Rehospitalization For Heart Failure Research Articles

Efficacy of native T1 mapping for patients with non-ischemic cardiomyopathy and ventricular functional mitral regurgitation undergoing transcatheter edge-to-edge repair

Abstract Background The objectives of this study were to investigate the efficacy of LV myocardial damage assessment by native T1 mapping obtained with cardiac magnetic resonance (CMR) for symptomatic heart failure (HF) patients with non-ischemic cardiomyopathy (NICM) and ventricular functional mitral regurgitation (VFMR) undergoing transcatheter edge-to-edge repair (TEER). Methods We studied 40 symptomatic HF patients with NICM and VFMR undergoing TEER. LV myocardial damage was defined as the native T1 Z-score which was converted from native T1 value obtained with CMR before TEER. The primary endpoint was defined as first re-hospitalization for HF or cardiovascular death over a median follow-up period of 12 months after TEER. Results Multivariable Cox-proportional hazards analysis showed that a native T1 Z-score was the only independent parameter associated with cardiovascular events (hazard ratio: 3.40, 95% confidential interval: 1.51-7.67), and patients with native T1 Z-score < 2.41 experienced significantly fewer cardiovascular events than those with a native T1 Z-score ≥ 2.41 (log-rank P = 0.001). Moreover, such a low native T1 Z-score and more severe VFMR in an effective regurgitant orifice area (EROA) ≥ 0.30 cm2 was associated with fewer cardiovascular events than for a high native T1 Z-score of ≥ 2.41 and less severe VFMR of EROA < 0.30 cm2 (log-rank P = 0.002). Conclusion Assessment of baseline LV myocardial damage by means of native T1 Z-score obtained with CMR without the use of gadolinium-based contrast media is a valuable additional parameter for better management of symptomatic NICM patients with reduced LVEF and VFMR following TEER.

Environmental noise exposure is associated with one-year survival after a first myocardial infarction

Abstract Introduction Although several studies have shown a link between environmental noise exposure and risk of acute Myocardial Infarction (MI), only few studies have investigated its association with prognosis after MI. We aimed was to analyze the relationship between residential environmental noise exposure and one-year prognosis after a first MI. Methods This observational, longitudinal study was conducted from data collected by a French observatory (RICO) from 2004 to 2009. The outcome was defined by Major Adverse Cardiovascular Events (MACE). Medical data were collected from patients hospitalized for an acute MI from patients registered in the database between January 1st, 2004, and December 31st, 2008, with the following criteria: first MI, aged 18 years or older, with a valid home address and residing in a French urban unit, and who survived at least 28 days after the acute MI were included in the present study. Environmental noise and air pollutants exposure were considered at the residence of the patients. Noise exposure was quantified for two time periods: daily (LAeq,24h) and at night (Lnight) with an annual average. Two outdoor air pollutants were considered: nitrogen dioxide (NO2) and particulate matter with an aerodynamic diameter ≤ 10 µm (PM10). Air pollution exposure levels within the 30 days preceding a major cardiac event (MACE) were estimated. MACE were defined as cardiac death, re-hospitalisation for heart failure, recurrent MI, emergency revascularization, stroke, angina and or unstable angina Results Among the 864 subjects included, most were male (64%), the median age was at 69 y. Nineteen percent (N = 164) presented a MACE during the one year follow-up, and the most frequent were cardiac death (32%). For each 10 dB(A) increase during Lnight , the hazard ratio (HR) of MACE was 1.25 (95% IC 1.09 to 1.43), independently of air pollutants and other confounding. This effect was modified by age and gender. Conclusion and relevance: Our findings suggest for the first time a strong association between noise exposure, in particular during the night, and prognosis at one year after a first MI. If confirmed by larger prospective studies, our study could help to identify original opportunities for environment-based secondary prevention strategies.

Left atrial reservoir strain and global longitudinal strain associates with re-hospitalization and mortality in patients admitted for acute heart failure

Abstract Background Left atrial reservoir strain (LAr) and global longitudinal strain (GLS) have emerged as useful parameters for the assessment of left ventricular diastolic function and the estimation of left ventricular filling pressures. Yet, there remains a gap of knowledge regarding the possible association of LAr and GLS with re-hospitalization and mortality in patients with acute heart failure (HF). Aims This study aims to investigate the association between LAr and GLS with re-hospitalization and mortality in patients admitted for acute HF. Methods Out of 526 enrolled patients admitted for acute HF, 142 (mean age 71, 25% women) were systematically evaluated for LAr and GLS using speckle tracking echocardiography. Multivariable Cox regression analyses, adjusting age, sex, current smoking prevalent atrial fibrillation, hypertension, kidney disease and plasma glucose, were used to assess the associations between continuous values of LAr and GLS with all-cause mortality and HF-related re-hospitalization. Results The median follow-up time to death of any cause and HF rehospitalization was 39 (interquartile range 14-66) and 22 (4-51) months, respectively. During follow up, 63 (44%) patients died, and 63 (44%) were re-hospitalized due to HF. Lower values of LAr were significantly associated with higher risk of mortality (HR 0.93; 95%CI 0.89-0.98, p=0.008). Similarly, lower GLS was associated with higher risk of mortality (HR 0.94; 95%CI 0.89-0.99, p=0.045). Only lower values of LAr were associated with higher risk of HF re-hospitalization in the multivariable model (HR 0.93; 95%CI 0.88-0.98, p=0.004). Conclusion In this prospective, long-term follow-up study of patients with acute heart failure, lower values of LAr and GLS showed prognostic significance, with lower values being indicative of poorer outcomes. Notably, LAr was associated with higher risk of both death and rehospitalization for heart failure, whereas GLS was solely associated with higher mortality risk. These echocardiographic parameters could be further investigated for risk assessment of patients with heart failure in order to identify those at higher risk of rehospitalization and death, thereby facilitating targeted interventions to improve their prognosis.KM-curves for or the Quartiles of LAr

