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Evidence suggests that atrial fibrillation (AF) could increase the risk of worsening kidney function (WKF) which is linked to an increased risk of stroke, bleeding, and death in AF patients. However, limited data exist regarding the factors that could lead to WKF in these patients. Therefore, we sought to identify the potential factors associated with the development of WKF in patients with non-valvular AF (NVAF). We analyzed prospectively recruited 1122 NVAF patients [men 71.9%, median age 73.0 years (interquartile range: 66.0-79.0)] with a baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m 2 from the Hokuriku-Plus AF Registry. The primary outcome was incident WKF, defined as the %eGFR change from the baseline ≥ 30% during the follow-up period. We evaluated the association between baseline variables and incident WKF using univariate and multivariate Cox proportional hazard models. We also evaluated the non-linear association between the identified factors and incident WKF. During a median follow-up period of 3.0 years (interquartile range: 2.7-3.3), incident WKF was observed in 108 patients (32.6 per 1000 person-years). Compared to the patients without incident WKF, the patients with incident WKF were older and had a higher prevalence of heart failure (HF), diabetes mellitus (DM), and vascular disease at baseline. Those who experienced incident WKF also had higher diastolic blood pressure, lower hemoglobin, lower eGFR, higher B-type natriuretic peptide (BNP) and used warfarin more frequently. Upon multivariate analysis, age ≥ 75 years, HF, DM, and anemia were independently associated with incident WKF. Additionally, age and hemoglobin were linearly associated with the risk of incident WKF, whereas a J- or U-shaped association was observed for HbA1c and BNP. Age ≥ 75 years, HF, DM, and anemia were associated with the development of WKF in Japanese patients with NVAF. In patients with these risk factors, a careful monitoring of the kidney function and appropriate interventions may be important when possible., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan., Methods and results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5-5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56-6.21), the CHA 2 DS 2 -VASc score (1.35, 1.18-1.54), and concomitant HCM (2.48, 1.16-4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72-4.43), older age (1.07, 1.05-1.10), lower body mass index (0.95, 0.91-0.99), a history of HF (2.49, 1.77-3.52), and lower left ventricular ejection fraction (0.98, 0.97-0.99) were significantly associated with the development of HF., Conclusions: Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.

Background: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear., Methods and results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group., Conclusions: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Heart failure (HF) can cause metabolic imbalances, leading to anabolic resistance and increased energy expenditure, which often results in weight loss and cachexia. Comprehensive cardiac rehabilitation (CR), including exercise, nutritional support, and risk management, is crucial for enhancing the health and quality of life of patients with HF and is expected to play a central role in the prevention and treatment of HF-associated cachexia. However, the prevalence of cachexia in patients with HF undergoing comprehensive outpatient CR is currently unknown, and the detailed characteristics including of motor function of such patients remain undefined. Therefore, this cross-sectional study aimed to investigate the prevalence and characteristics of cachexia and the relationship between cachexia and lower limb motor function in patients with HF undergoing outpatient CR. This study included 115 consecutive patients with HF (43% male; mean age, 78 ± 8 years) who underwent comprehensive outpatient CR. The cachexia status was assessed according to the definition proposed by the Asian Working Group on Cachexia in 2023. The Short Physical Performance Battery (SPPB) and Mini Nutritional Assessment Short-Form (MNA-SF) were used to evaluate motor function of the lower limbs and nutritional status, respectively. Multivariate logistic regression analyses were used to examine the potential relationship between cachexia and low SPPB scores (≤ 9 points). The prevalence of cachexia was 30% in this study. Compared with those without cachexia, patients with cachexia were significantly older and showed notable reductions in body mass index, MNA-SF scores, handgrip strength, gait speed, and SPPB scores. A multivariate logistic regression analysis, adjusted for confounders, revealed that both age (odds ratio [OR], 1.129; 95% confidence interval [CI], 1.034-1.248; P = 0.016) and presence of cachexia (OR, 3.783; 95% CI, 1.213-11.796; P = 0.022) were independently associated with low SPPB scores. These findings highlight the importance of focusing on cachexia in patients with HF as part of a comprehensive outpatient CR and may be crucial in developing treatments to improve lower limb motor function in patients with HF who develops cachexia., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Familial hypercholesterolemia (FH) is associated with atherosclerotic cardiovascular disease (ASCVD). However, the prevalence of FH among a general population remains unknown, and it is unclear if FH is associated with other cardiovascular complications, including heart failure (HF) and atrial fibrillation (AF)., Methods: Analyses were conducted on individuals without a prior history of cardiovascular disease using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2022 (n = 4,126,642; median age, 44 years; 57.5% men). We defined FH as either LDL cholesterol ≥250 mg/dL or LDL cholesterol ≥175 mg/dL under the lipid-lowering medications under the assumption that lipid-lowering medications reduced LDL cholesterol by 30%. We assessed the associations between FH and composite outcomes, including, ASCVD (myocardial infarction, angina pectoris, and stroke), HF, and AF using Cox proportional hazard model., Results: We identified 11,983 (.29%) FH patients. In total, 181,150 events were recorded during the mean follow-up period of 3.5 years. The status FH was significantly associated with composite outcomes after adjustments (hazard ratio [HR]; 1.38, 95% confidence interval [CI]: 1.30-1.47, p < .001). Interestingly, the status FH was significantly associated with HF (HR: 1.48, 95% CI: 1.36-1.61, p < .001) and AF (HR: 1.33, 95% CI: 1.08-1.64, p < .001) in addition to angina pectoris (HR: 1.45, 95% CI: 1.33-1.58, p < .001) and stroke (HR: 1.19, 95% CI: 1.04-1.36, p < .001)., Conclusion: We found that the prevalence of FH was .29% in a general population. FH was significantly associated with a higher risk of developing cardiovascular disease, HF and AF., Lay Summary: We sought to identify the prevalence of FH among a general population, and to clarify whether FH increases the risk of not only ASCVD but also HF and AF., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Although angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) play critical roles in the treatment of heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF; left-ventricular ejection fraction ≤ 50%), the ideal timing for initiation in patients with acute heart failure (AHF) is unclear. We sought to clarify the timing and safety of ACEi/ARB prescription relative to hemodynamic stabilization (pre or post) in patients hospitalized with acute HFrEF/HFmrEF. This was a retrospective, observational analysis of electronic data of patients hospitalized for AHF at 17 Japanese hospitals. Among 9107 patients hospitalized with AHF, 2648 had HFrEF/HFmrEF, and 83.0% met the hemodynamic stabilization criteria within 10 days of admission. During hospitalization, 63.5% of patients with HFrEF/HFmrEF were prescribed an ACEi/ARB, 79.4% of which were prescribed pre-stabilization. In a multivariable analysis, patients treated with an ACEi/ARB pre-stabilization were more likely to have comorbid hypertension, diabetes mellitus, or ischemic heart disease. ACEi/ARB prescription timing was not associated with adverse events, including hypotension and renal impairment, and early prescription was associated with a lower incidence of subsequent worsening of HF. In clinical practice, more hospitalized patients with AHF received an ACEi/ARB before compared with after hemodynamic stabilization, and no safety concerns were observed. Moreover, early prescription may be associated with a lower incidence of worsening HF., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

The time-dependent changes in the natriuretic peptide families during sacubitril/valsartan (S/V) treatment remain obscure in the Asian heart failure (HF) cohort. Eighty-one outpatients with compensated HF were analyzed. The patients were divided into two groups based on the administration of S/V (n = 42) or angiotensin converting enzyme inhibitor (ACE-I; n = 39). Changes to the natriuretic peptide families and the daily dose of loop diuretics were evaluated 3 and 6 months after the intervention. The atrial natriuretic peptide (ANP) level was significantly increased (102 [63-160] pg/mL to 283 [171-614] pg/mL [3 months]; 409 [210-726] pg/mL [6 months]) in the S/V group but not in the ACE-I group. The dose of furosemide was significantly decreased during the six-month follow-up period in the S/V group (40 [20-40] mg to 20 [10-20] mg) but not in the ACE-I group. A multivariate logistic regression model showed that the presence of persistent atrial fibrillation (AF) and HF with a preserved left ventricular ejection fraction (HFpEF) was independently associated with a high delta-ANP ratio (≥ 4.5 ANP value on the start date/ANP value at 6 months; the mean value was used as the cutoff value) (odds ratio [OR]: 4.649, 95% CI 1.032-20.952 and OR: 7.558, 95% CI 1.427-40.042). The plasma level of ANP was increased, and the loop diuretic dose was decreased by the addition of neprilysin inhibitor therapy in patients with compensated HF. In patients with HFpEF and complicated persistent AF, neprilysin inhibitor therapy was associated with an increase in ANP., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Risk prediction for heart failure (HF) using machine learning methods (MLM) has not yet been established at practical application levels in clinical settings. This study aimed to create a new risk prediction model for HF with a minimum number of predictor variables using MLM. We used two datasets of hospitalized HF patients: retrospective data for creating the model and prospectively registered data for model validation. Critical clinical events (CCEs) were defined as death or LV assist device implantation within 1 year from the discharge date. We randomly divided the retrospective data into training and testing datasets and created a risk prediction model based on the training dataset (MLM-risk model). The prediction model was validated using both the testing dataset and the prospectively registered data. Finally, we compared predictive power with published conventional risk models. In the patients with HF (n = 987), CCEs occurred in 142 patients. In the testing dataset, the substantial predictive power of the MLM-risk model was obtained (AUC = 0.87). We generated the model using 15 variables. Our MLM-risk model showed superior predictive power in the prospective study compared to conventional risk models such as the Seattle Heart Failure Model (c-statistics: 0.86 vs. 0.68, p < 0.05). Notably, the model with an input variable number (n = 5) has comparable predictive power for CCE with the model (variable number = 15). This study developed and validated a model with minimized variables to predict mortality more accurately in patients with HF, using a MLM, than the existing risk scores., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

