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Background: Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients., Objectives: The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial., Methods: The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6- and 24-month follow-up., Results: Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (P interaction  = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved., Conclusions: In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079)., Competing Interests: Funding Support and Author Disclosures The COAPT trial was sponsored by Abbott. Dr Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, Merck Sharp and Dohme, and GE Healthcare. Dr Stassen has received funding from the European Society of Cardiology (European Society of Cardiology Training Grant App000064741). Dr Weissman is associate director of an academic echocardiography core laboratory (MedStar Health Research Institute) with institutional contracts with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Grayburn has received grant support from Abbott Vascular, Medtronic, Boston Scientific, Cardiovalve, Edwards Lifesciences, W. L. Gore, Medtronic, and NeoChord; and has received consulting fees from Abbott Vascular, Edwards Lifesciences, W. L. Gore, and 4C Medical. Dr Kar has received consulting fees and is an Advisory Board member at Boston Scientific; has received consulting fees and stock equity from Valcare; and has received consulting fees from W.L. Gore and Medtronic. Dr Lim has received research grant support from Abbott, Boston Scientific, Edwards, and Medtronic; has received consultant fees from LagonaTech, Valgen, and Venus; and is an Advisory Board member for Ancora and Philips. Dr Lindenfeld has received research grant support from AstraZeneca; and has received consulting fees from Abbott Vascular, CVRx, Edwards Lifesciences, RESMED, Relypsa, Boehringer Ingelheim, and V-Wave. Dr Abraham has received research grant support from the National Heart, Lung, and Blood Institute (National Institutes of Health 1 UG3/UH3 HL140144-01, 08/01/18-07/31/22, “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea [LOFT-HF]”); has received consulting income from Abbott Vascular, Boehringer-Ingelheim, and Zoll Respicardia; has received speaker honoraria from Impulse Dynamics; and has received salary support from V-Wave Medical. Dr Mack has served as coprimary investigator for the PARTNER Trial for Edwards Lifesciences and COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic. Dr Asch is the Director of the Core Laboratories at MedStar Health Research Institute, which has institutional contracts (no personal compensation) with Abbott, Neovasc, Ancora, Mitralign, Medtronic, Boston Scientific, Edwards Lifesciences, Biotronik, and Livanova. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic; and Dr Stone’s employer, Mount Sinai Hospital, has received research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Bax has received speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF., Methods and Results: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e ' (exE/ e ') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/ e '<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/ e '≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/ e '<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/ e '<15 but a high slope had NT-proBNP levels and H 2 FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope., Conclusions: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Background: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L -1 ·min -1 . A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown., Methods: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm 2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141)., Results: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P =0.036), indexed left atrial volume (OR per SD, 2.15; P =0.001), E/e' at rest (OR per SD, 1.61; P =0.012), mPAP/CO slope (OR per SD, 2.01; P =0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P =0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P =0.219). Peak Vo 2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area ( P <0.001). These results were confirmed in the validation cohort., Conclusions: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo 2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo 2 and mPAP/CO slope cumulatively improved risk stratification., Competing Interests: Disclosures None.

