Mitochondrial Structural Abnormalities and Cardiac Reverse Remodeling in Patients With Systolic Dysfunction.

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.

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0-2.

BACKGROUND: The clinical significance of echocardiographic left ventricular hypertrophy (LVH) in risk stratification of left atrial appendage (LAA) thrombogenic milieu, as a surrogate for cardioembolic risk, in patients with atrial fibrillation (AF) and HA2DS2-VASc scores of 0-2 is unknown. METHODS AND RESULTS: We enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0-2 who underwent transesophageal echocardiography. LAA thrombogenic milieu was defined as the presence of a thrombus, severe spontaneous echo contrast, sludge in the LAA, or LAA flow velocity ≤ 20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium were obtained using transthoracic echocardiography. Among the 707 patients, 77 (10.9 %) exhibited LVH. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH group (32.5 % vs. 2.5 %, p < 0.001). LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and left atrium volume index) (odds ratio [OR]: 7.54, 95 % confidence interval [CI]: 3.49-16.29, p < 0.001 and OR: 7.16, 95 % CI: 3.26-15.73, p < 0.001, respectively). Moreover, LVH provided incremental value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and left atrium reservoir strains (p < 0.001). CONCLUSION: Echocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0-2.

Usefulness of hypochloremia at the time of discharge to predict prognosis in patients with chronic heart failure after hospitalization.

BACKGROUND: Hypochloremia has been suggested as a strong marker of mortality in hospitalized patients with heart failure (HF). This study aimed to clarify whether incorporating hypochloremia into pre-existing prognostic models improved the performance of the models. METHODS: We tested the prognostic value of hypochloremia (<97 mEq/L) measured at discharge in hospitalized patients with HF registered in the REALITY-AHF and NARA-HF studies. The primary outcome was 1-year mortality after discharge. RESULTS: Among 2496 patients with HF, 316 (12.6 %) had hypochloremia at the time of discharge, and 387 (15.5 %) deaths were observed within 1 year of discharge. The presence of hypochloremia was strongly associated with higher 1-year mortality compared to those without hypochloremia (log-rank: p < 0.001), and this association remained even after adjustment for the Get With the Guideline-HF risk model (GWTG-HF), anemia, New York Heart Association (NYHA) classification, and log-brain natriuretic peptide (BNP) [hazard ratio (HR) 1.64; p < 0.001]. Furthermore, adding hypochloremia to the prediction model composed of GWTG-HF + anemia + NYHA class + log-BNP yielded a numerically larger area under the curve (0.740 vs 0.749; p = 0.059) and significant improvement in net reclassification (0.159, p = 0.010). CONCLUSIONS: Incorporating the presence of hypochloremia at discharge into pre-existing risk prediction models provides incremental prognostic information for hospitalized patients with HF.

Prevalence and Prognostic Implications of Changes in Tricuspid Regurgitation Severity in Acute Heart Failure.

BACKGROUND: Tricuspid regurgitation (TR), prevalent in acute heart failure (AHF), has a poor prognosis; however, the dynamics of TR severity during hospitalization and its prognostic implications remain unclear. We investigated TR dynamism during hospitalization and its prognostic impact in AHF. METHODS AND RESULTS: This is a post hoc analysis of a prospective multicenter study of patients with AHF who underwent echocardiographic TR severity evaluation at admission and before discharge. The primary end point was a combined of 1-year all-cause mortality and HF rehospitalization after discharge. Among 1079 participants, TR severity changed dynamically, with 60.3% of those with moderate TR and 29.6% of those with severe TR at admission being diagnosed as no or mild TR at discharge. In 3 groups stratified by changes in TR severity, the persistent TR groups had a higher incidence of the primary end point than the resolution and absence groups. In adjusted analyses, the persistent group (hazard ratio, 1.37; 95% confidence interval, 1.04-1.80), but not the resolution group (hazard ratio, 1.07; 95% confidence interval, 0.79-1.44), had a higher primary end point incidence than the absence group. CONCLUSIONS: TR severity at admission in patients with AHF can change dynamically and is associated with subsequent prognosis. Significant TR that remains even after decongestive therapy might be a target for further treatment in hospitalized patients with AHF.