The Short Physical Performance Battery (SPPB) is a well-established tool to assess the lower extremity physical performance status. The purpose of this study is to examine the impact of brain natriuretic peptide (BNP) levels and SPPB scores on short-term readmission in older patients with heart failure (HF). This prospective cohort study enrolled 325 patients with HF who were hospitalized for acute decompensated HF between November 2017 and December 2021. Variables were analyzed using the Cox proportional hazards model, receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis. The 107 patients who met the inclusion criteria were divided into readmission (within 90 days of discharge; n = 25) and non-readmission (n = 82) groups. Multivariate analysis revealed that BNP level and SPPB score were independent risk factors for readmission within 90 days after discharge. Patients were classified into three groups according to the BNP and SPPB cutoff values calculated using ROC curves. The risk of readmission was significantly higher in Group 3 (BNP ≥ 384 pg/mL and SPPB ≤ 7 points) than in Group 1 (BNP < 384 pg/mL and SPPB > 7 points; hazard ratio: 27.68, 95% confidence interval: 3.672 - 208.700, P = 0.0012). Our study showed that HF patients with high BNP levels and low SPPB scores have a dramatically increased risk of readmission within 90 days of discharge., (© 2022. Springer Japan KK, part of Springer Nature.)

Recently, we have been working on enhancing the effectiveness of treatment for acute heart failure (HF) through team-based care. This study was designed to assess the benefits of this initiative by quantifying the prognostic impact on HF patients receiving treatment at our hospital. We identified 1977 consecutive HF patients (mean age 78.3 ± 11.9 years) being discharged from our hospital between February 2015 and December 2018, divided them by admission year, and tracked changes over time, with 2015 as a reference. The postdischarge clinical outcome measures were defined as a composite of all-cause death or rehospitalization for HF, all-cause death, and rehospitalization for HF. The risk of a composite of all-cause death or rehospitalization for HF was lower in 2017 (adjusted hazard ratio, 0.72; 95% confidence interval: 0.57 to 0.91; p = 0.005) and 2018 (adjusted hazard ratio, 0.78; 95% confidence interval: 0.61 to 0.99; p = 0.045) than in 2015, and that of all-cause death was lower in 2017 (adjusted hazard ratio, 0.72; 95% confidence interval: 0.53 to 0.98; p = 0.04) and 2018 (adjusted hazard ratio, 0.60; 95% confidence interval: 0.43 to 0.85; p = 0.004) than in 2015, but that of rehospitalization for HF was not significantly different through the study period. The mortality rate decreased at the end of the study period, but the rate of rehospitalization for HF did not. The benefits of team-based care were difficult to evaluate by quantification., (© 2022. Springer Japan KK, part of Springer Nature.)

Patients hospitalized for acute heart failure (HF) tend to experience declines in physical function and activities of daily living (ADL) due to bed rest and restricted mobilization. This could result in some patients being transferred to rehabilitation hospitals. This study aims to examine the relationship between discharge disposition and 1-year readmission and mortality rates in HF patients. Nine hundred fifty six consecutive HF patients who were hospitalized for acute decompensated HF and underwent rehabilitation were divided into two groups: home (returned home) or transfer (transferred to rehabilitative or long-term care hospital units due to decline in physical function and/or ADL) groups. The primary and secondary outcomes were 1-year readmission and mortality rates after discharge, respectively. Of the 956 patients, 8.6% (n = 82) were transferred to rehabilitative or long-term care hospital units. Over a 1-year follow-up period, all-cause and HF readmission rates were 50.1% (n = 479) and 27.2% (n = 260), respectively. The transfer group had significantly lower readmission rates compared to home group after adjusting for the pre-existing risk factors (hazard ratio for all-cause and HF readmission: 0.600 and 0.552, 95% CI 0.401-0.897 and 0.314-0.969; P = 0.013 and P = 0.038, respectively). There was no significant relationship between discharge disposition and all-cause mortality rate. Low ADL defined as Barthel index < 60 points was identified as a predictor of all-cause and HF readmission among the home group (odds ratio for all-cause and HF readmission rates: 2.156 and 1.847, 95% CI 1.026-4.531 and 1.036-2.931; P = 0.043 and P = 0.037, respectively). This multi-center study demonstrated that HF patients transferred to rehabilitative or long-term care hospital units after an acute hospitalization had a significantly decreased 1-year all-cause and HF readmission rates compared to patients who returned to their home. These findings may help in selecting a discharge disposition for older HF patients with ADL decline., (© 2022. Springer Japan KK, part of Springer Nature.)

The HATCH score is employed as a risk assessment tool for atrial fibrillation (AF) development. However, the impact of the HATCH score on the long-term adverse outcomes in patients with acute heart failure (AHF) remains unknown. We investigated the clinical value of the HATCH score in patients with AHF. From a multicenter AHF registry, we retrospectively evaluated 1543 consecutive patients who required hospitalization owing to AHF (median age, 78 [69-85] years; 42.3% women) from January 2012 to December 2019. These patients were divided into five risk groups based on their HATCH score at admission (scores 0, 1, 2, 3, and 4-7). The correlation between the HATCH score and the composite outcome, including all-cause mortality and re-hospitalization due to HF, was analyzed using Kaplan-Meier and Cox proportional-hazard analyses. The median HATCH score was 2 [1-3], and the median age was 78 years (69-85 years). During the follow-up period (median, 16.8 months), the composite endpoint occurred in 691 patients (44.8%), including 416 (27%) patients who died (with 65 [4.2%] in-hospitalization deaths) and 455 (29.5%) patients requiring re-hospitalizations due to HF. The Kaplan-Meier analysis showed a significant increase in the composite endpoint with an increasing HATCH score (log-rank, p < 0.001). The multivariate Cox regression model revealed that the HATCH score was an independent predictor of the composite endpoint (hazard ratio [HR] 1.181; 95% confidence interval [CI]: 1.111-1.255; p < 0.001) with all-cause mortality (HR 1.153, 95% CI 1.065-1.249; p < 0.001) and re-hospitalizations due to HF (HR 1.21; 95% CI 1.124-1.303; p < 0.001) in patients with AHF, regardless of the presence or absence of AF, ejection fraction, and etiology. The HATCH score is an independent predictor of adverse outcomes in patients with AHF., (© 2022. Springer Japan KK, part of Springer Nature.)

Despite emerging recognition of interactions between heart failure (HF) and liver dysfunction, the impact of cardiac hepatopathy on patients with HF undergoing cardiac resynchronization therapy (CRT) has not been fully elucidated. Albumin-bilirubin (ALBI) score is a new assessment of liver function. The relationship between liver dysfunction severity based on ALBI score and clinical outcomes of patients with HF receiving CRT is unclear. Clinical records of 274 patients who underwent CRT device implantation between March 2003 and October 2020 were retrospectively investigated. ALBI score was calculated based on serum albumin and total bilirubin levels obtained before CRT device implantation. Patients were divided into three groups based on ALBI score: first tertile (ALBI ≤  - 2.62, n = 91)), second tertile (- 2.62 < ALBI <  - 2.13, n = 92), and third tertile (ALBI ≥  - 2.13, n = 91). The study endpoint was all-cause mortality. The third tertile group had more advanced NYHA functional class, lower hemoglobin levels, and higher total bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and N-terminal Pro-B-type natriuretic peptide levels (all p < 0.05). The third tertile group also had a higher prevalence of moderate or severe tricuspid regurgitation and higher tricuspid regurgitation pressure gradient (all p < 0.05). CRT response rates were significantly lower in the third tertile group. During a median (interquartile range) follow-up of 30 (9-60) months, 104 (37.9%) patients died. The third tertile group had significantly higher rates of all-cause mortality (log-rank p < 0.001). Higher ALBI score was significantly associated with all-cause mortality, even after adjusting for clinically relevant factors, a conventional validated risk score, and echocardiographic parameters related to right HF (all p < 0.01). Higher ALBI score before CRT device implantation is associated with HF severity, hepatic congestion and impairment due to right HF, lower CRT response, and higher all-cause mortality in CRT recipients., (© 2021. Springer Japan KK, part of Springer Nature.)

