HF-related Death Research Articles

Heart failure after left atrial appendage occlusion: Insights from the LAAOS III randomized trial.

The left atrial appendage (LAA) produces natriuretic peptides and its removal or occlusion might increase the risk of heart failure (HF). We aimed to investigate the incidence of HF after LAA occlusion or removal (LAAO) in the Left Atrial Appendage Occlusion Study (LAAOS III). Patients (n = 4811) with atrial fibrillation (AF) and a CHA2DS2-VASc score ≥2, who were having cardiac surgery for another indication, were randomized to undergo surgical LAAO or not. We compared the composite outcome of HF-related hospitalizations and HF death between the two groups. HF assessment required clinical and radiographic evidence of HF. Analyses included a landmark analysis before and after 30 days and subgroups. Mean age was 71.2 years, 67.5% were male and 57.0% had prior HF. Over a mean follow-up of 3.8 years, 396 (8.3%) patients met the composite HF outcome: 209 (8.8%) with LAAO (n = 2379) and 187 (7.8%) without LAAO (n = 2391) (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.92-1.37, p = 0.25). There was no difference between the two groups in the first 30 days (1.6% vs. 1.1%; p = 0.12) and thereafter (7.6% vs. 7.1%; p = 0.57). Subgroups based on age, sex, body mass index, AF type, prior HF, cardiac rhythm or left ventricular ejection fraction showed consistent results. There was no difference in HF outcomes with LAAO between the cut-and-sew (HR 0.93, 95% CI 0.70-1.23, p = 0.62) versus other closure methods (HR 1.05, 95% CI 0.77-1.41, p = 0.77). Left atrial appendage occlusion or removal at the time of cardiac surgery does not appear to alter the risk of HF-related hospitalization or death. ClinicalTrials.gov NCT01561651.

Abstract 4122048: Disparities in Heart Failure-Related Mortality Among Reproductive-Aged Women in the United States from 1999 to 2019

Introduction: Heart failure (HF) majorly affects the elderly, but can also affect the younger population. This study aims to examine the trends of HF-related deaths among reproductive-aged women in the United States (US). Method: We conducted a retrospective analysis using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, extracting data through ICD-10 codes I11, I13.0, I13.2, and I50 to find HF-related deaths among women aged 15-44 from 1999 to 2019. We examined demographic disparities in HF mortality rates over time, considering age, ethnicity, and geographic areas. Results were reported as age-adjusted mortality rate (AAMR) and 95% confidence interval (CI). Joinpoint regression assessed trend changes and annual percentage change (APC). Results: Between 1999 and 2019, a total of 43,683 women aged 15-44 died from HF in the US, with an AAMR of 3.5 per 100,000 (95% CI: 3.5-3.5). The AAMR increased from 2.6 in 1999 to 4.8 in 2019. Non-Hispanic Black women had the highest AAMR at 10.2, while Hispanics had the lowest at 1.8. Geographically, the South was the most affected region with an AAMR of 4.6, contributing to nearly half (48.9%) of all deaths. States including Massachusetts, Oregon, New Hampshire, and Minnesota had the lowest AAMRs. Rural areas showed a higher AAMR compared to urban areas (4.4 Vs. 3.3). The age group (35-44) accounted for the majority of deaths (73.7%). Conclusion: HF-related mortality among reproductive-aged women increased from 1999 to 2019, with the highest burden among non-Hispanic Black women and those in the Southern region. Enhancing access to care, particularly in rural areas, and implementing targeted prevention programs are vital to reducing mortality rates.

Abstract 4122035: The Distinct Natural History, Phenotype Spectrum, Familial Penetrance and Clinical Outcomes in Desmin ( DES )-Associated Cardiomyopathy

Background: Pathogenic/likely pathogenic variants (P/LP) in the desmin ( DES ) gene cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes. Research Questions: Limited data suggest that patients with P/LP DES variants have a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease requiring pacemaker implantation (CCD-PM), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, heart transplant, HF-related death). However, small cohort sizes have limited full clinical characterization. Aims: We aimed to describe the natural history, phenotype spectrum, familial penetrance and MACE in patients with P/LP DES variants identified via clinical genetic testing. Methods: We conducted a systematic review and individual patient data meta-analysis of cardiac and skeletal myopathy phenotypes and MACE (CCD-PM, VA and HF events) in patients with P/LP DES variants by retrieving publications from Medline (PubMed) and Embase. Diagnosis of cardiomyopathy or MACE were both considered evidence of cardiac involvement. Results: Out of 4,212 screened records, 72 met inclusion criteria. In total, 230 patients were included (52.6% male, 52.2% probands, median age: 31 years at first evaluation [22.0; 42.8]). Eighty-five (37.0%) patients showed isolated cardiac involvement, 89 (38.7%) cardiac and skeletal muscle involvement, 39 (17.0%) only skeletal muscle involvement, and 17 (7.4%) had neither phenotype. Overall, 130 (56.5%) patients were diagnosed with a cardiomyopathy and 134 (57.4%) patients developed MACE (96 [41.7%] had CCD-PM, 36 [15.7%] sustained VA, and 43 [18.7%] HF events). Familial cardiac disease penetrance was 69.1% (76/110) in relatives with P/LP DES variants. Out of 40 patients who presented with isolated CCD-PM phenotype, 18 (45.0%) were diagnosed with a cardiomyopathy after 6 [2.0; 16.0] years of follow-up. In multivariable analysis, male sex and non-missense variants were associated with higher risk of sustained VA (HR 2.71, p=0.008, and HR 4.62, p<0.001, respectively) and HF events (HR 2.63, p=0.005, and HR 2.79, p=0.015). Conclusions: DES cardiomyopathy demonstrates a distinct natural history, characterized by high familial penetrance and a high MACE burden. Male patients and those carrying non-missense variants are at higher risk for sustained VA events and may benefit from primary preventive ICD implantation even in the absence of severe LV systolic dysfunction.