Association Between Right Bundle Branch Block and Ventricular Arrhythmia in Patients With Cardiac Sarcoidosis.

Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown. Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS. Methods: This was a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients with Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of CS. Eligible patients were divided into two groups based on the presence or absence of RBBB at the time of diagnosis. The primary outcome was serious ventricular arrhythmia events (SVAEs), defined as a combination of sudden cardiac death and documented ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Results: Overall, 312 patients were studied, with 155 (49.7%) patients presenting with RBBB (RBBB group). Patients in the RBBB group had a higher prevalence of basal interventricular septum (IVS) thinning and prominent late gadolinium enhancement in the basal IVS on cardiac magnetic resonance imaging than those in the non-RBBB group. During a median follow-up of 3.0 years (IQR: 1.6-6.0 years), 66 patients experienced SVAE. In multivariable Cox regression analysis, the RBBB group was independently associated with a higher incidence of SVAEs (HR: 1.93 [95% CI: 1.14-3.28]; P = 0.015). Conclusions: In patients with CS, RBBB was an independent predictor of SVAEs, which might reflect the specific scar distribution that is predominant in the IVS.

Effectiveness of Embolization for Pulmonary Arteriovenous Malformations from Distal of the Last Normal Branch of the Pulmonary Artery.

Purpose: This retrospective study of patients with pulmonary arteriovenous malformations aims to assess the efficacy of embolization distal to the origin of the last normal branch of the pulmonary artery. Material and Methods: A total of 30 consecutive patients with 38 untreated pulmonary arteriovenous malformations underwent coil embolization distal to the origin of the last normal branch of the pulmonary artery between September 2015 and October 2021. The median (interquartile range) age of patients (5 males, 25 females) was 59 years (50-68 years old), and the median (interquartile range) sizes of the feeding artery and sac were 2.9 mm (2.3-3.8 mm) and 6.7 mm (5.4-9.7 mm), respectively. The technical success rate, persistence rate, and treatment-related complications were evaluated. Technical success was defined as the inability to identify the draining vein on feeding arteriography after coil embolization. Persistence was assessed using time-resolved magnetic resonance angiography. Results: Coil embolization was successful in all patients (100%). There was no persistence during a median (interquartile range) follow-up period of 23 months (10-45 months) for the 38 pulmonary arteriovenous malformations embolized with coils. No major complications were reported. Only minor complications following embolization occurred in 4 of 36 sessions, including local pain in 2 sessions (6%) and hemosputum in 2 sessions (6%). Conclusions: Embolization distal to the origin of the last normal branch of the pulmonary artery is effective in preventing the persistence of pulmonary arteriovenous malformations.

Metabolic remodeling and calcium handling abnormality in induced pluripotent stem cell-derived cardiomyocytes in dilated phase of hypertrophic cardiomyopathy with MYBPC3 frameshift mutation.

Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patients with HCM develop a dilated phase of hypertrophic cardiomyopathy (D-HCM) and have poor prognosis; however, its pathogenesis is unclear and few pathological models exist. This study established disease-specific human induced pluripotent stem cells (iPSCs) from a patient with D-HCM harboring a mutation in MYBPC3 (c.1377delC), a common causative gene of HCM, and investigated the associated pathophysiological mechanisms using disease-specific iPSC-derived cardiomyocytes (iPSC-CMs). We confirmed the expression of pluripotent markers and the ability to differentiate into three germ layers in D-HCM patient-derived iPSCs (D-HCM iPSCs). D-HCM iPSC-CMs exhibited disrupted myocardial sarcomere structures and an increased number of damaged mitochondria. Ca2+ imaging showed increased abnormal Ca2+ signaling and prolonged decay time in D-HCM iPSC-CMs. Cell metabolic analysis revealed increased basal respiration, maximal respiration, and spare-respiratory capacity in D-HCM iPSC-CMs. RNA sequencing also showed an increased expression of mitochondrial electron transport system-related genes. D-HCM iPSC-CMs showed abnormal Ca2+ handling and hypermetabolic state, similar to that previously reported for HCM patient-derived iPSC-CMs. Although further studies are required, this is expected to be a useful pathological model for D-HCM.