Predictors of Right vEntricular Failure aftER LVAD implantation: PREFER LVAD study

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

Phenotype of patients with severe aortic stenosis and small aortic annulus: how does it impact on hemodynamics and on transcatheter aortic valve implantation outcomes

Abstract Background Discordant grading of severe aortic stenosis can result from a tight aortic valve area (<1cm2) with a low transvalvular mean gradient (<40 mmHg). Small aortic annulus dimensions and low flow status may contribute to discordant grading of severe aortic stenosis. However, the frequency of patients with small aortic annulus and discordant grading, along with their characteristics and outcomes after intervention, remains unknown. Purpose To investigate the frequency of discordant grading severe aortic stenosis in patients with a small aortic annulus and to evaluate their clinical characteristics, as well as outcomes after transcatheter aortic valve implantation (TAVI). Methods Patients with an aortic annulus diameter < 23 mm determined by cardiac computed tomography who underwent TAVI between 2018 to 2023 were retrospectively evaluated. Patients were followed for the occurrence of the composite endpoint of of all-cause mortality, rehospitalizations for heart failure, non-fatal myocardial infarction, and non-fatal stroke. Results Among 230 patients with severe aortic stenosis and a small aortic annulus, 52 (23%) had discordant gradient (24 with low flow low gradient (LFLG) and 28 with normal flow low gradient (NFLG)) while 120 (52%) exhibited normal flow high gradient (NFHG) and 58 (25%) had low flow high gradient (LFHG). The majority of the patients were female (Table 1). Differences were noted among the three groups regarding aortic transvalvular gradients, stroke volume index and ejection fraction. During a median follow-up of 2 years, the composite endpoint occurred in 20% of the total cohort. Patients with discordant grading severe aortic stenosis experienced the worse outcome (Figure1). Conclusions Most patients with severe aortic stenosis and small annulus have high gradient and only 23% of patients presented discordant grading. Patients with discordant grading severe aortic stenosis showed worse outcomes, suggesting potential delays in referral due to challenges in diagnosing severe aortic stenosis among patients with small aortic annulus.Basal clinical characteristicsKaplan-Meier survival curves

Growth differentiation factor-15 and 5-years cardiovascular risk in chest pain patients presenting to the emergency department: a multicenter cohort study

Abstract Background Growth differentiation factor 15 (GDF-15) has been explored as a prognostic biomarker in multiple disease entities, including ischemic heart disease and heart failure (HF), but its role as a prognostic marker in chest pain patients presenting to the emergency department (ED) is unknown. Purpose To investigate the association between GDF-15 and 5-year all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE), and to evaluate its prognostic incremental value. Methods Patients presenting to the ED with acute chest pain were prospectively enrolled in an international multicenter diagnostic study. GDF-15 concentrations were measured in a blinded fashion upon ED presentation. Follow-ups were performed at 3 months, 1-, 2- and 5-years. MACE was defined as the composite of cardiovascular mortality, acute myocardial infarction, stroke, and HF rehospitalization. Associations between GDF-15 and each prognostic outcome were modeled using multivariable Cox proportional hazard regression fitting restricted cubic splines to continuous variables. The magnitude of the effect of each GDF-15 unit change on multivariable-adjusted models was assessed graphically using dose-response plots. To compute an HR for the dose-response plots we chose a GDF-15 value of 1200 pg/mL as a reference value as this has been chosen in previous literature1. For the restricted cubic splines three knots were used. The added prognostic value of GDF-15 was evaluated by the increase in the C-statistic between a base and an extended model and the fraction of new information (FNI) provided by GDF-15. Results A total of 4779 chest pain patients had baseline GDF-15 values available. The median age was 61 [48-74] and 33% were female. Higher GDF-15 levels were more strongly associated with heart failure, kidney dysfunction, older age, hypertension, diabetes and coronary artery disease. GDF-15 was independently associated with 5-years all-cause mortality, cardiovascular mortality and MACE (Figure). When adding GDF-15 to a rich-for-prior-information base model which included age, sex, cardiovascular risk factors, creatinine, cardiac troponin and NT-proBNP, GDF-15 provided relevant incremental prognostic discrimination for 5-years all-cause death and cardiovascular death. (Table). Conclusions In chest pain patients presenting to the emergency department, GDF-15 concentration on admission was associated with 5-years all-cause mortality, cardiovascular mortality, and MACE. In addition, it provided relevant incremental prognostic information when added on top of troponin and NT-proBNP, the two current prognostic gold standard biomarkers.FigureTable

The impact of the 2022 definition of pulmonary hypertension on long-term clinical outcomes in patients with heart failure with preserved ejection fraction

