Endpoint Of Heart Failure Research Articles

SGLT2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials

SGLT2 inhibitors are strongly recommended in guidelines to treat patients with heart failure with reduced ejection fraction, but their clinical benefits at higher ejection fractions are less well established. Two large-scale trials, DELIVER and EMPEROR-Preserved, in heart failure with mildly reduced or preserved ejection fraction have been done, providing power to examine therapeutic effects on cardiovascular mortality and in patient subgroups when combined with the earlier trials in reduced ejection fraction. We did a prespecified meta-analysis of DELIVER and EMPEROR-Preserved, and subsequently included trials that enrolled patients with reduced ejection fraction (DAPA-HF and EMPEROR-Reduced) and those admitted to hospital with worsening heart failure, irrespective of ejection fraction (SOLOIST-WHF). Using trial-level data with harmonised endpoint definitions, we did a fixed-effects meta-analysis to estimate the effect of SGLT2 inhibitors on various clinical endpoints in heart failure The primary endpoint for this meta-analysis was time from randomisation to the occurrence of the composite of cardiovascular death or hospitalisation for heart failure. We assessed heterogeneity in treatment effects for the primary endpoint across subgroups of interest. This study is registered with PROSPERO, CRD42022327527. Among 12 251 participants from DELIVER and EMPEROR-Preserved, SGLT2 inhibitors reduced composite cardiovascular death or first hospitalisation for heart failure (hazard ratio 0·80 [95% CI 0·73-0·87]) with consistent reductions in both components: cardiovascular death (0·88 [0·77-1·00]) and first hospitalisation for heart failure (0·74 [0·67-0·83]). In the broader context of the five trials of 21 947 participants, SGLT2 inhibitors reduced the risk of composite cardiovascular death or hospitalisation for heart failure (0·77 [0·72-0·82]), cardiovascular death (0·87 [0·79-0·95]), first hospitalisation for heart failure (0·72 [0·67-0·78]), and all-cause mortality (0·92 [0·86-0·99]). These treatment effects for each of the studied endpoints were consistently observed in both the trials of heart failure with mildly reduced or preserved ejection fraction and across all five trials. Treatment effects on the primary endpoint were generally consistent across the 14 subgroups examined, including ejection fraction. SGLT2 inhibitors reduced the risk of cardiovascular death and hospitalisations for heart failure in a broad range of patients with heart failure, supporting their role as a foundational therapy for heart failure, irrespective of ejection fraction or care setting. None.

Early Surgery for Patients With Asymptomatic Severe Aortic Stenosis: A Meta-Analysis of Randomized Controlled Trials.

Guidelines provide class I recommendations for aortic valve intervention for patients with symptomatic severe aortic stenosis (AS) or reduced ejection fraction, but the cornerstone of management for asymptomatic patients has been watchful waiting. This is based on historical nonrandomized data, but randomized controlled trials (RCTs) have now been performed of early surgical aortic valve replacement (SAVR) for asymptomatic severe AS. We performed a meta-analysis of RCTs comparing early SAVR to watchful waiting for asymptomatic severe AS, focusing on individual end points of death and heart failure (HF) hospitalization. We systematically identified all RCTs comparing early SAVR to watchful waiting in patients with asymptomatic severe AS and synthesized the data in a random-effects meta-analysis. The prespecified primary end point was all-cause mortality. Two trials randomizing 302 patients were included. Early SAVR lead to a 55% reduction in all-cause mortality (hazard ratio, 0.45; 95% confidence interval, 0.24-0.85; P = .014). There was no heterogeneity (I2 = 0.0%). Early SAVR also lead to a 79% reduction in HF hospitalization (hazard ratio, 0.21; 95% confidence interval, 0.05-0.96; P = .044). In patients with severe asymptomatic AS and normal ejection fraction, early SAVR reduces death and HF hospitalization compared to initial conservative management. This challenges current treatment standards and has implications for the clinical care of these patients and for guidelines.

