Background:The effectiveness of weight loss (WL) in preventing blood pressure (BP) elevation is common knowledge; however, the effect of sex differences is not known.

Methods and Results:Health checkup data from Kagoshima Kouseiren Medical Healthcare Center for middle-aged participants (40–49 years old) with mild obesity (body mass index [BMI] 25.0–29.9 kg/m²) who had examination data for 2 follow-up time-points (after 3 and 10 years) were analyzed. Propensity score (PS) matching using data from the first examination was used to match participants with a decrease in BMI ≥1.0 kg/m²at 3 years (WL group) with those with a BMI decrease <1.0 kg/m²or weight gain (non-WL group). BP values were compared after 3 and 10 years between the 2 groups, as was the prevalence of hypertension after 10 years. PS matching resulted in 232 men and 160 women in each group. Among women, systolic BP (SBP) and hypertension prevalence after 10 years were significantly lower in the WL than non-WL group (P<0.01 and P<0.05, respectively). There were no significant differences in SBP and hypertension prevalence after 10 years in men in the 2 groups.

Conclusions:There were sex differences in the effectiveness of WL in preventing future BP elevation in mildly obese middle-aged participants: WL prevented future BP elevation and hypertension onset in women, but not in men.

Background:Although the aged population is increasing in developed countries, clinical evidence on super-elderly heart failure (HF) patients is scarce. This study determined the characteristics and outcomes of Japanese hospitalized super-elderly HF patients (aged ≥90 years) using a nationwide inpatient database.

Methods and Results:A comprehensive analysis was performed of 447,818 HF patients in the Diagnosis Procedure Combination database who were hospitalized and discharged between January 2010 and March 2018. Among the study population, 243,028 patients (54.3%) were aged ≥80 years and 64,628 patients (14.4%) were aged ≥90 years. The percentage of elderly patients increased over time. Elderly patients were more likely to be female and had a higher New York Heart Association functional class at admission. Invasive and advanced procedures were rarely performed, whereas infectious complications were more common in patients with older age. Length of hospital stay and in-hospital mortality increased with age. Multivariable logistic regression analysis fitted with a generalized estimating equation showed higher in-hospital mortality in patients aged ≥80 and ≥90 years (odds ratios 1.99 and 3.23, respectively) compared with those aged <80 years.

Conclusions:The number of hospitalized super-elderly HF patients has increased, and these patients are associated with worse clinical outcomes. The results of this study may be useful in establishing an optimal management strategy for super-elderly HF patients in the era of HF pandemic.

Background:Little is known about factors associated with elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) at the convalescent stage and their effects on 1-year outcomes in patients with heart failure with preserved ejection fraction (HFpEF).

Methods and Results:This study included 469 patients with HFpEF. Elevated NT-proBNP was defined as the highest quartile. The first 3 quartiles (Q1–Q3) were combined together for comparison with the fourth quartile (Q4). Median NT-proBNP concentrations in Q1–Q3 and Q4 were 669 and 3,504 pg/mL, respectively. Multivariate logistic regression analysis revealed that low albumin (odds ratio [OR] 2.44; 95% confidence interval [CI] 1.35–4.39; P=0.003), low estimated glomerular filtration rate (OR 5.83; 95% CI 3.46–9.83; P<0.001), high C-reactive protein (OR 2.09; 95% CI 1.21–3.63; P=0.009), and atrial fibrillation at discharge (OR 2.33; 95% CI 1.40–3.89; P=0.001) were associated with elevated NT-proBNP. Cumulative rates of all-cause mortality and heart failure rehospitalization were significantly higher in Q4 than in Q1–Q3 (P=0.001 and P<0.001, respectively). Incidence and hazard ratios of these adverse events increased when the number of associated factors for elevated NT-proBNP clustered together (P<0.001 and P=0.002, respectively).

Conclusions:In addition to atrial fibrillation, extracardiac factors (malnutrition, renal impairment and inflammation) were associated with elevated NT-proBNP at the convalescent stage, and led to poor prognosis in patients with HFpEF.

Background:Serum electrolyte concentrations on admission and after the administration of loop diuretics may be associated with prognosis in patients hospitalized due to acute heart failure (AHF). This study investigated the prognostic impact of early changes in chloride (Cl) concentrations after diuretic administration, according to stratified Cl concentrations on admission, in AHF.