Abstract @ Backgrounds: In recent years, the definitions of pulmonary hypertension (PH) have been revised for early diagnosis and risk stratification of patients with PH. Using the 2015 definitions, the development of a precapillary component of PH in addition to a postcapillary PH was associated with right heart dysfunction and poor prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). However, the prognostic impact of revised definitions of PH in patients with HFpEF has not been fully evaluated. Purpose We investigated the impact of the 2018 and 2022 ESC/ERS definitions of PH on long-term clinical outcomes using data from a prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF). Methods A total of 250 patients hospitalised with acute HF who underwent right heart catheterisation after initial HF treatment were divided into PH categories according to the 2018 and 2022 definitions: isolated postcapillary PH (Ipc-PH), precapillary PH, combined postcapillary and precapillary PH (Cpc-PH), and unclassified PH. The incidence of the composite endpoint of all-cause death and HF rehospitalisation after discharge was compared across the PH categories. Results The overall prevalence of PH defined as a mPAP > 20 mmHg was 54%. Applying the 2022 definition, 42 patients (17%) were reclassified as either precapillary PH or Cpc-PH, resulting in a significant increase in the propotion of patients classified as having PH with a precapillary component (precapillary PH and Cpc-PH) compared with the 2018 definition (26% vs. 11%, p<0.0001). At a median follow-up of 822 days after discharge, PH with a precapillary component was associated with poor clinical outcomes according to the 2018 definition (Figure 1A), but according to the 2022 definition, clinical outcomes did not differ across the PH categories (Figure 1B). PVR ≥3 Wood units (WU) was a significant prognostic indicator, but there was no significant difference between the PVR 2-3 WU and PVR ≤2 WU categories (Figure 2). Conclusions The 2022 definition showed no association between PH classification and clinical outcomes. In patients with HFpEF, PVR ≥3 WU was identified as the key factor increasing the risk of all-cause death and HF hospitalisation.Figure 1Figure 2

Prognostic role of right ventricular-pulmonary artery coupling assessed by TAPSE/PASP ratio in patients with heart failure and mildly reduced ejection fraction

Abstract Background The development of right ventricular (RV)-pulmonary arterial (PA) coupling has resulted in a novel and comprehensive index for evaluating RV function in relation to the underlying RV afterload. In patients with heart failure (HF), it is acknowledged that RV-PA uncoupling are features that are associated with poor outcome. The RV-PA coupling index can be readily assessed non-invasively using the ratio of two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). However, few studies have defined the prognostic impact of the TAPSE/PASP ratio in patients with HF and mildly reduced EF (HFmrEF). Methods From the prospective cohort study of 1,410 hospitalized HF patients (age 68+/-15, men 62%) between August 2015 and September 2019, this study enrolled 191 HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41–49%) patients whose TAPSE and PASP were measured during hospitalization and discharged alive. We studied the prognostic impact of TAPSE/PASP ratio on HFmrEF patients using by cut-off value obtained from receiver operating characteristic (ROC) analysis. The primary and secondary endpoints was defined as the all-cause death and HF re-hospitalization after discharge, respectively. Results During median follow-up of 38 [23–52] months, 48 patients (25%) died. The deceased patients had a significantly older (median 75 vs. 71 years, p<0.05), higher rate of ischemic heart disease (50% vs. 23%, p<0.05), elevated brain natriuretic peptide levels (325 vs. 159 pg/ml, p<0.05) and lower rate of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (65% vs. 80%, p<0.05) at discharge. In the ROC analysis, the cut-off value of TAPSE/PASP ratio for mortality was 0.46. Patients with TAPSE/PASP ≤0.46 had a significantly higher all-cause mortality (log-rank p<0.05) and had a tendency of higher rate of HF re-hospitalization than patients with TAPSE/PASP >0.46 (log-rank p=0.06) (Figure). Using multivariate analysis, the lower TAPSE/PASP ratio had an independent predictive value of prognosis in patients with HFmrEF (hazard ratio 2.16, 95% confidence interval; 1.08–3.92, p<0.05) (Table). Conclusion The TAPSE/PASP ratio has a significant prognostic value in patients with HFmrEF. The RV-PA uncoupling assessed by TAPSE/PASP ratio might be useful for risk assessment in patients with HFmrEF.

Left atrial reservoir strain as a prognostic indicator for cardiovascular events after mitral valvuloplasty