Long term risk of heart failure in individuals with childhood-onset type 1 diabetes

BackgroundWe aimed to evaluate the risk of heart failure in young adults with childhood-onset type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. We also examined risk factors and microvascular disease burden associated with the incidence of heart failure. MethodsParticipants in the EDC study without known baseline heart failure (n = 655) were enrolled and then followed for 25 years. “Any” heart failure comprised the underlying cause of death, primary reason for hospitalization, EDC clinic examination findings or self-report of a physician diagnosis. “Hard” heart failure was determined only by the underlying cause of death or primary reason for hospitalization. Incidence rates for heart failure were estimated using Poisson models. Cox models were constructed to examine the associations between risk factors and microvascular disease burden with incident heart failure. ResultsThe mean baseline age and diabetes duration were 27(8) years and 19 (8) years. Incidence for any and hard heart failure were 3.4 and 1.8/1000 person-years. Diabetes duration, ever smoking and triglycerides were significant risk factors of any heart failure; longer diabetes duration, lower estimated glomerular filtration rate and higher white blood cell count significantly predicted hard heart failure. A gradient association was observed between the number of microvascular disease (from 0 to 3) and “hard” heart failure endpoint but not “any” clinically defined heart failure. ConclusionYoung adults with long-duration type 1 diabetes had a high risk of heart failure. As microvascular disease burden increases so does the risk of heart failure independently of diabetes duration, A1c and coronary artery disease.

Atrioventricular Block Necessitating Chronic Ventricular Pacing After Tricuspid Valve Surgery in Patients With a Systemic Right Ventricle: Long-Term Follow-Up.

BackgroundPatients with transposition of the great arteries (TGA) after an atrial switch or congenitally corrected TGA (ccTGA) are prone to systemic right ventricular (sRV) failure. Tricuspid valve (TV) regurgitation aggravates sRV dysfunction. Timely TV surgery stabilizes sRV function, yet the development of atrioventricular (AV)-conduction disturbances in the course of sRV failure can contribute to sRV dysfunction through pacing-induced dyssynchrony. This study aims to explore the incidence, timing, and functional consequences of AV-block requiring ventricular pacing after TV surgery in patients with sRV.MethodsConsecutive adolescent and adult patients with an sRV who underwent TV surgery between 1989 and 2020 and followed-up at our center were included in this observational cohort study.ResultsThe data of 28 patients (53% female, 57% ccTGA, and a mean age at surgery 38 ± 13 years) were analyzed. The mean follow-up was 9.7 ± 6.8 years. Of the remaining 22 patients at the risk of developing high degree AV-block after TV surgery, 9 (41%) developed an indication for chronic ventricular pacing during follow-up, of which 5 (56%) within 24 months postoperatively (3 prior to hospital discharge). The QRS duration, a surrogate marker for dyssynchrony, was significantly higher in patients with chronic left ventricular pacing than in patients with native AV-conduction (217 ± 24 vs. 116 ± 23 ms, p = 0.000), as was the heart failure biomarker NT-pro-BNP [2,746 (1,242–6,879) vs. 495 (355–690) ng/L, p = 0.004] and the percentage of patients with ≥1 echocardiographic class of deterioration of systolic sRV function (27 vs. 83%, p = 0.001). Of the patients receiving chronic subpulmonary ventricular pacing (n = 12), 9 (75%) reached the composite endpoint of progressive heart failure [death, ventricular assist device implantation, or upgrade to cardiac resynchronization therapy (CRT)]. Only 4 (31%) patients with native AV-conduction (n = 13) reached this composite endpoint (p = 0.027).ConclusionPatients with a failing sRV who undergo TV surgery are prone to develop AV-conduction abnormalities, with 41% developing an indication for chronic ventricular pacing during 10 years of follow-up. Patients with chronic subpulmonary ventricular pacing have a significantly longer QRS complex duration, have higher levels of the heart failure biomarker NT-pro-BNP, and are at a higher risk of deterioration of systolic sRV function and progressive heart failure.

Primary Disease, Sex, and Racial Differences in Health-Related Quality of Life in Adolescents and Young Adults with Heart Failure.

Health-related quality of life (HRQOL) is an important clinical and research trial endpoint in adult heart failure and has been shown to predict mortality and hospitalizations in adult heart failure populations. HRQOL has not been adequately studied in the growing pediatric and young adult heart failure population. This study described HRQOL in adolescents and young adults (AYAs) with heart failure and examined primary disease, sex, race, and other correlates of HRQOL in this sample. Participants in this cross-sectional, single-center study included adolescent and young adults with heart failure and a parent/guardian. Patients and their parent/proxies completed the PedsQL, a well-established measure of HRQOL in pediatric chronic illness populations. HRQOL is impaired in AYAs with heart failure resulting from dilated, hypertrophic, or other cardiomyopathy, congenital heart disease, or post-transplant with rejection/complications. Patients identifying as white endorsed poorer total HRQOL than non-white patients (p = 0.002). Subscale analysis revealed significant correlations between female sex (p = 0.01) and white race (p = 0.01) with poorer self-reported physical functioning. Family income was unrelated to HRQOL. Functional status was strongly associated with total (p = 0.0003) and physical HRQOL (p < 0.0001). Sociodemographic and disease-specific risk and resilience factors specific to HRQOL in AYAs with heart failure include primary cardiac disease, race, sex, and functional status. Building upon extensive work in adult heart failure, utilization, and study of HRQOL as a clinical and research trial outcome is necessary in pediatric heart failure. Developing targeted interventions for those at greatest risk of impaired HRQOL is an important next step.