Diverse distribution patterns of segmental longitudinal strain are associated with different clinical features and outcomes in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) presents with diverse clinical courses, hardly predictable solely by the left ventricular (LV) ejection fraction (EF). Longitudinal strain (LS) offers distinct information from LVEF and exhibits various distribution patterns. This study aimed to evaluate the clinical significance of LS distribution patterns in DCM. METHODS: We studied 139 patients with DCM (LVEF ≤ 35%) who were admitted for heart failure (HF). LS distribution was assessed using a bull's eye map and the relative apical LS index (RapLSI), calculated by dividing apical LS by the sum of basal and mid-LS values. We evaluated the associations of LS distribution with cardiac events (cardiac death, LV assist device implantation, or HF hospitalization) and LV reverse remodeling (LVRR), as indicated by subsequent LVEF changes. RESULTS: Twenty six (19%) and 29 (21%) patients exhibited a pattern of relatively apical impaired or preserved LS (defined by RapLSI < 0.25 or > 0.75, signifying a 50% decrease or increase in apical LS compared to other segments), and the remaining patients exhibited a scattered/homogeneously impaired LS pattern. The proportion of new-onset heart failure and LVEF differed between the three groups. During the median 595-day follow-up, patients with relatively-impaired apical LS had a higher rate of cardiac events (both log-rank p < 0.05) and a lower incidence of LVRR (both p < 0.01) compared to patients with other patterns. RapLSI was significantly associated with cardiac event rates after adjusting for age, sex, and new-onset HF or global LS. CONCLUSION: DCM patients with reduced EF and distinct distribution patterns of impaired LS experienced different outcomes.

Percutaneous Covered Stenting in Splenic Vein for Left-sided Portal Hypertension Caused by Chronic Splenic Vein Obstruction.

Left-sided portal hypertension (LSPH), an uncommon manifestation of portal hypertension, is characterized by conditions such as isolated gastric varices and splenomegaly, which result from impeded splenic venous drainage in the presence of pancreatic disease. We employed a percutaneous transhepatic technique to achieve regression of isolated gastric varices by implanting a covered stent within a blocked splenic vein and by embolizing the posterior gastric vein and varices using N-butyl-2-cyanoacrylate. We report the successful treatment of stenting for LSPH by the covered stent placement.

Autocrine Regulation of Interleukin-6 via the Activation of STAT3 and Akt in Cardiac Myxoma Cells.

Plasma concentrations of a pleiotropic cytokine, interleukin (IL)-6, are increased in patients with cardiac myxoma. We investigated the regulation of IL-6 in cardiac myxoma. Immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) revealed that IL-6 and its receptors, IL-6 receptor (IL-6R) and gp130, co-existed in the myxoma cells. Myxoma cells were cultured, and an antibody array assay showed that a conditioned medium derived from the cultured myxoma cells contained increased amounts of IL-6. Signal transducer and activator of transcription (STAT) 3 and Akt were constitutively phosphorylated in the myxoma cells. An enzyme-linked immunosorbent assay (ELISA) showed that the myxoma cells spontaneously secreted IL-6 into the culture medium. Real-time PCR revealed that stimulation with IL-6 + soluble IL-6R (sIL6R) significantly increased IL-6 mRNA in the myxoma cells. Pharmacological inhibitors of STAT3 and Akt inhibited the IL-6 + sIL-6R-induced gene expression of IL-6 and the spontaneous secretion of IL-6. In addition, IL-6 + sIL-6R-induced translocation of phosphorylated STAT3 to the nucleus was also blocked by STAT3 inhibitors. This study has demonstrated that IL-6 increases its own production via STAT3 and Akt pathways in cardiac myxoma cells. Autocrine regulation of IL-6 may play an important role in the pathophysiology of patients with cardiac myxoma.

Assessment of renal congestion in a rat model with congestive heart failure using superb microvascular imaging.