Abstract Background In patients after mitral valvuloplasty (MVP), assessing valve function and heart failure (HF) is crucial for prognostic predictions. Left ventricular diastolic function assessed by transthoracic echocardiography (TTE) plays an important role in the evaluation of HF in general practice. However, post-mitral valve surgery patients are excluded from the left ventricular diastolic function assessment guidelines proposed by the American Society of Echocardiography in 2016 due to their low correlation with left ventricular diastolic function indices. On the contrary, the left atrial reservoir strain (LARS) before MVP is considered as a prognostic factor, reflecting left atrial dysfunction caused by mitral regurgitation. Nevertheless, there are limited reports on the relationship between LARS and cardiovascular (CV) events after MVP. Purpose The study aims to investigate the utility of LARS in predicting CV events after MVP. Methods The study included 249 patients who underwent TTE between January 2011 and January 2023 after MVP at our hospital. Patient background data, including NYHA classification, medical history, medications, blood tests, and TTE data, were collected at the time of follow-up TTE. LARS, left ventricular global longitudinal strain (LV-GLS), and right ventricular free wall strain (RV-FWSL) analysis were performed using a vender-independent external strain analysis software for all patients in the cohort. The primary endpoints were cardiovascular death and HF rehospitalization. The predictor of cardiovascular events was assessed using the Cox proportional hazards model and Kaplan-Meier curve (KMC). Results The mean age was 61±14 years, and 159 patients (64%) were male. The median time from surgery to TTE was 4.8 (1.0-6.8) years, 32 patients (13%) had events within 8.5 (3.7-10.8) years after TTE. The event groups had higher age, NYHA classification, and NT-pro BNP compared to the non-event group. TTE parameters such as left ventricular mass index, left ventricular end-diastolic volume and end-systolic volume were larger, and LV-GLS and LARS were significantly lower in the event group. In multivariate Cox proportional hazards models showed that LARS was also a prognostic indicator even after adjustment for several variables (Table 1). The KMC showed that LARS was associated with events regardless of left atrial volume index (Log-rank p <0.001, chi-square:31.03) (Figure 1). Conclusion LARS was strongly associated with CV events after MVP. We consider LARS to be a useful prognostic indicator after MVP.

Contemporary use of beta-blockers in the outpatient treatment of heart failure with atrial fibrillation

Abstract Background Evidence of the effectiveness of β-blockers in heart failure (HF) and atrial fibrillation (AF) in a contemporary cohort is controversial. This study investigated the association between the use of β-blockers and prognosis in outpatients across a broad spectrum of HF with AF. Methods Patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between 2014 and 2021. Associations of β-blocker use at discharge and prognosis were compared by propensity score matching among the AF or non-AF group. A multilevel mixed-effects survival model was used with hazard ratio (HR) and 95% confidence interval (CI). Results Among 428,650 patients discharged with HF in 4,433 hospitals, 175,174 (40.9%) were ≥85 years old, 151,873 (35.4%) had complicated AF, and 236,457 (55.2%) were β-blocker users. In a matched AF group, β-blocker use was associated with a lower composite outcome of all-cause mortality or HF rehospitalization (HR [95% CI], 0.95 [0.93–0.97]). A similar result was obtained in a matched non-AF group (0.95 [0.94–0.96]). In addition, the HRs in patients aged ≥85 years and female patients were 1.00 [0.98–1.02] and 1.01 [0.98–1.03] in the AF group and 1.03 [1.01–1.05] and 0.98 [0.97–1.00] in the non-AF group, respectively (Figure). Conclusions The favorable prognostic associations of β-blocker use were observed regardless of AF in outpatients across a broad spectrum of HF in a superaged society. However, β-blocker use may not be effective in older or female patients.

Impact of mitral transcatheter edge-to-edge repair in patients with advanced heart failure evaluated for heart transplantation

Abstract Background Heart transplantation is sometimes the only therapeutic option in patients with advanced heart failure (HF), impaired ventricular function and significant functional or secondary mitral regurgitation (MR). The shortage of organs and the limitations of the recipient make it necessary to consider other therapeutic alternatives in these patients, such as mitral transcatheter edge-to-edge repair (M-TEER). The MitraBridge registry has recently been published in which they analyze the potential effect of M-TEER in patients with advanced HF and moderate-severe MI who are candidates for heart transplantation (mean age 59 years, left ventricular ejection fraction (LVEF) 27%); after a mean follow-up of 24 months, complete in 82.4%, they report an overall survival of 78.5%, a combined event-free survival of 47%, with a 6.5 % need for urgent transplantation and an HF hospitalization rate after M-TEER of 44/100 patient-years. The aim of our study is to assess the impact of M-TEER on mortality and the combined events of death, HF rehospitalization and the need for urgent transplantation or a ventricular assistance device in patients with moderate-severe functional MI and advanced HF who have also been evaluated for cardiac transplantation in our hospital. Methods This is a retrospective analysis of a prospective registry. Of the patients treated by M-TEER for severe MI, we selected those with advanced HF (defined as LVEF≤35%, and/or advanced functional class (NYHA III-IV)) who had also been evaluated as possible candidates for inclusion in the heart transplant list. Results From November 2011 to December 2023, 191 patients were treated by M-TEER, of whom 38 patients met the established criteria (median age 59 years [48-65], 31 (81%) males, mean LVEF was 26 ± 6%). All patients had at least one previous hospitalization for HF and optimal medical treatment according to guidelines; the rest of the baseline clinical characteristics are listed in Table 1. During the follow-up after M-TEER, with a median of 34 months [7-70], the probability of overall survival at 2 years was 75.6%. The combined endpoint of death, need for urgent transplantation or a ventricular assist device, and rehospitalization for heart failure occurred in 26 patients with a 2-year event-free survival probability of 48% (Figure 1). Five patients (13%) were transplanted, one (2.6%) urgently. Prior to M-TEER therapy, the rate of HF hospitalization was 108 hospitalizations/100 patient-years, which was significantly reduced after the procedure to 33 hospitalizations/100 patient-years (rate ratio 0.31 [95% CI 0.21-0.45, p<0.0005]). Conclusions In patients with advanced HF and severe functional MR who are candidates for cardiac transplantation, M-TEER is an effective therapeutic alternative, achieving a survival rate of more than three-quarters of the patients at 2 years of follow-up, a significant reduction in HF hospitalizations, and a low rate of need for cardiac transplantation.