Abstract 4131228: Where Adults with Advanced Heart Failure Die: Insights from the CDC-WONDER Database

Background: Adults with heart failure (HF) are becoming more and more prevalent. The location of death and related disparities in these patients are poorly understood. Aim: The purpose of the study was to look at the locations of adult deaths from HF and identify any age, race, or ethnicity-related variations over a 25-year period. Methods: The Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Database provided death certificate data and the National Center for Health Statistics provided individual-level mortality data for the trend-level analysis of adults aged (20-64 and 65+ years) conducted from 1999-2023. Hospital, home, hospice and nursing home/long-term care were the categories for the places of death. Results: Between 1999 and 2023, a total of 7,644,759 adult deaths from HF were recorded (87.9% White, 53.4% female). HF-related deaths decreased from 1999 (3.60% and 143.6 AAMR) to 2010 (3.47% and 123.1 AAMR). From 2010 onwards, a gradual rise is seen, with the rate of HF deaths reaching 5.18% and 168.1 AAMR in 2023. Notably, deaths at home increased from 18.41% (50,648 of 275,132) in 1999 to 33.47% (132,470 of 395,826) in 2023 and deaths in hospice/nursing homes increased from 30.95% (85,144 of 275,132) in 1999 to 34.71% (116,634 of 336,014) in 2017 and then sudden fall was observed until 2023 to 29.54% (116,931 of 395,826). Older adults (65+) were more likely to die in inpatient facilities. Gender, ethnicity, and urbanization influenced the place of death, with males, whites, and those residing in large metropolitan areas more likely to die in medical facilities. Conclusion: Prioritize end-of-life planning for HF patients with poor prognosis, regardless of age, to improve quality of life and death.

Paracetamol and adverse cardiovascular outcomes in patients with heart failure

Abstract Background Paracetamol is the most widely used pain killer worldwide, yet its potential influence on cardiovascular events among patients with heart failure (HF) remains unclear. Thus, this study aims to investigate both the short-term and long-term effects of paracetamol use on all-cause mortality and cardiovascular events in HF patients. Methods Using the previously validated territory-wide clinical information registry, paracetamol use was identified among all eligible patients with HF (N = 211,409) from 2000 to 2020. A case-crossover design was used to investigate the associations between short-term use of paracetamols and all-cause mortality and cardiovascular outcomes. Defined daily dose (DDD) was used to evaluate the dose-response relationship. Additionally, the marginal structural design was applied to model paracetamol use as a time-varying exposure and evaluate its long-term effects during the follow-up period. Results Of all eligible subjects, the mean age was 73.2±12.3 years, and 43.6% was male. Over a median follow-up of 10.5 years (interquartile range: 5.7-15.8), 113,258 (53.6%) patients were re-hospitalised for HF, HF-related death occurred in 11,892 (5.6%) patients, incident myocardial infarction (MI) in 28223 (13.3%) patients, incident stroke in 26458 (12.5%) patients, cardiovascular death (CVD) in 72,175 (34.1%) patients and all-cause death in 123,505 (58.4%) patients. Associating HF rehospitalisation to previous paracetamol exposure using the case-crossover design displayed an elevated risk (OR 3.62, 95% CI 3.53-3.71). Associations were similar for MI (OR 5.77, 95% CI 5.50-6.05), stroke (OR 2.37, 95% CI 2.25-2.49), HF-related death (OR 1.86, 95% CI 1.75-1.98), CVD (OR 3.64, 95% CI 3.55-3.73), and all-cause mortality (OR 3.32, 95% CI 3.26-3.39). Moreover, compared with paracetamol users taking the reference dose, users of low, medium and high doses of paracetamol had 16%, 17% and 52% higher risk of HF rehospitalisation. During the long-term follow-up, the average weighted hazard ratio (HR) for HF rehospitalisation in paracetamol users was 2.48 (95% CI 2.46–2.50) as compared with paracetamol non-users after accounting for all-cause mortality as a competing risk. Similarly, the average weighted HR for incident MI or stroke was 2.71 (2.62-2.81) and 3.45 (3.34-3.57), respectively. However, neutral results were shown for HF-related death, CVD and all-cause mortality. Conclusion The use of paracetamol among patients with HF is common. Paracetamol was associated with adverse cardiovascular outcomes both in short-term and long-term follow-up with a dose-response relationship, while its impact on long-term mortality remained neutral. Future randomized controlled trials or experimental studies are warranted to gain a comprehensive understanding of the underlying mechanisms driving such associations between paracetamol and adverse cardiovascular outcomes.

