Outcomes of transcatheter aortic valve replacement in patients with cardiogenic shock.

AIMS: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed. METHODS AND RESULTS: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality. CONCLUSION: This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS.

Endovascular snare technique to facilitate delivery of self-expanding valve during transcatheter aortic valve-in-valve replacement in angulated aortas: A case series.

BACKGROUND: Transcatheter aortic valve-in-valve replacement (ViV) has been widely accepted as a less invasive alternative to treat failed aortic surgical or transcatheter bioprosthetic valves. Angulated aortas present an additional challenge, particularly when using self-expanding transcatheter heart valves (SE-THV). METHODS: Two patients with failed surgical bioprosthetic aortic valves and one patient with a failed transcatheter bioprosthetic aortic valve underwent transcatheter aortic ViV using SE-THV. All were deemed high-risk for surgical aortic valve replacement by a heart team. All three patients had initial failed SE-THV delivery using a conventional approach with subsequent successful delivery using the endovascular snare technique. RESULTS: In Cases 1 and 2, the SE-THV was biased towards the greater curve of the angulated aorta and behind the outer frame of the bioprosthetic valve frame. An endovascular snare was deployed through a secondary left femoral artery access, and the valve delivery system was advanced through the snare in the ascending aorta. The snare was tightened around the SE-THV capsule proximal to the hat-marker, allowing deflection of the SE-THV and successful delivery. In Case 3, the SE-THV interacted with the tall frame of a failed SE-THV. A snare via the left femoral artery was deployed in the descending artery. The SE-THV was advanced through the snare, and both the snare and SE-THV were advanced together to the ascending aorta where the SE-THV was deflected and successfully delivered. CONCLUSIONS: The endovascular snare technique is a feasible option for successful delivery of SE-THV during transcatheter aortic ViV in failed transcatheter or surgical bioprosthetic valves in angulated aortas.

Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics.

PURPOSE: Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies. METHODS: Seventy ST cases on clopidogrel identified from the PLATO trial (n = 58) and Mayo Clinic biorepository (n = 12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations. RESULTS: Poor metabolizers (n = 4) and rare CYP2C19*8, CYP2C19*15, and CYP2C19*11 alleles were identified only in ST cases. CYP2C19*17 heterozygote carriers were observed more frequently in cases (n = 29) than controls (n = 18). Functional studies of CYP2C19 exonic variants (n = 11) revealed 3 cases and only 1 control carrying a deleterious variant as determined by in vitro protein expression studies. Greater intronic variation unique to ST cases (n = 169) compared with controls (n = 84) was observed with predictions revealing 13 allele candidates that may lead to a potential disruption of splicing and a loss-of-function effect of CYP2C19 in ST cases. CONCLUSION: NGS detected CYP2C19 poor metabolizers and paradoxically greater number of so-called rapid metabolizers in ST cases. Rare deleterious exonic variation occurs in 4%, and potentially disruptive intronic alleles occur in 16% of ST cases. Additional studies are required to evaluate the role of these variants in platelet aggregation and clopidogrel metabolism.

Paravalvular Leak in Structural Heart Disease.

PURPOSE OF REVIEW: This review will summarize the growing importance of diagnosing and managing paravalvular leak associated with surgical and transcatheter valves. RECENT FINDINGS: The burden of paravalvular leak is increasing; however, advanced imaging techniques and high degree of clinical suspicion are required for diagnosis and management. The latest data from pivotal clinical trials in the field of transcatheter aortic valve replacement suggest that any paravalvular leak greater than mild was associated with worse clinical outcomes. Percutaneous techniques for paravalvular leak closure are now the preferred approach, and surgical repair is reserved for contraindications and unsuccessful procedures. Recent data from studies evaluating paravalvular leak closure outcomes report a greater than 90% success rate with a significant improvement in patient symptoms. Paravalvular leak is a growing problem in the structural heart disease arena. Percutaneous closure is successful in more than 90% of the procedures with a low complication rate.

Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction.

BACKGROUND: Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for high-risk cardiovascular diseases. However, the feasibility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome. METHODS AND RESULTS: Whole-genome expression microarray on blood samples from normal cardiac function controls (n=21) and first-time AMI patients (n=31) within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways. To determine molecular signatures at the time of AMI associated with long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially-expressed genes. Bioinformatic analysis of this differential gene-set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of genes involved in the developmental epithelial-to-mesenchymal transition pathway, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. CONCLUSION: Differentially regulated genes and modulated pathways were identified that were associated with recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients and warrants further study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes.

Participation in cardiac rehabilitation and survival after coronary artery bypass graft surgery: a community-based study.

BACKGROUND: Cardiac rehabilitation (CR) is recommended for all patients after coronary artery bypass surgery, yet little is known about the long-term mortality effects of CR in this population. METHODS AND RESULTS: We performed a community-based analysis on residents of Olmsted County, Minnesota, who underwent coronary artery bypass surgery between 1996 and 2007. We assessed the association between subsequent outpatient CR attendance and long-term survival. Propensity analysis was performed. Cox proportional hazards regression was then used to assess the association between CR attendance and all-cause mortality adjusted for the propensity to attend CR. We identified 846 eligible patients (age 66±11 years, 76% men, and 96% non-Hispanic whites) who survived at least 6 months after surgery, of whom 582 (69%) attended CR. During a mean (±SD) follow-up of 9.0±3.7 years, the 10-year all-cause Kaplan-Meier mortality rate was 28% (193 deaths). Adjusted for the propensity to attend CR, participation in CR was associated with a 10-year relative risk reduction in all-cause mortality of 46% (hazard ratio, 0.54; 95% confidence interval, 0.40-0.74; P<0.001) and a 10-year absolute risk reduction of 12.7% (number needed to treat=8). There was no evidence of a differential effect of CR on mortality with respect to age (≥65 versus <65 years), sex, diabetes, or prior myocardial infarction. CONCLUSIONS: CR attendance is associated with a significant reduction in 10-year all-cause mortality after coronary artery bypass surgery. Our results strongly support national standards that recommend CR for this patient group.

Current Update on Categorization of Migraine Subtypes on the Basis of Genetic Variation: a Systematic Review.

Migraine is a complex neurovascular disorder that is characterized by severe behavioral, sensory, visual, and/or auditory symptoms. It has been labeled as one of the ten most disabling medical illnesses in the world by the World Health Organization (Aagaard et al Sci Transl Med 6(237):237ra65, 2014). According to a recent report by the American Migraine Foundation (Shoulson et al Ann Neurol 25(3):252-9, 1989), around 148 million people in the world currently suffer from migraine. On the basis of presence of aura, migraine is classified into two major subtypes: migraine with aura (Aagaard et al Sci Transl Med 6(237):237ra65, 2014) and migraine without aura. (Aagaard K et al Sci Transl Med 6(237):237ra65, 2014) Many complex genetic mechanisms have been proposed in the pathophysiology of migraine but specific pathways associated with the different subtypes of migraine have not yet been explored. Various approaches including candidate gene association studies (CGAS) and genome-wide association studies (Fan et al Headache: J Head Face Pain 54(4):709-715, 2014). have identified the genetic markers associated with migraine and its subtypes. Several single nucleotide polymorphisms (Kaur et al Egyp J Neurol, Psychiatry Neurosurg 55(1):1-7, 2019) within genes involved in ion homeostasis, solute transport, synaptic transmission, cortical excitability, and vascular function have been associated with the disorder. Currently, the diagnosis of migraine is majorly behavioral with no focus on the genetic markers and thereby the therapeutic intervention specific to subtypes. Therefore, there is a need to explore genetic variants significantly associated with MA and MO as susceptibility markers in the diagnosis and targets for therapeutic interventions in the specific subtypes of migraine. Although the proper characterization of pathways based on different subtypes is yet to be studied, this review aims to make a first attempt to compile the information available on various genetic variants and the molecular mechanisms involved with the development of MA and MO. An attempt has also been made to suggest novel candidate genes based on their function to be explored by future research.