Prognostic impact of myocarditis as aetiology compared with dilated cardiomyopathy and ischaemic heart disease in heart failure

Abstract Background A subgroup of myocarditis can lead to heart failure. However, whether prognosis of myocarditis-induced heart failure differs from other heart failure remains largely unknown. Aim This study aimed to investigate the prognostic impact of myocarditis induced heart failure compared with heart failure with dilated cardiomyopathy and ischaemic heart disease as causes respectively in the overall population and a propensity score-matched cohort, based on patient-level data from the Swedish Heart Failure Registry (SwedeHF). Methods Patients with heart failure (HF) were enrolled from the SwedeHF (2003-2020) linked with the National Patient Register, and the Swedish Cause of Death Register. Endpoints were all-cause mortality, cardiovascular death, and hospital re-admissions, followed up from the index date until censoring or event. Results Of 54416 patients identified through the SwedeHF with HF, 418 hade myocarditis as aetiology (MC-HF), 6,871 with dilated cardiomyopathy (DCM-HF) and 47127 with ischemic heart diseases (IHD-HF). In general patients with MC-HF have shorter disease duration and less comorbidities compared with DCM-HF and IHD-HF, but older than DCM-HF and younger than IHD-HF. Compared with DCM-HF, MC-HF are associated with 29% higher risk for all cause mortality [(1.29 (1.07 - 1.55), p=0.0079] and 40% higher risk for cardiovascular death [ 1.40 (1.09 - 1.80), p=0.0088], and 19 % higher risk for heart failure rehospitalization [1.19 (1.03 - 1.37), p=0.018] and even higher risk by censoring within one-year . However, compared with IHD-HF, patients with MC-HF have similar risk for all cause mortality [0.95 (0.80 - 1.13), p=0.54], cardiovascular death [0.95 (0.75 - 1.20), p=0.65], and heart failure rehospitalization [0.93 (0.81 - 1.06), p=0.29]. Similar results were obtained from a propensity 1:2 matched cohort. No significant interactions were found regardless of age (< and < 70 years) , sex, LVEF (≥50%, 40-49%, 30-39% and < 30%) for all cause mortality comparing MC-HF vs DCM-HF, and MC-HF vs IHD-HF. Conclusion Patients with myocarditis-induced heart failure have worse outcome than heart failure due to dilated cardiomyopathy, with even higher risk during one year. This finding highlights the importance of early and more effective customized management of patients with myocarditis in particular those with high risk to develope heart failure.

Estimation of salt intake from urinalysis as a prognostic indicator in patients with heart failure

Abstract Background Restricting sodium consumption by reducing salt intake is crucial in heart failure management. The average salt intake in Japan is approximately 10 g/day, which is significantly higher than that in other countries. Therefore, the Japanese guidelines for heart failure recommend a target salt intake of less than 6 g/day. Purpose Excessive salt intake is a well-known risk factor for heart failure, but it has also been reported that excessive salt restriction does not affect clinical outcomes in patients with heart failure. Moreover, although previous reports have mainly focused on clinically stable patients with chronic heart failure, appropriate salt intake management in patients with unstable heart failure immediately after hospital discharge remains unexplored. Therefore, this study aimed to investigate the effect of salt intake management on patients with heart failure in the early post-discharge period. Methods The study was conducted between April 2015 and March 2023, and included 395 of 4,292 patients (mean age: 72 y; sex: 63% male) who were hospitalized owing to heart failure and whose salt intake was measured at early post-discharge. Salt intake was estimated via the Tanaka Method, using spot urine samples. The patients were divided into four groups based on the estimated salt intake: very low (< 4 g/day) (n = 24), low (≥ 4 and < 7 g/day) (n = 109), high (≥ 7 and < 10 g/day) (n = 149), and very high (≥ 10 g/day) (n = 113). The primary endpoint was all-cause rehospitalization within 1 year of discharge. Results During a median follow-up period of 303 days, 153 rehospitalization occurred. 96 were heart failure rehospitalization; others included infection, arrhythmia, dehydration etc. Spline curve analysis for estimated salt intake and rehospitalization (Fig. 1) showed a significant nonlinear curve (P = 0.017). Cox regression analysis (Fig. 2) revealed a significantly higher number of rehospitalization in the very low group (hazard ratio [HR]: 2.29; 95% confidence interval [CI]: 1.24–4.25; P = 0.009), compared with the low group, and a similar trend was also observed in the very high group (HR: 1.51; 95% CI: 0.99–2.31; P = 0.056). Subgroup analysis (Fig. 3) showed that the impact of estimated salt intake on rehospitalization, as represented by a U-shaped curve, was more pronounced in patients who were not treated with loop or thiazide diuretics. Conclusion The results of this study suggest that both excessive salt intake and excessive restriction may increase the risk of rehospitalization in patients with heart failure during the early post-discharge period. Additionally, the results indicate that estimation of salt intake using the Tanaka method may be particularly useful for patients not undergoing diuretic treatment. Conversely, patients with very low salt intake, potentially indicative of inadequate oral intake due to an impaired general condition, may require careful follow-up.