PURPOSE: Renal congestion is a therapeutic target in congestive heart failure. However, its detailed evaluation in a clinical setting is challenging. This study sought to assess renal congestion impairment using superb microvascular imaging (SMI), a simple and accessible method. METHODS: Dahl salt-sensitive rats, used as a model for congestive heart failure, underwent central venous pressure (CVP) measurements. Renal congestion was evaluated through measurements of renal medullary pressure (RMP) and assessment of renal perfusion using contrast-enhanced ultrasonography at both the early (control group) and heart failure phases (HF group). All rats were assessed with SMI. The region of interest (ROI) was set in interlobular vessels, interlobar vessels, and a combination of these areas. The area ratio was calculated from the color pixel count in the ROI divided by the total pixel count in the ROI. Intrarenal perfusion index (IRPI) was defined as (maximum area ratio-minimum area ratio) / maximum area ratio. RESULTS: There were no significant differences in renal function and left ventricular ejection fraction between the two groups. CVP, time-to-peak (TTP) in the medulla, and RMP were higher in the HF group than in the control group. In the HF group, IRPI, evaluated in the interlobular vessels, was significantly higher than in the control group. IRPI was positively correlated with TTP in the medulla (p = 0.028, R = 0.60) and RMP (p < 0.001, R = 0.84), indicating that IRPI reflected renal congestion. CONCLUSIONS: IRPI is a useful tool for assessing renal congestion in rats with congestive heart failure.

Recurrent protein-losing enteropathy complicated by postural right subclavian vein compression and right-sided thoracic duct.

We report the case of a 16-year-old female patient with protein-losing enteropathy that was suspected to be caused by thoracic duct congestion associated with postural compression of right subclavian vein. Non-contrast magnetic resonance lymphangiography showed that the thoracic duct connected to the right-sided venous angle of the right subclavian vein which was obstructed when her right arm was lifted. In this case, comprehensive screening of the lymphatics using non-contrast magnetic resonance lymphangiography, which is a minimally invasive tool with high spatial resolution, was helpful for the recognition of the specific pathophysiology. Learning objective: Lymphatic disorders associated with congenital heart disease can be fatal. The morphology and dysfunction of the lymphatic system are complicated, and when added to the complex hemodynamics inherent to congenital heart disease, the pathophysiology is more difficult to understand. To understand the complexity of the lymphatic disease, it is necessary to learn a systematic diagnostic process of lymphatic disorders. In the present case, it is beneficial to know the usefulness of non-contrast magnetic resonance lymphangiography to screen overall lymphatics.

Dynamic changes in echocardiographic parameters in acute decompensated heart failure: REALITY-ECHO.

BACKGROUND: Appropriate evaluation of hemodynamic status is vital in the management of acute heart failure (AHF). We aimed to investigate the changes in echocardiographic parameters during very acute phases of AHF and their association with clinical outcomes. METHODS: Patients who were admitted to four Japanese hospitals with AHF were prospectively enrolled. Comprehensive echocardiography and B-type natriuretic peptide (BNP) were assessed both on admission and the second day. RESULTS: A total of 271 patients (80 ±â€¯12 years old, 52 % male) was included. Overall, transmitral E velocity, E/A, tricuspid regurgitation pressure gradient (TRPG), and inferior vena cava diameter significantly decreased, and stroke volume and left ventricular ejection fraction showed a significant increase by the second day, whereas E/e' did not change. On the second day, BNP increased in 50 patients (18 %). Despite similar baseline characteristics, patients with increased BNP showed a significantly smaller improvement in transmitral flow parameters (E and A velocity, E/A, and flow patterns) and a smaller decrease in TRPG compared with patients with decreased BNP. Other echocardiographic parameter changes were not different between the groups. A combination of improvement in transmitral flow and TRPG was significantly associated with 90-day and 1-year composite events of all-cause death and heart failure hospitalization after adjustment by the Get With the Guidelines-Heart Failure risk score. CONCLUSIONS: Echocardiographic parameters show a dynamic change in the very acute phase of AHF. Several parameters, such as the transmitral flow and TRPG might be useful in monitoring favorable hemodynamic change.

Comparison of external dose estimates using different retrospective dosimetry methods in the settlements located near Semipalatinsk Nuclear Test Site, Republic of Kazakhstan.

