Worsening Heart Failure Research Articles

Vitamin D deficiency and secondary hyperparathyroidism in adult Fontan patients

BackgroundThe prevalence of vitamin D deficiency and secondary hyperparathyroidism (sHPT) in adult Fontan patients remains unstudied, and the role of vitamin D and parathyroid hormone (PTH) levels in assessing heart and circulatory failure in these patients is unclear. MethodsWe compared vitamin D deficiency and sHPT prevalence in adult Fontan patients (n = 35; mean age 33 ± 7.5 years) to adults with mild congenital heart disease (ACHD, n = 14). We analyzed associations between laboratory measurements, patient characteristics, and clinical events. FindingsVitamin D deficiency was highly prevalent in both Fontan patients and ACHD controls (76.5 % vs. 71.4 %, p = 0.726). sHPT was exclusively present in Fontan patients (31.4 %). PTH levels correlated with NYHA class (r = 0.412), O2 saturation (r = −0.39), systemic ventricular function (r = 0.465), and NT-proBNP levels (r = 0.742). 25-hydroxyvitamin D showed an inverse correlation with NYHA class and systemic ventricular function (both r ≤ −0.38). Fontan patients with sHPT had a higher incidence of prior hospitalization for worsening heart failure and atrial arrhythmias compared to Fontan patients without HPT or ACHD controls. (Hospitalization: Fontan with HPT vs. Fontan without HPT: OR 5.46 [95 % CI 1.25–23.86], p = 0.021; arrhythmia: Fontan with HPT vs. Fontan without HPT: OR 1.96 [95 % CI 1.13–3.4], p = 0.035; ACHD: OR 11.45 [95 % CI 1.7–77.28], p=<0.001). PTH showed significant correlation with inflammatory markers, particularly with GDF-15 (r = 0.8). ConclusionOur study is the first to demonstrate a high prevalence of vitamin D deficiency and sHPT in adult Fontan patients. As PTH strongly correlates with heart failure severity, it seems to be a promising biomarker in Fontan patients.

The Role of High-Sensitivity Troponin T Regarding Prognosis and Cardiovascular Outcome across Heart Failure Spectrum.

Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02-0.078) and 0.031 ng/mL (IQR 0.02-0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median (p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization (p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02-4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006-3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH (p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events (p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events.

Cost-Effectiveness of Sotagliflozin in SOLOIST-WHF

BackgroundThe efficacy of sotagliflozin in patients with diabetes and recent worsening of heart failure was shown in the SOLOIST-WHF trial. However, the cost-effectiveness of sotagliflozin in these patients has not been previously investigated. ObjectivesThe authors sought to determine the cost-effectiveness of sotagliflozin in patients with diabetes and recent worsening of heart failure. MethodsBased on SOLOIST-WHF trial data (N = 1,222), the authors constructed a Markov model to estimate the lifetime impact of sotagliflozin from a U.S. health care sector perspective. Cost data were sourced from the National Inpatient Sample. Life expectancy was modeled from census data and modified by the mortality rate in SOLOIST-WHF. Fatal and nonfatal event rates were carried forward from the trial data. Utility was assessed from the published reports. ResultsLifetime quality-adjusted life-years (QALYs) were 4.43 and 4.04 in the sotagliflozin and placebo groups, respectively, and lifetime costs were $220,113 and $188,198 in the sotagliflozin and placebo groups, respectively. The point estimate incremental cost-effectiveness ratio was $81,823 per QALY gained. The probability of being cost-effective was 3.6%, 67.5%, and 89.4% at willingness-to-pay thresholds of $50,000, $100,000, and $150,000, respectively, per QALY gained. ConclusionsIn patients with diabetes and recent worsening of heart failure, sotagliflozin is cost-effective in the U.S. using commonly accepted willingness-to-pay thresholds. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934)

Association Between Adherence to a 3-Month Cardiac Rehabilitation Program and Long-Term Clinical Outcomes in Japanese Patients With Cardiac Implantable Electronic Devices.

