Death In Heart Failure Patients Research Articles

Short Term Follow Up Wide QRS Complex Patient with Acute Decompensated Heart Failure at RSUD dr H. Moch Ansari Saleh January until June 2023

Background and aims : Heart failure always has a poor prognosis despite advances in medical treatment. Several studies have finally examined several predictors of mortality rates and the incidence of rehospitalization in the population of heart failure sufferers. Wide QRS complex duration is a predictor of poor prognosis in 20-30% of heart failure sufferers. This study aims to determine the relationship between wide complex QRS duration (>120ms) on the incidence of rehospitalization and death in heart failure patients at RSUD dr H Moch Ansari Saleh Banjarmasin for the period January to June 2023. Material and Methods : This study used analytical methods with a cross-sectional design which was carried out at RSUD dr H Moch Ansari Saleh Banjarmasin for the period January to June 2023. The sample for this study was 133 inpatients with congestive heart failure, consisting of 24 patients with wide complex QRS duration(> 120ms) and 109 patients with narrow QRS complex duration (<120ms). Variables reviewed included age, gender, electrocardiogram rhythm, history of diabetes mellitus, ejection fraction and NYHA classification Result : The results of Independent T Test stated, there was a significant difference between the duration of the wide QRS complex (>120ms) and the mortality rate (p<0.001) and NYHA classification (p<0.001) but there was no significant difference in the incidence of rehospitalization (p=0.354). Other variables such as age, gender, electrocardiogram picture, history of diabetes mellitus, and ejection fraction also did not show significant differences, this could be due to the small number of samples obtained and limited time in the study. Conclusion : There is a significant relationship between duration of wide complex QRS (>120ms) and mortality rate of congestive heart failure patients at RSUD dr H Moch Ansari Saleh, Banjarmasin for the period January to June 2023

Comparing the anti-remodeling effect of sacubitril/valsartan and angiotensin-converting enzyme inhibition on myocardial samples of advanced heart failure patients undergoing heart transplantation

Abstract Background In decreasing heart failure (HF) hospitalization and cardiovascular death in HF patients with reduced ejection fraction, Sacubitril/Valsartan (SAC/VAL) treatment was proved to be superior to angiotensin-converting enzyme inhibition (ACEi). According to recent experimental results and clinical data based on echocardiography and circulating biomarkers, this benefit might be at least partially attributed to a greater anti-remodeling effect. However, there is a lack of direct evidence from human myocardial samples for this assumption. Purpose Therefore, we aimed to compare the anti-remodeling effect of SAC/VAL treatment to ACEi on myocardial samples of HF patients undergoing heart transplantation (HTX). Methods We studied left ventricular (LV) samples of seventy advanced HF patients who underwent HTX and received either SAC/VAL (SAC/VAL group, N=32) or ACEi treatment (ACEi group, N=38) for at least three months prior to HTX. Furthermore, all patients received beta-blockers and mineralocorticoid receptor antagonists titrated to maximally tolerated or target dose. Our groups were matched for age, sex, ejection fraction and other clinical parameters. Patients with liver or kidney failure, mechanical circulatory support, systemic inflammatory/fibrotic diseases or positive inotrope treatment were excluded. Myocardial mRNA expression of fibrotic markers and B-type natriuretic peptide (BNP) were measured with qRT-PCR and normalized to glyceraldehyde 3-phosphate dehydrogenase expression. Interstitial fibrosis area was assessed histologically. Results Preoperative plasma N-terminal pro-BNP levels were similar in the two groups (SAC/VAL: 4363±752 pg/mL vs. ACEi: 4616±1020 pg/mL; p=0.911). In contrast, the mRNA level of BNP in the myocardium was lower in patients treated with SAC/VAL (SAC/VAL: 2.2±1.05 vs. ACEi: 5.2±1.74; p=0.006). TIMP metallopeptidase inhibitor 1 (SAC/VAL: 0.07±0.01 vs. ACEi: 0.13±0.02; p=0.011), TIMP metallopeptidase inhibitor 2 (SAC/VAL: 0.06±0.01 vs. ACEi: 0.11±0.01; p<0.001), collagen type I alpha 1 chain (SAC/VAL: 0.02±0.00 vs. ACEi: 0.08±0.02; p<0.001) and collagen type III alpha 1 chain (SAC/VAL: 0.12±0.02 vs. ACEi: 0.27±0.04; p<0.001) relative gene expressions were also decreased in the LV of SAC/VAL-treated patients. Histology analysis confirmed reduced interstitial myocardial fibrosis area in the SAC/VAL group as well (SAC/VAL: 7.2±0.4% vs. ACEi: 8.6±0.5%; p=0.031). Conclusions SAC/VAL treatment decreased the myocardial expression of BNP and fibrosis-related genes to a greater extent compared with ACEi in LV samples of patients undergoing HTX. Histological analysis also verified the differences in fibrosis. Thus, the anti-remodeling effect of SAC/VAL might be superior to ACEi even in advanced HF.