The prognostic and incremental value of T1 mapping for predicting adverse events in hypertrophic cardiomyopathy

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), the prognostic value of native T1 and extracellular volume fraction (ECV) for adverse cardiovascular events has not been well defined. Methods Consecutive 663 participants with HCM who underwent cardiovascular magnetic resonance (CMR) were recruited. The follow-up endpoints included heart failure (HF)-related death and sudden cardiac death (SCD) or aborted SCD. Results During the median follow-up time of 44 months (interquartile range [IQR]: 23 to 66.0 months), 56 (8.4%) participants reached composite endpoints including 38 (5.7%) with SCD or aborted SCD, 16 (2.4%) with HF-related death and 2 (0.3%) with heart transplantation. On multivariable Cox proportional hazards regression analyses, native T1 including late gadolinium enhancement (LGE) from three short axes were significantly associated with cardiac death (basal native T1: hazard ratio [HR], 1.06 per 10 ms increase; 95% confidence interval [CI], 1.02 to 1.09; middle native T1: HR, 1.05 per 10 ms increase; 95% CI, 1.01 to 1.09; apical native T1: HR, 1.04 per 10 ms increase; 95% CI, 1.02 to 1.07; all P < 0.05) after adjustment for non-sustained ventricular tachycardia, history of syncope, the extent of LGE, left atrial size, and NYHA class. Conversely, only basal ECV was associated with cardiac death (basal ECV including LGE area: HR, 1.08 per 1% increase, 95%CI, 1.03 to 1.13, P = 0.001; basal ECV excluding LGE: HR, 1.1 per 1% increase; 95%CI, 1.04 to 1.16; P < 0.001) In addition, participants with increased mean native T1 (≥1349.4 ms) or basal ECV(≥ 29.4%) were more likely to suffer from cardiac death in the entire study cohort or the subgroup with low LGE extent (<15%) or low ESC risk score (<6%) (all P < 0.05). Furthermore, the addition of mean LV native T1 (≥1349.4 ms) or basal ECV (≥ 29.4%) to current risk factors in the guidelines could further improve prediction for the composite endpoint (C-index increased to 0.719 from 0.521 for the AHA/ACC risk model, P < 0.001; C index increased to 0.709 from 0.514 for the ESC risk model; P < 0.001). Conclusions In this study of patients with HCM, mean native T1 of three short axes and basal ECV were independently associated with cardiac death and added incremental value to conventional clinical predictors for patients with HCM.Figure 1.Demonstrative images.Figure 2 Incremental Value of T1 mapping

Time taken for cardiology care and one-year results for primary care physicians' referrals for cardiology consultation in heart failure patients: clinical implications for heart failure management

Abstract Background and Purpose The clinical trajectory of patients with heart failure (HF) is characterised by frequent episodes of decompensation requiring urgent medical assistance, hospitalisations, and an increased risk of mortality. HF clinical guidelines recommend early visits by health professionals after hospital discharge, yet little evidence exists regarding the associations between delayed medical attention and outcomes in HF patients. To assess the clinical impact of the time taken to receive cardiology care for referrals from primary care physicians (PCPs) to a cardiology department in HF patients, we selected 6,859 HF patients who visited the cardiology service at least once between 2010 and 2021. Methods Using an interrupted time series regression model, we analysed the impact of integrating e-consultations into the healthcare model (implemented in 2013) and evaluated the time taken to receive cardiology care, as well as all-cause, cardiovascular (CV), and HF-related hospital admissions and mortality. The primary objective of this analysis was to examine the associations between delays in cardiology care following a PCP referral and 1-year outcomes (HF-related, cardiovascular, and total hospitalisations; and HF-related, cardiovascular, and total mortality). Results Almost 50% were women, and the mean age was 77.8 years. Arterial hypertension (79.6%), diabetes (34%), atrial fibrillation (51.4%), ischemic heart disease (20.4%), and cerebrovascular disease were the most prevalent comorbidities. The mean time from PCP referral to cardiology consultation in the overall population was 22.3 days: <8 days in 53.9%, 8-14 days in 17.1%, 15-30 days in 15.9%, and >30 days in 13.0% of patients, respectively. One year after cardiology consultation, 68.6% of patients required assistance in an Emergency Department; 22.5% were hospitalised for any cause, 14.9% for cardiovascular reasons, and 9.2% for HF-related issues. Moreover, total mortality at 1-year was 8.6%, comprising 4.3% cardiovascular mortality and 1.3% HF-related deaths. Multivariate analysis of the relationship between the time taken to receive cardiology care and 1-year outcomes revealed a significant increased risk associated with a longer delay in cardiology assistance, particularly evident in the subgroup of patients with previous hospital admissions due to worsening HF (see Table). Conclusions Throughout the follow-up period, a reduced time taken to receive care was independently associated with better 1-year outcomes. We believe that our experience can contribute to the development of a more efficient ambulatory care pathway for HF patients, especially those at high risk, such as those with a history of hospitalisation due to worsening events. Our findings further support the clinical guideline recommendation for early contact by health professionals following hospital discharge, extending it to include PCP referrals for cardiology consultations.

Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation

Abstract Background Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic. Purpose We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF. Methods We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin < 12 g/dL in females and hemoglobin < 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status. Results A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (< -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p < 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%. Conclusions Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.

Heart Failure Risk Assessment Using Biomarkers in Patients With Atrial Fibrillation: Analysis From COMBINE-AF

BackgroundHeart failure (HF) is common among patients with atrial fibrillation (AF), and accurate risk assessment is clinically important. ObjectivesThe goal of this study was to investigate the incremental prognostic performance of N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and growth differentiation factor (GDF)-15 for HF risk stratification in patients with AF. MethodsIndividual patient data from 3 large randomized trials comparing direct oral anticoagulants (DOACs) with warfarin (ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48], and RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy]) from the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) cohort were pooled; all patients with available biomarkers at baseline were included. The composite endpoint was hospitalization for HF (HHF) or cardiovascular death (CVD), and secondary endpoints were HHF and HF-related death. Cox regression was used, adjusting for clinical factors, and interbiomarker correlation was addressed using weighted quantile sum regression analysis. ResultsIn 32,041 patients, higher biomarker values were associated with a graded increase in absolute risk for CVD/HHF, HHF, and HF-related death. Adjusting for clinical variables and all biomarkers, NT-proBNP (HR per 1 SD: 1.68; 95% CI: 1.59-1.77), hs-cTnT (HR: 1.39; 95% CI: 1.33-1.44), and GDF-15 (HR: 1.20; 95% CI: 1.15-1.25) were significantly associated with CVD/HHF. The discrimination of the clinical model improved significantly upon addition of the biomarkers (c-index: 0.70 [95% CI: 0.69-0.71] to 0.77 [95% CI: 0.76-0.78]; likelihood ratio test, P < 0.001). Using weighted quantile sum regression analysis, the contribution to risk assessment was similar for NT-proBNP and hs-cTnT for CVD/HHF (38% and 41%, respectively); GDF-15 provided a statistically significant but lesser contribution to risk assessment. Results were similar for HHF and HF-related death, individually, and across key subgroups of patients based on a history of HF, AF pattern, and reduced or preserved left ventricular ejection fraction. ConclusionsNT-proBNP, hs-cTnT, and GDF-15 contributed significantly and independently to the risk stratification for HF endpoints in patients with AF, with hs-cTnT being as important as NT-proBNP for HF risk stratification. Our findings support a possible future use of these biomarkers to distinguish patients with AF at low or high risk for HF.

Natural History, Phenotype Spectrum and Clinical Outcomes of Desmin (DES)-Associated Cardiomyopathy.

Pathogenic/likely pathogenic (P/LP) desmin (DES) variants cause heterogeneous cardiomyopathy and/or skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACE), including cardiac conduction disease (CCD), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, LVAD/cardiac transplant, HF-related death), in patients with P/LP DES variants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization. We aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with P/LP DES variants through a systematic review and individual patient data meta-analysis using published reports. We searched Medline (PubMed) and Embase for studies that evaluated cardiac phenotypes in patients with P/LP DES variants. Cardiomyopathy diagnosis or occurrence of MACE were considered evidence of cardiac involvement/penetrance. Lifetime event-free survival from CCD, sustained VA, HF events, and composite MACE was assessed. Out of 4,212 screened publications, 71 met the inclusion criteria. A total of 230 patients were included (52.6% male, 52.2% probands, median age: 31 years [22.0; 42.8] at first evaluation, median follow-up: 3 years [0; 11.0]). Overall, 124 (53.9%) patients were diagnosed with cardiomyopathy, predominantly dilated cardiomyopathy (14.8%), followed by restrictive cardiomyopathy (13.5%), whereas other forms were less common: arrhythmogenic cardiomyopathy (7.0%), hypertrophic cardiomyopathy (6.1%), arrhythmogenic right ventricular cardiomyopathy (5.2%), and other forms (7.4%). Overall, 132 (57.4%) patients developed MACE, with 96 [41.7%] having CCD, 36 [15.7%] sustained VA, and 43 [18.7%] HF events. Familial penetrance of cardiac disease was 63.6% among relatives with P/LP DES variants. Male sex was associated with increased risk of sustained VA (HR 2.28, p=0.02) and HF events (HR 2.45, p=0.008). DES cardiomyopathy exhibits heterogeneous phenotypes and distinct natural history, characterized by high familial penetrance and substantial MACE burden. Male patients face higher risk of sustained VA events.

