Importance:As transcatheter aortic valve replacement (TAVR) is considered for younger and lower-risk populations, the durability of bioprosthetic valves is increasingly important. Limited data exist on long-term (7 years and beyond) valve durability. Objective:To report 7-year valve durability outcomes for low-risk patients with symptomatic severe aortic stenosis treated with TAVR vs surgery. Design, Setting, and Participants:Between March 2016 and October 2017, a total of 1000 patients were enrolled at 71 centers in the US and Canada and randomized to undergo TAVR vs surgery. The patient population for the present analysis consisted of all patients who underwent valve implantation (495 with TAVR and 453 with surgery). The last 7-year follow-up occurred in March 2025. Interventions:Patients were randomized to balloon-expandable TAVR with the SAPIEN 3 valve or surgery with any commercially available valve. Main Outcomes and Measures:The main outcomes of this analysis were stage 2 or 3 bioprosthetic valve dysfunction (BVD) related to structural valve deterioration (SVD), thrombosis, or endocarditis; all-cause bioprosthetic valve failure (BVF); BVF related to SVD; and aortic valve reintervention at 7 years. Analyses are presented as cumulative incidence rates with death as a competing risk. Results:The mean (SD) age of the study population was 73.5 (6.0) years, and 657 participants (69.3%) were male. Of 671 patients who were still alive and enrolled in the study at 7-year follow-up, 537 (80.0%) were available for echocardiographic analysis. Cumulative incidence rates of stage 2 or 3 SVD-related BVD (7.3% vs 7.6%; hazard ratio [HR], 0.96; 95% CI, 0.59-1.57; P = .88), all-cause BVF (6.9% vs 7.5%; HR, 0.91; 95% CI, 0.55-1.49; P = .69), SVD-related BVF (3.9% vs 5.3%; HR, 0.72; 95% CI, 0.39-1.36; P = .31), and valve reintervention (6.0% vs 5.5%; HR, 1.09; 95% CI, 0.62-1.90; P = .77) were low and similar for TAVR and surgery, respectively. Stage 2 or 3 thrombosis-related BVD (subclinical and clinical) occurred more frequently with TAVR (5.2% vs 0.9%; HR, 5.52; 95% CI, 1.92-15.85; P < .001), although most events occurred within 3 years and few progressed to BVF. Rates of stage 2 or 3 endocarditis-related BVD were also low and similar (0.4% in the TAVR group vs 0.5% in the surgery group; HR, 0.85; 95% CI, 0.12-6.07; P = .87). The proportion of patients alive and free of all-cause BVF was 73.4% (331/451) with TAVR vs 74.8% (288/385) with surgery (P = .69). Conclusions and Relevance:In this ad hoc analysis of a randomized clinical trial among low-risk patients with symptomatic severe aortic stenosis randomized to TAVR or surgery, both TAVR and surgery demonstrated comparable and sustained valve durability, with low and similar rates of SVD, all-cause BVF, and reintervention through 7 years. These findings may inform discussions of valve replacement strategies. Trial Registration:ClinicalTrials.gov Identifier: NCT02675114.