Management of Ventricular Arrhythmias in Heart Failure: Can Less Be More?

Ventricular arrhythmias (VAs) affect many patients with heart failure and underlying structural heart disease and are associated with significant morbidity and mortality. Antiarrhythmic drugs are often the initial treatment, but medication alone often fails to sufficiently suppress VAs. While catheter ablation (CA) remains the gold standard for treatment of VAs, CA is an invasive procedure and can be associated with periprocedural complications including acute clinical decompensation. Thus, there is an important need for alternative therapies. Recent advances in risk stratification and the development of new ablation technologies may reduce some of the periprocedural complications and limitations of CA. In addition, less invasive therapies for VAs may provide an alternative treatment strategy for patients in both the acute and chronic setting. For patients acutely admitted with ventricular tachycardia electrical storm (VT-ES) or recurrent VT and cardiogenic shock, risk stratification tools have been developed to identify patients at high risk of acute hemodynamic decompensation during CA. These patients require a multidisciplinary approach and might need mechanical circulatory support (MCS) if CA is selected as the treatment strategy. Alternatively, less invasive therapies targeting the autonomic nervous system may be reasonable. In the chronic setting, developments in medical therapy have reduced the risk of sudden cardiac death in heart failure patients and stereotactic whole-body radiation (SBRT) has evolved as a potential, non-invasive therapy. Further research is needed to personalize VA therapy for individual patients.

Skeletal muscle index as a prognostic marker for sudden cardiac death in heart failure patients with reduced ejection fraction

Abstract Background The association between sarcopenia and sudden cardiac death remains unclear. Therefore, this study aimed to explore the association between sarcopenia, sudden cardiac death, and all-cause mortality in heart failure (HF) patients with reduced ejection fraction based on the skeletal muscle index (SMI) predicted by a formula. Methods A total of 300 patients with heart failure who were admitted to our Hospital, National Center for Cardiovascular Diseases, between March 2013 and November 2015 and met the inclusion criteria were retrospectively analyzed. Baseline SMI was divided into two groups: lower than or equal to the median (n=151) and higher than the median (n=149). The primary endpoints were a composite outcome of sudden cardiac death (SCD) or an equivalent event (sustained ventricular events, or appropriate implantable cardioverter-defibrillator (ICD) therapy).The secondary end point was all-cause mortality. Results The average follow-up period was 24.40 ± 14.07 months. Atotal of 42 patients (42/300,14.0%) experienced sudden cardiac death or an equivalent event, and 97 patients (97/300, 32.2%) experienced all-cause mortality. Analysis of the Kaplan–Meier survival curves showed that patients with an SMI lower than or equal to the median had a higher risk of sudden cardiac death (P=0.0015) and all-cause mortality (P<0.0001). Multivariate Cox analysis showed that an SMI lower than the median was an independent risk factor for sudden cardiac death (hazard ratio (HR): 2.837, 95% confidence interval (CI): 1.009–7.980, P=0.048) and all-cause mortality (HR: 2.597, 95% CI: 1.384–4.871, P=0.003). Conclusions Decreased SMI significantly increased the risk of sudden cardiac death and all-cause mortality in patients with HF and reduced ejection fraction. In a HF population with reduced ejection fraction, attention should be paid to the effect of sarcopenia on prognosis, and active intervention is expected to improve the prognosis of patients.

Association of serum albumin with heart failure mortality with NYHA class IV in Chinese patients: Insights from PhysioNet database (version 1.3)

BackgroundStudies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. ObjectivesWe aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. MethodsA total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. ResultsCompared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. ConclusionSerum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.