The biogenic amine, histamine, is found predominantly in mast cells, as well as specific histaminergic neurons. Histamine exerts its many and varied actions via four G-protein-coupled receptors numbered one through four. Histamine has multiple effects on cardiac physiology, mainly via the histamine 1 and 2 receptors, which on a simplified level have opposing effects on heart rate, force of contraction, and coronary vasculature function. In heart failure, the actions of the histamine receptors are complex, the histamine 1 receptor appears to have detrimental actions predominantly in the coronary vasculature, while the histamine 2 receptor mediates adverse effects on cardiac remodeling via actions on cardiomyocytes, fibroblasts, and even endothelial cells. Conversely, there is growing evidence that the histamine 3 receptor exerts protective actions when activated. Little is known about the histamine 4 receptor in heart failure. Targeting histamine receptors as a therapeutic approach for heart failure is an important area of investigation given the over-the-counter access to many compounds targeting these receptors, and thus the relatively straight forward possibility of drug repurposing. In this review, we briefly describe histamine receptor signaling and the actions of each histamine receptor in normal cardiac physiology, before describing in more detail the known role of each histamine receptor in adverse cardiac remodeling and heart failure. This includes information from both clinical studies and experimental animal models. It is the goal of this review article to bring more focus to the possibility of targeting histamine receptors as therapy for heart failure., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sleep disorders and sleep duration have attracted considerable attention as potential modifiable risk factors for the development and progression of heart failure (HF). However, whether these sleep behaviors could aggravate the underlying cardiac condition remains ambiguous. We evaluated the associations between the levels of plasma B-type natriuretic peptide (BNP) and sleep-disordered breathing (SDB), sleep quality and quantity, or daytime sleepiness in cardiovascular diseases (CVD) patients. A total of 1717 consecutive patients with CVD [median age, 66 years (55-74 years); female, 27.5%] were enrolled. SDB was screened by nocturnal pulse oximetry; sleep quality and quantity were determined by Pittsburg Sleep Quality Index, and daytime sleepiness was examined by Epworth Sleepiness Scale. The median plasma BNP level was 54.9 pg/ml (23.5-146.4 pg/ml). Multiple regression analyses showed that the BNP level in the highest quintile (BNP > 181.8 pg/ml) was associated with SDB (severe: OR, 5.88; 95% CI 3.17-10.88; moderate: OR, 3.62; 95% CI 2.17-6.02; mild: OR, 2.22: 95% CI 1.42-3.47). There were no significant associations between other sleep parameters and higher BNP levels. The relationship between SDB and BNP levels was unchanged regardless of the previous history of symptomatic HF. SDB was independently associated with the elevated plasma BNP level in patients with a variety of CVD., (© 2021. Springer Japan KK, part of Springer Nature.)

Tricuspid regurgitation (TR) is a common condition that is independently associated with high mortality rates in patients with heart failure (HF). Several studies have demonstrated the clinical efficacy of add-on tolvaptan in patients hospitalized for HF. However, the effects of add-on tolvaptan in patients with significant TR are less well understood. Among the patients with moderate-to-severe TR assessed by transthoracic echocardiography during hospitalization for congestive HF, 39 patients who could complete the clinical course after starting add-on tolvaptan were included in the study. Rehospitalization due to HF and cardiac death were defined as adverse cardiac events in this study. We investigated the presence or absence of cardiac events within 2 years following the introduction of tolvaptan and evaluated echocardiographic functional parameters associated with cardiac events. The average patient age was 75 ± 14 years, and 23 patients (59%) experienced adverse cardiac events within 2 years after add-on tolvaptan administration. Serum creatinine (mg/dL) and brain natriuretic peptide (pg/mL) concentrations at discharge were significantly higher in patients with cardiac events than in those without cardiac events {1.48 [1.02-1.58] vs. 1.07 [0.79-1.41], p = 0.03; 526 [414-1044] vs. 185 [104-476], p = 0.01, respectively}. The presence or absence of past hospitalization for HF was also significantly higher in the event-positive group compared to event-free group (78 vs. 44%, p = 0.04). Comparison of echocardiographic parameters revealed that patients with cardiac events had a significantly lower left ventricular ejection fraction (40 ± 16 vs. 49 ± 15%, p = 0.049) and lower right ventricular fractional area change (RVFAC) (35 ± 12 vs. 45 ± 10%, p = 0.008) than those without cardiac events. Multiple logistic regression analysis revealed that RVFAC and past hospitalization for HF were independently associated with cardiac events following the introduction of tolvaptan (odds ratio, 0.934 and 4.992; p = 0.048 and 0.04, respectively). Right ventricular contractility as well as past history of admission for HF, left ventricular ejection fraction, renal function, and brain natriuretic peptide level at discharge may reflect the clinical outcomes after HF hospitalization in patients with significant TR who were treated with tolvaptan., (© 2021. Springer Japan KK, part of Springer Nature.)

The effects of outpatient cardiac rehabilitation (OCR) implementation and home nursing-care services (HNS) use are not well defined in patients with heart failure (HF) with mid-range or preserved left-ventricular ejection fraction (EF) (HFmrEF or HFpEF). Through a post-hoc analysis of the HF registry in Hiroshima Prefecture of Japan (REAL-HF), we investigated the current conditions and significance of OCR and HNS in HFmrEF or HFpEF patients. The REAL-HF enrolled adult patients hospitalized with HF in eight regional core hospitals. Patients discharged home were followed for conditions of OCR and HNS and the primary endpoints (all-cause death or unscheduled readmission) for 1 year. The patients were classified into HF with reduced EF (< 40%) (HFrEF) or HFmrEF (40% ≤ EF < 50%) or HFpEF (EF ≥ 50%) group. We followed 195 HFrEF and 381 HFmrEF or HFpEF patients. OCR was generally underutilized, especially in HFmrEF or HFpEF patients (rate of completion [5-month program], 3.2%), whereas HFmrEF or HFpEF patients were more likely to use HNS after discharge home than HFrEF patients (44.1% vs. 27.2%, P < 0.0001). Patients with the use of HNS generally had lower scores of Mini-Mental State Examination and EuroQol 5 dimensions than those without. Multivariate analysis adjusted for medical and social factors showed that the completion of OCR was a strong negative predictor of the primary endpoints both in HFrEF (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.75; P = 0.025) and HFmrEF or HFpEF (HR 0.11; 95% CI 0.01-0.78; P = 0.028) patients, whereas the use of HNS was a positive predictor only in HFmrEF or HFpEF patients (HR 1.41; 95% CI 1.00-1.97; P = 0.047). In conclusion, continuous OCR, despite its inadequate implementation, was associated with favorable overall outcomes, while the necessity for HNS related to impaired cognitive function and quality of life was associated with poorer overall outcomes in HFmrEF or HFpEF patients discharged home. Further study is warranted to fully consider the factors related to OCR implementation and HNS use., (© 2021. Springer Japan KK, part of Springer Nature.)

The effect of the oral selective vasopressin V2-receptor antagonist tolvaptan for chronic phase therapy on patients with FMR remains unclear. We aimed to determine the efficacy of oral tolvaptan in patients with significant functional mitral regurgitation (FMR) to reduce the mortality and rehospitalization due to worsening heart failure (HF). We enrolled 219 patients (mean age 76 ± 9 years, 59.4% men) who were admitted at our hospital due to congestive HF during different two 1-year periods. The patients were divided into 2 groups: those who had significant FMR (MR ≥ grade 2 [n = 76]) and those who did not (MR < grade 2 [n = 143]) at discharge. The patients were further divided into a study group that received tolvaptan during follow-up and a control group that did not receive tolvaptan. We used an inverse probability of treatment weighting method with the primary end point defined as overall all-cause mortality and rehospitalization due to worsening HF within 1 year. Of the 76 patients with significant FMR at discharge, 2 of 20 (10%) who were administered tolvaptan died and 8 (40%) were readmitted to a hospital. Of the 56 patients who did not receive tolvaptan, 2 (3.5%) died and 18 (27.5%) required rehospitalization. After multiple adjustments, there were no significant differences for overall survival and rehospitalization between the groups (log-rank p = 0.700 and 0.510, respectively). Our results suggest that oral tolvaptan administration in addition to conventional diuretics had less impact on outcomes in patients with significant FMR., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: Plasma ghrelin levels can be elevated in patients with acute heart failure (AHF). This study aimed to analyze the temporal changes and prognostic value of ghrelin levels in patients with AHF., Methods: This prospective study included patients with AHF at the Cardiology Department, Weifang People's Hospital (May 2018-October 2019), and age- and sex-matched healthy controls. Plasma ghrelin levels were measured. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate whether ghrelin levels could predict major cardiac adverse events (MACEs) during a 1-year follow-up., Results: Finally, 92 patients with AHF and 50 healthy controls were enrolled. Ghrelin levels were higher in patients with AHF at 1, 3, 12, and 24 h compared with controls (all P < 0.01). Ghrelin levels in the AHF group were higher at 3 and 12 h than at 1 and 24 h (P < 0.001). Ghrelin level at 3 h in patients with AHF was negatively correlated with the left ventricular end-diastolic diameter and left ventricular ejection fraction (both P < 0.05). MACEs occurred in 48 patients with AHF. Ghrelin levels were higher in the MACE group than in the non-MACE group at 1 (P = 0.011) and 3 h (P = 0.034). Multivariable regression showed that ghrelin level at 3 h was independently associated with MACEs [OR = 0.629, 95% confidence interval (CI): 0.515-0.742, P = 0.010], but the area under the ROC curve was only 0.629 (95% CI 0.515-0.742)., Conclusions: Plasma ghrelin levels are elevated in AHF and patients with MACEs during follow-up., (© 2021. Springer Japan KK, part of Springer Nature.)