The objective of this study was to evaluate the association between comprehensive cardiac rehabilitation (CCR) completion and long-term clinical outcomes in patients with cardiac implantable electronic devices (CIED). This retrospective cohort study included 834 patients with CIED who participated in CCR, which included a cardiopulmonary exercise test or 6-min walk test. Patients with a left ventricular ejection fraction ≤40%, predicted peak oxygen uptake ≤80%, or B-type natriuretic peptide level ≥80pg/mL were eligible. The primary outcome was all-cause mortality. After excluding 241 patients with duplicate records and 69 who underwent CCR in the outpatient department, the data of 524 patients were analyzed. Mean age was 64±15yr, 389 (74%) patients were men, left ventricular ejection fraction was 31±15%, and 282 (54%) patients had a history of hospitalization for worsening heart failure. Of the patients referred for CCR, 294 (56%) completed the program, and an additional 230 patients started but did not complete CCR. Over a 3.7-yr median follow-up period, all-cause mortality occurred in 156 (30%) patients. Completers had lower all-cause mortality rates than non-completers (log-rank 15.77, P <.001). After adjusting for prognostic baseline characteristics, completers had 58% lower all-cause mortality risks than non-completers (HR=0.42; 95% CI, 0.27-0.64, P <.001). Three-mo CCR program completion was associated with lower mortality risks in patients with CIED. New programs or management methods are needed to decrease mortality risks, especially for those who cannot complete CCR programs.

Lived Bodily Experience of Worsening Heart Failure from Acute Exacerbation to Recovery: A Phenomenological Study.

Patients with heart failure have difficulty recognizing and identifying changes in bodily sensations, despite the importance of symptom monitoring. The way patients with heart failure experience their bodies from exacerbation to recovery is poorly understood. We aimed to describe the lived bodily experience of heart failure from exacerbation to recovery. Participatory observations and interviews were conducted in seven patients admitted to the intensive care unit with worsening heart failure. Benner's interpretive phenomenology was used for analysis. Four major themes were identified: a non-functional body becomes the central concern and an object; being conscious of bodily changes before hospitalization when asked; the central concern shifted to daily life and the body becomes the background; and having a feeling of death in the body that no longer functions or a weakened body after recovery. This study found that patients with heart failure were conscious and concerned about their bodies changing as they underwent rapid changes during exacerbations and recovery. In addition, immediately after their bodies recovered and until they were discharged from the hospital, they looked toward their daily lives through their bodily experiences during heart failure exacerbation. The lived bodily experience of heart failure, which is less conscious in daily life, is made conscious through storytelling in the period immediately following recovery from an acute exacerbation and can be the basis for subsequent self-care exploration.

Safety of Diltiazem for Acute Management of Atrial Fibrillation (AF) in Patients with Heart Failure and Reduced Ejection Fraction in the Emergency Department

BackgroundDiltiazem is an effective rate control agent for atrial fibrillation with rapid ventricular rate (AF RVR). However, its negative inotropic effects may increase the risk for worsening heart failure in patients with a reduced ejection fraction (EF). ObjectivesThis observational study aims to describe the incidence of worsening heart failure in patients who receive intravenous diltiazem for acute atrial fibrillation management. MethodsAdult patients that received diltiazem in the emergency department (ED) for AF RVR (heart rate ≥ 100 beats/min) from 2021 to 2022 and had a prior documented EF were included. The primary outcome is worsening heart failure within 24 h of diltiazem administration. Secondary outcomes include return ED visits and death within 7 days. EF percentage was compared across outcomes using Wilcoxon rank-sum tests. Outcomes were compared by reduced EF (< 50%) and preserved EF (≥ 50%). Continuous data were summarized with medians and interquartile ranges, and categorical features were summarized with frequency counts and percentages. Wilcoxon rank-sum tests were used for numeric outcomes and chi-squared tests or Fisher's exact tests for categorical outcomes, with a p-value < 0.05 considered statistically significant. ResultsThere were 674 patients with AF RVR that received diltiazem, and 386 patients met the inclusion criteria for analysis. Baseline demographics included a median age of 72 (64–81) years, with 14.5% of patients having a prior diagnosis of congestive heart failure. EF < 50% was identified in 13.7% of patients (n = 53), of which approximately 30% of these patients safely discharged home after receiving i.v. diltiazem. The primary outcome of worsening heart failure occurred in 7/41 (17%) and 10/207 (4.8%) patients with reduced and preserved ejection fractions, respectively, who were admitted to the hospital (p = 0.005). ConclusionThe development of worsening heart failure is multifactorial and may include the use of diltiazem in critically ill patients requiring hospital admission.

Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status: Insights From the VICTORIA Trial

BackgroundType 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis. ObjectivesThis study sought to investigate the impact of T2DM on outcomes in patients enrolled in VICTORIA and assess the efficacy of vericiguat in patients with and without T2DM. MethodsPatients with HF with reduced ejection fraction were randomized to receive vericiguat or placebo in addition to standard therapy. The primary outcome was a composite of cardiovascular death or first heart failure hospitalization (HFH). A Cox proportional hazards model was used to calculate HRs and 95% CIs to assess if the effect of vericiguat differed by history of T2DM. ResultsOf 5,050 patients enrolled, 3,683 (72.9%) had glycosylated hemoglobin (HbA1c) measured at baseline. Of these, 2,270 (61.6%) had T2DM, 741 (20.1%) had pre-T2DM, 449 (12.2%) did not have T2DM, and 178 (4.8%) had undiagnosed T2DM. The risks of the primary outcome, HFH, and all-cause and cardiovascular mortality were high across all categories. The efficacy of vericiguat on the primary outcome did not differ in patients stratified by T2DM by history (HR: 0.92; 95% CI: 0.81-1.04), T2DM measured by HbA1c (HR: 0.77; 95% CI: 0.49-1.20), and pre-T2DM measured by HbA1c (HR: 0.88; 95% CI: 0.68-1.13) and in those with normoglycemia (HR: 1.02: 95% CI: 0.75-1.39; P for interaction = 0.752). No significant differences were observed in subgroups with respect to the efficacy of vericiguat on HFH and all-cause or cardiovascular death. ConclusionsIn this post hoc analysis of VICTORIA, vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction regardless of T2DM status. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [Mk-1242-001] [VICTORIA]; NCT02861534)

Loop diuretic discontinuation in chronic heart failure patients: A retrospective study

Introduction and ObjectivesThe use of loop diuretics is central in managing congestion in heart failure (HF), but their impact on prognosis remains unclear. In euvolemic patients, dose reduction is recommended, but there is no recommendation on their discontinuation. This study aims to assess the impact of loop diuretic discontinuation on the prognosis of outpatients with HF with reduced ejection fraction. MethodsThis retrospective cohort study collected data from medical records of patients followed in an outpatient HF clinic at a university hospital center. Patients were included if they had been on loop diuretics and these were discontinued. Demographic, clinical and laboratory data were collected, and number and type of congestive events during the one-year period after discontinuation were recorded. ResultsAmong 265 patients on loop diuretics, almost half (129) discontinued them at some point. Patients had optimized medical therapy, low median age, low New York Heart Association class, low B-type natriuretic peptide values, normal blood pressure, controlled heart rate and kidney function within normal limits. Among 122 patients with one year of follow-up, 18 (14.8%) had a congestive event. Fifteen events (83.3%) were low-dose diuretic reinitiation at a scheduled visit. There were only three worsening heart failure events (2.5%) during the one-year period. A significant improvement in kidney function from discontinuation to the one-year follow-up appointment was also observed. ConclusionsIn our cohort, loop diuretic discontinuation was possible and safe in a large proportion of patients. The results should be interpreted with caution and cannot be extrapolated to a broader population of HF patients.