Development and validation of a novel combinatorial nomogram model to predict in-hospital deaths in heart failure patients

BackgroundThe purpose of this study was to develop a Nomogram model to identify the risk of all-cause mortality during hospitalization in patients with heart failure (HF).MethodsHF patients who had been registered in the Medical Information Mart for Intensive Care (MIMIC) III and IV databases were included. The primary outcome was the occurrence of all-cause mortality during hospitalization. Two Logistic Regression models (LR1 and LR2) were developed to predict in-hospital death for HF patients from the MIMIC-IV database. The MIMIC-III database were used for model validation. The area under the receiver operating characteristic curve (AUC) was used to compare the discrimination of each model. Calibration curve was used to assess the fit of each developed models. Decision curve analysis (DCA) was used to estimate the net benefit of the predictive model.ResultsA total of 16,908 HF patients were finally enrolled through screening, of whom 2,283 (13.5%) presented with in-hospital death. Totally, 48 variables were included and analyzed in the univariate and multifactorial regression analysis. The AUCs for the LR1 and LR2 models in the test cohort were 0.751 (95% CI: 0.735∼0.767) and 0.766 (95% CI: 0.751–0.781), respectively. Both LR models performed well in the calibration curve and DCA process. Nomogram and online risk assessment system were used as visualization of predictive models.ConclusionA new risk prediction tool and an online risk assessment system were developed to predict mortality in HF patients, which performed well and might be used to guide clinical practice.

Plasma levels of intact parathyroid hormone and congestion burden in heart failure: clinical correlations and prognostic role

Abstract Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen-creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283-573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL-area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Impact of adherence to guideline-directed therapy on risk of death in HF patients across an ejection fraction spectrum.

How different degrees of adherence to guideline-directed medical therapy (GDMT) affect mortality risk in patients with heart failure (HF) in a real-world clinical setting is poorly understood. This study sought to investigate how different levels of adherence to GDMT were associated with the risk of all-cause mortality in patients with HF across a spectrum of left ventricular ejection fractions (LVEFs) in a real-world clinical setting. A total of 64610 HF patients with no missing value of LVEF from the Swedish Heart Failure Registry were included in the study. Patients were divided according to different LVEFs (<30%, 30-39%, 40-49%, and≥50%) and stratified by an adherence score (good, moderate, or poor) according to the triple, double, and single one usage of GDMT: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists. The outcome is time to all-cause mortality. The mean age of the whole cohort was 73.9±12.1years, and the proportion of patients in LVEF<30%, 30-39%, 40-49%, and≥50% groups was 27.6%, 26.9%, 22.1%, and 23.3%, respectively. Patients with LVEF<30% had the highest mortality rate, almost 20% higher than those with LVEF≥50% {hazard ratio [HR] [95% confidence interval (CI)]: 0.80 [0.71-0.90], P<0.001}. After treatment of GDMT with good adherence, patients with LVEF<30% had similar mortality to those with LVEF≥50% [HR (95% CI): 0.97 (0.86-1.10), P=0.664]. However, the percentage of moderate or poor GDMT was alarmingly high, with good adherence only in 20% of the patients. Good adherence to GDMT works best in patients with LVEF<50%, whereas moderate adherence to GDMT varies in efficacy depending on the components of the drug combinations.

Association of living alone with clinical outcomes in patients with heart failure: A systematic review and meta-analysis.

Living alone is an objective sign of social isolation. It is uncertain whether living alone worsens clinical outcomes in heart failure (HF) patients. We aimed to assess how living alone affected clinical outcomes in individuals with HF. We searched the electronic databases of PubMed, Embase, and Cochrane from 1990 to April 2022 for studies comparing living alone with HF. A random-effects model with inverse variance was used to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Seven studies were deemed to meet the standards. In patients with HF, compared with living with others, living alone was associated with an elevated risk of any hospitalization at the 30-day (HR: 1.78, 95% CI: 1.09-2.89), 90-day (HR: 1.24, 95% CI: 1.02-1.51), or ≥1-year (HR: 1.14, 95% CI: 1.04-1.26) follow-up periods. HF patients living alone also had a greater risk of any hospitalization or death at the 30-day (HR: 1.56, 95% CI: 1.15-2.11), 90-day (HR: 1.26, 95% CI: 1.05-1.50), and ≥1-year (HR: 1.18, 95% CI: 1.09-1.28) follow-up periods. However, patients living alone had no increased risk of all-cause death at the 30-day (HR: 1.0, 95% CI: 0.19-5.36), 90-day (HR: 0.46, 95% CI: 0.03-7.42), or ≥ 1-year (HR: 1.10, 95% CI: 0.73-1.67) follow-up periods. In comparison to living with others, living alone was associated with an increased risk of any hospitalization but not all-cause death in HF patients.

