Advanced RV-PA uncoupling was defined as RV free wall longitudinal strain/RV systolic pressure ≤0.5%/mm Hg. The primary endpoint was a composite of all-cause mortality or HF hospitalization at 24-month follow-up.ResultsA total of 372 patients underwent speckle-tracking echocardiography, and 70.2% had advanced RV-PA uncoupling. By multivariable analysis, advanced RV-PA uncoupling was strongly associated with an increased risk for the primary 24-month endpoint of death or HF hospitalization (HR: 1.87; 95% CI: 1.31-2.66; P = 0.0005). A similar association was present for all-cause mortality alone (HR: 2.57; 95% CI: 1.54-4.29; P = 0.0003). The impact of RV-PA uncoupling was consistent in patients randomized to TEER and GDMT alone. Compared with GDMT alone, the addition of TEER improved 2-year outcomes in patients with (48.0% vs 74.8%; HR: 0.51; 95% CI: 0.37-0.71) and those without (28.8% vs 47.8%; HR: 0.51; 95% CI: 0.27-0.97) advanced RV-PA uncoupling (P_interaction = 0.98).ConclusionsIn the COAPT trial, advanced RV dysfunction assessed by RV-PA uncoupling was a powerful predictor of 2-year adverse outcomes in patients with HF and SMR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial]; NCT01626079)     

Health Status Changes and Outcomes in Patients With Heart Failure and Mitral Regurgitation: COAPT Trial

BackgroundIn the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) with the MitraClip rapidly improved health status and reduced the long-term risks for death and heart failure (HF) hospitalization in patients with HF and severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT).ObjectivesThe aim of this study was to examine if early health status changes were associated with long-term clinical outcomes in the COAPT population.MethodsThe association between change in health status (Kansas City Cardiomyopathy Questionnaire overall summary score [KCCQ-OS]) from baseline to 1 month and the composite rate of death or HF hospitalization between 1 month and 2 years in the COAPT trial were evaluated, and whether treatment (TMVr or GDMT alone) modified this association was tested.ResultsAmong 551 patients with HF and severe secondary mitral regurgitation who were alive at 1 month, those randomized to TMVr were more likely than those randomized to GDMT alone to achieve a ≥10-point improvement in KCCQ-OS from baseline to 1 month (TMVr, 58%; GDMT alone, 26%). Early improvement in KCCQ-OS was inversely associated with the risk for death or HF hospitalization between 1 month and 2 years (p < 0.001). When analyzed as a continuous variable, a 10-point increase in KCCQ-OS was associated with a 14% lower risk for death or HF hospitalization (hazard ratio: 0.86; 95% confidence interval: 0.81 to 0.92; p < 0.001), with no significant interaction with treatment group (p_interaction = 0.17). After adjusting for demographic and clinical factors, the association between change in KCCQ-OS and outcomes was strengthened (hazard ratio: 0.79; 95% confidence interval: 0.73 to 0.86; p < 0.001).ConclusionsIn patients with HF and severe secondary mitral regurgitation, a short-term change in disease-specific health status was strongly associated with the subsequent long-term risk for death or HF hospitalization. These findings reinforce the prognostic utility of serial KCCQ-OS assessments to identify patients at risk for poor long-term clinical outcomes in this population. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial]; NCT01626079)     

Baseline Functional Capacity and Transcatheter Mitral Valve Repair in Heart Failure With Secondary Mitral Regurgitation