Catheter-Based Cardiopulmonary Nerve Stimulation Impacts Left Ventricular Contractility And Relaxation: First In Human Experience

Introduction There are limited strategies addressing the reversible hypoperfusion and fluid retention observed in acute decompensated heart failure (ADHF). Aberrant autonomic reflex physiology is believed to contribute to clinical decompensation. Our previous work demonstrated catheter-based cardiopulmonary nerve stimulation (CPNS) can increase cardiac contractility. Objective The study objective was to evaluate short-term safety and feasibility of a novel CPNS System. Methods Subjects (n=18) undergoing a catheterization procedure or ICD/CRT implant were studied. After the index procedure, the investigational CPNS neuromodulation catheter was delivered to the right PA. Stimulus sequences were used to evoke cardiac responses. Changes in LV contractility (LV dP/dt max), LV relaxation (LV dP/dt min), arterial blood pressure, and heart rate were measured with and without stimulation over a period of 1-3 hours. Results No adverse events occurred over the course of the study. Fifteen (15) of the eighteen (18) subjects (83%) exhibited increased contractility with CPNS (stimulation time between 60 -120 seconds). The increase in LV contractility was substantial 60% [6, 173%]. LV relaxation 18% [-11, 70%], mean arterial pressure 13% [-1, 60%], arterial pulse pressure 26% [-3, 80%], and estimated stroke volume calculated from pulse pressure +13% [-12,70] also increased while HR was relatively unchanged 1% [-20, +13%]. Conclusions CPNS to increase cardiac contractility is feasible and likely safe. Heart rate neutral changes in LV contractility, relaxation, and arterial blood pressure were reproducible over the short period of testing. Additional and longer-term studies are required to assess the impacts on clinical heart failure endpoints. There are limited strategies addressing the reversible hypoperfusion and fluid retention observed in acute decompensated heart failure (ADHF). Aberrant autonomic reflex physiology is believed to contribute to clinical decompensation. Our previous work demonstrated catheter-based cardiopulmonary nerve stimulation (CPNS) can increase cardiac contractility. The study objective was to evaluate short-term safety and feasibility of a novel CPNS System. Subjects (n=18) undergoing a catheterization procedure or ICD/CRT implant were studied. After the index procedure, the investigational CPNS neuromodulation catheter was delivered to the right PA. Stimulus sequences were used to evoke cardiac responses. Changes in LV contractility (LV dP/dt max), LV relaxation (LV dP/dt min), arterial blood pressure, and heart rate were measured with and without stimulation over a period of 1-3 hours. No adverse events occurred over the course of the study. Fifteen (15) of the eighteen (18) subjects (83%) exhibited increased contractility with CPNS (stimulation time between 60 -120 seconds). The increase in LV contractility was substantial 60% [6, 173%]. LV relaxation 18% [-11, 70%], mean arterial pressure 13% [-1, 60%], arterial pulse pressure 26% [-3, 80%], and estimated stroke volume calculated from pulse pressure +13% [-12,70] also increased while HR was relatively unchanged 1% [-20, +13%]. CPNS to increase cardiac contractility is feasible and likely safe. Heart rate neutral changes in LV contractility, relaxation, and arterial blood pressure were reproducible over the short period of testing. Additional and longer-term studies are required to assess the impacts on clinical heart failure endpoints.