Enhancing Quality of Life (QOL) And Cardiac Function in Heart Failure Patients Through Integrated Tele-Cardiopulmonary Rehabilitation And Psychological Support: A Prospective Study

Introduction: Herat failure (HF) is one global pandemic affecting millions of people across the globe. Patients with HF report decreased functional capacity, increased dyspnea and weariness, and a diminished ability to do daily tasks. In previous years there was much advancement in pharmacological therapy against heart failure. Several studies have shown that cardiopulmonary rehabilitation programs are safe and effective in improving functional capacity and quality of life while decreasing readmission rates and all-cause death in heart failure patients. However, heart failure patients' psychological status is often unknowingly neglected, leading to poor quality of life. Methods: This prospective Study was initiated in May 2022, was conducted for 18 months, and was completed in October 2022. This study is a prospective study of heart failure patients, the effect of an integrated approach of tele-cardiopulmonary rehabilitation along with psychologist-guided psychological support enhancing the quality of life. The patients satisfying the inclusion criteria without exclusion criteria were randomized to intervention and control groups. Results: The age group of the mean (years)+/- SD(67+/-14.4) in the Intervention Group and (66+/- 14) in the Control group. Both the groups comprised female participants, 63% in the Intervention group and 68% in the control group. The initial evaluation was done at the beginning of this prospective study. The follow-ups were done in 6 weeks, 12 weeks, and 24 weeks. Clinical examination, 6-Minute Walk Test, peak VO2 evaluation in a cardiopulmonary exercise test, and echocardiography with LVGLS measurements. During the study period, it was noted that there were substantial improvements in LVGLS, 6-Minute Walk Test distance, peak VO2, and Quality of Life. Conclusion: In Conclusion, based on the findings of this prospective study, the integrated approach of tele- cardiopulmonary rehabilitation and psychological support in heart failure patients has tremendous benefits and remarkable improvement in Quality of Life. As the life span improves, that leads to more heart failure patients presently and in the future. Along with pharmacotherapy against heart failure, telerehabilitation, and psychological support should be emphasized from the beginning of heart failure treatment to achieve a better quality of life. Considering the importance of Rehabilitation, through this study, it would not be wrong to suggest an additional pillar of heart failure treatment along with four other robust pillars in the guidelines

Efficacy of Early Catheter Ablation for Atrial Fibrillation After Admission for Heart Failure

BackgroundAdvances in catheter ablation (CA) for atrial fibrillation (AF) have improved the prognosis of patients with heart failure (HF) and AF. However, its optimal timing remains to be fully elucidated. ObjectivesThe aim of this study was to investigate the prognostic impact of early CA in patients with HF and AF hospitalized for worsening HF. MethodsFrom JROADHF (Japanese Registry of Acute Decompensated Heart Failure) (n = 13,238), patients with HF and AF who underwent CA within 90 days after admission for HF (early CA; n = 103) and those who did not (control; n = 2,683) were identified. Mortality was compared between these groups in the crude cohort, as well as in the propensity-matched cohort (n = 83 in each group). ResultsIn the crude cohort, all-cause mortality was significantly lower in the early CA group than in the control group (log-rank P < 0.001; HR: 0.38; 95% CI: 0.24-0.60). In the matched cohort, all-cause mortality was likewise significantly lower in the early CA group (log-rank P = 0.014; HR: 0.47; 95% CI: 0.25-0.88). Cardiovascular death and HF mortality were significantly lower in both cohorts (crude: Gray’ test: P < 0.001 and P = 0.005; subdistribution HR: 0.28 [95% CI: 0.13-0.63] and HR: 0.31 [95% CI: 0.13-0.75]; matched: Gray’s test: P = 0.006 and P = 0.017; subdistribution HR: 0.24 [95% CI: 0.08-0.70] and HR: 0.28 [95% CI: 0.09-0.84], respectively). ConclusionsIn a nationwide representative real-world cohort, CA for AF within 90 days after admission for HF was associated with improved long-term outcomes, including cardiovascular and HF death in patients with HF and AF.