Assessment of venous congestion with venous excess ultrasound score in the prognosis of acute heart failure in the emergency department: a prospective study.

In acute decompensated heart failure (HF), systemic venous congestion contributes to patients' symptoms and hospital admissions. The purpose of our study is to determine if venous congestion, examined using the venous excess ultrasound (VExUS) score, predicts HF-related hospitalization and mortality in patients admitted to the emergency department (ED) with acute decompensated HF. Fifty patients admitted for acute HF in ED underwent ultrasound (US) assessment according to the VExUS score within the first 24 and 72 h. All patients were followed up with a telephone call at 30 and 60 days after hospital discharge. On admission, 56% had a VExUS score of 3. After 72 h, 32% had no more signs of congestion at the Doppler VExUS examination (inferior vena cava < 2 cm, VExUS score of 0); a similar percentage still exhibited a VExUS score of 3 despite therapy. Eighty per cent of patients were hospitalized after admission to the ED, while six (15%) died in-hospital; all exhibited a first-assessment VExUS score of 3. No patient with a VExUS score < 3 died during the study. During short-term follow-up, 18 patients were readmitted to the ED for acute decompensated HF. Ninety-four per cent of the readmitted patients had a VExUS score of 3 at the Doppler assessment at the first ED admission. Severe venous congestion, defined as a VExUS score of 3 at the initial assessment of patients with acute decompensated HF, predicts inpatient mortality, HF-related death, and early readmission.

Demographic trends of cardiorenal and heart failure deaths in the United States, 2011-2020.

Heart failure (HF) and kidney disease frequently co-occur, increasing mortality risk. The cardiorenal syndrome results from damage to either the heart or kidney impacting the other organ. The epidemiology of cardiorenal syndrome among the general population is incompletely characterized and despite shared risk factors with HF, differences in mortality risk across key demographics have not been well described. Thus, the primary goal of this study was to analyze annual trends in cardiorenal-related mortality, evaluate if these trends differed by age, sex, and race or ethnicity, and describe these trends against a backdrop of HF mortality. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database was used to examine cardiorenal- and HF-related mortality in the US between 2011and 2020. International Classification of Diseases, 10 Revision codes were used to classify cardiorenal-related deaths (I13.x) and HF-related deaths (I11.0, I13.0, I13.2, and I50.x), among decedents aged 15 years or older. Decedents were further stratified by age group, sex, race, or ethnicity. Crude and age-adjusted mortality rates (AAMR) per 100,000 persons were calculated. A total of 97,135 cardiorenal-related deaths and 3,453,655 HF-related deaths occurred. Cardiorenal-related mortality (AAMR, 3.26; 95% CI: 3.23-3.28) was significantly lower than HF-related mortality (AAMR, 115.7; 95% CI: 115.6-115.8). The annual percent change (APC) was greater and increased over time for cardiorenal-related mortality (2011-2015: APC, 7.1%; 95% CI: 0.7-13.9%; 2015-2020: APC, 19.7%, 95% CI: 16.3-23.2%), whereas HF-related mortality also increased over that time period, but at a consistently lower rate (2011-2020: APC, 2.4%; 95% CI: 1.7-3.1%). Mortality was highest among older and male decedents for both causes. Cardiorenal-related deaths were more common in non-Hispanic or Latino Blacks compared to Whites, but similar rates were observed for HF-related mortality. A larger proportion of cardiorenal-related deaths, compared to HF-related deaths, listed cardiorenal syndrome as the underlying cause of death (67.0% vs. 1.2%). HF-related deaths substantially outnumber cardiorenal-related deaths; however, cardiorenal-related deaths are increasing at an alarming rate with the highest burden among non-Hispanic or Latino Blacks. Continued surveillance of cardiorenal-related mortality trends is critical and future studies that contain detailed biomarker and social determinants of health information are needed to identify mechanisms underlying differences in mortality trends.

Clinical significance and prognostic value of right bundle branch block in permanent pacemaker patients.