Hemodynamic and Clinical Determinants of Left Atrial Enlargement in Liver Transplant Candidates

New-onset heart failure is a frequent complication after orthotopic liver transplantation (OLT). Left atrial enlargement (LAE) may be a sign of occult left heart disease. Our primary objective was to determine invasive hemodynamic and clinical predictors of LAE and then investigate its effect on post-transplant outcomes. Of 609 subjects who received OLT between January 1, 2010, and October 1, 2018, 145 who underwent preoperative right-sided cardiac catheterization and transthoracic echocardiography were included. Seventy-eight subjects (54%) had pretransplant LAE. Those with LAE had significantly lower systemic vascular resistance with higher cardiac and stroke volume index (61.0 vs 51.7 ml/m2; p <0.001), but there was no difference in pulmonary artery wedge pressure. There was a linear relation between left atrial volume index and stroke volume index (R2=0.490, p<0.001), but not pulmonary artery wedge pressure. The presence of severe LAE was associated with a reduced likelihood (hazard ratio=0.26, p=0.033) of reaching the composite end point of new-onset systolic heart failure, heart failure hospitalization, or heart failure death within 12 months post-transplant. There was also a significant reduction in LAE after transplantation (p=0.013). In conclusion, LAE was common in OLT recipients and was more closely associated with stroke volume than left heart filling pressures. The presence of LAE was associated with a reduced likelihood of reaching composite outcomes and tended to regress after transplant.

Fine Fibrillatory Wave as a Risk Factor for Heart Failure Events in Patients With Atrial Fibrillation: The Fushimi Atrial Fibrillation (AF) Registry.

BackgroundThe clinical significance of fibrillatory wave on electrocardiography during atrial fibrillation (AF) is poorly understood. The aim of the current study was to explore the association of fine fibrillatory wave with heart failure (HF) in AF.Methods and ResultsThe current study enrolled 2442 patients with AF whose baseline ECG during AF rhythm was available from a community‐based prospective survey, the Fushimi AF Registry. The impact of fine fibrillatory wave, defined as the amplitude of fibrillatory waves <0.1 mV, on the primary composite HF end point (a composite of hospitalization attributable to HF or cardiac death) was examined. Fine fibrillatory wave was observed in 589 patients (24.1%). Patients with fine fibrillatory wave were older, and had a higher prevalence of sustained AF, preexisting HF, and larger left atrial diameter than those with coarse fibrillatory wave. During the median follow‐up duration of 5.9 years, the cumulative incidence of the primary composite HF end point was significantly higher in patients with fine fibrillatory wave than in those with coarse fibrillatory wave (5.3% versus 3.6% per patient‐year, log‐rank P<0.001). The higher risk associated with fine fibrillatory wave was consistent even for individual components of the primary composite HF end point. On multivariable analysis, fine fibrillatory wave became an independent predictor for the primary composite HF end point (hazard ratio, 1.31; 95% CI, 1.07–1.61; P=0.01).ConclusionsCompared with coarse fibrillatory wave, fine fibrillatory wave was more prevalent in patients with a larger left atrial diameter or those with sustained AF and was independently associated with a higher risk of HF events.RegistrationURL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000005834.

Phenotypic Presentations of Heart Failure Among Patients With Chronic Inflammatory Diseases.

ObjectiveCharacterize incident heart failure (HF) phenotypes among patients with various chronic inflammatory diseases (CIDs).BackgroundSeveral CIDs are associated with increased HF risk, but differences in HF phenotypes across CIDs are incompletely understood. No prior studies to our knowledge have manually adjudicated HF phenotypes across a CID spectrum.MethodsWe screened for patients with—and controls without—CIDs who had possible HF, then hand-adjudicated HF endpoints. Possible HF resulted from a single HF administrative code; HF was deemed definite/probable vs. absent using standardized, validated criteria. We queried adjudicated HF patients' charts to define specific HF phenotypes, then compared clinical, demographic, and HF phenotypic characteristics for HF patients with specific CIDs vs. non-CID controls using Fisher's exact test.ResultsOut of 415 possible HF patients, 192 had definite/probable HF. Significant differences in HF phenotypes existed across CIDs. Isolated right-sided HF was present in 27.8% of patients with SSc and adjudicated HF, which is more than twice as common as it was in any other CID. Left ventricular systolic dysfunction was most common in patients with HIV and lupus (SLE); mean LVEF was 45.0% ± 18.6% for HIV and 41.3% ± 17.1% for SLE, but was 57.7% ± 10.7% for SSc. Those with HIV and multiple CIDs were most likely to have coronary artery disease.ConclusionsDifferent CIDs present with different phenotypes of physician-adjudicated HF, potentially reflecting different underlying inflammatory pathophysiologies. Larger studies are needed to confirm these findings, as are mechanistic studies focused on understanding specific immunoregulatory contributors to HF.