Hyponatremia and lower normal serum sodium levels are associated with an increased risk of all-cause death in heart failure patients.

To explore the relationship between the serum sodium level on admission and all-cause mortality in HF patients. A single-center retrospective cohort study. Patients hospitalized with HF at the Heart Failure Center, FuwaiHospital, from November 2008 to November 2018 were enrolled. A total of 3649 patients were included, and the mean sodium level was 137.19 ± 4.36 mmol/L, with a range from 115.6 to 160.9 mmol/L. During a median follow-up of 1101 days, mortality occurred in 1413 (38.7%) hospital survivors. After adjustment for age, sex, and other potential confounders, patients with sodium levels <135 mmol/L (hazard ratio [HR]: 1.67; 95% confidence interval [CI]: 1.29-2.16) and 135-137 mmol/L (HR: 1.34; 95% CI: 1.01-1.78) had an increased risk of all-cause mortality compared to those with sodium levels of 139-141 mmol/L.

Izazovi terapije srčane insuficijencije kod gojaznih pacijenata

Obesity is one of the most significant independent risk factor for developing heart failure (HF) through direct and indirect mechanisms. Excessive secretion of aldosterone and activation of the renin-angiotensin system (RAAS) in obese patients leads to sodium retention and an increase in extracellular volume, which contributes to the development of heart failure and increased cardiovascular risk. Abdominal visceral obesity is associated not only with an increased risk for the development of heart failure with preserved ejection fraction (HFpEF), but also with a high risk for the development of diabetes mellitus and hypertension in both sexes, but more dominantly in women, with an increase in incidence with menopause. Multiple studies and meta-analyses have confirmed that obese patients with heart failure regardless of ejection fraction (HFpEF and HFrEF) have better survival compared to those of normal or underweight, a phenomenon known as the obesity paradox. The HF-ACTION trial showed that even small improvements in cardiorespiratory fitness could lead to significant improvements in cardiovascular outcomes, reducing the impact of the obesity paradox on the clinical outcome of heart failure. The ESC recommendations for heart failure advise weight loss in order to prevent cardiovascular disease in obese and overweight patients, and gradual weight loss should be considered in patients with heart failure and BMI &gt; 35 kg/m2 , while in patients with heart failure and BMI&lt;35 kg/m2 , weight loss is not recommended. The goal of bariatric procedures is to prevent or delay the onset of heart failure, not only by reducing body weight but also by reducing risk factors. The randomized DAPA-HF trial showed that the use of dapagliflozin proved to reduce the composite outcome of worsening heart failure or cardiovascular death in heart failure patients with BMI&gt;30 kg/m2 and in HF patients with BMI&lt;30 kg/m2 . The EMPEROR-preserved and DELIVER trials showed that therapy with SGLT2 inhibitors in patients with HFpEF and BMI&gt;30kg/m2 reduces the risk of hospitalization and cardiovascular death. It is recommended that patients in the terminal stage of heart failure in the pre-transplantation period and placed on the list for heart transplantation achieve target values of BMI&lt;30 kg/m2 in order to achieve a better clinical outcome and reduce mortality after transplantation.