In patients undergoing pacemaker implantation with no prior history of heart failure (HF), the presence of left bundle branch block (LBBB) has been identified as an independent predictor of HF-related death or hospitalization, while the prognostic significance of right bundle branch block (RBBB) remains uncertain. We aimed to assess the long-term risk of all-cause mortality in patients with a standard indication for permanent pacing and normal or moderately depressed left ventricular function when RBBB is detected at the time of implantation. We retrospectively enrolled 1348 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center, from January 1990 to December 2022. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. The baseline 12-lead electrocardiogram revealed an RBBB in 241 (18%) and an LBBB in 98 (7%) patients. During a median follow-up of 65 [25th-75th percentile: 32-117] months, 704 (52%) patients died. The combined endpoint of cardiovascular death or HF hospitalization was reached by 173 (13%) patients. On multivariate analysis, RBBB was confirmed as an independent predictor of death [hazard ratio, 1.33; 95% confidence interval (CI), 1.09-1.63; P = 0.005]. However, when considering the combined endpoint of cardiovascular death and HF hospitalization, this endpoint was independently associated with LBBB (hazard ratio, 2.13; 95% CI, 1.38-3.29; P < 0.001), but not with RBBB. In patients with standard pacemaker indications and normal or moderately depressed left ventricular function, the presence of basal RBBB was an independent predictor of mortality. However, it was not associated with the combined endpoint of cardiovascular death and HF hospitalization.

Incidence and predictors of heart failure events following cardiac surgery in patients with atrial fibrillation - insights from the LAAOS-III trial

Abstract Background Atrial fibrillation (AF) is a common comorbidity in patients undergoing cardiac surgery and further increases the risk of incident heart failure (HF). However, only limited data exist on HF events following surgery in patients with AF. Methods The Left Atrial Appendage Occlusion Study (LAAOS) III was a randomized trial evaluating concomitant left atrial appendage occlusion in patients with AF undergoing cardiac surgery. In this secondary analysis, we aimed to identify independent predictors of the composite outcome of HF hospitalization or HF-related death following discharge, using a multivariable Cox model – incorporating sex, age (≥65 vs &amp;lt;65 years), systolic blood pressure (≤140 vs &amp;gt;140 mmHg), body mass index (BMI; &amp;lt;25 vs 25-29.9 vs ≥30 kg/m2), diabetes mellitus (DM), prior HF diagnosis, prior stroke, ischemic heart disease (IHD), heart valve surgery, AF history duration, rhythm on discharge electrocardiogram, and trial allocation. Supplementary analyses were undertaken to further assess the continuous variables using cubic spline regression. Results Of 4770 patients enrolled, in-hospital death occurred in 201 (4.2%) and complete discharge data were available for 4564 (95.7%). During a median follow up of 3.9 years, 533 (11.7%) of 4564 patients were hospitalized for HF. In total, 873 (19.1%) died after discharge, including 95 HF-related deaths. The composite outcome of HF hospitalization or HF-related death occurred at an annualized event rate of 3.31%/year [95% confidence interval: 3.04-3.60]. The independent risk factors included age (event rate of 3.64%/year vs 2.03%/year for ≥65 vs &amp;lt;65 years; hazard ratio (HR) 1.71 [1.32-2.21]), DM (4.71%/year vs 2.71%/year for with vs without DM; HR 1.59 [1.34-1.90]), prior HF diagnosis (4.27%/year vs 2.17%/year for with vs without HF; HR 2.00 [1.66-2.41]), IHD (3.63%/year vs 2.85%/year for with vs without IHD; HR 1.26 [1.03-1.54]), AF history duration (3.81%/year vs 2.89%/year for &amp;gt;2 vs &amp;lt;0.5 years; HR 1.23 [1.01-1.50]), and AF rhythm at discharge (3.87%/year vs 2.68%/year for AF vs non-AF rhythm; HR 1.31 [1.09-1.58]). The supplementary spline analyses further revealed a positive correlation between BMI and the risk of the composite outcome (p-value 0.042). Conclusions In patients with AF undergoing cardiac surgery, post-discharge HF hospitalization and HF-related death occurred at a rate of 3.31% per year. Our study identified several significant risk factors including advanced age, higher BMI, DM, prior HF diagnosis, IHD, AF history &amp;gt;2 years, and AF rhythm at discharge.The associations of HF with age and BMI

The impact of comorbidities and substance use on heart failure events and major ventricular arrhythmias in phospholamban p.(Arg14del) positive individuals