The dynamics of urine sodium concentration after intra-venous furosemide in patients with acute heart failure

Abstract Background The urine sodium concentration measured at 2 hours after the administration of intravenous (IV) furosemide in patients with acute heart failure (AHF) is recommended as a marker to assess the responsiveness to IV furosemide. However, little is known regarding the dynamics of natriuresis in the very acute phase after IV furosemide and its association with prognosis in patients with AHF. Purpose The aim of this study is to investigate the dynamics of natriuresis in the very acute phase after IV furosemide and its prognostic implication in patients with AHF. Methods DIURESIS-AHF (Diuretic Resistance Measured by Sodium Excretion and Urine Output in Acute Heart Failure) is a multicenter, prospective, and observational study that evaluated the urine samples at the time of 0h, 1h, 2h, 6h, and 24h after the first administration of IV furosemide in hospitalized patients with AHF. Results After excluding 20 patients who needed additional IV furosemide within the first 6 hours, and 9 patients with missing data about 1h-spot urine sample, 84 patients with AHF (79±8 years, 55% men) were analyzed. Median N-terminal pro-brain natriuretic peptide levels at admission were 4722 [interquartile: 2616-8095] pg/mL, and median first IV furosemide doses were 20 [interquartile:20-20] mg. 29 combined event of all-cause death and heart failure rehospitalization were observed during a 1-year follow-up after registration. Urine sodium concentration corrected for urine creatinine concentration peaked 1 hour and decreased at 2 hours after IV furosemide. Kaplan-Meier curve analysis indicated that 1h urine sodium concentration below 50 mEq/L was significantly associated with a high incidence of composite endpoint (Log-rank P=0.033), and this association was retained even after adjusting for age and sex (hazard ratio, 2.37 [95% CI, 1.03-5.45]; P=0.042), but 2h urine sodium below 50 mEq/L was not associated with a poor prognosis (Log-rank; P=0.630). Conclusions Urinary sodium excretion after IV furosemide administration peaked at 1 hour after IV furosemide and decreased at 2 hours in patients with AHF. The urine sodium concentration below 50 mEq/L at 1 hour, but not 2 hours, was associated with adverse events.Urine Na trajectoriesKaplan Meier curves

The prognostic impact of tricuspid regurgitation improvement after left-sided valvular interventions

Abstract Background Tricuspid regurgitation is a common bystander in patients with left-sided valvular heart disease such as mitral regurgitation (MR) or aortic stenosis (AS). Data on the prognostic impact of potential TR improvement after interventions for left sided valvar disease is scarce. Objectives This study aimed to assess incidence and prognostic value of TR improvement after left-sided valvular interventions (M-TEER and TAVI) using merged data from two prospective single-center registries. Methods The merged database included all consecutive patients with symptomatic left-sided valvular heart disease (MR or AS) undergoing either M-TEER or TAVI from 2008 until 2023. The prognostic impact of baseline TR severity and TR improvement was assessed using Kaplan-Meier estimates and stepwise Cox regression. TR improvement was defined as a reduction in TR severity at discharge by at least one grade compared to baseline in patients with ≥moderate TR at baseline. Results A total of 4,461 patients undergoing left-sided valvular interventions (M-TEER: N=663; TAVI: N=3,798) were eligible for study inclusion (age 81.0 years [IQR 76.2-84.7], 52.7% male). TR severity at baseline was none or mild in 70.9% (N=3,161), moderate in 19.4% (N=864), and severe in 9.8% (N=436). Patients with ≥moderate TR at baseline showed significantly higher rates of all-cause mortality (p<0.001) and of the combined endpoint after 3 years (p<0.001), compared to patients with none or mild TR. This finding was consistent for the M-TEER and TAVI subgroups. Among patients with ≥moderate TR at baseline (N=1,300), 499 patients (38.4%) showed TR improvement by at least one grade following left-sided valvular intervention, while TR did not improve in 801 patients (61.6%). In the overall study population, patients with TR improvement showed lower rates of all-cause mortality (p<0.001) and the combined endpoint after 3 years (p=0.006) (Figure 1A, 1B). This finding was consistent only in the subgroup of patients undergoing M-TEER (p=0.013 and p=0.003), but not for patients undergoing TAVI (p=0.12 and 0.62) (Figure 2A, 2B). Following stepwise Cox regression (incl. adjustment for treatment), TR ≥moderate at baseline was independently associated with death (p=0.0019) and combined death or HF rehospitalization (p=0.0068) 3 years after intervention (Figure 3A,3B). TR improvement was independently associated with survival (p=0.015) and combined survival or absent HF rehospitalization (p=0.032) 3 years after intervention (Figure 4A, 4B). Conclusions Patients with TR improvement after left sided valvular interventions showed significantly better clinical outcomes compared to those without. These results reinforce the need for assessment for TR assessment before and after left-sided valvular interventions and may identify patients that qualify for subsequent TR intervention.