Aims: We sought to evaluate the mechanism of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart failure with reduced ejection fraction (HFrEF)., Methods and Results: The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II-III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11 C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (-4.5 mmHg; p = 0.026) and systolic blood pressure (-9.8 mmHg; p = 0.0007), myocardial perfusion (-0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (-296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088)., Conclusions: We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background Left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information over LV ejection fraction in patients with heart failure (HF) and secondary mitral regurgitation. We examined the prognostic impact of LV GLS improvement in this population. Methods and Results The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial randomized symptomatic patients with HF with severe (3+/4+) mitral regurgitation to transcatheter edge-to-edge repair with the MitraClip device plus maximally tolerated guideline-directed medical therapy (GDMT) versus GDMT alone. LV GLS was measured at baseline and 6-month follow-up. The relationship between the improvement in LV GLS from baseline to 6 months and the composite of all-cause death or HF hospitalization between 6- and 24-month follow-up were assessed. Among 383 patients, 174 (45.4%) had improved LV GLS at 6-month follow-up (83/195 [42.6%] with transcatheter edge-to-edge repair+GDMT and 91/188 [48.4%] with GDMT alone; P =0.25). Improvement in LV GLS was strongly associated with reduced death or HF hospitalization between 6 and 24 months ( P <0.009), with similar risk reduction in both treatment arms ( P interaction =0.40). By multivariable analysis, LV GLS improvement at 6 months was independently associated with a lower risk of death or HF hospitalization (hazard ratio [HR], 0.55 [95% CI, 0.36-0.83]; P =0.009), death (HR, 0.48 [95% CI, 0.29-0.81]; P =0.006), and HF hospitalization (HR, 0.50 [95% CI, 0.31-0.81]; P =0.005) between 6 and 24 months. Conclusions Among patients with HF and severe mitral regurgitation in the COAPT trial, improvement in LV GLS at 6-month follow-up was associated with improved outcomes after both transcatheter edge-to-edge repair and GDMT alone between 6 and 24 months. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Patients with heart failure (HF) and reduced ejection fraction (HFrEF) are complex patients who often have a high prevalence of co-morbidities and risk factors. In the present study, we investigated the prognostic significance of left ventricular (LV) global longitudinal strain (GLS) along with important clinical and echocardiographic variables in patients with HFrEF. Patients who had a first echocardiographic diagnosis of LV systolic dysfunction, defined as LV ejection fraction ≤45%, were selected. The study population was subdivided into 2 groups based on a spline curve analysis derived optimal threshold value of LV GLS (≤10%). The primary end point was occurrence of worsening HF, whereas the composite of worsening HF and all-cause death was chosen for the secondary end point. A total of 1,873 patients (mean age 63 ± 12 years, 75% men) were analyzed. During a median follow-up of 60 months (interquartile range 27 to 60 months), 256 patients (14%) experienced worsening HF and the composite end point of worsening HF and all-cause mortality occurred in 573 patients (31%). The 5-year event-free survival rates for the primary and secondary end point were significantly lower in the LV GLS ≤10% group compared with the LV GLS >10% group. After adjustment for important clinical and echocardiographic variables, baseline LV GLS remained independently associated with a higher risk of worsening HF (hazard ratio 0.95, 95% confidence interval 0.90 to 0.99, p = 0.032) and the composite of worsening HF and all-cause mortality (hazard ratio 0.94, 95% confidence interval 0.90 to 0.97, p = 0.001). In conclusion, baseline LV GLS is associated with long-term prognosis in patients with HFrEF, independent of various clinical and echocardiographic predictors., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) is an effective therapy in selected patients with advanced heart failure that reduces all-cause mortality at short-term follow-up. However, data regarding long-term mortality after CRT implantation are scarce, with no separate analysis available of the covariates associated with respectively short-term and long-term outcomes. Accordingly, the present study evaluated the risk factors associated with short-term (2-year follow-up) versus long-term (10-year follow-up) mortality after CRT implantation. Patients who underwent CRT implantation and had echocardiographic evaluation before implantation were included in the present study. The primary end point was all-cause mortality, and independent associates of short-term (2-year follow-up) and long-term (10-year follow-up) mortality were compared. In total, 894 patients (mean age 66 ± 10 years, 76% males) who underwent CRT implantation were included in the present study. The cumulative overall survival rates for the total population were 91%, 71%, and 45% at 2-, 5- and 10-year follow-up, respectively. Multivariable Cox regression analysis showed that short-term mortality was associated with both clinical and echocardiographic variables at the moment of CRT implantation; whereas long-term mortality was predominantly associated with baseline clinical parameters and was less strongly associated with baseline echocardiographic parameters. In conclusion, at long-term (10-year) follow-up, a significant proportion (45%) of patients with advanced heart failure who underwent CRT implantation were still alive. Importantly, the risk assessment for short-term (2-year follow-up) and long-term (10-year follow-up) mortality differ considerably, which may influence clinical decision making., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Left atrial (LA) function is a strong