Abstract Background Patients with the phospholamban (PLN) p.(Arg14del) variant can develop a severe cardiomyopathy, characterized by progressive heart failure (HF) and major ventricular arrhythmias (VA). However, there is a marked variability in disease expression among affected individuals. There is still a considerable gap of knowledge regarding the influence of comorbidities and substance use on disease progression. Purpose The aim of this study is to investigate whether specific comorbidities and substance use are associated with HF events or major VA events in PLN p.(Arg14del) positive individuals. Method Logistic regression analysis was conducted was conducted in a retrospective cohort of 880 PLN p.(Arg14del) positive individuals (N=847 without heart failure at baseline, N=810 without major arrhythmia at baseline and N=780 without both). Comorbidities and substance use at baseline were assessed in univariable and multivariable models with respect to HF events, major VA events, and a composite endpoint of these two referred to as ‘severe phenotype’. Heart failure was defined as heart failure hospitalization, left ventricle assist device implantation, heart transplantation or HF-related death. Major VA was defined as sustained VA, appropriate implantable cardioverter defibrillator intervention, or (aborted) sudden cardiac death. Results Of all tested comorbidities, only renal dysfunction defined as an eGFR (CKD-EPI) &amp;lt;60 ml/min per 1.73 m² was significantly and independently associated with all endpoints (p&amp;lt;0.001). In the substance use analysis, prior history of smoking was associated with heart failure and a severe phenotype (p&amp;lt;0.002 and p&amp;lt;0.021), however actively smoking was not associated with both endpoints. Conclusion Renal dysfunction and a history of smoking were the only factors identified to be associated with worse outcomes in PLN p.(Arg14del) positive individuals. Whether renal dysfunction signifies a risk factor or an early manifestation of disease has to be further elucidated.

A time-dependent analysis of sacubitril/valsartan and gliflozins benefits in patients receiving cardiac resynchronization therapy

Abstract Background While sacubitril/valsartan (ARNi), gliflozins (or SGLT2i) and cardiac resynchronization therapy (CRT) are firmly recognized as cornerstones of therapy for heart failure with reduced ejection fraction (HFrEF), robust evidence validating the long-term efficacy of their combination remains elusive. The few data suggesting a synergistic advantage of these drugs alongside CRT have not rigorously considered their time-varying administration, leading to potential selection bias, since only patients with longer initial survival could commence these treatments. As a result, the literature to date lacks a comprehensive and persuasive demonstration of the additional survival benefits conferred by ARNi and gliflozins over CRT alone in HFrEF. Purpose To evaluate the impact of ARNi and gliflozins on reducing cardiovascular and overall mortality among HFrEF patients undergoing CRT. Methods Patients with heart failure and an ejection fraction ≤ 35%, who were referred for CRT-D implantation from 2015 to 2023, were retrospectively recruited for the study. These patients were grouped into two cohorts: those not receiving drugs (no drugs group) and those treated with ARNi and/or SGLT2i (ARNi/SGLT2i group). Importantly, ARNi and SGLT2i treatments were considered as time-dependent covariates in order to account for patients who initiated or discontinued therapy during follow-up. Results The cohort included 183 ischemic and non-ischemic HFrEF patients (148 male [80.9 %], 113 ischemic [61.7 %], median [IQR] age 73 [65-80] years). 117 (74 %) patients started ARNi (61, 52.1 %), gliflozins (7, 6 %) or both drugs (49, 41.9 %) and were assigned to ARNi/SGLT2i group. During a median follow-up of 5.67 (CI 95 %, 5 – 6.5) years, 63 (34.4 %) patients died, of whom 47 (74.6 %) died of cardiovascular HF-related death. Specifically, 44 (of whom 35 (79 %) due to HF-related death) died in the no drugs group vs 19 (12 (63 %) due to HF-related death) in ARNi/SGLT2i patients. At univariable analysis (Panel A in the Figure), ARNi and/or SGLT2i treatments reduced all-cause (HR 0.59 [0.34-1.02], p = 0.056) and cardiovascular (HR 0.47 [0.24-0.92], p = 0.029) mortality. However, after multivariable adjustment for key covariates (1-year CRT response, age, atrial fibrillation, baseline LVEF, chronic obstructive pulmonary disease, glomerular filtration rate), the survival benefits of ARNi and SGLT2i use diminished, and the only factor strongly associated with reduced mortality risk remained 1-year positive response to CRT (Panel B). Conclusions Despite their recognized therapeutic benefits, ARNi and SGLT2i have not demonstrated additional survival benefit compared to CRT alone in patients with HFrEF. A 1-year positive response to CRT remains the most significant prognostic factor. Further studies with larger sample sizes and extended follow-up periods are needed to confirm this hypothesis, also evaluating whether the timing of introduction of these medications may impact survival.

Clinical significance and prognostic value of right bundle branch block in permanent pacemaker patients

Abstract Aim In patients undergoing pacemaker implantation with no prior history of heart failure (HF), the presence of left bundle branch block (LBBB) has been identified as an independent predictor of HF-related death or hospitalization, while the prognostic significance of right bundle branch block (RBBB) remains uncertain. We aimed to assess the long-term risk of all-cause mortality in patients with a standard indication for permanent pacing and normal or moderately depressed left ventricular function when RBBB is detected at the time of implantation. Methods We retrospectively enrolled 1348 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center, from January 1990 to December 2022. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. Results The baseline 12-lead electrocardiogram revealed an RBBB in 241 (18%) and an LBBB in 98 (7%) patients. During a median follow-up of 65 [25th-75th percentile: 32-117] months, 704 (52%) patients died. The combined endpoint of cardiovascular death or HF hospitalization was reached by 173 (13%) patients. On multivariate analysis, RBBB was confirmed as independent predictor of death (Hazard Ratio, 1.33; 95% CI, 1.09–1.63; P=0.005). However, when considering the combined endpoint of cardiovascular death and HF hospitalization, this endpoint was independently associated with LBBB (Hazard Ratio, 2.13; 95% CI, 1.38–3.29; P&amp;lt;0.001), but not with RBBB. Conclusions In patients with standard pacemaker indications and normal or moderately depressed LV function the presence of basal RBBB was an independent predictor of mortality. However, it was not associated with the combined endpoint of cardiovascular death and HF hospitalization.Time to event

Heart Failure-Related Death in Subjects With Atrial Fibrillation in the United States, 1999 to 2020.