Role of Imaging Genetics in Alzheimer's Disease: A Systematic Review and Current Update.

BACKGROUND: Alzheimer's disease is a neurodegenerative disorder characterized by severe cognitive, behavioral, and psychological symptoms, such as dementia, cognitive decline, apathy, and depression. There are no accurate methods to diagnose the disease or proper therapeutic interventions to treat AD. Therefore, there is a need for novel diagnostic methods and markers to identify AD efficiently before its onset. Recently, there has been a rise in the use of imaging techniques like Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) as diagnostic approaches in detecting the structural and functional changes in the brain, which help in the early and accurate diagnosis of AD. In addition, these changes in the brain have been reported to be affected by variations in genes involved in different pathways involved in the pathophysiology of AD. METHODOLOGY: A literature review was carried out to identify studies that reported the association of genetic variants with structural and functional changes in the brain in AD patients. Databases like PubMed, Google Scholar, and Web of Science were accessed to retrieve relevant studies. Keywords like 'fMRI', 'Alzheimer's', 'SNP', and 'imaging' were used, and the studies were screened using different inclusion and exclusion criteria. RESULTS: 15 studies that found an association of genetic variations with structural and functional changes in the brain were retrieved from the literature. Based on this, 33 genes were identified to play a role in the development of disease. These genes were mainly involved in neurogenesis, cell proliferation, neural differentiation, inflammation and apoptosis. Few genes like FAS, TOM40, APOE, TRIB3 and SIRT1 were found to have a high association with AD. In addition, other genes that could be potential candidates were also identified. CONCLUSION: Imaging genetics is a powerful tool in diagnosing and predicting AD and has the potential to identify genetic biomarkers and endophenotypes associated with the development of the disorder.

Stroke Risk After Mitral Valve Interventions: A Systematic Review and Network Meta-Analysis.

Previous research indicates varying stroke rates after mitral valve (MV) interventions. This study aimed to compare postprocedural stroke risks after transcatheter and surgical MV interventions. Electronic databases were searched from inception to February 2024 for studies comparing stroke rates after mitral transcatheter edge-to-edge repair (mTEER), surgical MV repair/replacement, or guideline-directed medical therapy (GDMT). Primary end points were all-time and early (<30 days) stroke. Secondary outcomes included new-onset atrial fibrillation and 1-year all-cause mortality. A frequentist network meta-analysis was employed to compare outcomes. The network meta-analysis included 18 studies (3 randomized controlled trials and 15 observational), with 51,703 patients. mTEER was associated with a decreased risk of all-time (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.41 to 0.89) and early stroke (OR 0.41, 95% CI 0.33 to 0.51) compared with surgery, and a similar risk of all-time (OR 1.54, 95% CI 0.76 to 3.12) and early stroke (OR 2.12, 95% CI 0.53 to 8.47) compared with GDMT. Conversely, surgery was associated with an increased risk of all-time (OR 2.55, 95% CI 1.17 to 5.57) and early stroke (OR 5.15, 95% CI 1.27 to 20.84) compared with GDMT. There were no statistically significant differences in the risk of new-onset atrial fibrillation (OR 0.38, 95% CI 0.11 to 1.31) and 1-year all-cause mortality (OR 1.43, 95% CI 0.91 to 2.24) between mTEER versus surgery. In conclusion, mTEER was associated with a lower risk of stroke and similar risks of new-onset atrial fibrillation and 1-year mortality compared with surgical MV interventions. Further studies are needed to understand the mechanisms of stroke and to determine strategies to reduce stroke risk after MV interventions.

Association of time to reperfusion with left ventricular function and heart failure in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: a systematic review.