Atrial fibrillation and heart failure are two common cardiovascular conditions that frequently coexist, and it has been widely demonstrated that in patients with chronic heart failure, atrial fibrillation is associated with a significant increase in the risk of all-cause death and all-cause hospitalization. Nevertheless, there is no unanimous consensus in the literature on how to approach this category of patients and which therapeutic strategy (rhythm control or frequency control) is the most favorable in terms of prognosis; moreover, there is still a lack of data comparing the different ablative techniques of atrial fibrillation in terms of efficacy, and many of the current trials do not consider current ablative techniques such as high-power short-duration ablation index protocol for radiofrequency pulmonary vein isolation. Eventually, while several RCTs have widely proved that in patients with heart failure with reduced ejection fraction, ablation of atrial fibrillation is superior to medical therapy alone, there is no consensus regarding those with preserved ejection fraction. For these reasons, in this review, we aim to summarize the main updated evidence guiding clinical decision in this complex scenario, with a special focus on the most recent trials and the latest meta-analyses that examined the role of catheter ablation (CA) in rhythm control in patients with AF and HF. [ABSTRACT FROM AUTHOR]

Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5–7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, the pulmonary and systemic circulations are separated [the morphological right ventricle (RV) is connected to the aorta and the morphological left ventricle (LV) is connected to the pulmonary artery]. This anomaly is included in the group of developmental disorders of embryonic heart conotruncal irregularities, and their pathogenesis is multifactorial. The anomaly's development is influenced by genetic, epigenetic, and environmental factors. It can occur either as an isolated anomaly, or in association with other cardiac defects. The typical concomitant cardiac anomalies that may occur in patients with D-TGA include ventriculoseptal defects, patent ductus arteriosus, left ventricular outflow tract obstruction (LVOTO), mitral and tricuspid valve abnormalities, and coronary artery variations. Correction of the defect during infancy is the preferred treatment for D-TGA. Balloon atrial septostomy (BAS) is necessary prior to the operation. The recommended surgical correction methods include arterial switch operation (ASO) and atrial switch operation (AtrSR), as well as the Rastelli and Nikaidoh procedures. The most common postoperative complications include coronary artery stenosis, neoaortic root dilation, neoaortic insufficiency and neopulmonic stenosis, right ventricular (RV) outflow tract obstruction (RVOTO), left ventricular (LV) dysfunction, arrhythmias, and heart failure. Early diagnosis and treatment of D-TGA is paramount to the prognosis of the patient. Improved surgical techniques have made it possible for patients with D-TGA to survive into adulthood. [ABSTRACT FROM AUTHOR]

Objective. We aimed to examine the benefits of catheter ablation on left heart structure and function in patients with persistent atrial fibrillation (AF) accompanied by heart failure (HF) with preserved ejection fraction (HFpEF), in comparison with the benefits in patients with AF accompanied by HF with reduced ejection fraction (HFrEF) or patients with no HF. Methods. A total of 399 patients with nonvalvular persistent AF who underwent catheter ablation from 2015 to 2021 were retrospectively included sixty‐seven patients with recurrence of AF within 1 year were excluded, as well as 53 patients who failed to be followed up at (12 ± 1) months after the procedure. Finally, 279 patients who fulfilled the criteria were included and divided into these groups: the HFpEF group (left ventricular ejection fraction (LVEF) ≥50% and N‐Terminal Pro‐Brain Natriuretic Peptide (NT‐proBNP) ≥125 pg/ml or E/e′ ≥15, n = 116), HFrEF group (LVEF <50%, n = 48), and no HF group (NT‐proBNP <125 pg/ml, n = 115). The endpoints were changes in image‐based functional status from baseline to 1 year, including echocardiogram and speckle‐tracking echocardiography. Results. The left atrial structure of patients with HFpEF decreased significantly 1 year after catheter ablation (left atrial anteroposterior dimension: 41.48 ± 4.53 mm vs. 38.64 ± 4.40; left atrial mediolateral dimension: 41.99 ± 5.52 vs. 38.24 ± 4.63 mm; left atrial superoinferior dimension: 61.36 ± 6.73 vs. 56.44 ± 6.97 mm). The left atrial and left ventricular volumes were significantly reduced and the ejection fraction was increased in all three groups, with HFrEF patients benefiting more. In the speckle‐tracking echocardiography indexes, significant improvements were observed in left atrial strain (16.83 ± 6.91 vs. 28.05 ± 9.92), left atrial storage function (0.97 ± 0.38 vs. 1.49 ± 0.58), and left atrial pump function (−1.15 ± 0.55 vs. −1.68 ± 0.75) among HFpEF patients after 1 year, with no changes in left atrial conduit function (−1.55 ± 0.62 vs. −1.50 ± 0.54). In addition to the above improvements in left atrial structure and function, there was no significant improvement in left ventricular diastolic function in patients with HFpEF (E/e′, 14.11 ± 5.52 vs. 14.30 ± 7.25, P = 0.85). Conclusion. Catheter ablation is beneficial in restoring sinus rhythm in patients with persistent AF with coexisting HFpEF, significantly decreasing the left atrial size, improving left atrial storage function and left atrial pump function, and increasing left atrial and left ventricular ejection fraction. [ABSTRACT FROM AUTHOR]

Aims In patients with advanced heart failure requiring dobutamine infusion, it is usually recommended to initiate beta-blockers after weaning from dobutamine. However, beta-blockers are sometimes initiated under dobutamine infusion in a real-world scenario. The association between such early beta-blocker initiation with clinical outcomes is unknown. Therefore, this study investigates the association between initiating beta-blockers under dobutamine infusion and survival outcomes. Methods and results This observational study with a multicentre inpatient-care database emulated a pragmatic randomized controlled trial (RCT) of the beta-blocker initiation strategy. First, 1151 patients on dobutamine and not on beta-blockers on the day of heart failure admission (Day 0) were identified. Among 1095 who met eligibility criteria, patients who were eventually initiated beta-blockers under dobutamine infusion by Day 7 (early initiation strategy) were 1:1 matched to those who were not initiated (conservative strategy). The methods of cloning, censoring, and weighting were applied to emulate the target trial. Patients were followed up for up to 30 days. The primary outcome was all-cause death. Among 780 matched patients (median age, 81 years), the adjusted hazard ratio was 1.11 (95% confidence interval 0.75–1.64, P = 0.59) for the early initiation strategy. The estimated 30-day all-cause mortalities in the early initiation strategy and the conservative strategy were 19.3% (10.6–30.7) and 16.2% (9.2–25.3), respectively. The results were consistent when we used different days to determine strategies (i.e. 5 and 9) instead of 7 days. Conclusion The present observational study emulating a pragmatic RCT found no positive or negative association between beta-blocker initiation under dobutamine infusion and overall survival. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) is a type of cardiomyopathy usually precipitated by either emotional or physical stress and potentially leading to reversible heart failure. There is emerging evidence indicating an interaction between the brain and the heart in patients with TTS. Nevertheless, these new insights are not reflected in the current clinical approach to TTS. The application of novel and existing imaging modalities for the evaluation of brain–heart interactions is an interesting approach that could potentially augment diagnostic and prognostic yield, as well as improve our pathophysiologic understanding in the context of TTS. In this opinion piece, we discuss the evidence supporting a brain–heart interaction in patients with TTS and discuss how a combined evaluation of brain–heart interactions could potentially be implemented. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little is known regarding the risk stratification for incident HF in AF patients, especially with preserved left ventricular ejection fraction (LVEF). Methods and results: The Fushimi AF Registry is a community-based prospective survey of AF patients. From the registry, 3002 non-valvular AF patients with preserved LVEF and with the data of antero-posterior left atrial diameter (LAD) at enrolment were investigated. Patients were stratified by LAD (<40, 40-44, 45-49, and ≥50 mm) with backgrounds and HF hospitalization incidences compared between groups. Of 3002 patients [mean age, 73.5 ± 10.7 years; women, 1226 (41%); paroxysmal AF, 1579 (53%); and mean CHA2DS2-VASc score, 3.3 ± 1.7], the mean LAD was 43 ± 8 mm. Patients with larger LAD were older and less often paroxysmal AF, with a higher CHA2DS2-VASc score (all P < 0.001). Heart failure hospitalization occurred in 412 patients during the median follow-up period of 6.0 years. Larger LAD was independently associated with a higher HF hospitalization risk [LAD ≥ 50 mm: hazard ratio (HR), 2.36; 95% confidence interval (CI), 1.75-3.18; LAD 45-49 mm: HR, 1.84; 95% CI, 1.37-2.46; and LAD 40-44 mm: HR, 1.34; 95% CI, 1.01-1.78, compared with LAD < 40 mm) after adjustment by age, sex, AF type, and CHA2DS2-VASc score. These results were also consistent across major subgroups, showing no significant interaction. Conclusion: Left atrial diameter is significantly associated with the risk of incident HF in AF patients with preserved LVEF, suggesting the utility of LAD regarding HF risk stratification for these patients. [ABSTRACT FROM AUTHOR]