The prevalence and impact of changes in the severity of secondary TR during hospitalization in acute heart failure

Abstract Background Secondary tricuspid regurgitation (TR) is a prevalent entity in patients hospitalized for acute heart failure (AHF), and concomitant moderate or severe TR at admission has been demonstrated to be associated with a poor prognosis. However, no study has described the trajectories of the severity of secondary TR during admission, and the prognostic implications of changes in the severity of secondary TR. Purpose This study aimed to investigate the dynamism of secondary TR observed during hospitalization due to worsening heart failure, and its prognostic impact in patients with AHF. Methods A post-hoc analysis of 1,061 consecutive patients hospitalized with AHF was performed, enrolled in the prospective, multicenter Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure (REALITY-AHF). Patients included in the study underwent a comprehensive echocardiographic examination within 24 hours of admission and again prior to discharge. Patients were divided into four groups based on the TR severity at admission and discharge: none to mild TR at both admission and discharge (no/no group), moderate to severe TR at admission but improved to none to mild TR at discharge (resolution group), none to mild TR at admission but moderate to severe TR at discharge (worsening group), and moderate to severe TR at both admission and discharge (persistent group). The primary endpoint was the composite of 1-year all-cause mortality and HF re-hospitalization after discharge. Results The no/no, resolution, worsening, and persistent groups included 479 (45%), 275 (26%), 85 (8%), and 222 patients (21%), respectively. The no/no group and the resolution group had significantly lower tricuspid regurgitant pressure gradients prior to discharge compared to the worsening and persistent groups (P<0.001). Also, right ventricular dysfunction evaluated at discharge, defined by tricuspid annular plane systolic excursion <17 mm, was more prevalent in the worsening (65.7%) and persistent groups (66.4%) compared to the no/no (43.7%) and resolution (53.2%) groups (P<0.001). Compared to the no/no group, the worsening and persistent groups, but not the resolution group, were associated with a higher incidence of the primary endpoint (Log-rank: P<0.001). This association remained significant in an adjusted Cox regression analysis, with the worsening group (hazard ratio: 1.48, 95% confidence interval [CI]: 1.01–2.20) and persistent group (hazard ratio: 1.35, 95% CI: 1.01–1.83) independently associated with the primary endpoint, but not the resolution group (hazard ratio: 1.10, 95% CI: 0.81–1.49). Conclusions In patients hospitalized for AHF, the severity of secondary TR is dynamic, and changes in the severity of TR are significantly associated with prognosis. Our study results underscore the importance of repetitive evaluation of TR in hospitalized patients with AHF.

Transcatheter aortic valve replacement with balloon-expandable and self-expandable valves in Japanese patients with large annulus: the OCEAN-TAVI registry

Abstract Background East Asians have smaller aortic valve complexes than individuals from Western countries, and few studies have reported transcatheter aortic valve replacement (TAVR) outcomes in Asian patients with a large annulus. Purpose We aimed to compare the acute and long-term outcomes of TAVR using balloon-expandable valves (BEVs) and self-expandable valves (SEVs) in Asian patients with a large annulus. Methods We retrospectively analyzed the data from the Optimized transCathEter vAlvular interveNtion Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. A large annulus was defined by annular area ≥ 500 mm2 and average diameter ≥ 25 mm in computed tomography scans. The primary endpoint was the 3-year all-cause mortality. Secondary endpoints were 3-year heart-failure rehospitalization (HFR) after TAVR, acute outcomes of TAVR, and changes in valve function on echocardiography 2 years after TAVR. Results Among 773 patients, 671 (86.8%) underwent BEV-TAVR. The SEV-TAVR group showed a significantly higher incidence of above-moderate perivalvular leakage (2.1% vs. 7.8%; P < 0.001), and included a significantly greater percentage of patients who required postoperative pacemaker implantation (6.1% vs. 11.8%; P = 0.035). The incidence of moderate-to-severe prosthesis–patient mismatch did not differ between the two groups. The Kaplan–Meier curve showed no significant intergroup differences in the 3-year all-cause mortality and HFR rates (log-rank P = 0.900), and the echocardiography-indexed effective orifice area and mean transaortic valve pressure gradient at 2 years post-TAVR did not differ significantly between the two groups. Conclusions The benefits of BEV-TAVR may outweigh those of SEV-TAVR in patients with a large annulus.

Efficacy and safety of ambulatory, weekly, high-intensity intravenous diuretic strategy for congestion-refractory heart failure patients: insights from the DEA-HF prospective randomized clinical trial

