Although left ventricular (LV) diastolic dysfunction is often associated with hypertension, little is known regarding its underlying pathophysiological mechanism. Here, we show that the actin cytoskeletal regulator, Rho-associated coiled-coil containing kinase-2 (ROCK2), is a critical mediator of LV diastolic dysfunction. In response to angiotensin II (Ang II), mutant mice with fibroblast-specific deletion of ROCK2 (ROCK2 ^Postn–/– ) developed less LV wall thickness and fibrosis, along with improved isovolumetric relaxation. This corresponded with decreased connective tissue growth factor (CTGF) and fibroblast growth factor–2 (FGF2) expression in the hearts of ROCK2 ^Postn–/– mice. Indeed, knockdown of ROCK2 in cardiac fibroblasts leads to decreased expression of CTGF and secretion of FGF2, and cardiomyocytes incubated with conditioned media from ROCK2-knockdown cardiac fibroblasts exhibited less hypertrophic response. In contrast, mutant mice with elevated fibroblast ROCK activity exhibited enhanced Ang II–stimulated cardiac hypertrophy and fibrosis. Clinically, higher leukocyte ROCK2 activity was observed in patients with diastolic dysfunction compared with age- and sex-matched controls, and correlated with higher grades of diastolic dysfunction by echocardiography. These findings indicate that fibroblast ROCK2 is necessary to cause cardiac hypertrophy and fibrosis through the induction CTGF and FGF2, and they suggest that targeting ROCK2 may have therapeutic benefits in patients with LV diastolic dysfunction.

Background: Remote dielectric sensing (ReDS™) is an electromagnetic-based technology used to noninvasively measure lung fluid levels. The association between ReDS values and invasively measured hemodynamics, particularly among those with small physics, remains unknown. Methods: Consecutive patients with chronic heart failure who were admitted to our institute and underwent invasive right heart catheterization as well as simultaneous ReDS measurement at clinically stable conditions between September and November 2021 were prospectively included. The colinearity between ReDS values and pulmonary capillary wedge pressure was studied. Results: In total, 30 patients (median 79 (73, 84) years old, 13 men) were included. Median ReDS value was 26% (22%, 28%). ReDS values had a moderate collinearity with pulmonary capillary wedge pressure (r = 0.698, p < 0.001), even among those with a body height < 155 cm. ReDS values with a cutoff of 28% predicted a pulmonary capillary wedge pressure > 15 mmHg with sensitivity 0.70 and specificity 0.75. Conclusions: An electromagnetic-based engineering ReDS might be a potential tool to estimate cardiac pressure in patients with heart failure, including those with small physics.

Background: The accuracy of the remote dielectric sensing (ReDS^TM) system, which is a noninvasive electromagnetic-based technology to quantify lung fluid levels, particularly among those with small body size, remains uncertain. Methods: Hospitalized patients with and without heart failure underwent assessment of lung fluid levels with ReDS and successive chest computed tomography imaging. We performed a correlation analysis of the ReDS measurement, representing lung fluid levels, and computed tomography-derived high attenuation area percentage, which also provides a spatial quantification of lung fluid level. Results: A total of 46 patients (median 76 years old, 28 men), including 28 patients with heart failure, were included. The median ReDS value was 28% (interquartile: 23%, 33%), and the median percentage of high attenuation area was 21.6% (14.4%, 28.5%). ReDS values and percentage of high attenuation area were moderately correlated (r = 0.65, p < 0.001), irrespective of the existence of heart failure. ReDS value independently predicted the percentage of high attenuation area seen on computed tomography (p < 0.001). Conclusions: The ReDS system may be a promising, noninvasive tool to quantify fluid lung levels, as validated by comparison with chest computed tomography imaging. Further studies are warranted to validate the utility and applicability of this technology to a variety of clinical scenarios.