BACKGROUND: Shorter time to reperfusion is associated with a significant reduction in mortality; however, its association with heart failure (HF) is not clearly documented. We conducted a systematic review to examine the association between time to reperfusion and incident HF and/or left ventricular dysfunction. METHODS: MEDLINE/OVID, EMBASE, Cochrane Library, and Web of Science databases were searched from January 1974 to May 2012 for studies that reported the association between time to reperfusion and incident HF or left ventricular ejection fraction (LVEF) in patients undergoing primary percutaneous coronary intervention. RESULTS: Of 362 nonduplicate abstracts, 71 studies were selected for full-text review. Thirty-three studies were included in the final review, of which 16 were single-center studies, 7 were population-based studies, 7 were subanalyses from randomized controlled trials, and 3 were based on national samples. The pooled data demonstrate that every 1-hour delay in time to reperfusion is associated with a 4% to 12% increased risk of new-onset HF and a 4% relative increase in the risk of incident HF during follow-up. Early reperfusion was associated with a 2% to 8% greater LVEF before discharge and a 3% to 12% larger improvement in absolute LVEF at follow-up compared with the index admission. CONCLUSIONS: This systematic review presents evidence that longer time to reperfusion is not only associated with worsened left ventricular systolic function and new-onset HF at the time of index admission, but also with increased risk of HF and reduced improvement in left ventricular systolic function during follow-up.

Dietary intakes and familial correlates of overweight/obesity: a four-cities study in India.

BACKGROUND: The prevalence of overweight and obesity among children is increasing in India. However, knowledge of, attitude towards and practice of health and nutrition in mothers and children have not been researched. OBJECTIVE: To assess knowledge of, attitude towards and practice of nutrition, physical activity and other lifestyle practices in a nationally representative sample of urban children and mothers in India. METHODS: A cross-sectional observational study of 1,800 children aged 9-18 years and their mothers, using qualitative (focus group) and quantitative (semi-structured survey) data. RESULTS: The overall prevalence of overweight/obesity among the children was 19.2% in males and 18.1% in females; 64.8% of mothers were either overweight [body mass index (BMI) 23.0-24.9; 23.3%] or obese (BMI >25.0; 41.5%). Household family income, related socioeconomic factors, and overweight in mothers were most significantly associated with obesity in children (all p ≤ 0.001). Dietary consumption patterns (snacking, fast food etc.) showed a marked association between mothers and children (all p ≤ 0.000). Focus group discussion revealed several interesting attitudes and misconceptions among children ('home-cooked food is old fashioned') and mothers ('a child with chubby cheeks is healthy, not fat'). Importantly, only a few mothers understood that excess weight or diets are contributory factors of morbidities in children or themselves. CONCLUSIONS: This study highlights the poor knowledge, faulty attitudes and practices of urban Asian Indian mothers and their children in a highly correlated manner. These knowledge gaps must be addressed to formulate effective strategies for the prevention of obesity and related metabolic disorders.

Transcatheter Tricuspid Interventions: Past, Present, and Future.

Tricuspid regurgitation (TR) etiologies include primary valve pathology or secondary (functional) regurgitation from increased hemodynamic pressure or volume on the right side of the heart. Patients with severe TR have a worse prognosis independent of all other variables. Surgical treatment for TR has mostly been limited to patients undergoing concomitant left-sided cardiac surgery. The results and durability of surgical repair or replacement are not well defined. For patients with significant and symptomatic TR, transcatheter techniques would be beneficial, but these techniques and devices have been slow to develop. Much of the delay is a result of neglect and challenges in defining the symptoms associated with TR. In addition, the anatomic and physiological aspects of the tricuspid valve apparatus present unique challenges. Several devices and techniques are in various phases of clinical investigation. This review highlights the current landscape of transcatheter tricuspid interventions and future opportunities. It is imminent that these therapies become commercially available and widely adopted to have a significant positive impact on millions of patients that have been neglected.

Mitral Interventions in Heart Failure.