ObjectivesThe aim of this study was to determine the prognostic utility of baseline functional status and its impact on the outcomes of transcatheter mitral valve repair (TMVr) in patients with heart failure (HF) with secondary mitral regurgitation (SMR).BackgroundThe COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial demonstrated that TMVr with the MitraClip in patients with HF with moderate to severe or severe SMR improved health-related quality of life. The clinical utility of a baseline assessment of functional status for evaluating prognosis and identifying candidates likely to derive a robust benefit from TMVr has not been previously studied in patients with HF with SMR.MethodsThe COAPT study was a multicenter, randomized, controlled, parallel-group, open-label trial of TMVr with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone in patients with HF, left ventricular ejection fraction 20% to 50%, and moderate to severe or severe SMR. Baseline functional status was assessed by 6-min walk distance (6MWD).ResultsPatients with 6MWD less than the median (240 m) were older, were more likely to be female, and had more comorbidities. After multivariate modeling, age (p = 0.005), baseline hemoglobin (p = 0.007), and New York Heart Association functional class III/IV symptoms (p < 0.0001) were independent clinical predictors of 6MWD. Patients with 6MWD <240 m versus ≥240 m had a higher unadjusted and adjusted rate of the 2-year composite of all-cause death or HF hospitalization (64.4% vs. 48.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.19 to 1.98; p = 0.001). However, there was no interaction between baseline 6MWD and the relative effectiveness of TMVr plus GDMT versus GDMT alone with respect to the composite endpoint (p = 0.633).ConclusionsBaseline assessment of functional capacity by 6MWD was a powerful discriminator of prognosis in patients with HF with SMR. TMVr with the MitraClip provided substantial improvements in clinical outcomes for this population irrespective of baseline functional capacity.     

Prediction of Death or HF Hospitalization in Patients With Severe FMR: The COAPT Risk Score

BackgroundThere are limited data on the predictors of death or heart failure hospitalization (HFH) in patients with heart failure (HF) with functional mitral regurgitation (FMR).ObjectivesThe aim of this study was to develop a predictive risk score using the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial database.MethodsIn COAPT, 614 symptomatic patients with HF and moderate to severe or severe FMR were randomized to MitraClip implantation plus guideline-directed medical therapy (GDMT) or GDMT alone. A risk score for the 2-year rate of death or HFH was generated from Cox proportional hazards models. The predictive value of the model was assessed using the area under the curve of receiver-operating characteristic plots. Kaplan-Meier curves were generated to estimate the proportion of patients experiencing death or HFH across quartiles of risk.ResultsDuring 2-year follow-up, 201 patients (64.4%) in the GDMT-alone group and 133 patients (44.0%) in the MitraClip group experienced death or HFH (P < 0.001). A risk score containing 4 clinical variables (New York Heart Association functional class, chronic obstructive pulmonary disease, atrial fibrillation or flutter, and chronic kidney disease) and 4 echocardiographic variables (left ventricular ejection fraction, left ventricular end-systolic dimension, right ventricular systolic pressure, and tricuspid regurgitation) in addition to MitraClip treatment was generated. The area under the curve of the risk score model was 0.74, and excellent calibration was present. The relative benefit of MitraClip therapy in reducing the 2-year hazard of death or HFH was consistent across the range of baseline risk.ConclusionsA simple risk score of clinical, echocardiographic, and treatment variables may provide useful prognostication in patients with HF and severe FMR.     

Effect of Mitral Valve Gradient After MitraClip on Outcomes in Secondary Mitral Regurgitation: Results From the COAPT Trial

ObjectivesThe authors sought to evaluate the association between mean mitral valve gradient (MVG) and clinical outcomes among patients who underwent MitraClip treatment for secondary mitral regurgitation (SMR) in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial.BackgroundIn the COAPT trial, patients with heart failure (HF) and severe SMR who remained symptomatic despite guideline-directed medical therapy had marked 2-year reductions in mortality and HF hospitalizations after treatment with MitraClip.MethodsMitraClip-treated patients were divided into quartiles (Q) based on discharge echocardiographic MVG (n = 250). Endpoints including all-cause mortality, HF hospitalization, and health status measures at 2 years were compared between quartiles.ResultsMean MVG after MitraClip was 2.1 ± 0.4 mm Hg, 3.0 ± 0.2 mm Hg, 4.2 ± 0.5 mm Hg, and 7.2 ± 2.0 mm Hg in Q1 (n = 63), Q2 (n = 61), Q3 (n = 62), and Q4 (n = 64), respectively. There was no difference across quartiles in the 2-year composite endpoint of all-cause mortality or HF hospitalization (43.2%, 49.2%, 40.6%, and 40.9%, respectively; p = 0.80), nor in improvements in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire score, or 6-min walk time. Results were similar after adjustment for baseline clinical and echocardiographic characteristics, post-procedure MR grade, and number of clips (all-cause mortality or HF hospitalization Q4 [44.6%] vs. Q1 to Q3 [40.3%]; adjusted hazard ratio: 1.23, 95% confidence interval: 0.60 to 2.51; p = 0.57).ConclusionsAmong HF patients with severe SMR, higher MVGs on discharge did not adversely affect clinical outcomes following MitraClip. These findings suggest that in select patients with HF and SMR otherwise meeting the COAPT inclusion criteria, the benefits of MR reduction may outweigh the effects of mild-to-moderate mitral stenosis after MitraClip.     