This retrospective observational study aimed to examine the relationships of maximum walking speed (MWS) with peak oxygen uptake (peak VO2) and anaerobic threshold (AT) obtained by cardiopulmonary exercise testing (CPX) in patients with heart failure. The study participants were 104 consecutive men aged ≥ 20 years who had been hospitalized or had undergone outpatient care at our hospital for heart failure between February 2019 and January 2023. MWS was measured in a 5-m section with a 1-m run-up before and after the course. Multivariable analysis was used to examine the association between MWS and peak VO2 and AT by CPX. The Pearson correlation coefficient showed that MWS was positively correlated with percent-predicted peak VO2 and percent-predicted AT (r = 0.463, p < 0.001; and r = 0.485, p < 0.001, respectively). In the multiple linear regression analysis employing percent-predicted peak VO2 and percent-predicted AT as the objective variables, only MWS demonstrated a significant positive correlation (standardized β: 0.471, p < 0.001 and 0.362, p < 0.001, respectively). Multiple logistic regression analyses, using an 80% cutoff in percent-predicted peak VO2 and AT, revealed that only MWS was identified as a significant factor in both cases (odds ratio [OR]: 1.239, 95% confidence interval [CI]: 1.071–1.432, p = 0.004 and OR: 1.469, 95% CI: 1.194–1.807, p < 0.001, respectively). MWS was correlated with peak VO2 and AT in male patients with heart failure. The MWS measurement as a screening test for exercise tolerance may provide a simple means of estimating peak VO2 and AT in heart failure patients. [ABSTRACT FROM AUTHOR]

The contribution of the right ventricle (RV) to cardiac output is negligible in normal resting conditions when pressures in the pulmonary circulation are low. However, the RV becomes relevant in healthy subjects during exercise and definitely so in patients with increased pulmonary artery pressures both at rest and during exercise. The adaptation of RV function to loading rests basically on an increased contractility. This is assessed by RV end-systolic elastance (Ees) to match afterload assessed by arterial elastance (Ea). The system has reserve as the Ees/Ea ratio or its imaging surrogate ejection fraction has to decrease by more than half, before the RV undergoes an increase in dimensions with eventual increase in filling pressures and systemic congestion. RV-arterial uncoupling is accompanied by an increase in diastolic elastance. Measurements of RV systolic function but also of diastolic function predict outcome in any cause pulmonary hypertension and heart failure with or without preserved left ventricular ejection fraction. Pathobiological changes in the overloaded RV include a combination of myocardial fibre hypertrophy, fibrosis and capillary rarefaction, a titin phosphorylation-related displacement of myofibril tension–length relationships to higher pressures, a metabolic shift from mitochondrial free fatty acid oxidation to cytoplasmic glycolysis, toxic lipid accumulation, and activation of apoptotic and inflammatory signalling pathways. Treatment of RV failure rests on the relief of excessive loading. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a rare and severe condition characterized by chamber dilation and impaired contraction of the left ventricle. It constitutes a fundamental etiology for profound heart failure and abrupt cardiac demise, rendering it a prominent clinical indication for heart transplantation (HTx) among both adult and pediatric populations. DCM arises from various etiologies, including genetic variants, epigenetic disorders, infectious insults, autoimmune diseases, and cardiac conduction abnormalities. The maintenance of cardiac function involves two distinct types of immune cells: resident immune cells and recruited immune cells. Resident immune cells play a crucial role in establishing a harmonious microenvironment within the cardiac tissue. Nevertheless, in response to injury, cardiomyocytes initiate a cytokine cascade that attracts peripheral immune cells, thus perturbing this intricate equilibrium and actively participating in the initiation and pathological remodeling of dilated cardiomyopathy (DCM), particularly during the progression of myocardial fibrosis. Additionally, immune cells assume a pivotal role in orchestrating the inflammatory processes, which are intimately linked to the prognosis of DCM. Consequently, understanding the molecular role of various immune cells and their regulation mechanisms would provide an emerging era for managing DCM. In this review, we provide a summary of the most recent advancements in our understanding of the molecular mechanisms of immune cells in DCM. Additionally, we evaluate the effectiveness and limitations of immunotherapy approaches for the treatment of DCM, with the aim of optimizing future immunotherapeutic strategies for this condition. [ABSTRACT FROM AUTHOR]

Background and Aims Ghrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes. Methods and results In a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3. Conclusion In patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT05277415 [ABSTRACT FROM AUTHOR]

While coronary heart disease remains a global cause of mortality, the prevalence of heart failure (HF) is increasing in developed countries including Japan. The continuously increasing aging population and the relatively low incidence of ischemic origins are features of the HF background in Japan. Information about nuclear cardiology practice and prognosis has accumulated, thanks to the multicenter prognostic J-ACCESS investigations (Series 1‒4) over two decades in Japan. Although the rate of hard cardiac events is lower in Japan than in the USA and Europe, similar predictors have been identified as causes of major adverse cardiac events. The highest proportion (50–75%) of major events among patients indicated for nuclear cardiology examinations in the J-ACCESS registries is severe HF requiring hospitalization. Therefore, the background and the possible reasons for the higher proportion of severe HF events in Japan require clarification. Combinations of age, myocardial perfusion defects, left ventricular dysfunction, and comorbid diabetes and chronic kidney disease are major predictors of cardiovascular events including severe HF. Although the Japanese Circulation Society has updated its clinical guidelines to incorporate non-invasive imaging modalities for diagnosing chronic coronary artery disease, the importance of risk-based approaches to optimal medical therapy and coronary revascularization is emphasized herein. [ABSTRACT FROM AUTHOR]

Aims: Contemporary estimates of heart failure (HF) prevalence in Japan are scarce. We aimed to estimate HF prevalence and trends in Japan using nationally representative, large administrative claims databases. Methods and results: This retrospective analysis used data from the Japan Medical Data Center (JMDC) (age ≤74 years) and the Medical Data Vision (MDV) (all ages) databases (study period: 1 January 2014–31 December 31 2019). We calculated HF prevalence using crude and sex‐/age‐standardized models (weighting based on Japanese census data, 2014–2019). Among 8 954 313 individuals aged ≤74 years from JMDC, and 27 920 174 of all ages from MDV, the cumulative 6 year (2014–2019) crude and sex‐/age‐standardized prevalence of HF per 1000 persons (95% confidence intervals) in Japan was 21.80 [21.70, 21.89] and 41.79 [30.25, 56.11] using JMDC and 65.09 [65.00, 65.18] and 60.95 [46.94, 77.62], respectively, using MDV. We observed an increasing yearly trend in crude HF prevalence per 1000 persons: 11.12 in 2014 and 14.69 in 2019 for JMDC; 58.09 and 77.18, respectively, for MDV. There was an overall increasing trend of comorbidities over time (2014–2019) among HF patients, especially in type 2 diabetes, malignant cancer, chronic kidney disease, and atrial fibrillation. From 2014 to 2019, the percentage of patients in JMDC with type 2 diabetes increased from 15.4% to 20.8% and 23.4% to 31.5% in MDV; malignant cancer frequency increased from 16.5% to 20.1% in JMDC and 18.8% to 23.9% in MDV; frequency of chronic kidney disease increased from 14.8% to 17.7% in JMDC and 18.2% to 22.7% in MDV; and frequency of atrial fibrillation increased from 13.6% to 15.6% in JMDC and 23.8% to 29.0% in MDV. Conclusions: We estimated that the prevalence of HF in Japan was 2.2–3.7% for patients aged ≤74 during the period 2014–2019 using the JMDC database, while the prevalence for patients of all ages was 6.5% using the MDV database. [ABSTRACT FROM AUTHOR]