prognostic marker in patients with heart failure and functional mitral regurgitation (MR). Although cardiac resynchronization therapy (CRT) has shown to improve MR severity, the interaction between a reduction in MR severity and an increase in LA function, as well as its association with outcomes, has not been investigated., Methods and Results: LA reservoir strain (RS) was evaluated with speckle tracking echocardiography in patients with at least moderate functional MR undergoing CRT implantation. MR improvement was defined as at least 1 grade improvement in MR severity at 6 months after CRT implantation. The primary endpoint was all-cause mortality. A total of 340 patients (mean age 66 ± 10 years, 73% male) were included, of whom 200 (59%) showed MR improvement at 6 months follow-up. On multivariable analysis, an improvement in MR severity was independently associated with an increase in LARS (odds ratio 1.008; 95% confidence interval 1.003-1.013; P = 0.002). After multivariable adjustment, including baseline and follow-up variables, an increase in LARS was significantly associated with lower mortality. MR improvers showing LARS increasement had the lowest mortality rate, whereas outcomes were not significantly different between MR non-improvers and MR improvers showing no LARS increasement (P = 0.236)., Conclusion: A significant reduction in MR severity at 6 months after CRT implantation is independently associated with an increase in LARS. In addition, an increase in LARS is independently associated with lower all-cause mortality in patients with heart failure and significant functional MR., Competing Interests: Conflict of interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre received research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis and Medtronic. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. J.J.B. received speaker fees from Abbott Vascular. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Worsening heart failure (HF), defined as hospitalization for worsening signs and symptoms of HF or the need for urgent intravenous diuretics, is often considered a surrogate of poor prognosis in clinical trials. However, data on the prognostic implications of worsening HF in patients with HF and reduced ejection fraction is limited. Patients who had a first echocardiographic diagnosis of left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) ≤45%, were identified. Worsening HF was defined as hospitalization for HF or urgent need for intravenous diuretics. All-cause mortality was chosen as the study end point. A total of 1,801 patients (mean age 64 ± 12 years, 74% men) were analyzed. Worsening HF was observed in 275 patients (15%) during a median follow-up of 20 months, while, 435 patients (24%) died during a median follow-up of 60 months (Interquartile range 28 to 60 months). The 5-year survival rate was significantly lower in the worsening HF cohort compared with the non-worsening HF cohort (Log-rank p <0.0001), and it was significantly different between the worsening HF cohort and the nonworsening HF cohort for LVEF ≤25% (log-rank p <0.0001) and LVEF 26% to 34% (log-rank p = 0.038) but not for LVEF 35% to 45% (log-rank p = 0.14). After adjustment for important clinical and echocardiographic predictors, worsening HF was independently associated with a higher risk of all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.09 to 1.96, p = 0.011). In conclusion, worsening HF, defined by HF hospitalization or the urgent need for intravenous diuretics, is independently associated with poor long-term prognosis in patients with HF and reduced ejection fraction., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT) on TR severity and long-term outcome., Methods and Results: Tricuspid regurgitation severity was assessed at baseline and 6 months after CRT implantation, using a multiparametric approach. Patients were divided into four groups: (i) no or mild TR without progression; (ii) no or mild TR with progression to significant (moderate-severe) TR; (iii) significant TR with improvement to no or mild TR; and (iv) significant TR without improvement. The primary endpoint was all-cause mortality. A total of 852 patients (mean age 65 ± 11 years, 77% male) were included. At baseline, 184 (22%) patients had significant TR, with 75 (41%) showing significant improvement at 6-month follow-up. After a median follow-up of 92 (50-137) months, 494 (58%) patients died. Patients with significant TR showing improvement at follow-up had better outcomes than those showing no improvement (P = 0.016). On multivariable analysis, no or mild TR progressing to significant TR [hazard ratio (HR) 1.745; 95% confidence interval (CI): 1.287-2.366; P < 0.001] and significant TR without improvement (HR 1.572; 95% CI: 1.198-2.063; P = 0.001) were independently associated with all-cause mortality, whereas significant TR with improvement at follow-up was not (HR: 1.153; 95% CI: 0.814-1.633; P = 0.424)., Conclusion: Improvement of significant TR after CRT is observed in a substantial proportion of patients, highlighting the potential benefit of CRT for patients with HF having significant TR. Significant TR at 6 months after CRT is independently associated with increased long-term mortality., Competing Interests: Conflict of interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre received research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. J.J.B. received speaker fees from Abbott Vascular. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD, and GE Healthcare. All remaining authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery., Methods: Patients with significant TR who underwent TV surgery were divided into 4 right heart failure stages according to the presence of right ventricular (RV) dysfunction and clinical signs of right heart failure: stage 1 was defined as no RV dysfunction and no signs of right heart failure; stage 2 indicated RV dysfunction without signs of right heart failure; stage 3 included RV dysfunction and signs of right heart failure; and stage 4 was defined as RV dysfunction and refractory signs of right heart failure at rest., Results: A total of 278 patients [mean age 64 (12), 49% males] were included, of whom 34 (12%) patients were classified as stages 1 and 2, 141 (51%) as stage 3 and 103 (37%) as stage 4 right heart failure. The majority of patients (91%) had TV surgery concomitant to left-sided valve surgery or coronary artery bypass grafting and 95% underwent TV annuloplasty. Cumulative survival rates were 89%, 78% and 61% at 1 month, 1 year and 5 years, respectively. Stages 1 and 2 and stage 3 were independently associated with better survival compared to stage 4 (hazard ratio: 0.391 [95% confidence interval: 0.186-0.823] and 0.548 [95% confidence interval: 0.369-0.813], respectively)., Conclusions: Patients with significant TR undergoing TV surgery and diagnosed without advanced right heart failure have better survival as compared to patients with right heart failure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Left ventricular (LV) systolic dysfunction in cardiac amyloidosis (CA) is associated with poor prognosis. This study aimed to investigate the prognostic implications of right ventricular (RV) systolic dysfunction in CA. A total of 93 patients diagnosed with CA who underwent standard and speckle-tracking echocardiography were included. During a median follow-up of 17 (5 to 38) months, 42 patients (45%) died. Nonsurvivors were more likely to present with immunoglobulin light-chain amyloidosis and New York Heart Association class III to IV heart failure symptoms. Regarding the echocardiographic characteristics, nonsurvivors had a higher LV apical ratio, worse LV diastolic function, and worse RV systolic function (evaluated with both tricuspid annular plane systolic excursion and RV free wall strain). RV free wall strain was independently associated with all-cause mortality in several multivariable Cox regression models and had incremental prognostic value over conventional parameters of RV function when added to a basal model (including heart failure symptoms, amyloidosis phenotype, and LV global longitudinal strain). Based on spline curve analysis and Youden index, a value of 16% for RV free wall strain was identified as the optimal cutoff to predict outcome and patients with RV free wall strain <16% had a significantly worse short- and long-term survival during follow-up (1- and 3-year cumulative survival: 81% vs 31% and 67% vs 20%, respectively, p <0.001). In conclusion, RV systolic dysfunction is independently associated with poor outcome in patients with CA and the use of advanced echocardiographic parameters, such as RV free wall strain, may be of aid for better risk stratification., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT)., Objective: The purpose of this study was to evaluate the impact of baseline LV volumes on LV reverse remodeling after CRT and whether this is associated with improved survival., Methods: Patients were stratified into quintiles according to baseline LV end-diastolic volume indexed for body surface area (LVEDVi). LV reverse remodeling was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up after CRT. Independent associates of LV remodeling were assessed and long-term mortality rates were compared between patients with and without LV reverse remodeling (across LVEDVi quintiles)., Results: A total of 864 patients were included (mean age 66 ± 10 years; 657 patients (76%) were male), of whom 101 (12%) were in quintile 1 (<65 mL/m 2 ), 272 (32%) in quintile 2 (65-95 mL/m 2 ), 247 (29%) in quintile 3 (95-125 mL/m 2 ), 151 (18%) in quintile 4 (125-155 mL/m 2 ), and 93 (11%) in quintile 5 (>155 mL/m 2 ). Patients with larger baseline LVEDVi had worse survival after CRT (log-rank, P = .019). The cumulative 10-year survival was significantly better in patients with vs without LV reverse remodeling (48.7% vs 33.9%; P < .001). Significant LV reverse remodeling was observed in all LVEDVi quintiles. In addition, patients with LV reverse remodeling had superior survival than did patients without LV reverse remodeling, regardless of baseline LVEDVi quintile (log-rank, P < .05 for all)., Conclusion: Many patients with larger baseline LV volumes still show significant LV reverse remodeling after CRT and had superior survival (regardless of baseline LV volumes) than did patients without LV reverse remodeling. Therefore, CRT should not be denied on the basis of severe LV dilatation., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Left