Patients with heart failure with reduced ejection fraction who have secondary mitral regurgitation (SMR) have poorer outcomes and quality of life than those without SMR. Guideline-directed medical therapy is the cornerstone of SMR treatment. Careful evaluation of landmark trials using mitral transcatheter edge-to-edge repair in SMR has led to an improved understanding of who will benefit from percutaneous interventions with emphasis on a multidisciplinary approach. The success with mitral transcatheter edge-to-edge repair in SMR has also spurred the evaluation of its role in populations that were not initially studied, such as end-stage heart failure and cardiogenic shock. A spectrum of transcatheter devices in development and clinical trials promise to further provide a growing array of management options for heart failure with reduced ejection fraction patients with symptomatic SMR.

Impact of Transcatheter Mitral Valve Repair Availability on Volume and Outcomes of Surgical Repair.

BACKGROUND: The impact of transcatheter edge-to-edge repair (TEER) on national surgical mitral valve repair (MVr) volume and outcomes is unknown. OBJECTIVES: This study aims to assess the impact of TEER availability on MVr volumes and outcomes for degenerative mitral regurgitation. METHODS: MVr volume, 30-day and 5-year outcomes, including mortality, heart failure rehospitalization and mitral valve reintervention, were obtained from the Society of Thoracic Surgeons database linked with Medicare administrative claims and were compared within TEER centers before and after the first institutional TEER procedure. A difference-in-difference approach comparing parallel trends in coronary artery bypass grafting outcomes was used to account for temporal improvements in perioperative care. RESULTS: From July 2011 through December 2018, 13,959 patients underwent MVr at 278 institutions, which became TEER-capable during the study period. There was no significant change in median annualized institutional MVr volume before (32 [IQR: 17-54]) vs after (29 [IQR: 16-54]) the first TEER (P = 0.06). However, higher-risk (Society of Thoracic Surgeons predicted risk of mortality ≥2%) MVr procedures declined over the study period (P < 0.001 for trend). The introduction of TEER was associated with reduced risk-adjusted odds of mortality after MVr at 30 days (adjusted OR: 0.73; 95% CI: 0.54-0.99) and over 5 years (adjusted HR: 0.75; 95% CI: 0.66-0.86). These improvements in 30-day and 5-year mortality were significantly greater than equivalent trends in coronary artery bypass grafting. CONCLUSIONS: The introduction of TEER has not significantly changed overall MVr case volumes for degenerative mitral regurgitation but is associated with a decrease in higher-risk surgical operations and improved 30-day and 5-year outcomes within institutions adopting the technology.

Transcatheter Edge-to-Edge Repair in 5,000 Patients With Secondary Mitral Regurgitation: COAPT Post-Approval Study.

BACKGROUND: Real-world applicability of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized controlled trial (RCT) has been debated because of careful patient selection and the contrasting results of the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) RCT. OBJECTIVES: The COAPT-PAS (COAPT Post-Approval Study) was initiated to assess the safety and effectiveness of the MitraClip in patients with secondary mitral regurgitation (SMR). METHODS: COAPT-PAS is a prospective, single-arm, observational study of 5,000 consecutive patients with SMR treated with the MitraClip at 406 U.S. centers participating in the TVT (Transcatheter Valve Therapy) registry from 2019 to 2020. The 1-year outcomes from the COAPT-PAS full cohort and the COAPT-like and MITRA-FR-like subgroups who met RCT inclusion/exclusion criteria are reported. RESULTS: Patients in the COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less guideline-directed medical therapy than those in the COAPT or MITRA-FR RCTs. Patients in the COAPT-PAS full cohort and the COAPT-like (n = 991) and MITRA-FR-like (n = 917) subgroups achieved a 97.7% MitraClip implant rate, a similar and durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6%, respectively), a large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR-like), faster procedure times, similar or lower clinical event rates compared with the RCTs' MitraClip arms, and lower clinical event rates than the RCTs' guideline-directed medical therapy only arms. One-year heart failure hospitalizations was 18.9% in COAPT-PAS, 19.7% in COAPT-like compared with 24.9% in COAPT-RCT, and 28.7% in COAPT-PAS-MITRA-FR-like compared with 47.4% in MITRA-FR-RCT. CONCLUSIONS: This large, contemporary, real-world study reinforces the safety and effectiveness of the MitraClip System in patients with SMR, including those who met the COAPT or MITRA-FR RCT inclusion/exclusion criteria and patients excluded from the RCTs.