Relation of left atrial overload indices with prognostic endpoints in heart failure and preserved ejection fraction

AimsConsiderable variation in the relationships between the indices of left atrial (LA) volume and pressure could possibly affect the selection of medications or efforts to improve the prognoses of patients with heart failure and preserved ejection fraction (HFpEF). We aimed to clarify the association between the prognostic endpoint and LA overload indices in elderly patients with HFpEF.Methods and resultsWe analysed 898 patients with HFpEF hospitalized for acute decompensated heart failure (men/women: 406/492). Blood tests and transthoracic echocardiography were performed before discharge. The primary endpoint was re‐admission for heart failure or all‐cause mortality. Stroke volume (SV)/left atrial volume (LAV), an index for LA volume overload, was a significant prognostic factor of re‐admission for heart failure in the multivariable Cox hazard analysis adjusted for comorbidities [hazard ratio (HR) 0.616, 95% confidence interval (CI) 0.430–0.882, P = 0.008]. Additionally, the ratio of diastolic elastance (Ed) to arterial elastance (Ea), an index for LA pressure overload, was also significant (HR 1.444, 95% CI 1.014–2.058, P = 0.041). Furthermore, Ed/Ea, but not SV/LAV, was a significant prognostic factor of all‐cause mortality (HR 1.594, 95% CI 1.102–2.306, P = 0.013).ConclusionsThe index of LA overload for prognosis may differ according to the different endpoints in elderly patients with HFpEF.

Non-invasive right ventriculo-arterial coupling as a rehospitalization predictor in dilated cardiomyopathy: A comparison of five different methods

Right ventricular (RV) pulmonary artery coupling (RVPAC) is a predictor of outcome in left-sided heart failure (HF). Several echocardiographic estimates for RVPAC have been proposed. This study aimed to compare multiple non-invasive methods to calculate RVPAC and to assess its prognostic role in patients with dilated cardiomyopathy (DCM). We prospectively enrolled 60 stable patients with DCM. RVPAC was estimated using five methods: as the tricuspid annular plane excursion/pulmonary artery systolic pressure (PASP) ratio; as the RV global longitudinal strain/PASP ratio; as the RV free wall strain (RVFW-LS)/PASP ratio; as the three-dimensional (3D) RV ejection fraction (RVEF)/PASP ratio; and as the 3D RV stroke volume (SV)/end-systolic volume (ESV) ratio. Patients were followed for a mean period of 18 (9) months for the endpoint of HF rehospitalizations. Twenty-nine patients (48%) reached the endpoint. All RVPAC estimates were more impaired in those patients reaching the endpoint (P <0.001 for all) and all predicted rehospitalizations in un-adjusted analysis. RVFW-LS/PASP and RVEF/PASP remained independent predictors of events, after adjustment for clinical and echocardiographic confounders. Using cut-offs obtained from receiver operating characteristic (ROC) analysis, we found that patients with RVFW-LS/PASP >-0.40 and patients with RVEF/PASP <1.30 had a higher risk of HF rehospitalization (log-rank P = 0.001 and P = 0.002, respectively). RVFW-LS/PASP and RVEF/PASP as non-invasive estimates of RVPAC are independent predictors of HF rehospitalization in patients with DCM.

Clinical, echocardiographic and prognostic outcomes of patients with concordant and discordant high-gradient aortic stenosis in an Asian cohort.

Literature of patients with severe high-gradient aortic stenosis (HG AS) (mean pressure gradient [MPG] ≥ 40mmHg and aortic valve area [AVA] ≥ 1.0cm2) remains limited. This study seeks to compare the prognostic outcomes of patients with high-gradient concordant (HGCON-AS) and discordant AS (HGDIS-AS) in an Asian cohort. From 2010 to 2015, patients with moderate-to-severe AS with preserved left ventricular ejection fraction (LVEF ≥ 50%) were recruited and stratified into 3 groups based on index echocardiogram-(1) HGDIS-AS, (2) HGCON-AS and (3) moderate AS (MOD-AS). The primary study endpoints was all-cause mortality, with secondary endpoints of congestive heart failure (CHF) admissions and aortic valve replacement (AVR). Multivariable Cox regression was used and Kaplan-Meier curves were constructed to evaluate associations between HGDIS-AS, HGCON-AS and MOD-AS, and the study outcomes. A total of 467 patients were studied, comprising of 6.2% HGDIS-AS, 13.9% HGCON-AS and 79.9% MOD-AS patients. There was significantly higher AVR rates in the HGCON-AS group (58.5%), followed by HGDIS-AS (31.0%) and MOD-AS (4.6%), p < 0.001) groups. After adjusting for confounders, HGCON-AS was significantly associated with all-cause mortality (HR 3.082, 95% CI 1.479-6.420, p = 0.003) and CHF admissions (HR 12.728, 95% CI 2.922-55.440 p = 0.001) but not HGDIS-AS, with MOD-AS as the reference group. Both HGDIS-AS (HR 7.715, 95% CI 2.927-20.338; p < 0.001) and HGCON-AS (HR 21.960, 95% CI 10.833-44.515, p < 0.001) were independent predictors of AVR. After exclusion of reversible high-flow states, HGDIS-AS patients appear to have a more favourable prognostic profile compared to HGCON-AS patients. Large prospective interventional studies examining the prognostic differences between the two groups will be the next important step.