Population pharmacokinetics of ramipril in patients with chronic heart failure: A real-world longitudinal study.

In patients with chronic heart failure (CHF), the use of angiotensin-converting enzyme inhibitors, including ramipril, is recommended to reduce the risk of heart failure worsening, hospitalisation, and death. Our aim was to investigate the influence of body composition on the pharmacokinetics of ramipril and its active metabolite ramiprilat and to evaluate the changes in pharmacokinetics after prolonged therapy. Twenty-three patients with CHF who were on regular therapy with ramipril participated at the first study visit ( median age 77 years, 65 % male, and 70 % New York Heart Association Class II); 19 patients attended the second study visit and the median time between the two visits was 8 months. Pharmacokinetics were assessed using a nonlinear mixed-effects parent-metabolite model comprising two compartments for ramipril and one compartment for ramiprilat. The influence of body size and composition was best described by an allometric relationship with fat-free mass. In addition, ramipril clearance was related to patient age and daily ramipril dose, while clearance of ramiprilat was influenced by glome rular filtration rate and daily ramipril dose. There were no clinically relevant changes in the pharmacokinetics of ramipril and ramiprilat between the study visits. Due to the relatively stable pharmacokinetics of ramipril, regular outpatient visits at 6-month intervals seem appropriate to evaluate ramipril therapy.

Evaluation of ivabradine plus beta-blocker versus beta-blocker alone in addition to standard care in reducing hospitalization and major adverse cardiovascular event in patients with chronic heart failure: a prospective observational study in tertiary care hospital in central India

BackgroundIn recent years, there has been an increase in cases of heart failure, ultimately leading to an increase in hospitalization for heart failure (HF) and cardiovascular mortality. The aim of our study was to evaluate ivabradine combined with beta-blocker versus beta-blocker alone in addition to standard care for chronic heart failure, followed for a period of 6 months for the rate of hospitalization and major adverse cardiovascular event (MACE) in patients with reduced left ventricular ejection fraction (LVEF < 35%).ResultsA total of 64 patients were included in this observational study with 30 patients in the ivabradine + beta-blocker (IVA + BB) group and 34 in the beta-blocker (BB) group. The median (IQR) age of the study sample was 57 (50–62) and 58.5 (55–67) in IVA + BB and BB groups, respectively, with LVEF < 35%. The incidence of the primary endpoint of composite MACE (MI, stroke, death, worsening of HF) was 5 in both groups. The mean heart rate was significantly decreased (p < 0.001) at 3-month and 6-month follow-up from baseline in the ivabradine + beta-blocker group as compared to the beta-blocker group alone, while it significantly increased in the beta-blocker group at 3 months (p < 0.01) and also at sixth months (p < 0.05). Parameters such as the New York Heart Association (NYHA) class and the Minnesota Living with Heart Failure questionnaire (MLWHFQ) were also assessed but did not show significant change.ConclusionOverall, observations from the study results show that IVA + BB seems to be overall well tolerated in the study sample, with a somewhat smaller decrease in hospitalization and a delay in MACE events in the sample population enrolled in a tertiary care hospital in India. Further exploration in a larger sample is required concerning the Indian population.

Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.

We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.

Pulsed field ablation-based superior vena cava isolation in the presence of defibrillator leads