atrial (LA) function is a marker of prognosis in patients with heart failure. The prognostic implications of an improvement in LA function in addition to an improvement in left ventricular (LV) function after cardiac resynchronization therapy (CRT) implantation are unknown. This study aimed to evaluate the prognostic value of a significant change in LA reservoir strain (RS) and/or LV global longitudinal strain (GLS) after initiation of CRT., Methods and Results: LARS and LVGLS were measured with speckle-tracking echocardiography. Significant improvement in LARS and LVGLS was defined as a percentage change of +5% and +20% at 6 months after CRT implantation, respectively. Patients were divided into three groups: no significant reverse remodelling (no improvement in LARS and LVGLS), incomplete reverse remodelling (improvement in LARS or LVGLS), and complete reverse remodelling (improvement in LARS and LVGLS). The primary endpoint was all-cause mortality. A total of 923 patients (mean age 65 ± 10 years, 77% male) were included, of which 221 (24%) had complete reverse remodelling, 414 (45%) incomplete reverse remodelling, and 288 (31%) no significant reverse remodelling. Five-years' mortality was 24%, 29%, and 36% for patients with complete, incomplete, and no significant reverse remodelling, respectively (P < 0.001). On multivariable analysis, complete reverse remodelling (hazard ratio 0.477; 95% confidence interval: 0.362-0.628; P < 0.001) was associated with the lowest risk of mortality., Conclusions: Patients with complete reverse remodelling have a lower mortality risk than those showing incomplete or no significant reverse remodelling. The use of integrated LA and LV deformation imaging may improve risk-stratification of CRT recipients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Background: Cardiac resynchronization therapy (CRT) candidates often present with significant mitral and tricuspid regurgitation, pulmonary hypertension and right ventricular dysfunction when referred for device implantation. This study investigated the prognostic value of a novel cardiac staging system, based on the extent of cardiac remodeling prior to implantation., Methods: Data were collected from an ongoing registry of CRT recipients. Patients were divided into 4 groups according to the extent of cardiac remodeling: group 1: left ventricular systolic dysfunction, group 2: left atrial dilatation and/or significant mitral regurgitation, group 3: pulmonary arterial hypertension and/or significant tricuspid regurgitation and group 4: right ventricular systolic impairment. Patients were followed up for the occurrence of all-cause mortality., Results: A total of 844 patients (age 65 ± 10 years, 77% men) were included. Of the overall population, 145 (17%) patients were in group 1, 161 (19%) in group 2, 157 (19%) in group 3 and 381 (45%) in group 4. After a median follow-up of 95 (51-145) months, 517 (61%) patients died. Patients in groups 2, 3 and 4 had significantly higher mortality rates than those in group 1 (p = 0.025, p < 0.001 and p < 0.001, respectively). On multivariable analysis, groups 3 (HR 1.415; 95% CI 1.024-1.957; p = 0.032) and 4 (HR 1.599; 95% CI 1.204-2.123; p = 0.001) were independently associated with all-cause mortality., Conclusions: Most CRT candidates already present with extensive cardiac remodeling at the time of referral. Detection of the extent of cardiac remodeling before CRT implantation results in improved risk-stratification, and underscores the need for early referral., (Copyright © 2022. Published by Elsevier B.V.)

Background: The benefit of de novo cardiac resynchronisation therapy (CRT) implantation in selected patients with heart failure is well known. The number of upgrade procedures is increasing but data on clinical response and outcome are less well documented as compared to de novo implantation., Objectives: To investigate the efficacy and outcome of CRT upgrade procedures in patients with existing cardiac implantable electronic devices (CIEDs)., Methods: Baseline characteristics, change in New York Heart Association (NYHA) functional class, echocardiographic parameters, life-threatening ventricular tachyarrhythmias, all-cause mortality and mode of death were evaluated in CRT patients with the comparison between de novo and upgrade CRT procedures., Results: About 410 patients (CRT upgrade/ de novo CRT, n  = 97/313) were followed for 63.5 ± 38.1 months. Upgrade patients were older (75.5 ± 8.1 vs 69.9 ± 10.7 years; p  < 0.001), had more often an ischaemic cause of heart failure (58.8% vs 45.4%; p  = 0.021), a higher NYHA functional class ( p  = 0.004) and a higher comorbidity burden. Improvement in left ventricular ejection fraction (LVEF) was higher in the de novo CRT group (8.4 ± 9.9 vs 11.0 ± 10.3%; p  = 0.035). Clinical response was similar between both groups (60.5 vs 62.5%; p  = 0.793), as was mortality at 1 year (8.2 vs 5.8%; p  = 0.351) and at last follow-up (33.0 vs 28.8%; p  = 0.447). The proportion of cardiovascular related deaths was similar between both groups (46.9% vs 38.9%; p  = 0.531)., Conclusions: Patients with CRT upgrade procedures have similar symptomatic improvements, as well as 1 year and long-term outcome as compared to patients with de novo CRT implantation.