Aims: Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline‐directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β‐blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. Methods: This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple‐drug therapy (TT) and non‐triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Results: Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all‐cause mortality (HR 0.656, 95% CI 0.447–0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380–0.946, P = 0.028), any‐cause rehospitalization (HR 0.687, 95% CI 0.541–0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565–0.948, P = 0.018). Conclusions: In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend extending the use of dual antiplatelet therapy (DAPT) beyond 1 year in patients with an acute coronary syndrome (ACS) and a high risk of ischaemia and low risk of bleeding. No data exist about the implementation of this strategy in older adults from routine clinical practice. Methods: We conducted a Spanish multicentre, retrospective, observational registry-based study that included patients with ACS but no thrombotic or bleeding events during the first year of DAPT after discharge and no indication for oral anticoagulants. High bleeding risk was defined according to the Academic Research Consortium definition. We assessed the proportion of cases of extended DAPT among patients 65 ≥ years that went beyond 1 year after hospitalisation for ACS and the variables associated with the strategy. Results: We found that 48.1% (928/1,928) of patients were aged ≥ 65 years. DAPT was continued beyond 1 year in 32.1% (298/928) of patients ≥ 65; which was a similar proportion as with their younger counterparts. There was no significant correlation between a high bleeding risk and DAPT duration. Contrastingly, there was a strong correlation between the extent of coronary disease and DAPT duration (p < 0.001). Other variables associated with extended DAPT were a higher left ventricle ejection fraction, a history of heart failure and a prior stent thrombosis. Conclusion: There was no correlation between age and extended use of DAPT beyond 1 year in older patients with ACS. DAPT was extended in about one-third of patients ≥ 65 years. The severity of the coronary disease, prior heart failure, left ventricle ejection fraction and prior stent thrombosis all correlated with extended DAPT. [ABSTRACT FROM AUTHOR]

We aimed to identify combinations of clinical factors that predict heart failure (HF) onset using a novel limitless-arity multiple-testing procedure (LAMP). We also determined if increases in numbers of predictive combinations of factors increases the probability of developing HF. We recruited people without HF who received health check-ups in 2010, who were followed annually for 4 years. Using 32,547 people, LAMP was performed to identify combinations of factors of fewer than four factors that could predict the onset of HF. The ability of the method to predict the probability of HF onset based on the number of matching predictive combinations of factors was determined in 275,658 people. We identified 549 combinations of factors for the onset of HF. Then we classified 275,658 people into six groups who had 0, 1–50, 51–100, 101–150, 151–200 or 201–250 predictive combinations of factors for the onset of HF. We found that the probability of HF progressively increased as the number of predictive combinations of factors increased. We identified combinations of variables that predict HF onset. An increased number of matching predictive combinations for the onset of HF increased the probability of HF onset. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease is the most common cause of morbidity and mortality worldwide. Diabetes mellitus increases cardiovascular risk. Heart failure and atrial fibrillation are associated comorbidities that share the main cardiovascular risk factors. The use of incretin-based therapies promoted the idea that activation of alternative signaling pathways is effective in reducing the risk of atherosclerosis and heart failure. Gut-derived molecules, gut hormones, and gut microbiota metabolites showed both positive and detrimental effects in cardiometabolic disorders. Although inflammation plays a key role in cardiometabolic disorders, additional intracellular signaling pathways are involved and could explain the observed effects. Revealing the involved molecular mechanisms could provide novel therapeutic strategies and a better understanding of the relationship between the gut, metabolic syndrome, and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background : We sought to compare the outcomes of patients receiving combination therapy of diuretics and neurohormonal blockers, with a matched cohort with monotherapy of loop diuretics, using real-world big data. Methods : This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 78,685 patients who were first hospitalized with heart failure (HF) between April 2015 and March 2017. Propensity score (PS) was estimated with logistic regression model, with neurohormonal blockers (angiotensin-converting enzyme inhibitor: ACEi or angiotensin receptor blocker : ARB, β-blockers and mineralocorticoid receptor antagonists : MRA) as the dependent variable and 24 clinically relevant covariates to compare the in-hospital mortality between monotherapy of loop diuretics and combination therapies. Results : On PS-matched analysis, patients with ACEi/ARB, β-blockers, and MRA had lower total in-hospital mortality and in-hospital mortality within 7 days, 14 days and 30 days. In the sub-group analysis, regardless of clinical characteristics including elderly people and cancer, patients treated with a combination of loop diuretics and neurohormonal blockers had significantly lower in-hospital mortality than matched patients. Conclusions : Our data indicate the benefits of guideline-directed medical therapy to loop diuretics in the management of HF. [ABSTRACT FROM AUTHOR]

Aims: Acute decompensated heart failure (ADHF) is a frequent cause of hospitalization for patients with heart disease, and ADHF patients are at high risk of heart failure (HF) re‐hospitalization. Residual congestion at discharge is also a strong predictor of poor outcomes and re‐hospitalization for ADHF patients. However, the impact of residual congestion at discharge on worsening renal function (WRF) in both high‐aged and older patients remains uncertain because previous studies of WRF in ADHF patients were conducted for older patients. We therefore designed and conducted a retrospective, population‐based study using the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) Registry to investigate the association of residual congestion at discharge with WRF in ADHF patients according to age. Methods and results: We studied 966 hospitalized ADHF patients with a mean age of 80.2 ± 11.4 years from among 1971 listed in the KUNIUMI Registry. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level during the hospital stay compared with the value on admission. The primary endpoint was defined as cardiovascular death or HF re‐hospitalization after discharge over a mean follow‐up period of 2.0 ± 0.1 years. The primary endpoint was recorded for 369 patients (38.2%). As expected, patients with both WRF and residual congestion at discharge had significantly less favourable outcomes compared with those without one of them, and patients without either of these two characteristics had the most favourable outcomes, whereas those with residual congestion and with WRF had the least favourable outcomes. Moreover, WRF was significantly associated with worse outcomes for high‐aged patients ≥80 years old, but not for those <80 years old if decongested. Multivariable Cox regression analysis showed that both residual congestion at discharge and WRF were the independent predictors of outcomes for high‐aged patients, but residual congestion at discharge, not WRF, was the independent predictor of outcomes for older patients. Conclusions: Association of residual congestion at discharge with WRF for hospitalized ADHF patients can differ according to age. Our findings showed the importance of WRF and residual congestion at discharge for high‐aged ADHF patients and of aggressive diuresis to alleviate congestion for older ADHF patients for better management of such patients in a rapidly ageing society. [ABSTRACT FROM AUTHOR]

Aims: Abnormal left ventricular diastolic response to preload stress can be an early marker of heart failure (HF). The aim of this study was to assess clinical course in patients with HF with preserved ejection fraction (HFpEF) who underwent preload stress echocardiography. In the subgroup analysis, we assessed the prognosis of patients with unstable signs during preload stress classified by treatment strategies. Methods and results: We prospectively conducted preload stress echocardiographic studies between January 2006 and December 2013 in 211 patients with HFpEF. Fifty‐eight patients had abnormal diastolic reserve during preload stress (unstable impaired relaxation: unstable IR). Of 58 patients with unstable IR, 19 patients were assigned to additional therapy by increased or additional therapy and 39 patients were assigned to standard therapy. Composite outcomes were prespecified as the primary endpoint of death and hospitalization for deteriorating HF. During a median period of 6.9 years, 19 patients (33%) reached the composite outcome. Unstable group with standard therapy had significantly shorter event‐free survival than stable group. Patients with uptitration of therapy had longer event‐free survival than those with standard therapy group after adjustment of laboratory data (hazard ratio, 0.20, 95% confidence interval, 0.05–0.90; P = 0.036); the 10 year event‐free survival in patients with and without uptitration of therapy was 93% and 51%, respectively (P = 0.023). Conclusions: Patients with unstable sign had significantly shorter event‐free survival than patients with stable sign. After additional therapy, the prognosis of patients with unstable signs improved. This technique may impact decision‐making for improving their prognosis. [ABSTRACT FROM AUTHOR]

