Circulation Journal最新文献

Background: Previous studies have demonstrated that a shorter hospital stay reduces adverse outcomes in heart failure (HF), primarily in observational study settings. This trend was further emphasized during the COVID-19 pandemic, resulting in case-control study-like results.

Methods and results: A subanalysis was conducted on 239 patients from a Japanese multicenter cohort study (HINODE), encompassing 32 months before and 6 months after pandemic onset. The duration of hospitalization and clinical outcomes were compared between these 2 periods in HF patients who received guideline-directed medical and cardiac implantable electronic device (CIED) therapy. The duration of HF hospitalization was significantly shortened by 41.1% (95% confidence interval [CI] 6.7-62.8%) during the pandemic period (median 13 days; interquartile range [IQR] 6-19 days) compared with the prepandemic period (median 21 days; IQR 12-38 days). Nonetheless, the incidence rate (IR) of outcomes in the pandemic group was similar (ventricular arrhythmia, HF events, HF and cardiac hospitalization) or lower (all-cause hospitalization [IR ratio 0.6; 95% CI 0.4-1.0]) compared with the prepandemic group. The odds ratio of adverse events was also similar between the 2 groups.

Conclusions: A significant reduction in hospitalization duration during the COVID-19 pandemic was associated with similar or improved clinical outcomes for guideline-adherent HF patients. Current hospitalization durations for advanced HF patients are likely unnecessarily long, and efforts to reduce them are warranted.

Background: Selexipag, an oral prostacyclin (PGI₂) receptor agonist, is approved for adult patients with pulmonary arterial hypertension (PAH). This study evaluated the efficacy and safety of selexipag for Japanese pediatric patients with PAH.

Methods and results: The study enrolled 6 patients who received selexipag twice daily at an individualized dose based on body weight; maintenance doses were determined for each patient by 12 weeks after starting administration. Efficacy, including pulmonary hemodynamics, was evaluated after 16 weeks, and efficacy and safety were further evaluated 52 weeks after treatment was initiated in the last enrolled patient. The mean (±SD) change in the pulmonary vascular resistance index from baseline to Week 16 (the primary endpoint of the study) was -5.55±6.88 Wood units·m²; improvements were also seen in other pulmonary hemodynamic parameters. The 6-min walk distance increased and N-terminal pro-B-type natriuretic peptide decreased up to Week 64, but the between-subject variability was large. The World Health Organization functional class was improved in 1 of 6 patients at Week 16 and in 2 of 4 patients at Week 64. No patient worsened. The major side effects of selexipag were those characteristic of PGI₂, and the safety profile of selexipag was similar to that in adult patients.

Conclusions: The efficacy and safety of selexipag in Japanese pediatric patients with PAH were demonstrated.

Background: The primary prevention of atrial fibrillation (AF), which increases mortality through complications including stroke and heart failure, is important. Excessive salt intake and low potassium intake are risk factors for cardiovascular disease; however, their association with AF remains inconclusive. This study investigated the association between sodium- and potassium-related urinary markers and AF prevalence.

Methods and results: Data from the Tohoku Medical Megabank Project Community-based Cohort Study were used in this cross-sectional study. The urinary sodium-to-potassium (Na/K) ratio and estimated 24-h sodium and potassium excretion were calculated using spot urine samples and categorized into quartiles (Q1-Q4). The prevalence of AF was the primary outcome. Of the 26,506 participants (mean age 64.8 years; 33.2% males) included in this study, 630 (2.4%) had AF. Using Q1 as the reference group, the odds ratios for AF prevalence in Q4 were 1.35 (95% confidence interval [CI] 1.07-1.73) and 1.59 (95% CI 1.20-2.12) for 24-h estimated urinary Na/K ratio and estimated 24-h sodium excretion, respectively. Estimated 24-h potassium excretion was not associated with AF prevalence.

