Incidence and risk factors of hypotension-related adverse events among Japanese patients with heart failure receiving sacubitril/valsartan or enalapril: Results from the PARALLEL-HF study.

BACKGROUND: The PARALLEL-HF trial showed that treatment with sacubitril/valsartan resulted in more symptomatic hypotension versus enalapril in Japanese patients with heart failure (HF) and reduced ejection fraction, similar to PARADIGM-HF. Use of sacubitril/valsartan in these patients may be limited by concerns regarding hypotension. METHODS: This post-hoc analysis characterized hypotension-related adverse events (AEs) and their effects on efficacy using data from PARALLEL-HF, in which patients received sacubitril/valsartan 200 mg twice daily or enalapril 10 mg twice daily. RESULTS: Of 223 patients, 28.2 % experienced hypotension-related AEs and incidence was higher with sacubitril/valsartan versus enalapril (hazard ratio, 2.2; 95 % CI, 1.3-3.8; p = 0.0027). However, reduction in mean systolic blood pressure from baseline to study end did not significantly differ (sacubitril/valsartan: -2.2 mmHg vs enalapril: -1.3 mmHg; p = 0.6895). Patients who experienced hypotension-related AEs had lower mean body mass index, higher median N-terminal pro-brain natriuretic peptide at randomization, and more frequent history of stroke. Hypotension-related AEs leading to treatment discontinuation were not significantly different for sacubitril/valsartan versus enalapril (3.4 % vs 6.9 %, p = 0.5957). Reduction in risk of cardiovascular death or HF hospitalization was similar with sacubitril/valsartan versus enalapril in patients with or without hypotension-related AEs. CONCLUSIONS: Incidence of hypotension-related AEs was higher in the sacubitril/valsartan versus enalapril group but did not affect risk of cardiovascular death or HF hospitalization, which was similar between treatment groups.

Pharmacological and Device-Based Intervention for Preventing Heart Failure After Acute Myocardial Infarction　- A Clinical Review.

In patients with acute myocardial infarction (MI), heart failure (HF) is one of the most common complications that is associated with a significant burden of mortality and healthcare resources. The clinical benefits of key HF drugs, the so-called "4 pillars" or "fantastic 4", namely ß-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitor, and sodium-glucose cotransporter 2 inhibitors, have been established in patients with HF with reduced ejection fraction, whereas the effects of these drugs are not comprehensively appreciated in patients with acute MI. This review summarizes current evidence on pharmacological and device-based interventions for preventing HF after acute MI.

Association Between Clonal Hematopoiesis and Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy.

Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis.

Different Impact of Immunosuppressive Therapy on Cardiac Outcomes in Systemic Versus Isolated Cardiac Sarcoidosis.

Isolated cardiac sarcoidosis (iCS) is increasingly recognized; however, its prognosis and the efficacy of immunosuppressive therapy remain undetermined. We aimed to compare the prognosis of iCS and systemic sarcoidosis including cardiac involvement (sCS) under immunosuppressive therapy.We retrospectively reviewed the clinical data of 42 patients with sCS and 30 patients with iCS diagnosed at Kyushu University Hospital from 2004 through 2022. We compared the characteristics and the rate of adverse cardiac events including cardiac death, fatal ventricular tachyarrhythmia, and heart failure hospitalization between the 2 groups. The median follow-up time was 1535 [interquartile range, 630-2555] days, without a significant difference between the groups. There were no significant differences in gender, NYHA class, or left ventricular ejection fraction. Immunosuppressive agents were administered in 86% of sCS and in 73% of iCS patients (P = 0.191). When analyzed only with patients receiving immunosuppressive therapy (sCS, n = 36; iCS, n = 21), the cardiac event-free survival was significantly lower in iCS than sCS (37% versus 79%, P = 0.002). Myocardial LGE content at the initial diagnosis was comparable in both groups. The disease activity was serially evaluated in 26 sCS and 16 iCS patients by quantitative measures of FDG-PET including cardiac metabolic volume and total lesion glycolysis, representing 3-dimensional distribution and intensity of inflammation in the entire heart. Although iCS patients had lower baseline disease activity than sCS patients, immunosuppressive therapy did not attenuate disease activity in iCS in contrast to sCS.iCS showed a poorer response to immunosuppressive therapy and a worse cardiac prognosis compared to sCS despite lower baseline disease activity.