Abstract Introduction Only a minority of operators in the MANIFEST-PF multinational survey performed superior vena cava isolation by means of pulsed field ablation (PFA). This is the first report of off-label PFA-mediated superior vena cava isolation in the presence of defibrillator leads. Purpose Aim of this study was to evaluate the effect of PFA applications in the superior vena cava in the terms of alterations in pacing, sensing, or impedance parameters, inappropriate anti-tachycardia pacing, ICD shock and leads dislodgment. Methods Five patients with a history of dilated cardiomyopathy, dual chamber defibrillator implantation, and worsening heart failure because of persistent atrial fibrillation (AF) underwent catheter ablation of AF. Three of the patients had dual coil defibrillator leads. PFA was selected for the index procedure in these decompensated heart failure patients with enlarged atria focusing beyond pulmonary vein isolation in posterior wall and roof ablation as well as in superior vena cava isolation. Results Basket configuration and two sets of two lesions at the trunk of the vessel (with rotation between each pair) were used for superior vena cava isolation in the presence of atrial and defibrillator leads, without any impact on device and leads measurements or sinus node function. All patients were in AF and cardioverted into sinus rhythm post- superior vena cava isolation. They remained at sinus rhythm at regular 3-month follow-up while device interrogation revealed intact sinus node function. Conclusion PFA applications in the superior vena cava of AF patients with implanted defibrillators confirmed that it is a safe and feasible method regardless of energy application adjacent to the leads.

Physiologist-led management of heart failure patients using cardiac implantable electronic device diagnostics during COVID-19: a 2-year UK perspective

Abstract Background/ Introduction The COVID-19 pandemic prompted greater use of remote monitoring capabilities of cardiac implantable electronic devices (CIED). The HeartLogic Index incorporated within certain Boston Scientific CIEDs uses device-derived physiological parameters to generate a score which may be predictive of worsening heart failure (HF). We aimed to define the utility of a novel service, led by cardiac physiologists acting autonomously upon HeartLogic Index alerts, to guide HF patient care during the pandemic. Purpose To assess the utility of a physiologist-led HF service, using CIED diagnostics combined with clinical assessment, to improve HF management. Methods In a single-centre prospective study, 153 Boston Scientific CRT/ICD patients were reviewed over a 2-year period using the integrated HeartLogic algorithm. In response to a HeartLogic alert indicating worsening HF, the patient was contacted by a cardiac physiologist using a structured telephone triage to assess HF symptoms. In those deemed as being at risk of decompensated HF based on clinical assessment, an intervention was made e.g. face-to-face physiologist-led clinical assessment, consultant review, medication optimisation. Results During the 2-year audit, 748 alerts were received from 60 patients, the majority of which had a HF implant indication (n=42). Twenty-one patients within the study population required an intervention due to worsening HF. Following intervention, there were no further hospitalisations within this group. Five hospitalisations were documented during the audit, only 3 of which were HF related. Of these HF hospitalisations, one patient denied HF symptoms at the time of telephone contact, one had a HF decompensation due to deteriorating renal failure and the final patient had a disconnected remote monitor. During the 2-year audit, there were a total of 13 deaths, 3 of which were classified as caused by HF. Conclusion A physiologist-led service may be of clinical utility within this complex patient population, with the audit results demonstrating favourable outcomes with a low rate of mortality and HF hospitalisations. The addition of this service can act to streamline the time from patient presentation to HF review, and therefore improve patient care.

Reduced heart failure hospitalizations and improved quality of life in cardiac amyloidosis patients undergoing atrial fibrillation ablation

Abstract Background Cardiac amyloidosis (CA) has been associated with an increased risk of atrial arrhythmias and development and worsening of heart failure due to infiltration of the amyloid protein in the atrial wall. Few data exist regarding prognosis, symptoms, and quality of life after catheter ablation of atrial fibrillation in this category of patients. Objective The study evaluates the outcome of hospitalization for heart failure and quality of life in cardiac amyloidosis patients with atrial fibrillation after catheter ablation. Methods This is a study including 102 consecutive patients from two different centers with an established diagnosis of amyloidosis ATTR that underwent their first AF catheter ablation for persistent AF. They underwent pulmonary vein (PV) isolation + isolation of left atrial posterior wall and superior vena cava. Additionally, extrapulmonary triggers were identified and ablated. Post procedure, patients were followed up routinely with ECG during office visits, 7-day Holter monitor and event recorders during the first year followed by biannual checkups during the remaining part of the follow-up period. Quality of life (QoL) was measured using The Minnesota Living Heart Failure Questionnaire (MLHFQ) before Catheter ablation and after 18 months follow up; QoL was compared with T-test. Results 102 patients (mean age 72 ± 6) were included in the study. After 18 months follow up, 72 patients (70.6%) remained arrhythmia-free without antiarrhythmic drugs (Group 1), whereas 30 patients (29.4%) experienced recurrence (Group 2). In Group 1, 9 patients were hospitalized for heart failure, in contrast to 18 patients in Group 2, indicating a higher rate of heart failure hospitalizations associated with arrhythmia recurrence (p=0.02). The Quality of life in group 1 was 62 ±12 points before ablation and 63±16 points at 18 months follow up (p=0.17) while in group 2 was 68±16 points before ablation and 86±12 points at 18 months follow up (p&amp;lt;0.001). Conclusion Catheter ablation for AF in patients with cardiac amyloidosis is associated with reduced hospitalizations for heart failure, along with improvement in QoL.