Transcatheter Mitral Valve Repair in Cardiogenic Shock and Mitral Regurgitation: A Patient-Level,Multicenter Analysis

ObjectivesThe aim of this study was to evaluate the outcome of transcatheter mitral valve repair (TMVr) in patients with cardiogenic shock and significant mitral regurgitation (MR).BackgroundPatients in cardiogenic shock with severe MR have a poor prognosis in the setting of conventional medical therapy. Because of its favorable safety profile, TMVr is being increasingly used as an acute therapy in this population, though its efficacy remains unknown.MethodsA multicenter, collaborative, patient-level analysis was conducted. Patients with cardiogenic shock and moderate to severe (3+) or severe (4+) MR who were not surgical candidates were treated with TMVr. The primary outcome was in-hospital mortality. Secondary outcomes included 90-day mortality, heart failure (HF) hospitalization, and the combined event rate of 90-day mortality and HF hospitalization following dichotomization by TMVr device success.ResultsBetween January 2011 and February 2019, 141 patients across 14 institutions met the inclusion criteria. In-hospital mortality occurred in 22 patients (15.6%), at 90 days in 38 patients (29.5%), and at one year in 55 patients (42.6%). Median length of hospital stay following TMVr was 10 days (interquartile range: 6 to 20 days). HF hospitalization occurred in 26 patients (18.4%) at a median of 73 days (interquartile range: 26 to 546 days). When stratified by TMVr procedural results, successful TMVr reduced rates of in-hospital mortality (hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.13 to 0.98; p = 0.04), 90-day mortality (HR: 0.36; 95% CI: 0.16 to 0.78; p = 0.01), and the composite of 90-day mortality and HF hospitalization (HR: 0.41; 95% CI: 0.19 to 0.90; p = 0.03).ConclusionsTMVr may improve short- and intermediate-term mortality in high-risk patients with cardiogenic shock and moderate to severe MR. Randomized studies are needed to definitively establish MR as a therapeutic target in patients with cardiogenic shock.     

Incidence and Outcomes of Pneumonia in Patients With Heart Failure

BackgroundThe incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).ObjectivesThis study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials.MethodsThe authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro–B-type natriuretic peptide).ResultsIn PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58).ConclusionsThe incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711)     

Guideline-Directed Medical Therapy and Long-Term Mortality and Amputation Outcomes in Patients Undergoing Peripheral Vascular Interventions

BackgroundLack of guideline-directed medical therapy (GDMT) in patients undergoing peripheral vascular interventions (PVIs) may increase mortality and amputation risk.ObjectivesThe authors sought to study the association between GDMT and mortality/amputation and to examine GDMT variability among providers and health systems.MethodsWe performed an observational study using patients in the Vascular Quality Initiative registry undergoing PVI between 2017 and 2018. Two-year all-cause mortality and major amputation data were derived from Medicare claims data. Compliance with GDMT was defined as receiving a statin, antiplatelet therapy, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker if hypertensive. Propensity 1:1 matching was applied for GDMT vs no GDMT and survival analyses were performed to compare outcomes between groups.ResultsOf 15,891 patients undergoing PVIs, 48.8% received GDMT and 6,120 patients in each group were matched. Median follow-up was 9.6 (IQR: 4.5-16.2) months for mortality and 8.4 (IQR: 3.5-15.4) for amputation. Mean age was 72.0 ± 9.9 years. Mortality risk was higher among patients who did not receive GDMT versus those on GDMT (31.2% vs 24.5%; HR: 1.37, 95% CI: 1.25-1.50; P < 0.001), as well as, risk of amputation (16.0% vs 13.2%; HR: 1.20; 95% CI: 1.08-1.35; P < 0.001). GDMT rates across sites and providers ranging from 0% to 100%, with lower performance translating into higher risk.ConclusionsAlmost one-half of the patients receiving PVI in this national quality registry were not on GDMT, and this was associated with increased risk of mortality and major amputation. Quality improvement efforts in vascular care should focus on GDMT in patients undergoing PVI.     

Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial

BackgroundData on PCSK9 inhibition in chronic kidney disease (CKD) is limited.ObjectivesThe purpose of this study was to compare outcomes with evolocumab and placebo according to kidney function.MethodsThe FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized individuals with clinically evident atherosclerosis and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl or non–high-density lipoprotein cholesterol ≥100 mg/dl to evolocumab or placebo. The primary endpoint (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization), key secondary endpoint (cardiovascular death, myocardial infarction, or stroke), and safety were analyzed according to chronic kidney disease (CKD) stage estimated from CKD-epidemiology estimated glomerular filtration rate.ResultsThere were 8,077 patients with preserved kidney function, 15,034 with stage 2 CKD, and 4,443 with ≥stage 3 CKD. LDL-C reduction with evolocumab compared with placebo at 48 weeks was similar across CKD groups at 59%, 59%, and 58%, respectively. Relative risk reduction for the primary endpoint was similar for preserved function (hazard ratio [HR]: 0.82; 95% CI: 0.71 to 0.94), stage 2 (HR: 0.85; 95% CI: 0.77 to 0.94), and stage ≥3 CKD (HR: 0.89; 95% CI: 0.76 to 1.05); p_int = 0.77. Relative risk reduction for the secondary endpoint was similar across CKD stages (p_int = 0.75)—preserved function (HR: 0.75; 95% CI: 0.62 to 0.90), stage 2 (HR: 0.82; 95% CI: 0.72 to 0.93), stage ≥3 (HR: 0.79; 95% CI: 0.65 to 0.95). Absolute RRs at 30 months for the secondary endpoint were −2.5% (95% CI: -4.7% to -0.4%) for stage ≥3 CKD compared with −1.7% (95% CI: -2.8% to 0.5%) with preserved kidney function. Adverse events, including estimated glomerular filtration rate decline, were infrequent and similar regardless of CKD stage.ConclusionsLDL-C lowering and relative clinical efficacy and safety of evolocumab versus placebo were consistent across CKD groups. Absolute reduction in the composite of cardiovascular death, MI, or stroke with evolocumab was numerically greater with more advanced CKD. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633)     

Impact of Surgical and Transcatheter Aortic Valve Replacement in Low-Gradient Aortic Stenosis: A Meta-Analysis

ObjectivesThe aim of this study was to assess the impact of aortic valve replacement (AVR) on survival in patients with each subclass of low-gradient (LG) aortic stenosis (AS) and to compare outcomes following surgical AVR (SAVR) and transcatheter AVR (TAVR).BackgroundLG severe AS encompasses a wide variety of pathophysiology, including classical low-flow, LG (LF-LG), paradoxical LF-LG, and normal-flow, LG (NF-LG) AS, and uncertainty exists regarding the impact of AVR on each subclass of LG AS.MethodsPubMed and Embase were queried through October 2020 to identify studies comparing survival with different management strategies (SAVR, TAVR, and conservative) in patients with LG AS. Pairwise meta-analysis comparing AVR versus conservative management and network meta-analysis comparing SAVR versus TAVR versus conservative management were performed.ResultsThirty-two studies with a total of 6,515 patients and a median follow-up time of 24.2 months (interquartile range: 36.5 months) were included. AVR was associated with a significant decrease in all-cause mortality in classical LF-LG (hazard ratio [HR]: 0.42; 95% confidence interval [CI]: 0.36 to 0.48), paradoxical LF-LG (HR: 0.41; 95% CI: 0.29 to 0.57), and NF-LG (HR: 0.41; 95% CI: 0.27 to 0.62) AS compared with conservative management. SAVR and TAVR were each associated with a decrease in all-cause mortality in classical LF-LG (HR: 0.46 [95% CI: 0.38 to 0.55] and 0.49 [95% CI: 0.37 to 0.64], respectively), paradoxical LF-LG (HR: 0.42 [95% CI: 0.28 to 0.65] and 0.42 [95% CI: 0.25 to 0.72], respectively), and NF-LG (HR: 0.40 [95% CI: 0.21 to 0.77] and 0.46 [95% CI: 0.26 to 0.84], respectively) AS compared with conservative management. No significant difference was observed between SAVR and TAVR.ConclusionsIn all subclasses of LG AS, AVR was associated with a significant decrease in all-cause mortality regardless of surgical or transcatheter approach.     

Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation

BackgroundMalignancy is a major cause of late post-heart transplantation (HT) mortality. Sirolimus (SRL) exerts antiproliferative properties and its long-term use in HT as primary immunosuppression (IS) is associated with decreased mortality risk that is not fully explained by attenuation of cardiac allograft vasculopathy progression.ObjectivesThis study sought to examine whether conversion from calcineurin inhibitor (CNI)-based to SRL-based IS was associated with decreased risk of malignancy post-HT.MethodsOverall, 523 patients underwent HT between 1994 and 2016 at a single institution. The main outcomes included incidence of overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]), post-transplantation lymphoproliferative disorders (PTLD), and first and subsequent primary occurrences of NMSC post-HT.ResultsThe study identified 307 patients on SRL-based and 216 on CNI-based maintenance IS. Over a median follow-up of 10 years after HT, overall de novo malignancies (non-NMSC) occurred in 31% of CNI patients and in 13% of SRL patients (adjusted hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.18 to 0.62; p < 0.001). The incidence of the first NMSC was similar in the SRL and CNI groups (HR: 0.92; 95% CI: 0.66 to 1.28; p = 0.62). However, conversion to SRL was significantly associated with a decreased risk of subsequent primary occurrences of NMSC compared with that of CNI (adjusted HR: 0.44; 95% CI: 0.28 to 0.69; p < 0.001). The adjusted PTLD risk was significantly decreased in the SRL group (HR: 0.13; 95% CI: 0.03 to 0.59; p = 0.009). Late survival post-HT was markedly decreased in patients who developed non-NMSC, PTLD, or non-PTLD compared with patients who did not develop these malignancies, whereas NMSC had no significant effect on survival.ConclusionsConversion to SRL was associated with a decreased risk of all de novo malignancies, PTLD, and subsequent primary occurrences of NMSC after HT. These findings provided further explanation of the late survival benefit with long-term SRL use.     

Age-Related Outcomes After Transcatheter Aortic Valve Replacement: Insights From the SwissTAVI Registry

ObjectivesThe aim of this study was to investigate age-related outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) as assessed in a nationwide, prospective, multicenter cohort study.BackgroundTAVR is the preferred treatment for elderly patients with severe aortic stenosis and is expanding into lower age groups.MethodsData from the SwissTAVI Registry were analyzed. Clinical outcomes were compared between patients 70 years of age or younger (n = 324), 70 to 79 years of age (n = 1,913), 80 to 89 years of age (n = 4,353), and older than 90 years of age (n = 507). Observed deaths were correlated with expected deaths in the general Swiss population using standardized mortality ratios.ResultsBetween February 2011 and June 2018, 7,097 patients (mean age 82.0 ± 6.4 years, 49.6% women) underwent TAVR at 15 hospitals in Switzerland. Procedural characteristics were similar; however, older patients more often had discharge to the referring hospital or a rehabilitation facility after TAVR. Using adjusted analyses, a linear trend for mortality (30-day adjusted hazard ratio [HR_adj]: 1.45; 95% confidence interval [CI]: 1.18 to 1.77; 1-year HR_adj: 1.12; 95% CI: 1.01 to 1.24), cerebrovascular accidents (30-day HR_adj: 1.35; 95% CI: 1.09 to 1.66; 1-year HR_adj: 1.21; 95% CI: 1.02 to 1.45), and pacemaker implantation (30-day HR_adj: 1.23; 95% CI: 1.12 to 1.34; 1-year HR_adj: 1.19; 95% CI: 1.09 to 1.30) was observed with increasing age. Furthermore, standardized mortality ratios were 12.63 (95% CI: 9.06 to 17.58), 4.09 (95% CI: 3.56 to 4.74), 1.63 (95% CI: 1.50 to 1.78), and 0.93 (95% CI: 0.76 to 1.14) for TAVR patients in relation to the Swiss population <70, 70 to 79, 80 to 89 and ≥90 years of age, respectively.ConclusionsIncreasing age is associated with a linear trend for mortality, stroke, and pacemaker implantation during early and longer-term follow-up after TAVR. Standardized mortality ratios were higher for TAVR patients younger than 90 years of age compared with expected rates of mortality in an age- and sex-matched Swiss population. (SWISS TAVI Registry; NCT01368250)     