Influenza Vaccination and Cardiovascular Events in Japanese Patients With Heart Failure　- Findings From the PARALLEL-HF Trial.

Background: Influenza is associated with an increased risk for cardiovascular events in patients with heart failure (HF). This study aimed to investigate the prevalence of influenza vaccination among Japanese patients with HF enrolled in the PARALLEL-HF (Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) trial and the association between receiving influenza vaccination and cardiovascular events including death or HF hospitalization. Methods and Results: In PARALLEL-HF, in which 223 patients with HF and reduced ejection fraction (HFrEF) were randomized to the angiotensin-receptor neprilysin inhibitor (sacubitril/valsartan) or enalapril, 97 (43%) received influenza vaccination. Influenza vaccination tended to be associated, though statistically not significant, with a lower risk for all-cause death (adjusted hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.32-1.39) and cardiopulmonary or influenza-related hospitalization or death (adjusted HR: 0.72; 95% CI: 0.46-1.11) in propensity score-adjusted models. Conclusions: The influenza vaccination rate in Japanese patients with HFrEF who were well managed on guideline-directed medical therapy was suboptimal despite recommendations from clinical practice guidelines. However, importantly, it could be associated with better clinical benefits.

Impact of sympathetic hyperactivity induced by brain microglial activation on organ damage in sepsis with chronic kidney disease.

BACKGROUND: Sympathetic nerve activity (SNA) plays a central role in the pathogenesis of several diseases such as sepsis and chronic kidney disease (CKD). Activation of microglia in the paraventricular nucleus of the hypothalamus (PVN) has been implicated in SNA. The mechanisms responsible for the adverse prognosis observed in sepsis associated with CKD remain to be determined. Therefore, we aimed to clarify the impact of increased SNA resulting from microglial activation on hemodynamics and organ damage in sepsis associated with CKD. METHODS AND RESULTS: In protocol 1, male Sprague-Dawley rats underwent either nephrectomy (Nx) or sham surgery followed by cecal ligation and puncture (CLP) or sham surgery. After CLP, Nx-CLP rats exhibited decreased blood pressure, increased heart rate, elevated serum creatinine and bilirubin levels, and decreased platelet count compared to Nx-Sham rats. Heart rate variability analysis revealed an increased low to high frequency (LF/HF) ratio in Nx-CLP rats, indicating increased SNA. Nx-CLP rats also had higher creatinine and bilirubin levels and lower platelet counts than sham-CLP rats after CLP. In protocol 2, Nx-CLP rats were divided into two subgroups: one received minocycline, an inhibitor of microglial activation, while the other received artificial cerebrospinal fluid (CSF) intracerebroventricularly via an osmotic minipump. The minocycline-treated group (Nx-mino-CLP) showed attenuated hypotensive and increased heart rate responses compared to the CSF-treated group (Nx-CSF-CLP), and the LF/HF ratio was also decreased. Echocardiography showed larger left ventricular dimensions and inferior vena cava in the Nx-mino-CLP group. In addition, creatinine and bilirubin levels were lower and platelet counts were higher in the Nx-mino-CLP group compared to the Nx-CSF-CLP group. CONCLUSIONS: In septic rats with concomitant CKD, SNA was significantly enhanced and organ dysfunction was increased. It has been suggested that the mechanism of exacerbated organ dysfunction in these models may involve abnormal systemic hemodynamics, possibly triggered by activation of the central sympathetic nervous system through activation of microglia in the PVN.

Efficacy and safety of the urate-lowering agent febuxostat in chronic heart failure patients with hyperuricemia: results from the LEAF-CHF study.

Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure (CHF). To determine whether febuxostat, a urate-lowering agent, may improve clinical outcomes in CHF patients, we conducted a multicenter, prospective, randomized, open-label, blinded endpoint study with a treatment period of 24 weeks. We randomly assigned Japanese outpatients diagnosed with both CHF with reduced left ventricular ejection fraction (LVEF < 40%) and asymptomatic hyperuricemia (serum uric acid [UA] levels > 7.0 mg/dl and < 10.0 mg/dl) to either a febuxostat group (n = 51) or a control group (n = 50). The primary efficacy endpoint was the change in log-transformed plasma B-type natriuretic peptide (BNP) levels from baseline to week 24 (or at discontinuation). The secondary efficacy endpoints were the changes in LV systolic or diastolic function evaluated by echocardiography, New York Heart Association (NYHA) class, hemoglobin, and estimated glomerular filtration rate from baseline to week 24, and the change in log-transformed plasma BNP levels or serum UA levels from baseline to weeks 4, 8, 12, 16 and 20 (BNP) or weeks 4, 8, 12, 16, 20 and 24 (serum UA). The primary safety endpoints were occurrence of all-cause death or major cardiovascular events. The mean age of participants was 70 years; 14% were female. The febuxostat group and the control group did not differ with respect to the primary efficacy endpoint (p = 0.13), although the decrease in log-transformed plasma BNP levels from baseline to each of weeks 4, 8, 12, 16 and 20 was greater in the febuxostat group. There were no significant differences between the two groups in the primary safety endpoints or the secondary efficacy endpoints except reduced serum UA levels in the febuxostat group. Febuxostat did not reduce plasma BNP levels at week 24 in patients with CHF, but it appeared safe with no increase in major cardiovascular events and all-cause or cardiovascular mortality.

Patient Outcomes in Very Elderly Patients With Non-Valvular Atrial Fibrillation　- ANAFIE Registry.

Background: The All Nippon Atrial Fibrillation In the Elderly Registry provides real-world insights into non-valvular atrial fibrillation (NVAF) in >30,000 elderly Japanese patients (aged ≥75 years), including >2,000 nonagenarians. We aimed to investigate outcomes in these patients by age and oral anticoagulant (OAC) type. Methods and Results: This prospective, multicenter, observational, cohort, 2-year follow-up study included elderly patients with NVAF who were able to attend hospital visits. The incidences of stroke/systemic embolic events (SEE), major bleeding, intracranial hemorrhage (ICH), cardiovascular death, all-cause death, and major adverse cardiovascular or neurological events (MACNE) were evaluated by age. Incidence rates increased significantly with age. Stroke/SEE, major bleeding, and ICH incidences plateaued in patients aged ≥90 years. Direct OACs (DOACs) yielded a numerically lower event incidence vs. warfarin in all age groups and endpoints, except for major bleeding in patients aged ≥90 years. DOACs (vs. warfarin) were significantly associated with a lower risk of stroke/SEE, major bleeding, and ICH in the ≥80-<85 years group, and reduced cardiovascular and all-cause death in the ≥75-<80 years group. In the ≥90 years subgroup, major bleeding history was a risk factor for all-cause death. Conclusions: Although DOAC vs. warfarin offers potential benefits for stroke prevention, limitations occurred in reducing major bleeding among those aged ≥90 years, indicating a potential benefit of very-low-dose DOAC for this demographic.

Hemoglobin Level Can Predict Heart Failure Hospitalization in Patients with Advanced Heart Failure Awaiting Heart Transplantation without Inotropes or Mechanical Circulatory Support.

Although anemia is a common comorbidity that often coexists with heart failure (HF), its clinical impact in patients with advanced HF remains unclear. We investigated the impact of hemoglobin levels on clinical outcomes in patients with advanced HF listed for heart transplantation without intravenous inotropes or mechanical circulatory support.We retrospectively reviewed the clinical data of patients listed for heart transplantation at our institute who did not receive intravenous inotropes or mechanical circulatory support between 2011 and 2022. We divided the patients into those with hemoglobin levels lower or higher than the median value and compared the composite of all-cause death and HF hospitalization within 1 year from the listing date.We enrolled consecutive 38 HF patients (27 males, 49.1 ± 10.8 years old). The median hemoglobin value at the time of listing for heart transplantation was 12.9 g/dL, and 66.7% of the patients had iron deficiency. None of the patients in either group died within 1 year. The HF hospitalization-free survival rate was significantly lower in the lower hemoglobin group (40.9% versus 81.9% at 1 year, P = 0.020). Multivariate Cox proportional hazards model analysis showed that hemoglobin as a continuous variable was an independent predictor for HF hospitalization (odds ratio 0.70, 95% confidence interval 0.49-0.97, P = 0.030).Hemoglobin level at the time of listing for heart transplantation was a predictor of hospitalization in heart-transplant candidates without intravenous inotropes or mechanical circulatory support.