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial

Abstract Background Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers flecainide and propafenone (SCB) in patients with cardiovascular disease. Purpose SCB were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. Methods We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm-control therapy) and primary efficacy outcome (cardiovascular death, stroke and hospitalization for worsening of heart failure or acute coronary syndrome) during SCB-intake for ERC patients (n=1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation &amp;gt;25% on therapy. Results Flecainide or propafenone was given to 689 patients (age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with heart failure; 41 with prior myocardial infarction, CABG or PCI and 26 with left ventricular hypertrophy &amp;gt;15mm; median therapy duration 1,153 [237, 1,828] days). The primary efficacy outcome occurred less often in patients treated with SCB (3/100 (99/3,316) patient-years) than in patients who never received SCB (SCBnever 4.9/100 (150/3,083) patient-years, p&amp;lt;0.001). There were numerically fewer primary safety outcomes in patients receiving SCB (2.9/100 (96/3,359) patient-years) than in SCBnever patients (4.2/100 (135/3,220) patient-years, adjusted p=0.015). Sinus rhythm at 2 years was similar between groups (SCB 537/610 (88); SCBnever 472/579 (82)). Conclusion Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including selected patients with stable cardiovascular disease such as coronary artery disease and stable heart failure.

Cost-effectiveness of sotagliflozin for the treatment of patients with diabetes and recent worsening heart failure.

Aim: To assesses the cost-effectiveness of sotagliflozin for the treatment of patients hospitalized with heart failure and comorbid diabetes. Materials & methods: Ade novo cost-effectiveness model with a Markov structure was created for patients hospitalized for heart failure with comorbid diabetes. Outcomes of interest included hospital readmissions, emergency department visits and all-cause mortality measured over a 30-year time horizon. Baseline event frequencies were derived from published real-world data studies; sotagliflozin's efficacy was estimated from SOLOIST-WHF. Health benefits were calculated quality-adjusted life years (QALYs). Costs included pharmaceutical costs, rehospitalization, emergency room visits and adverse events. Economic value was measured using the incremental cost-effectiveness ratio (ICER). Results: Sotagliflozin use decreased annualized rehospitalization rates by 34.5% (0.228 vs 0.348, difference: -0.120), annualized emergency department visits by 40.0% (0.091 vs 0.153, difference: -0.061) and annualized mortality by 18.0% (0.298 vs 0.363, difference: -0.065) relative to standard of care, resulting in a net gain in QAYs of 0.425 for sotagliflozin versus standard of care. Incremental costs using sotagliflozin increased by $19,374 over a 30-year time horizon of the patient, driven largely by increased pharmaceutical cost. Estimated ICER for sotagliflozin relative to standard of care was $45,596 per QALY. Conclusion: Sotagliflozin is a cost-effective addition to standard of care for patients hospitalized with heart failure and comorbid diabetes.