COAPT-Like Profile Predicts Long-Term Outcomes in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation

ObjectivesThe aim of this study was to evaluate whether fulfilling COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) criteria identifies patients with better outcomes after MitraClip treatment for secondary mitral regurgitation (SMR).BackgroundTo date, COAPT is the only trial showing a prognostic benefit of MitraClip implantation compared with conservative management.MethodsThree hundred four patients with SMR undergoing MitraClip placement in addition to optimal medical therapy at 3 European centers were analyzed. A COAPT-like profile was defined as absence of all the following criteria: severe left ventricular impairment, moderate to severe right ventricular dysfunction, severe tricuspid regurgitation, severe pulmonary hypertension, and hemodynamic instability. Freedom from all-cause death and from a composite endpoint (cardiovascular death and heart failure hospitalization) were evaluated at 2- and 5-year follow-up.ResultsA COAPT-like profile was observed in 65% of the population. Compared with non-COAPT-like patients, those fulfilling COAPT criteria had greater survival free from all-cause death and from the composite endpoint at both 2 year (75% vs. 55% and 67% vs. 47%; p < 0.001 for both) and 5-year (49% vs. 25% and 40% vs. 19%; p < 0.001 for both) follow-up. Among the non-COAPT-like patients, similar outcomes were observed in those fulfilling 1 or ≥1 criterion. Left ventricular impairment had a late impact on outcomes, while right ventricular impairment, pulmonary hypertension, and hemodynamic instability had early effects. COAPT-like profile was an independent predictor of long-term outcomes, as well as administration of neurohormonal antagonists, European System for Cardiac Operative Risk Evaluation II score, and previous heart failure hospitalization.ConclusionsA COAPT-like profile, including specific echocardiographic and clinical criteria, identifies patients with SMR who have a better prognosis after MitraClip implantation.     

Impact of Mitral Regurgitation Severity and Left Ventricular Remodeling on Outcome After MitraClip Implantation: Results From the Mitra-FR Trial

ObjectivesThis study aimed to identify a subset of patients based on echocardiographic parameters who might have benefited from transcatheter correction using the MitraClip system in the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial.BackgroundIt has been suggested that differences in the degree of mitral regurgitation (MR) and left ventricular (LV) remodeling may explain the conflicting results between the MITRA-FR and the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trials.MethodsIn a post hoc analysis, we evaluated the interaction between the intervention and subsets of patients defined based on MR severity (effective regurgitant orifice [ERO], regurgitant volume [RVOL] and regurgitant fraction [RF]), LV remodeling (end-diastolic and end-systolic diameters and volumes) and combination of these parameters with respect to the composite of death from any cause or unplanned hospitalization for heart failure at 24 months.ResultsWe observed a neutral impact of the intervention in subsets with the highest MR degree (ERO ≥30 mm², RVOL ≥45 ml or RF ≥50%) as in patients with milder MR degree. The same was seen in subsets with the milder LV remodeling using either diastolic or systolic diameters or volumes. When parameters of MR severity and LV remodeling were combined, there was still no benefit of the intervention including in the subset of patients with an ERO/end-diastolic volume ratio ≥ 0.15 despite similar ERO and LV end-diastolic volume compared with COAPT patients.ConclusionsIn the MITRA-FR trial, we could not identify a subset of patients defined based on the degree of the regurgitation, LV remodeling or on their combination, including those deemed as having disproportionate MR, that might have benefited from transcatheter correction using the MitraClip system. (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR]; NCT01920698)     