Ventricular Remodeling and Outcomes After Mitral Transcatheter Edge-to-Edge Repair in Heart Failure: The COAPT Trial.

BACKGROUND: The relationship between left ventricular (LV) remodeling and clinical outcomes after treatment of severe mitral regurgitation (MR) in heart failure (HF) has not been examined. OBJECTIVES: The aim of this study was to evaluate the association between LV reverse remodeling and subsequent outcomes and assess whether transcatheter edge-to-edge repair (TEER) and residual MR are associated with LV remodeling in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: Patients with HF and severe MR who remained symptomatic on guideline-directed medical therapy (GDMT) were randomized to TEER plus GDMT or GDMT alone. Baseline and 6-month core laboratory measurements of LV end-diastolic volume index and LV end-systolic volume index were examined. Change in LV volumes from baseline to 6 months and clinical outcomes from 6 months to 2 years were evaluated using multivariable regression. RESULTS: The analytical cohort comprised 348 patients (190 treated with TEER, 158 treated with GDMT alone). A decrease in LV end-diastolic volume index at 6 months was associated with reduced cardiovascular death between 6 months and 2 years (adjusted HR: 0.90 per 10 mL/m2 decrease; 95% CI: 0.81-1.00; P = 0.04), with consistent results in both treatment groups (Pinteraction = 0.26). Directionally similar but nonsignificant relationships were present for all-cause death and HF hospitalization and between reduced LV end-systolic volume index and all outcomes. Neither treatment group nor MR severity at 30 days was associated with LV remodeling at 6 or 12 months. The treatment benefits of TEER were not significant regardless of the degree of LV remodeling at 6 months. CONCLUSIONS: In patients with HF and severe MR, LV reverse remodeling at 6 months was associated with subsequently improved 2-year outcomes but was not affected by TEER or the extent of residual MR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).

3-Year Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis.

BACKGROUND: Randomized data comparing outcomes of transcatheter aortic valve replacement (TAVR) with surgery in low-surgical risk patients at time points beyond 2 years is limited. This presents an unknown for physicians striving to educate patients as part of a shared decision-making process. OBJECTIVES: The authors evaluated 3-year clinical and echocardiographic outcomes from the Evolut Low Risk trial. METHODS: Low-risk patients were randomized to TAVR with a self-expanding, supra-annular valve or surgery. The primary endpoint of all-cause mortality or disabling stroke and several secondary endpoints were assessed at 3 years. RESULTS: There were 1,414 attempted implantations (730 TAVR; 684 surgery). Patients had a mean age of 74 years and 35% were women. At 3 years, the primary endpoint occurred in 7.4% of TAVR patients and 10.4% of surgery patients (HR: 0.70; 95% CI: 0.49-1.00; P = 0.051). The difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: -1.8% at year 1; -2.0% at year 2; and -2.9% at year 3. The incidence of mild paravalvular regurgitation (20.3% TAVR vs 2.5% surgery) and pacemaker placement (23.2% TAVR vs 9.1% surgery; P < 0.001) were lower in the surgery group. Rates of moderate or greater paravalvular regurgitation for both groups were <1% and not significantly different. Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1 mm Hg TAVR vs 12.1 mm Hg surgery; P < 0.001) at 3 years. CONCLUSIONS: Within the Evolut Low Risk study, TAVR at 3 years showed durable benefits compared with surgery with respect to all-cause mortality or disabling stroke. (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients; NCT02701283).