Importance As transcatheter aortic valve replacement (TAVR) is considered for younger and lower-risk populations, the durability of bioprosthetic valves is increasingly important. Limited data exist on long-term (7 years and beyond) valve durability. Objective To report 7-year valve durability outcomes for low-risk patients with symptomatic severe aortic stenosis treated with TAVR vs surgery. Design, Setting, and Participants Between March 2016 and October 2017, a total of 1000 patients were enrolled at 71 centers in the US and Canada and randomized to undergo TAVR vs surgery. The patient population for the present analysis consisted of all patients who underwent valve implantation (495 with TAVR and 453 with surgery). The last 7-year follow-up occurred in March 2025. Interventions Patients were randomized to balloon-expandable TAVR with the SAPIEN 3 valve or surgery with any commercially available valve. Main Outcomes and Measures The main outcomes of this analysis were stage 2 or 3 bioprosthetic valve dysfunction (BVD) related to structural valve deterioration (SVD), thrombosis, or endocarditis; all-cause bioprosthetic valve failure (BVF); BVF related to SVD; and aortic valve reintervention at 7 years. Analyses are presented as cumulative incidence rates with death as a competing risk. Results The mean (SD) age of the study population was 73.5 (6.0) years, and 657 participants (69.3%) were male. Of 671 patients who were still alive and enrolled in the study at 7-year follow-up, 537 (80.0%) were available for echocardiographic analysis. Cumulative incidence rates of stage 2 or 3 SVD-related BVD (7.3% vs 7.6%; hazard ratio [HR], 0.96; 95% CI, 0.59-1.57; P = .88), all-cause BVF (6.9% vs 7.5%; HR, 0.91; 95% CI, 0.55-1.49; P = .69), SVD-related BVF (3.9% vs 5.3%; HR, 0.72; 95% CI, 0.39-1.36; P = .31), and valve reintervention (6.0% vs 5.5%; HR, 1.09; 95% CI, 0.62-1.90; P = .77) were low and similar for TAVR and surgery, respectively. Stage 2 or 3 thrombosis-related BVD (subclinical and clinical) occurred more frequently with TAVR (5.2% vs 0.9%; HR, 5.52; 95% CI, 1.92-15.85; P < .001), although most events occurred within 3 years and few progressed to BVF. Rates of stage 2 or 3 endocarditis-related BVD were also low and similar (0.4% in the TAVR group vs 0.5% in the surgery group; HR, 0.85; 95% CI, 0.12-6.07; P = .87). The proportion of patients alive and free of all-cause BVF was 73.4% (331/451) with TAVR vs 74.8% (288/385) with surgery ( P = .69). Conclusions and Relevance In this ad hoc analysis of a randomized clinical trial among low-risk patients with symptomatic severe aortic stenosis randomized to TAVR or surgery, both TAVR and surgery demonstrated comparable and sustained valve durability, with low and similar rates of SVD, all-cause BVF, and reintervention through 7 years. These findings may inform discussions of valve replacement strategies. Trial Registration ClinicalTrials.gov Identifier: NCT02675114

Many patients with severe aortic stenosis present with concomitant multivalvular heart disease. The management of this condition remains challenging and requires a multidisciplinary approach that integrates clinical, hemodynamic, and multimodality imaging data to define the most effective and durable treatment strategy. Although randomized evidence to guide treatment decisions in this setting is limited, percutaneous interventions to address additional valvular lesions are being increasingly adopted. This review provides an overview of the pathophysiology of valvular diseases commonly associated with severe aortic stenosis, highlighting their prognostic implications after surgical or transcatheter treatment and their impact on risk stratification and therapeutic management.

Background:In some patients with left ventricular assist devices (LVADs), unloading of the left ventricle (LV) and medical therapy may lead to improvement in LV systolic function, allowing for LVAD weaning. There are no guideline-directed parameters to help identify candidates for weaning and long-term outcomes remain imperfectly documented. In this study we aimed to assess the clinical and echocardiographic characteristics of weaned patients and evaluate their event-free survival after weaning. Methods:This investigation was a single-center retrospective study of patients who underwent a second- or third-generation LVAD implantation between 2009 and 2021. Results:Ninety-eight patients were included. Fourteen patients (14%) with LV recovery underwent LVAD weaning after a median support time of 309 days. Heart failure etiologies in weaned patients included toxic (recreational drugs) (n = 8, 57%), toxic (medication) (n = 2, 14%), ischemic (n = 2, 14%), or idiopathic dilated (n = 2, 14%) cardiomyopathy. In unweaned patients, heart failure was mostly attributed to ischemic (n = 35, 42%) and idiopathic dilated (n = 27, 32%) cardiomyopathy. Three months after implantation, patients who were eventually weaned had a higher LV ejection fraction (LVEF) (35% vs 19%, P = 0.001) and lower left ventricular end-diastolic diameter (LVEDD) (52 vs 60 mm, P = 0.03) than unweaned patients. At last follow-up after weaning, mean LVEF was 44 ± 6% and no death nor heart transplant had occurred. Conclusions:LVADs can induce LV reverse remodeling leading to myocardial recovery in a significant proportion of patients, especially those with toxic and nonischemic cardiomyopathies. Early reverse remodeling with decreasing LVEDD and improving LVEF at 3 months after implantation may suggest potential candidacy for LVAD weaning. Weaned patients maintain satisfactory LVEF recovery after weaning and have good long-term event-free survival.