Conclusions: AF prevalence was positively associated with the urinary Na/K ratio and estimated 24-h urinary sodium excretion, but not with estimated 24-h urinary potassium excretion. Although further prospective studies are warranted, the findings of this study suggest that salt intake may be a modifiable risk factor for AF.

Background: Accurate prediction of prognosis in transthyretin amyloid cardiomyopathy (ATTR-CM) is crucial for optimal treatment selection, including tafamidis, the only approved therapy for ATTR-CM. Although tafamidis has been proven to improve prognosis, the long-term serial changes in comprehensive parameters related to ATTR-CM, including cardiac biomarkers and imaging parameters, under tafamidis remain unknown.

Methods and results: In this study, we used Cox regression analysis on data from 258 consecutive patients diagnosed with ATTR-CM at Kumamoto University to determine prognostic factors. During clinical follow-up, the serial changes in parameters were compared between tafamidis-treated and tafamidis-naïve patients. An elevated high-sensitivity cardiac troponin T (hs-cTnT) level at baseline was identified as a stronger independent predictor of all-cause death compared with left ventricular ejection fraction (LVEF) and extracellular volume. During follow-up (median: 24.4 months), estimated glomerular filtration rate and LVEF declined significantly with time in both cohorts. Notably, serum hs-cTnT and B-type natriuretic peptide levels were significantly elevated in the tafamidis-naïve cohort compared to baseline, but this increase was prevented by tafamidis treatment.

Conclusions: Of the ATTR-CM-related parameters investigated, an increased hs-cTnT level at baseline was a promising determinant of poor prognosis. Long-term tafamidis treatment prevented a deterioration in cardiac biomarkers, and the measurement of these markers may enable appropriate monitoring of disease progression.

Catheter ablation is a widely used treatment modality for various cardiac tachyarrhythmias, including atrial and ventricular arrhythmias. Although it is generally considered safe, the procedure carries potential complications, with coronary artery injury being one of the most significant. The aim of this systematic review was to assess the incidence, mechanisms, contributing factors, diagnostic strategies, and preventive measures related to coronary artery injury in patients undergoing catheter ablation, including radiofrequency catheter ablation, cryoablation, and pulsed-field ablation.

Background: Fabry disease is a hereditary metabolic disorder caused by a decrease in or deficiency of the lysosomal enzyme α-galactosidase A. Enzyme replacement therapy or pharmacological chaperone therapy can improve prognosis, especially in patients in the early phase of cardiac involvement. Longitudinal strain (LS) evaluated using speckle tracking echocardiography can detect early contractile dysfunction. However, there have been no reports of LS in Japanese Fabry disease patients.

Methods and results: We recruited 56 patients with Fabry disease (22 men, 34 women) who were followed up at Jikei University Hospital. Fifty-eight control subjects without overt cardiac diseases were also included in the study. We evaluated LS in each patient, and the values of each of the 17 segments of the left ventricle (LV) were averaged, and global LS (GLS) was also calculated. GLS was significantly worse in Fabry disease patients without LV hypertrophy than in control subjects (-18.5±2.8% vs. -20.4±1.6%; P<0.05). In addition, Fabry disease patients without LV hypertrophy had significantly worse lateral LS (-16.4±5.0% vs. -19.3±1.8%; P<0.05), basal LS (-16.5±3.2% vs. -18.5±1.7%; P<0.05), and mid LS (-18.7±1.7% vs. -20.8±1.6%; P<0.05) than control subjects.

Conclusions: These results suggest that early contractile dysfunction in Fabry disease can be observed using GLS, lateral LS, basal LS, and mid LS, even without LV hypertrophy.

Background: Guideline-directed medical therapy has become an important component of heart failure (HF) therapy, with sacubitril/valsartan as one of the recommended drugs; however, the real-world prognostic implications of sacubitril/valsartan uptitration are unclear.