Aims: Hypoxia‐inducible factor‐prolyl hydroxylase (HIF‐PH) inhibitors have been developed for the treatment of renal anaemia; however, no study has evaluated the safety and efficacy of HIF‐PH inhibitors in patients with heart failure (HF). This study was designed to evaluate the safety and efficacy of daprodustat, a HIF‐PH inhibitor, in patients with HF and renal anaemia. Methods and results: We designed a pilot, multi‐centre, open‐label, randomized controlled study, in which 50 patients with HF complicated with chronic kidney disease and anaemia will be randomized 1:1 to either the daprodustat or control group at seven sites in Japan. Study entry requires New York Heart Association Class II HF symptoms or a history of hospitalization due to HF, an estimated glomerular filtration rate of <60 mL/min/1.73 m2, and a haemoglobin level of 7.5 to <11.0 g/dl. Patients randomized to the daprodustat group will be treated with oral daprodustat, and the dose will be uptitrated according to the changes in the haemoglobin level from previous visits. In this study, we will evaluate the impact of HIF‐PH inhibitors on cardiac function using advanced cardiovascular imaging modalities, including cardiac magnetic resonance imaging. The primary outcome is the haemoglobin level at 16 weeks of randomization, and all adverse events will be recorded and evaluated for any association with daprodustat treatment. Conclusion: Considering the hypothetical upside and downside of using HIF‐PH inhibitors in anaemic patients with HF and chronic kidney disease, and because there are virtually no safe and effective treatments for patients with anaemia not caused by iron deficiency, our study results will contribute significantly to this field. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is defined by increased left ventricular (LV) stiffness, impaired vascular compliance, and fibrosis. Although systemic inflammation, driven by comorbidities, has been proposed to play a key role, the precise pathogenesis remains elusive. To test the hypothesis that inflammation drives endothelial dysfunction in HFpEF, we used cardiosphere-derived cells (CDCs), which reduce inflammation and fibrosis, improving function, structure, and survival in HFpEF rats. Dahl salt-sensitive rats fed a high-salt diet developed HFpEF, as manifested by diastolic dysfunction, systemic inflammation, and accelerated mortality. Rats were randomly allocated to receive intracoronary infusion of CDCs or vehicle. Two weeks later, inflammation, oxidative stress, and endothelial function were analyzed. Single-cell RNA sequencing of heart tissue was used to assay transcriptomic changes. CDCs improved endothelial-dependent vasodilation while reducing oxidative stress and restoring endothelial nitric oxide synthase (eNOS) expression. RNA sequencing revealed CDC-induced attenuation of pathways underlying endothelial cell leukocyte binding and innate immunity. Exposure of endothelial cells to CDC-secreted extracellular vesicles in vitro reduced VCAM-1 protein expression and attenuated monocyte adhesion and transmigration. Cell therapy with CDCs corrects diastolic dysfunction, reduces oxidative stress, and restores vascular reactivity. These findings lend credence to the hypothesis that inflammatory changes of the vascular endothelium are important, if not central, to HFpEF pathogenesis. NEW & NOTEWORTHY We tested the concept that inflammation of endothelial cells is a major pathogenic factor in HFpEF. CDCs are heart-derived cell products with verified anti-inflammatory therapeutic properties. Infusion of CDCs reduced oxidative stress, restored eNOS abundance, lowered monocyte levels, and rescued the expression of multiple disease-associated genes, thereby restoring vascular reactivity. The salutary effects of CDCs support the hypothesis that inflammation of endothelial cells is a proximate driver of HFpEF. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a complex disease affecting young adults. It is a pathological condition impairing myocardium activity that leads to heart failure and, in the most severe cases, transplantation, which is currently the only possible therapy for the disease. DCM can be attributed to many genetic determinants interacting with environmental factors, resulting in a highly variable phenotype. Due to this complexity, the early identification of causative gene mutations is an important goal to provide a genetic diagnosis, implement pre-symptomatic interventions, and predict prognosis. The advent of next-generation sequencing (NGS) has opened a new path for mutation screening, and exome sequencing provides a promising approach for identifying causal variants in known genes and novel disease-associated candidates. We analyzed the whole-exome sequencing (WES) of 15 patients affected by DCM without overloading (hypertension, valvular, or congenital heart disease) or chronic ischemic conditions. We identified 70 pathogenic or likely pathogenic variants and 1240 variants of uncertain clinical significance. Gene ontology enrichment analysis was performed to assess the potential connections between affected genes and biological or molecular function, identifying genes directly related to extracellular matrix organization, transcellular movement through the solute carrier and ATP-binding cassette transporter, and vitamin B12 metabolism. We found variants in genes implicated to a different extent in cardiac function that may represent new players in the complex genetic scenario of DCM. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the association between serum UA levels and the mortality rate of AMI patients. We analyzed 5888 patients with successfully revascularized AMI (mean age: 64.0 ± 12.7 years). The subjects were divided into the high UA group (uric acid >6.5 mg/dL for males, >5.8 mg/dL for females) or the normal UA group based on initial serum UA level measured at admission. The primary outcome was all-cause mortality. A total of 4141 (70.3%) and 1747 (29.7%) patients were classified into the normal UA group and high UA groups, respectively. Over a median follow-up of 5.02 (3.07, 7.55) years, 929 (21.5%) and 532 (34.1%) patients died in each group. Cox regression analysis identified high UA levels as an independent predictor of all-cause mortality (unadjusted hazard ratio (HR) 1.69 [95% CI 1.52–1.88]; p < 0.001, adjusted HR 1.18 [95% CI: 1.05–1.32]; p = 0.005). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences. The predictive accuracies of conventional clinical factor discrimination and reclassification were significantly improved upon the addition of hyperuricemia (C-index 0.788 [95% CI 0.775–0.801]; p = 0.005, IDI 0.004 [95% CI 0.002–0.006]; p < 0.001, NRI 0.263 [95% CI 0.208–0.318]; p < 0.001). [ABSTRACT FROM AUTHOR]

Aims: Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF). Methods and results: This single‐centre observational study included 142 patients with HF who underwent CA for AF (median follow‐up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction <50%, n = 58). We compared the cumulative incidence and incidence rate of MACE, comprising all‐cause death, unplanned cardiovascular hospitalization (CVH), and HF hospitalization (HFH) between both groups and the number of HFH before and after CA in each group. Multivariate analysis was performed to identify the predictors of MACE in patients with HFpEF. The incidence of MACE was comparable between the groups (following the first procedure: HFpEF: 23%, 4.7/100 person‐years, vs. systolic HF: 28%, 6.6/100 person‐years, P = 0.18; last procedure: 20%, 4.8/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.21). Although the incidence of HFH was lower in patients with HFpEF than in those with systolic HF (first procedure: 14%, 2.9/100 person‐years, vs. 24%, 5.7/100 person‐years, P = 0.07; last procedure: 11%, 2.5/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.01), the incidence of CVH was higher (first procedure: 8%, 1.7/100 person‐years, vs. 5%, 1.2/100 person‐years, P = 0.74; last procedure: 6%, 1.4/100 person‐years, vs. 2%, 0.5/100 person‐years, P = 0.4). The number of HFH significantly decreased in both groups after CA (HFpEF: 1 hospitalization [the first and third quartiles: 0, 1] in pre‐CA, vs. 0 hospitalizations [0, 0] in post‐CA, P < 0.0001; systolic HF: 1 hospitalization [0, 1], vs. 0 hospitalizations [0, 0], P < 0.005). The proportion of HFH among total clinical events was significantly smaller in patients with HFpEF than in those with systolic HF (following the first procedure: 56% vs. 88%, P < 0.005; last procedure: 52% vs. 92%, P < 0.005). Conclusions: CA for AF could be beneficial for patients with HFpEF, similar to those with systolic HF. However, clinical events other than HFH should be considered cautiously in such patients. [ABSTRACT FROM AUTHOR]

Aims: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods and results: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best‐estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in‐hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5–13.3°C; IQR3 13.3–19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R2 = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per −1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140–100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per −1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in‐hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62). Conclusions: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF. [ABSTRACT FROM AUTHOR]

Cardiac cachexia is a catabolic muscle-wasting syndrome observed in approximately 1 in 10 patients with heart failure. Increased skeletal muscle atrophy leads to frailty and limits mobility, which impacts quality of life, exacerbates clinical care, and is associated with higher rates of mortality. Heart failure is known to exhibit a wide range of prevalence and severity when examined across individuals of different ages and with comorbidities related to diabetes, renal failure, and pulmonary dysfunction. It is also recognized that men and women exhibit striking differences in the pathophysiology of heart failure, as well as skeletal muscle homeostasis. Given that both skeletal muscle and heart failure physiology are in part sex-dependent, the diagnosis and treatment of cachexia in patients with heart failure may depend on a comprehensive examination of how these organs interact. In this review, we explore the potential for sex-specific differences in cardiac cachexia. We summarize advantages and disadvantages of clinical methods used to measure muscle mass and function and provide alternative measurements that should be considered in preclinical studies. In addition, we summarize sex-dependent effects on muscle wasting in preclinical models of heart failure, disuse, and cancer. Lastly, we discuss the endocrine function of the heart and outline unanswered questions that could directly impact patient care. [ABSTRACT FROM AUTHOR]