Reinforcement of pimobendan with guideline-directed medical therapy may reduce the rehospitalization rates in patients with heart failure: retrospective cohort study

BackgroundPimobendan reportedly improves the subjective symptoms of heart failure. However, evidence of improved prognosis is lacking. This study aimed to determine whether reinforcing guideline-directed medical therapy (GDMT) improved rehospitalization rates for worsening heart failure in patients administered pimobendan.MethodsA total of 175 patients with heart failure who were urgently admitted to our hospital for worsening heart failure and who received pimobendan between January 2015 and February 2022 were included. Of the 175 patients, 44 were excluded because of in-hospital death at the time of pimobendan induction. The remaining 131 patients were divided into two groups, the reduced ejection fraction (rEF) (n = 93) and non-rEF (n = 38) groups, and further divided into the GDMT-reinforced and non-reinforced groups.ResultsIn patients with rEF, the rate of rehospitalization for heart failure was significantly lower in the GDMT-reinforced group than in the non-reinforced group (log-rank test, P = .04). However, the same trend was not observed in the non-rEF group.ConclusionsReinforcing GDMT may reduce the heart failure rehospitalization rate in patients with pimobendan administration and rEF. However, multicenter collaborative research is needed.Trial registrationIRB Approval by the Nippon Medical School Hospital Ethics Committee B-2021-433 (April 10, 2023).

HYPERTROPHIC CARDIOMYOPATHY AND MYBPC3 VARIANT - A CLINICAL CASE

Abstract Introduction Hypertrophic cardiomyopathy is a primary pathology of the cardiac muscle. Sarcomeric forms of hypertrophic cardiomyopathy (HCM) often have autosomal dominant transmission. A pathogenetic or likely pathogenetic mutation affecting genes encoding sarcomeric proteins is present in 30-60% of cases. In this study, we present a case of a family affected by hypertrophic cardiomyopathy with a mutation classified as of uncertain significance in the MYBPC3 gene. Clinical Case Mr. AA, 74 years old, attended the cardiomyopathy outpatient clinic of our hospital in June 2021 due to worsening heart failure with an hypertrophic phenotype. His medical history reported an increase in the thickness of the interventricular septum (IVS) since 1985. In 2015, the patient underwent pacemaker implantation for symptomatic 2:1 atrioventricular block associated with syncope and complete left bundle branch block. Since 2016, he had paroxysmal atrial fibrillation complicated by an ischemic stroke in 2019 with subtherapeutic INR. Cardiac magnetic resonance imaging (MRI) or genetic evaluation had never been performed. During the visit, the patient reported that his sister (AG, 73 years old) had undergone tests due to diffuse negative T waves findings in a previous ECG, revealing the presence of a long myocardial bridge of the left anterior descending artery (LAD). No family history of sudden cardiac death was reported. The echocardiogram of AA showed LV hypertrophy (septal wall thickness/posterior wall thickness 18/15 mm, respectively) with an ejection fraction of 36%. Suspecting sarcomeric HCM, a genetic test (TruSight One Expanded Illumina) was performed, revealing two variants of uncertain significance in heterozygosity in the CACNA1C - Calcium Voltage-Gated Channel Subunit Alpha1 C gene (c.2460G&amp;gt;C p.(Lys820Asn)) and MYBPC3 gene (c.2030C&amp;gt;T p.(Pro677Leu)). After a few months, AG presented MRI results suggestive of HCM apical variant (Figure 1). The genetic consultant recommended family screening, and the pedigree is shown in Figure 2. All carriers of the CACNA1C mutation had a negative phenotype. AG's son, IF, 56 years old, carriers of MYBPC3 mutation, presented an MRI compatible with early-stage HCM (Figure 3). His son, carriers of MYBPC3 mutation as well, is now awaiting a cardiac MRI. Conclusions In the family presented here, the MYBPC3 variant (c.2030C&amp;gt;T p.(Pro677Leu)) appears to be correlated with the development of sarcomeric hypertrophic cardiomyopathy. Registry studies with a large sample size are desirable to accurately classify variants of uncertain significance, which are becoming more common due to the widespread use of genetic tests.