Impact of Mitral Regurgitation Etiology on Mitral Surgery After Transcatheter Edge-to-Edge Repair: From the CUTTING-EDGE Registry.

BACKGROUND: Although >150,000 mitral TEER procedures have been performed worldwide, the impact of MR etiology on MV surgery after TEER remains unknown. OBJECTIVES: The authors sought to compare outcomes of mitral valve (MV) surgery after failed transcatheter edge-to-edge repair (TEER) stratified by mitral regurgitation (MR) etiology. METHODS: Data from the CUTTING-EDGE registry were retrospectively analyzed. Surgeries were stratified by MR etiology: primary (PMR) and secondary (SMR). MVARC (Mitral Valve Academic Research Consortium) outcomes at 30 days and 1 year were evaluated. Median follow-up was 9.1 months (IQR: 1.1-25.8 months) after surgery. RESULTS: From July 2009 to July 2020, 330 patients underwent MV surgery after TEER, of which 47% had PMR and 53.0% had SMR. Mean age was 73.8 ± 10.1 years, median STS risk at initial TEER was 4.0% (IQR: 2.2%-7.3%). Compared with PMR, SMR had a higher EuroSCORE, more comorbidities, lower LVEF pre-TEER and presurgery (all P < 0.05). SMR patients had more aborted TEER (25.7% vs 16.3%; P = 0.043), more surgery for mitral stenosis after TEER (19.4% vs 9.0%; P = 0.008), and fewer MV repairs (4.0% vs 11.0%; P = 0.019). Thirty-day mortality was numerically higher in SMR (20.4% vs 12.7%; P = 0.072), with an observed-to-expected ratio of 3.6 (95% CI: 1.9-5.3) overall, 2.6 (95% CI: 1.2-4.0) in PMR, and 4.6 (95% CI: 2.6-6.6) in SMR. SMR had significantly higher 1-year mortality (38.3% vs 23.2%; P = 0.019). On Kaplan-Meier analysis, the actuarial estimates of cumulative survival were significantly lower in SMR at 1 and 3 years. CONCLUSIONS: The risk of MV surgery after TEER is nontrivial, with higher mortality after surgery, especially in SMR patients. These findings provide valuable data for further research to improve these outcomes.

Impact of cardiac rehabilitation on mortality and cardiovascular events after percutaneous coronary intervention in the community.

BACKGROUND: Although numerous studies have reported that cardiac rehabilitation (CR) is associated with reduced mortality after myocardial infarction, less is known about its association with mortality after percutaneous coronary intervention. METHODS AND RESULTS: We performed a retrospective analysis of data from a prospectively collected registry of 2395 consecutive patients who underwent percutaneous coronary intervention in Olmsted County, Minnesota, from 1994 to 2008. The association of CR with all-cause mortality, cardiac mortality, myocardial infarction, or revascularization was assessed with 3 statistical techniques: propensity score--matched analysis (n=1438), propensity score stratification (n=2351), and regression adjustment with propensity score in a 3-month landmark analysis (n=2009). During a median follow-up of 6.3 years, 503 deaths (199 cardiac), 394 myocardial infarctions, and 755 revascularization procedures occurred in the study subjects. Participation in CR, noted in 40% (964 of 2395) of the cohort, was associated with a significant decrease in all-cause mortality by all 3 statistical techniques (hazard ratio, 0.53 to 0.55; P<0.001). A trend toward decreased cardiac mortality was also observed in CR participants; however, no effect was observed for subsequent myocardial infarction or revascularization. The association between CR participation and reduced mortality rates was similar for men and women, for older and younger patients, and for patients undergoing elective or nonelective percutaneous coronary intervention. CONCLUSIONS: We found that CR participation after percutaneous coronary intervention was associated with a significant reduction in mortality rates. These findings add support to published clinical practice guidelines, performance measures, and insurance coverage policies that recommend CR for patients after percutaneous coronary intervention.