Aims Left atrial (LA) function is a strong prognostic marker in patients with heart failure and functional mitral regurgitation (MR). Although cardiac resynchronization therapy (CRT) has shown to improve MR severity, the interaction between a reduction in MR severity and an increase in LA function, as well as its association with outcomes, has not been investigated. Methods and results LA reservoir strain (RS) was evaluated with speckle tracking echocardiography in patients with at least moderate functional MR undergoing CRT implantation. MR improvement was defined as at least 1 grade improvement in MR severity at 6 months after CRT implantation. The primary endpoint was all-cause mortality. A total of 340 patients (mean age 66 ± 10 years, 73% male) were included, of whom 200 (59%) showed MR improvement at 6 months follow-up. On multivariable analysis, an improvement in MR severity was independently associated with an increase in LARS (odds ratio 1.008; 95% confidence interval 1.003–1.013; P = 0.002). After multivariable adjustment, including baseline and follow-up variables, an increase in LARS was significantly associated with lower mortality. MR improvers showing LARS increasement had the lowest mortality rate, whereas outcomes were not significantly different between MR non-improvers and MR improvers showing no LARS increasement (P = 0.236). Conclusion A significant reduction in MR severity at 6 months after CRT implantation is independently associated with an increase in LARS. In addition, an increase in LARS is independently associated with lower all-cause mortality in patients with heart failure and significant functional MR. [ABSTRACT FROM AUTHOR]

Aims: Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT) on TR severity and long-term outcome.Methods and Results: Tricuspid regurgitation severity was assessed at baseline and 6 months after CRT implantation, using a multiparametric approach. Patients were divided into four groups: (i) no or mild TR without progression; (ii) no or mild TR with progression to significant (moderate-severe) TR; (iii) significant TR with improvement to no or mild TR; and (iv) significant TR without improvement. The primary endpoint was all-cause mortality. A total of 852 patients (mean age 65 ± 11 years, 77% male) were included. At baseline, 184 (22%) patients had significant TR, with 75 (41%) showing significant improvement at 6-month follow-up. After a median follow-up of 92 (50-137) months, 494 (58%) patients died. Patients with significant TR showing improvement at follow-up had better outcomes than those showing no improvement (P = 0.016). On multivariable analysis, no or mild TR progressing to significant TR [hazard ratio (HR) 1.745; 95% confidence interval (CI): 1.287-2.366; P < 0.001] and significant TR without improvement (HR 1.572; 95% CI: 1.198-2.063; P = 0.001) were independently associated with all-cause mortality, whereas significant TR with improvement at follow-up was not (HR: 1.153; 95% CI: 0.814-1.633; P = 0.424).Conclusion: Improvement of significant TR after CRT is observed in a substantial proportion of patients, highlighting the potential benefit of CRT for patients with HF having significant TR. Significant TR at 6 months after CRT is independently associated with increased long-term mortality. [ABSTRACT FROM AUTHOR]

Aims Chronic pressure overload and right ventricular (RV) dysfunction can lead to RV–pulmonary artery (PA) uncoupling in patients with heart failure. The evolution and prognostic values of RV–PA coupling assessed by echocardiography in patients undergoing cardiac resynchronization therapy (CRT) have not been thoroughly investigated. The aim of this study was to evaluate the evolution and prognostic value of tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio in CRT recipients. Methods and results The RV–PA coupling was measured non-invasively with echocardiography using the TAPSE/PASP ratio at baseline and 6 month follow-up in CRT recipients. The cut-off value for TAPSE/PASP uncoupling was derived from spline curve analysis (i.e. <0.45 mm/mmHg). The primary endpoint was all-cause mortality. A total of 807 patients (age 66 ± 11 years, 76% men) were analysed. During a median follow-up of 97 (54–143) months, 483 (60%) patients died. Survival rates at 3 and 5 year follow-up were significantly lower for patients with a TAPSE/PASP ratio <0.45 mm/mmHg (76% and 58%, respectively), compared with those with a TAPSE/PASP ratio ≥0.45 mm/mmHg (91% and 82%, respectively) (P < 0.001). On multivariable analysis, TAPSE/PASP ratio <0.45 mm/mmHg (hazard ratio 1.437; 95% confidence interval: 1.145–1.805; P = 0.002) was independently associated with all-cause mortality, whereas TAPSE <17 mm (hazard ratio 1.237; 95% confidence interval: 0.990–1.546; P = 0.061) was not. In addition, no improvement of the TAPSE/PASP ratio after CRT implantation was independently associated with worse survival. Conclusions The TAPSE/PASP ratio at baseline is independently associated with long-term outcomes in CRT recipients. The baseline TAPSE/PASP ratio has incremental value over TAPSE, which does not take account of RV afterload. A lack of improvement in the TAPSE/PASP ratio after CRT implantation is associated with worse survival. [ABSTRACT FROM AUTHOR]