Background/Objectives: The recommendations for antithrombotic therapy after transcatheter edge-to-edge mitral valve repair (TEER) are empirical, and the benefit of antiplatelet (APT) or anticoagulation therapy (ACT) remains undetermined. The study sought to investigate the degree and the timing of coagulation and platelet marker activation after TEER. Methods: This was a prospective study including 46 patients undergoing TEER. The markers of coagulation activation, namely prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III (TAT), and the markers of platelet activation, namely soluble P-Selectin and soluble CD-40 ligand (sCD40L), were measured at baseline, 24 h, 1 month, and 1 year after TEER. Results: At discharge, 20 (43%) patients received APT (single: 16, dual: 4), 24 (52%) received ACT, and 2 (4%) had both single APT and ACT. Levels of F1 + 2 and TAT significantly increased at 24 h post TEER (both p < 0.001), rapidly returning to baseline levels at 1 month. However, levels of F1 + 2 and TAT remained higher at 1 month in patients without ACT compared to patients with ACT (respectively, 303.1 vs. 148.1 pmol/L; p < 0.001 and 4.6 vs. 3.0 µg/L; p = 0.020), with a similar trend at 1 year. Levels of soluble P-selectin and sCD40L remained stable at all times after TEER (respectively, p = 0.071 and p = 0.056), regardless of the APT. Conclusions: TEER is associated with an acute activation of the coagulation system, with no increase in platelet activation markers. Hence, the use of dual APT is questionable in this population. Our results raise the hypothesis that the optimal antithrombotic therapy after TEER could be short-term ACT over APT. Further larger studies are warranted.

Background:Aortic valve replacement (AVR) for chronic aortic regurgitation (AR) in the presence of reduced left ventricular ejection fraction (LVEF) is associated with greater surgical risk. Long-term outcomes remain poorly described in contemporary cohorts. Methods:Between 2004 and 2019, 122 patients underwent AVR for chronic severe AR with LVEF < 50%. Patients with severely reduced LVEF (< 35%; n = 37) were compared with those with mild to moderately reduced LVEF (35%-50%; n = 85). Results:Preoperative and intraoperative characteristics were similar in both groups. Operative mortality for the entire cohort was 1.6% (n = 2) and similar across the LVEF spectrum. Postoperatively, optimal medical therapy was achieved in most patients and > 25% of patients with LVEF < 35% benefited from cardiac resynchronization therapy. At latest follow-up, mean LVEF was 42 ± 12% in the severely reduced LVEF group (vs baseline 28 ± 5%; P < 0.001) and 51 ± 9% in the mild to moderately reduced LVEF group (vs baseline 46 ± 4%; P < 0.001). Freedom from cardiovascular death at 10 years was 87.2% in the severe group and 94.7% in the mild to moderate group (P = 0.10). Freedom from heart failure hospitalization at 10 years was higher in the mild to moderate group (96.3%) than in the severe group (88.3%; P = 0.009). Conclusions:In this contemporary cohort of patients who underwent AVR for chronic severe AR, patients with severely reduced LVEF treated with optimal medical therapy had operative mortality and freedom from cardiovascular death similar to patients with mild to moderately reduced LVEF. Favourable left ventricular remodelling was observed in both groups. Hospitalization for heart failure was < 15% in both groups at 10-year follow-up.