Effect of IL-1 Blockade With Anakinra on Heart Failure Outcomes in Patients With Anterior Versus Nonanterior ST Elevation Myocardial Infarction.

Patients with ST elevation myocardial infarction (STEMI) are at risk of future heart failure (HF), particularly those with anterior STEMI. Interleukin-1 (IL-1) is a key mediator of the inflammatory response, and its blockade has emerged as a potential therapeutic strategy to prevent HF events. The aim of this analysis was to explore the effects of anakinra, an IL-1 receptor antagonist, on HF outcomes based on anterior versus nonanterior location STEMI and to explore whether this effect is mediated through the amelioration of left ventricular systolic function and cardiac remodeling. We pooled data from 3 early phase randomized clinical trials. The primary end point was a composite of all-cause death and new-onset HF at 1-year follow-up. The left anterior descending coronary artery as culprit vessel was used to identify anterior STEMI. We included 139 patients, 47 (34%) with anterior STEMI and 92 (66%) with nonanterior STEMI. Anakinra significantly reduced the combined end point of death or new-onset HF in patients with anterior STEMI [4 (13%) vs. 7 (42%), log-rank P value = 0.049] and in patients with nonanterior STEMI [3 (6%) vs. 9 (24%), log-rank P value = 0.014]. We found no significant differences comparing anakinra versus placebo in interval changes in left ventricular ejection fraction and volumes in anterior and nonanterior STEMI. In conclusion, anakinra is associated with a reduction of HF events in patients with STEMI, irrespective of anterior or nonanterior location, or of changes in left ventricular ejection fraction or cardiac remodeling.

Prognostic value of pre-operative left atrial strain on composite endpoint in patients received aortic valve replacement for severe aortic stenosis: a retrospective cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Objective Severe aortic stenosis (AS) is the most common primary valvular heart disease, treatable only by aortic valve replacement (AVR). Current literatures have shown that severe AS may precede atrial dysfunction which predicts adverse outcomes. However, predictive value of pre-operative left atrial (LA) function on post-AVR clinical outcomes is uncertain. The study aims to evaluate the prognostic value of pre-operative LA strain on post AVR all-cause mortality and heart failure. Methods Patients aged 18 years old or above with severe AS were recruited and assessed using speckle-tracking echocardiography pre-operatively. Severe AS was defined according to 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease. Peak Atrial Longitudinal Strain (PALS) was measured as a surrogate of LA function. Patients with underlying pre-operative atrial fibrillation and other severe valvular heart diseases were excluded. High PALS was defined as PALS higher than 15.94%. Patients were followed up until death or end of the study. The primary endpoint is a composite endpoint of all-cause mortality and heart failure during hospitalisation. The association of LA function with composite endpoint of all-cause mortality and heart failure was evaluated by Cox Proportional Hazards analysis. Results A total of 128 patients (mean age 65.3.9 ± 9.4 years, 56.3% male) were analysed. Patients were followed up for a mean period of 3.9 ± 2.4years. A total of 65 of 128 patients (50.8%) belonged to low PALS group. During the study period, 23 patients developed events on the composite endpoint. Among those with composite endpoint, low PALS group accounted for 18 (78.3%) patients and high PALS group accounted for 5 (21.7%) patients. Higher PALS was independently associated with lower risk of composite endpoint of all-cause mortality and heart failure (HR, 0.33; 95% CI 0.117-0.916, p = 0.03) after adjustment for EuroSCORE II. Conclusion Higher PALS, a surrogate of LA function, is associated with a lower risk of composite endpoints of mortality and heart failure in patients with severe AS undergoing AVR, independent of EuroSCORE II. Evaluation of LA function by assessing speckle tracking derived PALS may aid in prognostication for patients undergoing AVR.