EVs-miR-17-5p attenuates the osteogenic differentiation of vascular smooth muscle cells potentially via inhibition of TGF-ß signaling under high glucose conditions.

Vascular calcification, which is a major complication of diabetes mellitus, is an independent risk factor for cardiovascular disease. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is one of the key mechanisms underlying vascular calcification. Emerging evidence suggests that macrophage-derived extracellular vesicles (EVs) may be involved in calcification within atherosclerotic plaques in patients with diabetes mellitus. However, the role of macrophage-derived EVs in the progression of vascular calcification is largely unknown. In this study, we investigated whether macrophage-derived EVs contribute to the osteogenic differentiation of VSMCs under high glucose conditions. We isolated EVs that were secreted by murine peritoneal macrophages under normal glucose (EVs-NG) or high glucose (EVs-HG) conditions. miRNA array analysis in EVs from murine macrophages showed that miR-17-5p was significantly increased in EVs-HG compared with EVs-NG. Prediction analysis with miRbase identified transforming growth factor ß receptor type II (TGF-ß RII) as a potential target of miR-17-5p. EVs-HG as well as miR-17-5p overexpression with lipid nanoparticles inhibited the gene expression of Runx2, and TGF-ß RII. Furthermore, we demonstrated that VSMCs transfected with miR-17-5p mimic inhibited calcium deposition. Our findings reveal a novel role of macrophage-derived EVs in the negative regulation of osteogenic differentiation in VSMCs under high glucose conditions.

Consensus statement on renal denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Consensus statement on renal denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: (1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or (2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Consensus Statement on Renal Denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Management and outcomes of heart failure hospitalization among older adults in the United States and Japan.

AIMS: Despite advances in therapies, the disease burden of heart failure (HF) has been rising globally. International comparisons of HF management and outcomes may reveal care patterns that improve outcomes. Accordingly, we examined clinical management and patient outcomes in older adults hospitalized for acute HF in the United States (US) and Japan. METHODS: We identified patients aged >65 who were hospitalized for HF in 2013 using US Medicare data and the Japanese Registry of Acute Decompensated Heart Failure (JROADHF). We described patient characteristics, management, and healthcare utilization and compared outcomes using multivariable Cox regression during and after HF hospitalization. RESULTS: Among 11 193 Japanese and 120 289 US patients, age and sex distributions were similar, but US patients had higher comorbidity rates. The length of stay was longer in Japan (median 18 vs. 5 days). While Medicare patients had higher use of implantable cardioverter defibrillator or cardiac resynchronization therapy during hospitalization (1.32% vs. 0.6%), Japanese patients were more likely to receive cardiovascular medications at discharge and to undergo cardiac rehabilitation within 3 months of HF admission (31% vs. 1.6%). Physician follow-up within 30 days was higher in Japan (77% vs. 57%). Cardiovascular readmission, cardiovascular mortality and all-cause mortality were 2.1-3.7 times higher in the US patients. The per-day cost of hospitalization was lower in Japan ($516 vs. $1323). CONCLUSIONS: We observed notable differences in the management, outcomes and costs of HF hospitalization between the US and Japan. Large differences in length of hospitalization, cardiac rehabilitation rate and outcomes warrant further research to determine the optimal length of stay and assess the benefits of inpatient cardiac rehabilitation to reduce rehospitalization and mortality.

Automated control of Impella maintains optimal left ventricular unloading during periods of unstable hemodynamics and prevents myocardial damage in acute myocardial infarction.