Aims This study evaluated the prognosis and prognostic factors of patients with cardiac sarcoidosis (CS), an underdiagnosed disease. Methods and results Patients from a retrospective multicentre registry, diagnosed with CS between 2001 and 2017 based on the 2016 Japanese Circulation Society or 2014 Heart Rhythm Society criteria, were included. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and documented fatal ventricular arrhythmia events (FVAE), each constituting exploratory endpoints. Among 512 registered patients, 148 combined events (56 heart failure hospitalizations, 99 documented FVAE, and 49 all-cause deaths) were observed during a median follow-up of 1042 (interquartile range: 518–1917) days. The 10-year estimated event rates for the primary endpoint, all-cause death, heart failure hospitalizations, and FVAE were 48.1, 18.0, 21.1, and 31.9%, respectively. On multivariable Cox regression, a history of ventricular tachycardia (VT) or fibrillation [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.59–4.00, P  < 0.001], log-transformed brain natriuretic peptide (BNP) levels (HR 1.28, 95% CI 1.07–1.53, P  = 0.008), left ventricular ejection fraction (LVEF) (HR 0.94 per 5% increase, 95% CI 0.88–1.00, P  = 0.046), and post-diagnosis radiofrequency ablation for VT (HR 2.65, 95% CI 1.02–6.86, P  = 0.045) independently predicted the primary endpoint. Conclusion Although mortality is relatively low in CS, adverse events are common, mainly due to FVAE. Patients with low LVEF, with high BNP levels, with VT/fibrillation history, and requiring ablation to treat VT are at high risk. [ABSTRACT FROM AUTHOR]

Aims: Cardiac rehabilitation (CR) is an evidence‐based, secondary preventive strategy that improves mortality and morbidity rates in patients with heart failure (HF). However, the implementation and continuation of CR remains unsatisfactory, particularly for outpatients with physical frailty. This study investigated the efficacy and safety of a comprehensive home‐based cardiac rehabilitation (HBCR) programme that combines patient education, exercise guidance, and nutritional guidance using information and communication technology (ICT). Methods and results: This study was a single‐centre, open‐label, randomized, controlled trial. Between April 2020 and November 2020, 30 outpatients with chronic HF (New York Heart Association II–III) and physical frailty were enrolled. The control group (n = 15) continued with standard care, while the HBCR group (n = 15) also received comprehensive, individualized CR, including ICT‐based exercise and nutrition guidance using ICT via a Fitbit® device for 3 months. The CR team communicated with each patient in HBCR group once a week via the application messaging tool and planned the training frequency and intensity of training individually for the next week according to each patient's symptoms and recorded pulse data during exercise. Dietitians conducted a nutritional assessment and then provided individual nutritional advice using the picture‐posting function of the application. The primary outcome was the change in the 6 min walking distance (6MWD). The participants' mean age was 63.7 ± 10.1 years, 53% were male, and 87% had non‐ischaemic heart disease. The observed change in the 6MWD was significantly greater in the HBCR group (52.1 ± 43.9 m vs. −4.3 ± 38.8 m; P < 0.001) at a 73% of adherence rate. There was no significant change in adverse events in either group. Conclusions: Our comprehensive HBCR programme using ICT for HF patients with physical frailty improved exercise tolerance and improved lower extremity muscle strength in our sample, suggesting management with individualized ICT‐based programmes as a safe and effective approach. Considering the increasing number of HF patients with frailty worldwide, our approach provides an efficient method to keep patients engaged in physical activity in their daily life. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunoglobulin is a group of proteins participating in process of inflammation. One of its subtypes is Immunoglobulin Gamma-4 (IgG4) which is related to a rare disease called IgG4-related disease and characterized by a process of fibrosis—deposition of fibers in different organs and inflammation, resulting in tissue damage and dysfunction including the heart muscle and vessels. There is a paucity of information regarding the potential link between of IgG4 and cardiovascular diseases. The purpose of this study is to assess the serum levels of IgG4 in patients with dilated cardiomyopathy (DCM), a disease characterized by cardiac muscle dysfunction of ischemic and non-ischemic origin. Ischemic heart disease is a disease in which heart muscle is damaged by inappropriate blood supply caused by blood vessel obstruction and may cause heart muscle dysfunction. Ninety-eight patients with ischemic and non-ischemic cardiomyopathy were included in this study. The serum concentrations of IgG4 were measured. Patients with DCM had significantly higher levels of IgG4 compared with the healthy control group (77.4 ± 64.0 vs. 50.3 ± 28.8 mg/dL, p < 0.01). Although there was no difference in the total IgG levels in patients with ischemic DCM, the serum concentrations of IgG4 were significantly higher than the corresponding values in the control group (89.8 ± 67.3 vs. 50.3 ± 28.8 mg/dL, p < 0.01). In conclusion, we found that patients with ischemic cardiomyopathy had increased blood levels of IgG4. Additional studies with a larger number of patients are needed to support and explain this finding. (1) Background: Immunoglobulin gamma subclass 4 (IgG4) is a serum protein belonging to the immunoglobulin superfamily. It has a central role in certain immune-mediated conditions defined as IgG4-related disease. There is a paucity of data regarding the potential association of IgG4 and cardiovascular diseases. Our aim is to study the serum levels of IgG4 in patients with ischemic and non-ischemic dilated cardiomyopathy (DCM). (2) Methods: patients with ischemic and non-ischemic DCM were included in this study. Non-ischemic DCM was defined as a left ventricular ejection fraction (LVEF) < 40% without coronary artery disease (CAD). Ischemic DCM was defined as a LVEF < 40% and proven CAD. The serum concentrations of IgG4 were measured by turbidimetry. (3) Results: Overall 98 patients with cardiomyopathy had significantly higher levels of IgG4 compared with the control group (77.4 ± 64.0 vs. 50.3 ± 28.8 mg/dL, p < 0.01). Although there was no difference in the total IgG levels in patients with ischemic DCM, the serum concentrations of IgG4 were significantly higher than the corresponding values in the control group (89.8 ± 67.3 vs. 50.3 ± 28.8 mg/dL; interquartile ranges: 40.4–126.5 vs. 31.8–66.8 mg/dL, p < 0.01). This was altered by gender and smoking. (4) Conclusions: The patients with ischemic DCM had increased serum concentrations of IgG4. Future studies are warranted to explore the potential role of an IgG4-mediated process in patients with heart failure with reduced LVEF. [ABSTRACT FROM AUTHOR]

Heart failure is associated with decreased tissue perfusion and increased venous congestion that may result in organ dysfunction. This dysfunction has been investigated extensively for many organs, but data regarding pancreatic (exocrine) dysfunction are scarce. In the present review we will discuss the available data on the mechanisms of pancreatic damage, how heart failure can lead to exocrine dysfunction, and its clinical consequences. We will show that heart failure causes significant impairment of pancreatic exocrine function, particularly in the elderly, which may exacerbate the clinical syndrome of heart failure. In addition, pancreatic exocrine insufficiency may lead to further deterioration of cardiovascular disease and heart failure, thus constituting a true vicious circle. We aim to provide insight into the pathophysiological mechanisms that constitute this reciprocal relation. Finally, novel treatment options for pancreatic dysfunction in heart failure are discussed. [ABSTRACT FROM AUTHOR]

Aims The HINODE study aimed to analyse rates of mortality, appropriately treated ventricular arrhythmias (VA), and heart failure in Japanese patients and compared with those in Western patients. Methods and results After treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (i) internal cardioverter-defibrillator (ICD), (ii) cardiac resynchronization therapy (CRT) defibrillator (CRT-D), (iii) standard medical therapy (‘non-device’: ND), or (iv) pacing (indicated for CRT; received pacemaker or CRT pacing). Cohorts 1–3 required a left ventricular ejection fraction ≤35%, a history of heart failure, and a need for primary prevention of sudden cardiac death based on two to five previously identified risk factors. Endpoint outcomes were adjudicated by the independent committees. ICD and CRT-D cohorts, considered as high-voltage (HV) cohorts, were pooled for Kaplan–Meier analysis and propensity-matched to Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) arm B and C patients. The study enrolled 354 patients followed for 19.6 ± 6.5 months, with a minimum of 12 months. Propensity-matched HV cohorts showed comparable VA (P = 0.61) and mortality rates (P = 0.29) for HINODE and MADIT-RIT. The ND cohort presented a high crossover rate to ICD therapy (6.1%, n = 7/115), and the CRT-D cohort showed elevated mortality rates. The pacing cohort revealed that patients implanted with pacemakers had higher mortality (26.0%) than those with CRT-Pacing (8.4%, P = 0.05). Conclusions The mortality and VA event rates of landmark trials are applicable to patients with primary prevention in Japan. Patients who did not receive guideline-indicated CRT devices had poor outcomes. [ABSTRACT FROM AUTHOR]