Empagliflozin and dapagliflozin increase Na current in human cardiomyocytes

Abstract Background Empagliflozin (EMPA) and dapagliflozin (DAPA) are sodium-glucose cotransporter 2 inhibitors (SGLT2i) used for the treatment of type 2 Diabetes Mellitus (T2DM). Both drugs reduce morbidity and mortality in heart failure (HF) patients with reduced or preserved ejection fraction, even in the absence of T2DM. Moreover, these drugs decrease ventricular arrhythmias and sudden cardiac death in HF patients. The sodium current (INa), carried by Nav1.5 channels, is responsible for cardiac action potential (AP) depolarization and determines excitability and conduction velocity. In HF patients, the expression of Nav1.5 channels is reduced, leading to a decrease of ventricular excitability that enhances the arrhythmic risk. Purpose We aimed to determine the effects of EMPA and DAPA on human cardiac INa and AP characteristics. Methods Peak INa and ventricular-like APs were recorded in cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) using patch-clamp techniques. INa was also recorded in CHO cells transiently transfected with human Nav1.5+Navβ1 channels. In all cases, EMPA or DAPA (1 μM) were added to culture media and incubated for 24-h. Results APs recorded in hiPSC-CMs exhibited automatic activity and incubation with EMPA or DAPA did not modify spontaneous beating frequency (0.39±0.04 Hz; P&amp;gt;0.05, n≥16). In cells driven at 1 Hz, none of the drugs modified resting membrane potential (−76.7±1.4 mV; P&amp;gt;0.05, n≥11), but significantly increased AP amplitude from 98.6±3.6 to 105±2.2 (DAPA) and 107±2.3 mV (EMPA) (P&amp;lt;0.05). Interestingly, only EMPA lengthened AP duration measured at 20%, 50%, and 90% (from 605.6±31.3 to 760.5±59.0 ms, P&amp;lt;0.05) of repolarization. In hiPSC-CMs EMPA increased maximum INa density by 64% (from −156.0±28.0 to −256.4±28.1 pA/pF, P&amp;lt;0.05, n≥7) and shifted the midpoint (Vh) of the inactivation curve to more hyperpolarized potentials (from −97.3±4.5 to −108.6±4.4 mV, P&amp;lt;0.05, n≥7). In turn, DAPA increased maximum INa density by 24% (to −193.8±26.6 pA/pF) and shifted the Vh of the activation curve to more negative potentials (from −47.2±1.6 mV to −55.5±2.8 mV, P&amp;lt;0.05), an effect that would increase the INa at negative potentials coinciding with channel opening. None of the drugs modified the time course of current activation or inactivation. In CHO cells, EMPA and DAPA effects on INa were identical to those observed on hiPSC-CM. These results suggest that both SGLT2i increase INa by enhancing Nav1.5 expression into the cell membrane, by a direct gating effect on the channel, or by a combination of both. Conclusions In human cardiomyocytes, EMPA and DAPA increase INa and the AP amplitude. Moreover, EMPA, but not DAPA, prolonged AP duration. We propose that EMPA and DAPA exhibit a unique mechanism that increases cardiac excitability and conduction velocity and could contribute to the prevention of arrhythmic events in HF patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia e innovaciόnInstituto de de Salud Carlos III

Plasma Levels of Intact Parathyroid Hormone and Congestion Burden in Heart Failure: Clinical Correlations and Prognostic Role.

Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen–creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283–573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL—area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Anthropometric parameters-derived estimation of muscle mass predicts all-cause mortality in heart failure patients.

Reduction in appendicular skeletal muscle mass index (ASMI) assessed by dual-energy X-ray absorptiometry (DEXA) has been shown to be independently associated with a higher mortality rate in patients with heart failure (HF). However, DEXA is not suitable for measurement of muscle mass in a daily clinical setting and in large population-based studies. The aim of this study was to determine whether ASMI predicted from anthropometric indicators (predicted ASMI) serves as an alternative to DEXA-measured ASMI for predicting all-cause death in HF patients. Data for 539 HF patients who received a DEXA scan and measurements of calf circumferences (CC) and mid-arm circumferences (MAC) in our hospital were analysed. Predicted ASMI was calculated as we previously reported: predicted ASMI (kg/m2 )=[0.214×weight (kg)+0.217×CC (cm)-0.189×MAC (cm)+1.098 (male=1, female=-1)+0.576]/height2 (m2 ). Low ASMI values were defined as <7.00kg/m2 and <5.40kg/m2 for men and women, respectively, according to the criteria of the Asian Working Group for Sarcopenia. The median follow-up period was 1.75years (interquartile range, 0.96-2.37years), and 79 patients (15%) died. Kaplan-Meier survival curves showed that patients with low DEXA-measured ASMI and patients with low predicted ASMI had significantly lower survival rates than those for patients with high ASMI. In multivariate Cox proportional hazard analyses adjusted for age, sex, logarithmic B-type natriuretic peptide, cystatin C based-estimated glomerular filtration rate, and gait speed, DEXA-measured ASMI [hazard ratio (HR), 0.982; 95% confidence interval (CI), 0.967-0.998; P=0.026] and predicted ASMI (HR, 0.979; 95% CI, 0.962-0.996; P=0.018) were independent predictors of all-cause mortality. Inclusion of predicted ASMI into the adjustment model significantly improved continuous net reclassification improvement (0.338; 95% CI, 0.103-0.572; P<0.01) and integrated discrimination improvement (0.020; 95% CI, 0.004-0.035; P<0.05) for predicting mortality after discharge. Predicted ASMI, as well as DEXA-measured ASMI, can predict all-cause death in HF patients, and calculation of predicted ASMI will be useful for detecting high-risk patients in a daily clinical setting and in large population-based studies.