Background: Sodium zirconium cyclosilicate (SZC), a newly introduced specific potassium binder, is introduced to treat hyperkalemia. However, the implications of SZC in up-titrating renin–angiotensin–aldosterone system inhibitors in patients with systolic heart failure remain unknown. Methods and Results: Patients with heart failure with left ventricular ejection fraction <50% and hyperkalemia who had completed 3-month SZC therapy were retrospectively included. Serum potassium levels, the dose of renin–angiotensin–aldosterone system inhibitors, and echocardiographic parameters during the 3-month SZC therapy as compared with the pretreatment 3-month period were investigated. A total of 24 patients (median 77 years old, 71% men, median left ventricular ejection fraction 41%) received a 3-month SZC therapy without any associated adverse events including hypokalemia. Compared with the pretreatment period, serum potassium levels decreased, doses of renin–angiotensin–aldosterone system inhibitors increased, and the left ventricular ejection fraction and plasma B-type natriuretic peptide levels improved following the 3-month SZC therapy (p < 0.05 for all). Conclusions: SZC may be a promising therapeutic option to improve hyperkalemia, indirectly allowing up-titration of renin–angiotensin–aldosterone system inhibitors and facilitating reverse remodeling in patients with heart failure with a left ventricular ejection fraction <50% and hyperkalemia.

Background: The six-minute walk test is a practical tool for assessing functional capacity in patients with a variety of etiologies including pulmonary disease and heart failure. Six-minute walk distance (6MWD) is associated with mortality and morbidity in patients with a variety of comorbidities. We aimed to assess the prognostic impact of baseline 6MWD in patients with severe aortic stenosis undergoing trans-catheter aortic valve replacement (TAVR). Methods: Patients with severe aortic stenosis who underwent a six-minute walk test after index admission and underwent TAVR between 2015 and 2022 were included in this retrospective study. Patients were followed up for two years or until November 2022 following TAVR. The impact of baseline 6MWD on the primary composite outcome, defined as all-cause death and all-cause readmission during the 2-year observation period following index discharge, was assessed. Results: A total of 299 patients (median age 86 years old, 85 men) were included. They received a 6-min walk test prior to TAVR, underwent successful TAVR procedures, and were discharged alive. The median baseline 6MWD was 204 (143, 282) meters. Shorter baseline 6MWD was associated with higher cumulative incidence of the primary outcome with an adjusted hazard ratio of 0.76 (95% confidence interval 0.58–1.01, p = 0.055) with a cutoff 6MWD of 178 m during the 2-year observation period after index discharge. Conclusions: Overall, functional capacity was impaired in the elderly patients with severe aortic stenosis prior to TAVR. Patients with severe aortic stenosis having shorter baseline 6MWD tended to have higher rates of morbidity and mortality after successful TAVR. The clinical implication of aggressive cardiac rehabilitation to improve patients’ functional capacity and 6MWD-guided optimal patient selection remain the future concerns.

Background: Small dense LDL-cholesterol is an established risk factor for atherosclerosis but is not routinely measured in daily practice. The association between small dense LDL-cholesterol and triglyceride, which in turn is routinely measured, in patients with acute coronary syndrome remains unknown. Methods: Consecutive patients with acute coronary syndrome who were admitted to our institute were prospectively included, and serum samples were obtained on admission. The association between small dense LDL-cholesterol and triglyceride was investigated. Results: Among 55 patients (median 71 years old, 64% men), median (interquartile range) small dense LDL-cholesterol was 23.6 (17.0, 36.0) and triglyceride was 101 (60, 134) mg/dL. Triglyceride level correlated with small dense LDL-cholesterol (r = 0.67, p < 0.001) and was an independent determinant of small dense LDL-cholesterol together with body mass index (p = 0.010 and p = 0.008, respectively). Those with high triglyceride and high body mass index had a 3-fold level of small dense LDL-cholesterol compared with those with low triglyceride and low body mass index (45.8 [35.0, 54.0] mg/dL versus 15.0 [11.6, 23.7] mg/dL, p = 0.001). Conclusions: Triglyceride level was a major determinant of small dense LDL-cholesterol in patients with acute coronary syndrome. Triglyceride level might be a useful and practical biomarker for risk stratification for patients with acute coronary syndrome together with body mass index.