Abstract Background Congestion and volume overload are strongly associated with low quality of life and pose a significant risk for both rehospitalization and mortality in heart failure (HF) patients. Despite the widespread use of diuretics in HF, the use of weekly, intravenous (IV), high-intensity diuretic treatment has not been prospectively studied in the setting of ambulatory congestion-refractory patients. Purpose To assess the efficacy and safety of weekly high-intensity diuresis regimens in a practical setting of ambulatory day care for chronically congested HF patients. Methods We performed a sub-analysis on data from a prospective, randomized, cross-over controlled study (DEA-HF) originally designed to compare diuresis regimens in the setting of an HF ambulatory daycare unit who had signs of congestion or volume overload despite adherence to guideline-directed medical therapy. Each patient received three different IV diuretic regimens, in one of six randomized sequences: IV furosemide 250mg; IV furosemide 250mg + oral metolazone 5mg; and IV furosemide 250mg + IV acetazolamide 500mg. All regimens given on the same chronological week were pooled, and diuresis efficacy was assessed by measuring excreted urine volume and sodium weight 6 hours post treatment initiation. Additional assessment at one week post each treatment included serum levels of NT-ProBNP, body weight and creatinine as well as congestion score based on the presence of ascites, pleural effusion and pedal edema. Statistical analysis was based on linear mixed models while accounting for the random effect of patient identity. Results A total of 42 patients were recruited. The mean age was 72±9 years, twenty-one subjects (50%) had LVEF ≥ 50%. 74% of patients were NYHA III class. All patients were on contemporary guidelines-directed HF therapy. Analysis of excreted sodium weight and urine volume revealed values of 4202.1±180.1 mg (Mean±SEM) and 1.77±0.07 liter per visit, respectively. No significant differences in efficacy were detected among treatments given in consecutive weeks (P= 0.80 and 0.69 for differences in sodium weight and urine volume, respectively). After 4 weeks, log(NT-ProBNP) was significantly decreased (P=0.044), accompanied by a significant decrease of 2.4±0.62 kg in body weight (P=0.0004) and of 0.92±0.44 points in congestion score (P=0.037). Serum creatinine level was only slightly increased by 0.19±0.04 mg/dl (P=0.0001), demonstrating the overall safety of the high-intensity diuresis strategy. Conclusions In ambulatory, congestion refractory HF patients a strategy based on high-intensity, weekly diuresis therapy was safe and effective for three consecutive weeks. The natriuresis response to the treatments was maintained, NT-ProBNP levels and congestion score were decreased. The strategy may be instrumental for ambulatory HF patients that require diuretic therapy intensification and may allow to prevent hospitalization.

SGLT2 inhibitor, a new bullet in heart failure management

The global health landscape is confronted with substantial challenges stemming from diabetes mellitus and heart failure (HF). The escalating incidence of diabetes mellitus (DM), in correlation with HF, underscores the imperative necessity for efficacious strategies in the realm of prevention and management. The most recent advancements in therapeutic approaches, specifically Sodium-glucose transporter 2 inhibitors (SGLT2i), present a promising prospect for enhancing outcomes and addressing the existing gaps in HF management. This paper aims to elucidate the significance of SGLT2i in the therapeutic management of both reduced and preserved heart failure, with or without the presence of DM. SGLT2i are new heart failure drugs. In trials, SGLT2i improved diastolic dysfunction, reduced oxidative stress, inflammation, fibrosis, and myofilament rigidity. The first SGLT2 inhibitor studies, EMPA-REG OUTCOME, DECLARE-TIMI 58, and CANVAS, showed that Empagliflozin and Canagliflozin reduced HF mortality and rehospitalization in type 2 diabetes mellitus (T2DM) patients. Dapagliflozin reduces HF hospitalizations without impacting T2DM mortality. Canagliflozin avoided creatinine rises, kidney disease deaths, and cardiovascular deaths in the CREDENCE Study. SGLT2i improve health in heart failure with preserved ejection fraction (HFpEF). SGLT2i improved health status statistically in the PRESERVED-HF and EMPEROR-Preserved investigations. SGLT2i became known as a promising therapeutic choice in the treatment of HF. The substantial evidence from prominent large-scale clinical trials has substantiated the cardiovascular and renal protective effects of SGLT2i. Furthermore, the benefits of these medications are relevant for individuals who have been diagnosed with heart failure with reduced ejection fraction (HFrEF), as well as those who are experiencing heart failure with preserved ejection fraction (HFpEF). Keyword: diabetes mellitus, heart failure, management, SGLT2 inhibitor

Triglyceride-glucose index predicts the prognosis of patients with ischemic cardiomyopathy

Abstract Objective A large number of studies have provided strong statistical evidence that the Triglyceride-glucose (TYG) index is associated with the development and prognosis of cardiovascular disease. However, little is known about the predictive value of TYG index for ischemic cardiomyopathy (ICM). This study aimed to investigate the predictive value of TYG index in patients with ICM. Methods Hospitalized patients ICM in our Hospital from April 2014 to December 2017 were included in this study. Inclusion criteria: previous definite diagnosis of coronary atherosclerotic heart disease (coronary angiography found one or more vessels stenosis > 50%) and echocardiography showed LVEF < 45 percent. In addition, the TYG index was calculated as follows :LN[fasting triglycerides (mg /dl)× fasting blood glucose (mg /dl)x1/2]. The endpoint of the study was MACE events, including all-cause death, myocardial infarction, ischemia-induced revascularization and heart failure (HF) rehospitalization. Results A total of 688 patients were included in this study and followed up for 1 year. In the multivariate Cox proportional hazards model, TYG index (adjusted HR 2.33 [95% CI: 1.30-4.20], P<0.01) were associated with an increased risk of MACE events, and the area under the ROC curve (AUC) was 0.604 (95%CI: 0.528-0.680, p <0.05). A total of 197 ICM patients with previously diagnosed diabetes were screened for analysis. We found that TYG index (adjusted HR 6.63 [95% CI: 2.15-20.47], P<0.01), and the AUC was 0.691 (95%CI: 0.562-0.820, p<0.05). Conclusion TYG index can predict the poor prognosis of ICM patients, and the predictive value of TyG index for ICM patients with diabetes is more significant.