BACKGROUND:Multivalvular heart disease (MVHD) is frequently encountered in patients undergoing transcatheter aortic valve replacement (TAVR). However, the long-term prognostic impact of MVHD in this population remains poorly characterised. The aim of this study was to evaluate the long-term clinical outcomes and echocardiographic evolution of MVHD after TAVR. METHODS:A total of 1918 consecutive patients with severe symptomatic aortic stenosis (AS) undergoing TAVR were included. MVHD was defined as the presence of moderate or greater mitral (MR) or tricuspid (TR) regurgitation before the procedure. Baseline, procedural, and follow-up data (median 4.0 years, interquartile range 2.8-5.2 years) were prospectively collected. Changes in MR and TR severity were assessed from baseline to the last available echocardiography evaluation. RESULTS:A total of 450 patients (23.5%) had MVHD at baseline. The presence of MVHD was associated with an increased all-cause mortality (adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.40; P = 0.011) and cardiovascular mortality (adjusted HR 1.29, 95% CI 1.04-1.61; P = 0.018) at follow-up. After adjustment, only baseline moderate or greater TR remained independently associated with all-cause mortality (HR 1.38, 95% CI 1.04-1.84; P = 0.027). At discharge, MR improved in 181 patients (40.2%), with similar rates across MR mechanisms (P = 0.582), and TR improved in 71 (15.8%). MVHD improvement was sustained over time, whereas the absence of recovery was associated with a higher risk of all-cause mortality and cardiovascular mortality up to 6 years. CONCLUSIONS:Patients with MVHD exhibit worse long-term outcomes after TAVR. Although TAVR provided sustained improvement of concomitant valvular lesions in about one-half of patients, lack of recovery at discharge predicted poorer long-term survival, highlighting the need for comprehensive baseline assessment and close echocardiographic follow-up in this high risk population.

The coexistence of coronary artery disease (CAD) and transthyretin cardiac amyloidosis (ATTR-CM) is increasingly recognized in clinical practice, especially in older adults. Although each condition has distinct pathophysiologic and imaging features, their association could be challenging for interpretation of imaging and diagnosis. This report presents a series of clinical cases that illustrate multimodality imaging findings in patients with coexisting CAD and ATTR-CM. It highlights the unique and overlapping features seen on echocardiography, cardiac magnetic resonance imaging, nuclear imaging, and coronarography. Special attention is given to diagnosis challenges that arise when these conditions coexist, and to the value of recognizing atypical findings of both CAD and ATTR-CM. The objectives of this report are to: 1) raise awareness of the possibility of ATTR-CM in patients with known CAD; and 2) discuss several specific multi-imaging features and specific findings encountered in clinical cases with concomitant CAD and ATTR-CM.

Aims There is a lack of studies investigating the pathophysiologic and phenotypic distinctiveness of aortic stenosis (AS). This heterogeneity has important implications for identifying optimal intervention timing and potential medical management. This study seeks to identify phenogroups of AS using unsupervised machine learning to improve risk stratification. Methods and results A total of 349 patients with asymptomatic AS from the PROGRESSA study were included in this analysis. Echocardiographic, clinical and blood sample data were used in the unsupervised clustering process. Longitudinal echocardiographic data were used to evaluate AS progression. Five clusters of patients were revealed using 18 variables selected by an unsupervised machine learning algorithm. Amongst them, aortic valvular phenotype, mean gradient, peak jet velocity (V-peak), and left ventricle stroke volume were selected as discriminatory variables. Following the clustering process, characteristics differed between clusters, including age, body mass index, and sex ratio (all P < 0.001). Of note, cluster 1 showed higher AS severity at baseline with significantly higher initial V-peak (344 [314; 376] cm/s) and calcium score (1257 [806; 1837] UA) (P < 0.001). Patients from cluster 1 had a faster AS progression (progression of V-peak = 22 [9; 39] cm/s/year), and calcium score (213 [111; 307] UA/year) (P < 0.001). Cluster 1 was also associated with a higher composite risk of mortality and aortic valve replacement when adjusted for age, sex, and baseline AS severity (P < 0.001). Conclusion Artificial intelligence-guided phenotypic classification revealed 5 distinct groups and enhanced risk stratification of patients with AS. This approach may be useful to optimize and individualize medical and interventional management of AS.