Methods and results: Patients with HF newly initiated on sacubitril/valsartan were registered in a retrospective multicenter study (REVIEW-HF). In all, 995 patients were divided into 3 groups according to the maximum dose achieved: high dose, sacubitril/valsartan 400 mg; intermediate dose, sacubitril/valsartan 200-<400 mg; and low dose, sacubitril/valsartan <200 mg. A total of 397 (39.9%) patients received high-dose sacubitril/valsartan; they had a significantly lower risk of mortality or HF hospitalization than patients in the low-dose (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.29-0.53; P<0.001) and intermediate-dose (HR 0.64; 95% CI 0.45-0.94; P=0.03) groups. In the multivariable Cox regression model, higher systolic blood pressure and maintained geriatric nutritional risk index were significantly associated with a higher incidence of achieving a high dose of sacubitril/valsartan. Patients who did not receive high-dose sacubitril/valsartan experienced more hypotension during the follow-up period, whereas hyperkalemia, severe renal events, and angioedema did not differ across the achieved dose classifications.

Conclusions: Patients who achieved sacubitril/valsartan uptitration had a better prognosis than those who did not. Before sacubitril/valsartan uptitration, patients need to monitor blood pressure closely to prevent worsening events.

Background: Mitochondrial dysfunction in the heart is associated with the development of heart failure (HF). However, the clinical consequences of mitochondrial structural abnormalities in patients with HF remain unexplored.

Methods and results: Ninety-one patients with left ventricular (LV) systolic dysfunction who underwent endomyocardial biopsy (EMB) were enrolled in the study. Myocardial specimens were obtained from the right ventricular septum. Specimens were characterized using electron microscopy to assess mitochondrial size, outer membrane disruption, and cristae disorganization. The primary endpoint was a composite of cardiovascular death and unplanned hospitalization for HF. Patients were classified into LV reverse remodeling (LVRR)-positive (n=52; 57.1%) and LVRR-negative (n=39; 42.9%) groups. Cristae disorganization was observed in 21 (23.1%) patients: 6 (11.5%) in the LVRR-positive group and 15 (38.5%) in the LVRR-negative group (P=0.005). During the 1-year post-EMB observation period, 16 patients (17.6%) met the primary endpoint, with 2 (2.2%) cardiovascular deaths and 14 (15.4%) HF hospitalizations. Cristae disorganization (P=0.002) was significantly associated with the endpoints, independent of age (P=0.115), systolic blood pressure (P=0.004), B-type natriuretic peptide level (P=0.042), and mitral regurgitation (P=0.003).

Conclusions: We classified mitochondrial structural abnormalities and showed that cristae disorganization was associated with LVRR and worse prognosis. These findings may affect the management of patients with HF and systolic dysfunction who undergo EMB.

Background: Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and cardiac function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-HCM. However, the efficacy and safety profiles of mavacamten in Japanese patients are unclear.

Methods and results: HORIZON-HCM is a Phase 3 single-arm study in Japanese patients with symptomatic obstructive HCM. The mavacamten starting dose was 2.5 mg; individualized dose titration occurred in Weeks 6-20 based on Valsalva left ventricular outflow tract (LVOT) gradient and resting left ventricular ejection fraction (LVEF). Overall, 38 patients were treated; 36 completed the 30-week primary treatment analysis period. Clinically significant improvements in postexercise LVOT gradient were observed after 30 weeks of treatment (mean change from baseline -60.7 mmHg). Improvements in N-terminal pro B-type natriuretic peptide, New York Heart Association class, and Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score were observed over 30 weeks, and mean LVEF was ≥74% at all visits. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 63.2% and 7.9% of patients, respectively; none resulted in treatment discontinuation. One patient experienced a transient asymptomatic reduction in LVEF to <50%. No deaths occurred during the study.

Conclusions: In Japanese patients with obstructive HCM, mavacamten was associated with similar improvements in LVOT gradients, cardiac biomarkers, and symptoms to those observed in EXPLORER-HCM. Treatment was well tolerated with no new safety concerns.