BACKGROUND: Left ventricular (LV) unloading by Impella, an intravascular microaxial pump, has been shown to exert dramatic cardioprotective effects in acute clinical settings of cardiovascular diseases. Total Impella support (no native LV ejection) is far more efficient in reducing LV energetic demand than partial Impella support, but the manual control of pump speed to maintain stable LV unloading is difficult and impractical. We aimed to develop an Automatic IMpella Optimal Unloading System (AIMOUS), which controls Impella pump speed to maintain LV unloading degree using closed-feedback control. We validated the AIMOUS performance in an animal model. METHODS: In dogs, we identified the transfer function from pump speed to LV systolic pressure (LVSP) under total support conditions (n = 5). Using the transfer function, we designed the feedback controller of AIMOUS to keep LVSP at 40 mmHg and examined its performance by volume perturbations (n = 9). Lastly, AIMOUS was applied in the acute phase of ischemia-reperfusion in dogs. Four weeks after ischemia-reperfusion, we assessed LV function and infarct size (n = 10). RESULTS: AIMOUS maintained constant LVSP, thereby ensuring a stable LV unloading condition regardless of volume withdrawal or infusion (±8 ml/kg from baseline). AIMOUS in the acute phase of ischemia-reperfusion markedly improved LV function and reduced infarct size (No Impella support: 13.9 ± 1.3 vs. AIMOUS: 5.7 ± 1.9%, P < 0.05). CONCLUSIONS: AIMOUS is capable of maintaining optimal LV unloading during periods of unstable hemodynamics. Automated control of Impella pump speed in the acute phase of ischemia-reperfusion significantly reduced infarct size and prevented subsequent worsening of LV function.

Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on the Severity and the Mortality of Acute Myocardial Infarction in Japan　- Analysis From the JROAD-DPC Database.

Background: Coronavirus disease 2019 (COVID-19) has impacted on cardiovascular disease. However, it remains unclear whether the COVID-19 pandemic has impacted on disease severity and patients' prognosis of acute myocardial infarction (AMI) in Japan. Methods and Results: We retrospectively accumulated data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) study (April 2019 to March 2021). Patients were divided into a before COVID-19 pandemic group or a during COVID-19 pandemic group. The proportion of patients who presented with cardiogenic shock (Killip class IV) was compared between groups, in association with 30-day mortality as the primary outcome. Killip class IV AMI significantly increased in the during COVID-19 pandemic group (15.7% vs. 14.5% in the before pandemic group, P<0.0001). The 30-day mortality was higher in the during COVID-19 pandemic group (9.6% vs. 9.2% in the before COVID-19 pandemic group, P=0.049). However, there was no significant difference in the adjusted 30-day mortality in each Killip class between the before and during COVID-19 pandemic groups. Conclusions: During the early stage of the COVID-19 pandemic in Japan, 30-day mortality of AMI increased, mainly because of the increase of Killip class IV AMI patients. However, irrespective of the COVID-19 pandemic, the adjusted 30-day mortality of each Killip classification group was unchanged.

Nationwide Survey on Transitional Care for Patients With Childhood-Onset Cardiomyopathy in Japan.

Background: Individuals transitioning into adulthood require age-appropriate medical care and delegation of decision-making authority from their parents to the patients themselves. Although there have been multiple observational and interventional studies on transitional care for patients with congenital heart disease (CHD) in the cardiovascular field, transitional care specific to childhood-onset cardiomyopathy (CM) remains unaddressed. Methods and Results: A nationwide questionnaire-based survey was performed in the pediatric cardiology departments of 151 facilities in Japan. Responses were obtained from 100 (66%) facilities with low transfer rates (<5%) for childhood-onset CM cases. The comparison between CHD-transferring and non-CHD-transferring facilities revealed a significantly higher transfer rate (83.9%) for childhood-onset CM cases in the CHD-transferring facilities (P<0.001). Regarding the transition programs, 72 (72%) facilities do not offer any programs for CM, while most (92%) facilities recognize its necessity. Finally, only 19 (19%) facilities provided a transition program, 10 of which were CHD based. Conclusions: To the best of our knowledge, this is the first study to demonstrate the poor transition/transfer care status of patients with childhood-onset CM in Japan. The transfer rate of CMs was lower than that of CHDs, and transition programs were less available. Referring to the system established for CHD could help develop a successful transitional care system for CM.

Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Chronic Effects of Adaptive Servo-Ventilation Therapy on Mortality and the Urgent Rehospitalization Rate in Patients Experiencing Recurrent Admissions for Heart Failure　- A Multicenter Prospective Observational Study (SAVIOR-L).

BACKGROUND: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF). METHODS AND RESULTS: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups. CONCLUSIONS: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.