BACKGROUND:The PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients with Aortic Stenosis) trial compared SAPIEN 3 transcatheter aortic valve replacement (TAVR) to surgery in low-risk patients with symptomatic, severe aortic stenosis. Echocardiographic outcomes at 5 years are unknown. OBJECTIVES:This study sought to compare 5-year echocardiographic results of TAVR and surgery in the PARTNER 3 trial. METHODS:Echocardiograms for 1,000 randomized patients were obtained at baseline, 30 days, 1 year, and annually through 5 years and were analyzed by a core lab consortium. The composite primary endpoint of death, stroke, or rehospitalization was adjudicated by a clinical events committee. RESULTS:At 5 years, ≥ mild aortic regurgitation was higher following TAVR vs surgery (24.5% vs 6.3%; P < 0.001), with low ≥ moderate aortic regurgitation in both groups. TAVR patients had higher mean transaortic gradient (12.8 ± 6.5 vs 11.7 ± 5.6 mm Hg; P < 0.001), stroke volume index (44.6 ± 9.7 vs 41.1 ± 9.2; P < 0.0001), and aortic valve area (1.87 ± 0.46 vs 1.82 ± 0.46; P = 0.895). Fewer TAVR patients had low-flow stroke volume index (P < 0.001) and left ventricular hemodynamic burden (valvulo-arterial impedance; P < 0.01). Tricuspid annular plane systolic excursion was also higher with TAVR (P < 0.001), as was right ventricular-to-pulmonary artery coupling (P < 0.0001). In the combined cohorts, 30-day moderate to severe prosthesis-patient mismatch, mild to severe aortic regurgitation, or low stroke volume index were not predictive of clinical outcomes; only low right ventricular-to-pulmonary artery coupling and high valvulo-arterial impedance at 30 days were associated with increased risk of the 5-year composite primary endpoint. CONCLUSIONS:In low-risk patients with severe aortic stenosis, TAVR, compared to surgery, was associated with similar, stable valve hemodynamics at 5 years with less frequent low-flow state, lower valvulo-arterial impedance, and better right ventricular function. (PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients with Aortic Stenosis [P3]; NCT02675114).

The increasing prevalence of amphetamine use has become a major public health concern in Canada. Among the many cardiovascular impacts of amphetamine use, dilated cardiomyopathy is emerging as a rare but morbid complication in young adults. This case report highlights the evolution of a patient with amphetamine-induced cardiomyopathy. We present a common clinical presentation of this disease and a novel approach to address certain treatment challenges in advanced heart failure in this patient population.

BACKGROUND:Myocardial infarction in essential thrombocythemia (ET) is a rare but severe complication of this myeloproliferative disorder, occurring in approximately 2% to 3% of the population. CASE SUMMARY:A 78-year-old man with calreticulin-mutated ET presented with massive anterior ST-segment elevation myocardial infarction (STEMI). Urgent coronary angiogram revealed subtotal left anterior descending artery stenosis due to heavy thrombus burden, leading to partial revascularization. His platelet count exceeded 1,200 × 109/L on admission, justifying prompt thrombocytapheresis in the coronary care unit. DISCUSSION:In acute symptomatic thrombohemorrhagic complications, the American Society for Apheresis designates thrombocytapheresis as a Class II recommendation. This case describes the novel use of thrombocytapheresis in the setting of anterior STEMI with ET. TAKE-HOME MESSAGES:STEMI complicating acutely decompensated ET is life threatening, and early thrombocytapheresis should be considered in select patients. This case demonstrates the potential benefit of more aggressive cytoreductive therapy in patients with ET and underlying cardiovascular risk factors.

In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has been increasingly recognised as a cause of heart failure. 99mTechnetium-labelled pyrophosphate (99mTc-PYP) scintigraphy has become the cornerstone of noninvasive ATTR-CM diagnosis once light chain cardiac amyloidosis (AL-CM) has been excluded. We present a case of hydroxychloroquine-induced cardiomyopathy (HCQ-CM) in a patient who presented with acute decompensated heart failure and positive 99mTc-PYP scintigraphy. This case illustrates that HCQ-CM can present as a phenocopy of amyloid cardiomyopathy and emphasises the importance of endomyocardial biopsy to confirm the diagnosis in patients receiving long-term hydroxychloroquine therapy.