Population-based data on heart failure (HF)-related death in patients with atrial fibrillation (AF) are lacking. We assessed HF-related death in people with AF in the United States over the past 21 years and examined differences by age, sex, race, ethnicity, urbanization, and census region. Data were extracted from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to determine trends in age-adjusted mortality rates per 100 000 people, due to HF-related death among subjects with AF aged ≥15 years. To calculate nationwide annual trends, we assessed the average annual percent change (AAPC) and annual percent change with relative 95% CIs using joinpoint regression. Between 1999 and 2020, 916 685 HF-related deaths (396 205 men and 520 480 women) occurred among US adults having a concomitant AF. The overall age-adjusted mortality rates increased (AAPC: +4.1% [95% CI, 3.8-4.4]; P<0.001), especially after 2011 (annual percent change, +6.8% [95% CI, 6.2-7.4]; P<0.001) in men (AAPC, +4.8% [95% CI, 4.4-5.1]; P<0.001), in White subjects (AAPC: +4.2% [95% CI, 3.9 to 4.6]; P<0.001) and in subjects aged <65 years (AAPC: +7.5% [95% CI, 6.7-8.4]; P<0.001). The higher percentage of deaths were registered in the South (32.8%). During the first year of the COVID-19 pandemic, a significant excess in HF-related deaths among patients with AF aged >65 years was observed. A worrying increase in the HF-related mortality rate among patients with AF has been observed in the United States over the past 2 decades.

The Prognostic Role of Global Longitudinal Strain and NT-proBNP in Heart Failure Patients Receiving Cardiac Resynchronization Therapy.

We aimed to evaluate whether baseline GLS (global longitudinal strain), NT-proBNP, and changes in these after cardiac resynchronization therapy (CRT) can predict long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). We enrolled 143 patients with stable ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiography were obtained before and 6 months after. The patients were followed up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint). A total of 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered CRT responders and 39 non-responders. At baseline, event-free patients had higher absolute GLS values (p < 0.001) and lower NT-proBNP serum levels (p < 0001) than those achieving the primary endpoint. A similar pattern was observed in favor of CRT responders vs. non-responders. On Cox regression analysis, baseline absolute GLS value (HR = 0.77; 95% CI, 0.51-1.91; p = 0.002) was beneficially associated with lower primary endpoint incidence, while baseline NT-proBNP levels (HR = 1.55; 95% CI, 1.43-2.01; p = 0.002) and diabetes presence (HR = 1.27; 95% CI, 1.12-1.98; p = 0.003) were related to higher primary endpoint incidence. In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

Neighborhood Disadvantage and Risk of Heart Failure: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status. We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005-2007). Neighborhood disadvantage was assessed using a Z score of 6 census tract variables (2000 US Census) and categorized as quartiles. Incident HF hospitalizations or HF-related deaths through 2017 were adjudicated. Multivariable-adjusted Cox regression was used to examine the association between neighborhood disadvantage and incident HF. Heterogeneity by diabetes was assessed using an interaction term. The mean age was 64.4 years, 39.5% were Black adults, 54.9% females, and 18.8% had diabetes. During a median follow-up of 10.7 years, there were 1125 incident HF events with an incidence rate of 3.3 (quartile 1), 4.7 (quartile 2), 5.2 (quartile 3), and 6.0 (quartile 4) per 1000 person-years. Compared to adults living in the most advantaged neighborhoods (quartile 1), those living in neighborhoods in quartiles 2, 3, and 4 (most disadvantaged) had 1.30 (95% CI, 1.06-1.60), 1.36 (95% CI, 1.11-1.66), and 1.45 (95% CI, 1.18-1.79) times greater hazard of incident HF even after accounting for known confounders. This association did not significantly differ by diabetes status (interaction P=0.59). For adults with diabetes, the adjusted incident HF hazards comparing those in quartile 4 versus quartile 1 was 1.34 (95% CI, 0.92-1.96), and it was 1.50 (95% CI, 1.16-1.94) for adults without diabetes. In this large contemporaneous prospective cohort, neighborhood disadvantage was associated with an increased risk of incident HF events. This increase in HF risk did not differ by diabetes status. Addressing social, economic, and structural factors at the neighborhood level may impact HF prevention.