Mid-wall striae fibrosis predicts heart failure admission, composite heart failure events, and life-threatening arrhythmias in dilated cardiomyopathy

Heart failure (HF) admission is a dominant contributor to morbidity and healthcare costs in dilated cardiomyopathy (DCM). Mid-wall striae (MWS) fibrosis by late gadolinium enhancement (LGE) imaging has been associated with elevated arrhythmia risk. However, its capacity to predict HF-specific outcomes is poorly defined. We investigated its role to predict HF admission and relevant secondary outcomes in a large cohort of DCM patients. 719 patients referred for LGE MRI assessment of DCM were enrolled and followed for clinical events. Standardized image analyses and interpretations were conducted inclusive of coding the presence and patterns of fibrosis observed by LGE imaging. The primary clinical outcome was hospital admission for decompensated HF. Secondary heart failure and arrhythmic composite endpoints were also studied. Median age was 57 (IQR 47–65) years and median LVEF 40% (IQR 29–47%). Any fibrosis was observed in 228 patients (32%) with MWS fibrosis pattern present in 178 (25%). At a median follow up of 1044 days, 104 (15%) patients experienced the primary outcome, and 127 (18%) the secondary outcome. MWS was associated with a 2.14-fold risk of the primary outcome, 2.15-fold risk of the secondary HF outcome, and 2.23-fold risk of the secondary arrhythmic outcome. Multivariable analysis adjusting for all relevant covariates, inclusive of LVEF, showed patients with MWS fibrosis to experience a 1.65-fold increased risk (95% CI 1.11–2.47) of HF admission and 1-year event rate of 12% versus 7% without this phenotypic marker. Similar findings were observed for the secondary outcomes. Patients with LVEF > 35% plus MWS fibrosis experienced similar event rates to those with LVEF ≤ 35%. MWS fibrosis is a powerful and independent predictor of clinical outcomes in patients with DCM, identifying patients with LVEF > 35% who experience similar event rates to those with LVEF below this conventionally employed high-risk phenotype threshold.

Long-term outcomes in a randomized controlled trial of multimodality imaging-guided left ventricular lead placement in cardiac resynchronization therapy.

This study aims to investigate the long-term occurrence of the composite endpoint of heart failure (HF) hospitalization or all-cause death (primary endpoint) in patients randomized to cardiac resynchronization therapy (CRT) using individualized multimodality imaging-guided left ventricular (LV) lead placement compared with a routine fluoroscopic approach. Furthermore, this study aims to evaluate whether inter-lead electrical delay (IED) is associated with improved response rate of this endpoint. We reviewed follow-up data until November 2020 for all 182 patients included in the ImagingCRT trial for the occurrence of HF hospitalization and all-cause death. During median (inter-quartile range) time to primary endpoint/censuring of 6.7 (3.3-7.9) years, the rate of the primary endpoint was 60% (n = 53) in the imaging group compared with 52% (n = 48) in the control group [hazard ratio (HR) 1.22, 95% confidence interval (CI) 0.83-1.81, P = 0.31]. Neither the risk of HF hospitalization (HR 1.11, 95% CI 0.62-1.99, P = 0.72) nor of all-cause death differed between treatment groups (HR 1.23, 95% CI 0.82-1.85, P = 0.32). The risk of the primary endpoint was significantly reduced among those with IED ≥100 ms when compared with those with IED <100 ms (HR 0.62, 95% CI 0.39-0.98, P = 0.04). In this study, an individualized multimodality imaging-guided strategy targeting LV lead placement towards the latest mechanically activated non-scarred myocardial segment during CRT implantation did not reduce HF hospitalization or all-cause death when compared with routine LV lead placement during long-term follow-up. Targeting the latest electrical activation should be studied as an alternative individualized strategy for optimizing LV lead placement in CRT recipients.