Background: Although recent studies have showed improved outcomes, aortic valve replacement (AVR) for chronic aortic regurgitation (AR) in the presence of reduced left ventricular ejection fraction (LVEF) is associated with a higher surgical risk. Contemporary long-term outcome remains poorly investigated. Methods: Between January 2004 and August 2019, we identified 122 patients who underwent AVR for pure chronic severe AR with LVEF less than 50%. Patients with severe reduced LVEF (<35%, n=37) were compared with those with mild to moderate reduced LVEF (35% to 50%, n=85). Results: Preoperative and intraoperative characteristics were similar in both groups. Operative mortality for the entire cohort was 1,6% (n=2) and similar across the LVEF spectrum. Postoperative intra-aortic balloon pump has been used in 2/37 patients with LVEF < 35% compared to 0/85 patients with LVEF 35-50% (p = 0.09). Patients with severely reduced LVEF had a longer length of stay (10.1±5.5 vs 7.8±3.5 days, p=0,02) while the rate of stroke, atrial fibrillation, acute renal failure, and pulmonary infection were similar between groups. Postoperatively, optimal medical therapy was achieved in most patients and more than a quarter of patients with LVEF < 35% benefited from cardiac resynchronization therapy. At the latest follow-up, mean LVEF was 42±12% in the severe reduced LVEF (vs. baseline 28±6%, p<0.001) and 51±9% in the mild to moderate reduced LVEF group (vs. baseline 45±4%, p<0.001). Freedom from cardiovascular (CV) death at ten years was 87.2% in the severe reduced LVEF group and 94.7% in patients with mild to moderate reduced LVEF (p=0.10). Freedom from heart failure (HF) hospitalization at ten years was higher in the mild to moderate reduced LVEF group (96.3%) than in the severely reduced LVEF group (88.3%) (p=0.009). Conclusion: In this contemporary cohort of patients undergoing AVR for chronic severe AR, patients with severely reduced EF treated with optimal guideline-directed medical therapy had a similar operative mortality and freedom from CV death than patients with mild to moderate reduced LVEF. Favorable left ventricular remodeling was observed in both groups at 1 year follow-up. Hospitalization for HF was low with less than 15% in both groups at 10 years follow-up; although rehospitalisation occurred more frequently in severe reduced LVEF group.

Left ventricular assist devices (LVAD) are increasingly used in refractory heart failure, mainly as a bridge to transplant or as destination therapy. LVAD unloading of the left ventricle (LV) can also promote myocardial recovery leading to improvement of the LV systolic function, allowing LVAD explantation. However, parameters associated with LVAD weaning and long-term outcomes are not well documented. The aim of this study was to assess the clinical and echocardiographic characteristics of weaned patients and to evaluate their event-free survival post-explantation. We conducted a single-center retrospective study recruiting patients who underwent a second or third generation LVAD implantation at a Canadian cardiology center between November 2009 and October 2021. A total of 98 patients underwent LVAD implantation during this period. All patients were on guideline-directed medical therapy (GDMT). Fourteen patients (14%) had significant LV recovery and were explanted/decommissioned after a median support time of 309 days (range 55-595 days). Toxic cardiomyopathy, defined as abuse of amphetamines (n=2), energy drinks (n=2) or multiple substances (n=6), was the most likely diagnosis in 10 of the weaned patients (71%). The LVEF was significantly higher and the left ventricular end-diastolic diameter (LVEDD) was significantly lower in weaned patients compared to unweaned patients after 3 months of support. Myocardial recovery manifested as pump thrombosis in 4 of the weaned patients (29%). Prior to explantation, 12 patients had a decrease in GDMT doses to minimize post explantation vasoplegia. After explantation, median follow-up time was 40 months (range 8-109 months) and the majority of patients were anticoagulated for 3 months. At last follow up, the LVEF was 44±6% and no patient had a LVEF below 35%. All patients were NYHA I or II and no death, heart transplant, or mechanical support initiation occurred. LVAD therapy can induce LV reverse remodeling leading to myocardial recovery in a significant proportion of patients, especially young patients with toxic and non-ischemic cardiomyopathies. Early reverse remodeling with decreasing LVEDD and improving LVEF at 3 months following implantation is associated with successful weaning. Pump thrombosis seems to be associated with LV reverse remodeling and weaning of mechanical support in certain patients. Weaned patients maintain satisfactory LVEF recovery after explantation and have good long-term event-free survival.