Development of interpretable machine learning models to predict in-hospital prognosis of acute heart failure patients.

In recent years, there has been remarkable development in machine learning (ML) models, showing a trend towards high prediction performance. ML models with high prediction performance often become structurally complex and are frequently perceived as black boxes, hindering intuitive interpretation of the prediction results. We aimed to develop ML models with high prediction performance, interpretability, and superior risk stratification to predict in-hospital mortality and worsening heart failure (WHF) in patients with acute heart failure (AHF). Based on the Kyoto Congestive Heart Failure registry, which enrolled 4056 patients with AHF, we developed prediction models for in-hospital mortality and WHF using information obtained on the first day of admission (demographics, physical examination, blood test results, etc.). After excluding 16 patients who died on the first or second day of admission, the original dataset (n=4040) was split 4:1 into training (n=3232) and test datasets (n=808). Based on the training dataset, we developed three types of prediction models: (i) the classification and regression trees (CART) model; (ii) the random forest (RF) model; and (iii) the extreme gradient boosting (XGBoost) model. The performance of each model was evaluated using the test dataset, based on metrics including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), Brier score, and calibration slope. For the complex structure of the XGBoost model, we performed SHapley Additive exPlanations (SHAP) analysis, classifying patients into interpretable clusters. In the original dataset, the proportion of females was 44.8% (1809/4040), and the average age was 77.9±12.0. The in-hospital mortality rate was 6.3% (255/4040) and the WHF rate was 22.3% (900/4040) in the total study population. In the in-hospital mortality prediction, the AUC for the XGBoost model was 0.816 [95% confidence interval (CI): 0.815-0.818], surpassing the AUC values for the CART model (0.683, 95% CI: 0.680-0.685) and the RF model (0.755, 95% CI: 0.753-0.757). Similarly, in the WHF prediction, the AUC for the XGBoost model was 0.766 (95% CI: 0.765-0.768), outperforming the AUC values for the CART model (0.688, 95% CI: 0.686-0.689) and the RF model (0.713, 95% CI: 0.711-0.714). In the XGBoost model, interpretable clusters were formed, and the rates of in-hospital mortality and WHF were similar among each cluster in both the training and test datasets. The XGBoost models with SHAP analysis provide high prediction performance, interpretability, and reproducible risk stratification for in-hospital mortality and WHF for patients with AHF.

Effects of Sacubitril/Valsartan vs Valsartan in De Novo vs Acute on Chronic HFpEF and HFmrEF

BackgroundDecompensated heart failure (HF) can be categorized as de novo or worsening of chronic HF. In PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF), among patients with an ejection fraction >40% that stabilized after worsening HF, sacubitril/valsartan led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and was associated with clinical benefit compared to valsartan. ObjectivesThis prespecified analysis characterized patients with de novo vs worsening chronic HF in PARAGLIDE-HF and assessed the interaction between HF chronicity and the effect of sacubitril/valsartan. MethodsPatients were classified as de novo (first diagnosis of HF) or chronic (known HF prior to the index event). Time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8 was analyzed using an analysis of covariance model. A win ratio consisting of time to cardiovascular death, number and times of HF hospitalizations during follow-up, number and times of urgent HF visits during follow-up, and time-averaged proportional change in NT-proBNP was assessed for each group. ResultsOf the 466 participants, 153 (33%) had de novo HF and 313 (67%) had chronic HF. De novo patients had lower rates of atrial fibrillation/flutter and lower creatinine. There was a nonsignificant reduction in NT-proBNP with sacubitril/valsartan vs valsartan for de novo (0.82; 95% CI: 0.62-1.07) and chronic HF (0.88; 95% CI: 0.73-1.07), interaction P = 0.66. The win ratio was nominally in favor of sacubitril/valsartan for both de novo (1.12; 95% CI: 0.70-1.58) and chronic HF (1.24; 95% CI: 0.89-1.71). ConclusionsThere is no interaction between HF chronicity and the effect of sacubitril-valsartan.