Prognostic value of right atrial strain derived from cardiovascular magnetic resonance in non-ischemic dilated cardiomyopathy

BackgroundThe value of right atrial (RA) function in cardiovascular diseases is currently limited. This study was to explore the prognostic value of RA strain derived from fast long axis method by cardiovascular magnetic resonance (CMR) in patients with non-ischemic dilated cardiomyopathy (DCM).MethodsWe prospectively enrolled patients with DCM who underwent CMR from June 2012 to March 2019 and 120 age- and sex-matched healthy subjects. Fast long-axis strain method was performed to assess the RA phasic function including RA reservoir strain, conduit strain, and booster strain. The predefined primary endpoint was all-cause mortality. The composite heart failure (HF) endpoint included HF death, HF readmission, and heart transplantation. Cox regression analysis and Kaplan–Meier survival curve were performed to describe the association between RA strain and outcomes.ResultsA total of 624 patients (444 men, mean 48 years) were studied. After a median follow-up of 32.5 months, 116 patients (18.6%) experienced all-cause mortality and 205 patients (32.9%) reached composite HF endpoint. RA function was impaired in DCM patients compared with healthy subjects (all P < 0.001). After adjustment for covariates, RA reservoir strain [hazard ratio (HR) (per 5% decrease) 1.19, 95% confidence interval (CI) 1.03–1.37, P = 0.022] and conduit strain [HR (per 5% decrease) 1.37, 95% CI 1.03–1.84, P = 0.033] were independent predictors of all-cause mortality. Moreover, RA strain added incremental prognostic value for the prediction of adverse cardiac events over baseline clinical and CMR predictors (all P < 0.05).ConclusionRA strain by fast long-axis analysis is independently associated with adverse clinical outcomes in patients with DCM.Trial registration: Trial registration number: ChiCTR1800017058; Date of registration: 2018-07-10 (Retrospective registration); URL: https://www.clinicaltrials.gov

Sex differences in treatment strategy for coronary artery aneurysms: Insights from the international Coronary Artery Aneurysm Registry.

IntroductionSex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD.MethodsPatients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding.ResultsFemale patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015).ConclusionsThese CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up.

Sacubitril/valsartan versus angiotensin inhibitors and arrhythmia endpoints in heart failure with reduced ejection fraction.

BackgroundAngiotensin receptor–neprilysin inhibitor (ARNI) therapy has been associated with improved survival for patients with symptomatic heart failure and reduced ejection fraction (HFrEF).ObjectivesWe performed a meta-analysis of arrhythmia endpoints from studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with HFrEF to assess for incremental benefit.MethodsWe searched PubMed, Embase, and ClinicalTrials.gov. Baseline study characteristics were collected and outcomes were sustained ventricular arrhythmias, atrial arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, sudden cardiac death (SCD), and biventricular (BiV) pacing rate.ResultsWe included 9 studies, 4 randomized trials, and 5 observational studies (5589 patients on ARNI vs 5615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 ± 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% ± 7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63–0.96; P = .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25–0.79; P = .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21–0.74; P = .004). Higher rates of BiV pacing were seen (mean difference 3.13, 95% CI 2.58–3.68; P < .00001) when compared with ACEIs/ARBs. No difference in atrial arrhythmias was seen.ConclusionARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.

Outpatient diuretic intensification as endpoint in heart failure with preserved ejection fraction trials: an analysis from TOPCAT.

Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a preserved ejection fraction (HFpEF) may experience frequent episodes of outpatient worsening HF. The aim of this study was to evaluate the frequency, prognostic impact, and the effect of spironolactone on outpatient diuretic intensification (ODI), among 1767 patients enrolled in TOPCAT-Americas. Time-updated Cox models and win ratio analysis. ODI was defined by a post-randomization loop diuretic dose increase or new initiation. The median follow-up was 2.9 years. At baseline, 1362 (77%) patients were taking loop diuretics. During the follow-up, 685 (38.8%) patients experienced ODI, which was associated with a higher risk of subsequent cardiovascular events and death [adjusted hazard ratio (HR) for HF hospitalization or cardiovascular death 1.67, 95% confidence interval (CI) 1.36-2.04; HR for cardiovascular death 2.17, 95% CI 1.64-2.87); and HR for all-cause mortality 1.75, 95% CI 1.41-2.16] (p< 0.001 for all outcomes). Adding ODI to the composite of HF hospitalization or cardiovascular death increased the event rate by three-fold in the placebo group (from 10.4 to 29.9 events per 100 person-years). Spironolactone treatment led to a 26% relative reduction of the extended composite of ODI or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65-0.85; p< 0.001) compared with a 16% relative reduction of HF hospitalization or cardiovascular death (HR 0.84, 95% CI 0.70-0.99; p= 0.044). Using win ratio provided similar estimates. In HFpEF, ODI was frequent and independently associated with subsequent cardiovascular events. Spironolactone significantly reduced an extended composite outcome incorporating ODI.