Mitral Regurgitation in Low-Flow,Low-Gradient Aortic Stenosis Patients Undergoing TAVR: Insights From the TOPAS-TAVI Registry

ObjectivesThis study sought to determine the incidence, clinical impact, and changes over time of mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR).BackgroundFew data exist on the clinical impact and changes in severity over time of MR in patients with LFLG-AS undergoing TAVR.MethodsA total of 308 TAVR candidates with LFLG-AS were included. Patients were categorized according to MR severity at baseline, and presence of MR improvement at 12-month follow-up. Clinical outcomes were assessed at 1 and 12 months (+ echocardiography), and yearly thereafter.ResultsBaseline mild and moderate-to-severe MR were present in 118 (38.3%) and 115 (37.3%) patients, respectively. MR was of functional and mixed etiology in 77.2% and 22.7% of patients, respectively. A total of 131 patients (42.5%) died after a median follow-up of 2 (1 to 3) years. Baseline moderate-or-greater MR had no impact on mortality (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 0.72 to 2.48) or heart failure hospitalization (HR: 1.02; 95% CI: 0.49 to 2.10). At 1-year follow-up, MR improved in 44.3% of patients and remained unchanged/worsened in 55.7%. The lack of MR improvement was associated with a higher risk of all-cause and cardiac mortality (HR: 2.02; 95% CI: 1.29 to 3.17; HR: 3.03; 95% CI: 1.27 to 7.23, respectively), rehospitalization for cardiac causes (HR: 1.50; 95% CI: 1.04 to 2.15), and an increased overall-mortality/heart failure rehospitalization (HR: 1.94; 95% CI: 1.25 to 3.02). A higher baseline left ventricular end-diastolic diameter and a higher increase in left ventricular ejection fraction were found to be independent predictors of MR improvement at 1-year follow-up (odds ratio: 0.69; 95% CI: 0.51 to 0.94; and odds ratio: 0.81; 95% CI: 0.67 to 0.96, respectively).ConclusionsMost TAVR candidates with LFLG-AS had some degree of MR, of functional origin in most cases. MR improved in about one-half of patients, with larger left ventricular size and a higher increase in left ventricular ejection fraction post-TAVR determining MR improvement over time. The lack of MR improvement at 1 year was associated with poorer outcomes.     

Impact of Transcatheter Mitral Valve Repair on Preprocedural and Postprocedural Hospitalization Rates

ObjectivesThe objective of this study was to determine the effect of transcatheter mitral valve repair (TMVr) on hospitalization rates by assessing pre- and postprocedural hospitalization patterns.BackgroundTMVr has emerged as the treatment of choice for selected patients with mitral regurgitation, but the impact of these procedures on hospital utilization remains unclear.MethodsAll patients who underwent TMVr in Ontario, Canada, between 2011 and 2017 were included in this observational study using population-based data. Hospitalization person-year rates were assessed in the years before and after TMVr and 4 predefined intervals: 1 to 30, 31 to 90, 91 to 182, and 183 to 365 days. Main outcomes of interest were all-cause and heart failure (HF) hospitalizations. Poisson regression models were used to compare incidence rates across all time periods.ResultsThe study cohort included 523 patients. In the year preceding TMVr, 66.2% of patients were hospitalized compared with 47.4% in the year following. There were stepwise increases in both all-cause and HF hospitalization rates in the periods preceding the index procedure, and all postprocedural periods had significantly lower hospitalization rates. The adjusted rate ratios for all-cause and HF-related hospitalization in the year after TMVr were 0.65 (95% CI: 0.56-0.76) and 0.38 (95% CI: 0.29-0.51), respectively. All time periods had significant reductions in all-cause and HF hospitalization in the adjusted analysis.ConclusionsIn this population-based study, significant reductions were observed in both all-cause and HF-related hospitalizations in all time periods after TMVr compared with the year prior. This suggests that TMVr has a sustained effect on hospitalization rates despite a high-risk population.