For correct assessment of health risks after low-dose irradiation, calculation of radiation exposure estimates is crucial. To verify the calculated absorbed doses, instrumental methods of retrospective dosimetry are used. We compared calculated and instrumental-based estimates of external absorbed doses in the residents of Dolon, Mostik and Cheremushki villages, Kazakhstan, affected by the first nuclear weapon test performed at the Semipalatinsk Nuclear Test Site (SNTS) on August 29, 1949. The 'instrumental' doses were retrospectively estimated using the Luminescence Retrospective Dosimetry (LRD) and Electron Spin Resonance (ESR) methods. Correlation between the calculated individual cumulative external absorbed whole-body doses based on typical input data and ESR-based individual doses in the same people was strong (r = 0.782). It was even stronger between the calculated doses based on individual questionnaires' input data and the ESR-based doses (r = 0.940). Application of the LRD method is useful for validation of the calculated settlement-average cumulated external absorbed dose to air. Reconstruction of external exposure can be supplemented with the data from later measurements of soil contamination with long-lived radionuclides, such as, 137Cs. Our results show the reliability of the calculational method used for the retrospective assessment of individual external doses.

Retroperitoneal capillary arteriovenous malformation mimicking a malignant neoplasm.

Introduction: Retroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations. Case presentation: A 72-year-old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27-mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast-enhanced computed tomography revealed a heterogeneously enhanced tumor with well-defined borders. Dynamic contrast-enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling-in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation. Conclusion: Herein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.

Longitudinal Changes in Natriuretic Peptides and Reverse Cardiac Remodeling in Patients with Heart Failure Treated with Sacubitril/Valsartan Across the Left Ventricular Ejection Traction Spectrum.

Sacubitril/valsartan improves outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the relationship between longitudinal changes in natriuretic peptides and echocardiographic parameters in patients with HF treated with sacubitril/valsartan across the left ventricular ejection fraction (LVEF) range is not fully understood.In patients with HF treated with sacubitril/valsartan, comprehensive data on natriuretic peptides, including atrial natriuretic peptide (ANP), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), BNP, and echocardiography, were measured after 6 months of treatment. We assessed the change in natriuretic peptides and echocardiographic parameters in LVEF classification subgroups.Among 49 patients, the median ANP concentration increased from 55 pg/mL at baseline to 78 pg/mL (P < 0.001). The NT-proBNP concentration decreased from 250 pg/mL to 146 pg/mL (P < 0.001). No significant change was observed in the BNP concentration (P = 0.640). The trajectories of each natriuretic peptide in patients with LVEF > 40% (n = 22) were similar to those in individuals with LVEF ≤ 40% (n = 27). Regardless of LVEF classification, echocardiography at 6 months showed a significant improvement in LVEF, left ventricular end-diastolic volume, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'). The reduction in natriuretic peptide concentration was related to LV reverse remodeling and decreased left and right atrial pressures assessed by E/e' and inferior vena cava diameter.Sacubitril/valsartan induced an increase in ANP, a reduction in NT-proBNP, and no change in plasma BNP, regardless of LVEF. It caused LV reverse remodeling, and the natriuretic peptide concentration changes were associated with structural and functional echocardiographic parameters.

Comprehensive Unloading Strategy for Rapid Heart Recovery Under Support With Impella.

The establishment of a strategy for rapid heart recovery in patients with cardiogenic shock is required. Impella is a percutaneous left ventricular (LV) assist device that maintains hemodynamic stability and also causes LV mechanical unloading. However, the timing at which Impella should be started and a systematic strategy after the start of Impella have not been established. We report a representative case of dilated cardiomyopathy requiring catecholamines and intra-aortic balloon pumping (IABP). The hemodynamics were unstable under IABP support, and withdrawal from IABP or catecholamines was considered impossible. However, the exchange of the IABP with Impella CP made it possible to suppress the heart rate with ivabradine, introduce intensive heart failure medication, and discontinue catecholamines. The patient was weaned from Impella 24 days after the start of the first Impella CP. Rapid heart recovery was achieved with favorable outcomes. We present a comprehensive strategy for rapid heart recovery using Impella in a patient with cardiogenic shock.

Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial.

Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.