A multicentric, 2 × 2 factorial, randomised, open-label trial to evaluate the clinical effectiveness of structured physical activity training and cognitive behavioural therapy versus usual care in heart failure patients: a protocol for the PACT-HF trial

Background: Heart failure (HF) is a multi-morbid chronic condition, which adversely affects the quality of life of the affected individual. Engaging the patient and their caregivers in self-care is known to reduce mortality, rehospitalisation and improve quality of life among HF patients. The PACT-HF trial will answer whether clinical benefits in terms of mortality and hospitalisation outcomes can be demonstrated by using a pragmatic design to explore the specific effects of physical activity, and cognitive behavioural therapy in HF patients in India. Methods: We will conduct a 2 × 2 factorial, randomized, open-label trial, which aims to see if rehabilitation strategies of structured physical activity training and cognitive behavioural therapy for depression and self-management reduce the risk of repeat hospitalisation and deaths in HF patients in India. Patients will be randomised to (1) physical activity + usual care (2) cognitive behaviour therapy + usual care, (3) physical activity + cognitive behaviour therapy + usual care, and (4) usual care at 1:1:1:1 ratio. Time to mortality will be the primary outcome. A composite of mortality and hospitalisation for HF will be the main secondary outcome. Additional secondary outcomes will include ‘days alive and out of hospital’, cumulative hospitalisation, quality of life, Minnesota Living with Heart Failure questionnaire score, depression score, six minutes walking distance, handgrip strength, and adherence to medicines and lifestyle. The effects of intervention on the primary outcome will be estimated from Cox proportional hazard models. For the continuous secondary outcome variables, differences between randomised groups will be estimated from linear mixed models or generalised estimating equations (GEE) as appropriate. Discussion: PACT-HF is designed to provide reliable evidence about the balance of benefits and risks conferred by physical activity and cognitive behavioural therapy-based cardiac rehabilitation for those with HF, irrespective of their initial disease severity.

A multicentric, 2 × 2 factorial, randomised, open-label trial to evaluate the clinical effectiveness of structured physical activity training and cognitive behavioural therapy versus usual care in heart failure patients: a protocol for the PACT-HF trial.

Background: Heart failure (HF) is a multi-morbid chronic condition, which adversely affects the quality of life of the affected individual. Engaging the patient and their caregivers in self-care is known to reduce mortality, rehospitalisation and improve quality of life among HF patients. The PACT-HF trial will answer whether clinical benefits in terms of mortality and hospitalisation outcomes can be demonstrated by using a pragmatic design to explore the specific effects of physical activity, and cognitive behavioural therapy in HF patients in India. Methods: We will conduct a 2 × 2 factorial, randomized, open-label trial, which aims to see if rehabilitation strategies of structured physical activity training and cognitive behavioural therapy for depression and self-management reduce the risk of repeat hospitalisation and deaths in HF patients in India. Patients will be randomised to (1) physical activity + usual care (2) cognitive behaviour therapy + usual care, (3) physical activity + cognitive behaviour therapy + usual care, and (4) usual care at 1:1:1:1 ratio. Time to mortality will be the primary outcome. A composite of mortality and hospitalisation for HF will be the main secondary outcome. Additional secondary outcomes will include 'days alive and out of hospital', cumulative hospitalisation, quality of life, Minnesota Living with Heart Failure questionnaire score, depression score, six minutes walking distance, handgrip strength, and adherence to medicines and lifestyle. The effects of intervention on the primary outcome will be estimated from Cox proportional hazard models. For the continuous secondary outcome variables, differences between randomised groups will be estimated from linear mixed models or generalised estimating equations (GEE) as appropriate. Discussion: PACT-HF is designed to provide reliable evidence about the balance of benefits and risks conferred by physical activity and cognitive behavioural therapy-based cardiac rehabilitation for those with HF, irrespective of their initial disease severity.

Area weighted unipolar voltage to predict heart failure death in patients with ischemic cardiomyopathy and ventricular tachycardia

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with ischemic cardiomyopathy (ICM) referred for catheter ablation (CA) of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodeling of the left ventricle (LV). Local unipolar voltages (UV) decrease with loss of viable myocardium. A UV mapping derived parameter that corrects for oversampling of the infarct area may reflect the total amount of remaining LV viable myocardium. Objective To evaluate if the newly proposed parameter, `area weighted unipolar voltage’ (awUV), can predict HF related death/LVAD/Heart transplant (HFD) in ICM. Methods Voltage maps from consecutive patients with ICM referred for CA of VT, were transferred to Paraview after valve area removal. AwUV was calculated by mathematically interpolating all mapping points weighted for relative distances divided by the LV endocardial surface. Unipolar low voltage areas (ULVA, UV&amp;lt;8.27mV) were measured as percentage of the total LV surface. Associations between clinical and mapping derived parameters and HFD (HF-related death/LVAD/heart transplant) were evaluated and validated in a second cohort of consecutive patients. Results Eighty-nine patients in the study group (age 68±8; LVEF 33% [IQR 24-40%]; ULVA 64% [IQR 46-86%]; awUV 7.01 [IQR 5.01-8.52]) and 69 patients in the validation group (age 68±9; LVEF 39% [IQR 29-44%]; ULVA 59% [IQR 43-77%]; awUV 7.60 [IQR 6.16-8.69]) were included. Follow-up was 32±17 months in the study group, 28±17 months in the validation group. HFD was 20% in the study group, 10% in the validation cohort. Patients with HFD had lower LVEF and awUV, and larger ULVA than patients without HFD (LVEF 23±10% vs. 35±11%; awUV: 5.12±1.92 vs. 7.75±2.64; LVA 86±21% vs. 60±23%, all P&amp;lt;0.001). Univariable analysis showed that LVEF, ULVA and awUV were associated with HFD (HR and 95% CI: LVEF 1.10 [1.05 – 1.16]; LVA 1.05 [1.02 – 1.08]; awUV 2.18 [1.58 – 3.40], all P&amp;lt;0.01). AwUV was superior to ULVA to predict HFD in likelihood ratio calculations (awUV: LR 5.66, P=0.02; LVA: 1.76 P=0.18) and ROC analysis (AUC awUV: 0.86; LVA 0.78). The optimal cut-off for awUV of&amp;lt;5.27 was highly accurate to predict HFD in the validation cohort (log-rank P&amp;lt;0.001). Conclusion The newly proposed parameter awUV, easily available from routine voltage mapping, may be useful at identifying ICM patients at risk for HFD.

Would be the minute ventilation variability an alternative to the dichotomous diagnosis of exercise oscillatory ventilation?

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CAPES and FAPERGS. Background Exercise oscillatory ventilation (EOV) is an abnormal ventilatory phenomenon observed in chronic heart failure (HF) patients usually defined as EOV-positive or EOV-negative based on a dichotomous diagnosis. Minute ventilation variability (vVE) can quantify the presence of these oscillations and assist the prognosis of patients. Purpose To analyse the sensitivity and specificity of vVE to predict 2-year all-causes of death in HF patients. Methods Data from 233 cardiopulmonary exercise tests from HF patients performed between 2011 and 2014 at an Italian heart centre were analysed. The vVE was defined by the standard deviation (SD) of VE normalized by the number of respiratory cycles (SD/n) during the exercise tests. The cut-off to predict 2-year mortality was determined by the receiver-operating characteristic (ROC) curve. Results Thirty-five deaths were registered at 2-years. The ROC curve indicated ≤ 54.9 as the better cut-off for vVE (32 deaths were registered in follow-up; Figure 1). The relative risk was 3.9 (1.3 to 12.4) with a hazard ratio of 2.7 (1.3 to 5.6) for 2-year mortality. Conclusion The vVE appears to be a sensitive alternative to quantify EOV and stratify high-risk cases from 2-year all-cause mortality.