Methods and Results:In all, 355 consecutive patients hospitalized due to AHF were included in this single-center retrospective cohort study. Patients were divided into 2 groups based on whether Cl decreased (n=196) or not (n=159) during the first 5 days in hospital. These 2 groups were further stratified according to Cl on admission into 4 groups: Group 1, decrease in Cl and no hypochloremia (n=127); Group 2, decrease in Cl and hypochloremia (n=69); Group 3, no decrease in Cl and no hypochloremia (n=50); and Group 4, no decrease in Cl and hypochloremia (n=109). The risk of death was significantly higher in the group without than with a decrease in Cl (all-cause death hazard ratio [HR] 1.79; 95% confidence interval [CI] 1.15–2.78; P=0.009). Group 4 had the worst prognosis and a significantly higher risk of death (all-cause death [vs. Group 1 as a reference], HR 2.51; 95% CI 1.45–4.32; P=0.001).

Conclusions:The absence of an early decline in Cl was associated with poor prognosis in AHF, especially in patients with hypochloremia on admission.

Background:Transthyretin amyloid cardiomyopathy is a progressive disease with a poor prognosis. There had been no specific treatment for transthyretin amyloid cardiomyopathy until tafamidis received expanded approval in March 2019 in Japan. However, the clinical efficacy of tafamidis remains unknown.

Methods and Results:We initiated tafamidis treatment in 9 patients (median age 78 years; 89% male) from May 2019 to April 2020. Within 6 months after initiation, 1 patient discontinued prematurely and 2 patients were hospitalized due to worsening heart failure, with 1 of these patients discontinuing therapy. There were no significant changes in plasma B-type natriuretic peptide and serum troponin I concentrations over the 6-month treatment period, but interventricular septum thickness increased in 3 of 6 patients.

Conclusions:Further evaluation of tafamidis therapy in a larger patient cohort with transthyretin amyloid cardiomyopathy is warranted to determine the optimal therapeutic strategy.

Background:Monocarboxylate transporter 9 (MCT9), an orphan transporter member of the solute carrier family 16 (SLC16), possibly reabsorbs uric acid in the renal tubule and has been suggested by genome-wide association studies to be involved in the development of hyperuricemia and gout. In this study we investigated the mechanisms regulating the expression of human (h) MCT9, its degradation, and physiological functions.

Methods and Results:hMCT9-FLAG was stably expressed in HEK293 cells and its degradation, intracellular localization, and urate uptake activities were assessed by pulse-chase analysis, immunofluorescence, and [¹⁴C]-urate uptake experiments, respectively. hMCT9-FLAG was localized on the plasma membrane as well as in the endoplasmic reticulum and Golgi apparatus. The proteasome inhibitors MG132 and lactacystine increased levels of hMCT9-FLAG protein expression with enhanced ubiquitination, prolonged their half-life, and decreased [¹⁴C]-urate uptake. [¹⁴C]-urate uptake was increased by both heat shock (HS) and the HS protein inducer geranylgeranylacetone (GGA). Both HS and GGA restored the [¹⁴C]-urate uptake impaired by MG132.

Conclusions:hMCT9 does transport urate and is degraded by a proteasome, inhibition of which reduces hMCT9 expression on the cell membrane and urate uptake. HS enhanced urate uptake through hMCT9.

Background:Sudden cardiac death (SCD) is a most devastating complication of hypertrophic cardiomyopathy (HCM). The aim of this study was to clarify the clinical features of HCM in patients who experienced SCD-relevant events in an aged Japanese community.

Methods and Results:In 2004, we established a cardiomyopathy registration network in Kochi Prefecture, and herein report on 293 patients with HCM who are followed as part of the registry. The mean (±SD) age at registration and diagnosis was 63±14 and 56±16 years, respectively. SCD-relevant events occurred in 19 patients during a mean follow-up period of 6.1±3.2 years (incidence rate 1.0%/year): sudden death in 9 patients, successful recovery from cardiopulmonary arrest in 4 patients, and appropriate implantable cardioverter–defibrillator discharge in 6 patients. At registration, 13 patients were in the dilated phase of HCM (D-HCM). During the follow-up period, HCM developed to D-HCM in 21 patients; thus, 34 patients in total had D-HCM. Multivariate analysis revealed that D-HCM at registration or during follow-up and detection of non-sustained ventricular tachycardia (NSVT) during follow-up were significant predictors of SCD-relevant events.

Conclusions:In this HCM population in an aged Japanese community, the annual rate of SCD-relevant events was 1.0%. HCM developed to D-HCM in a considerable number of patients, and D-HCM and NSVT were shown to be independently associated with an increased risk of SCD-relevant events.

Background:Post hoc analysis was used to investigate the effects of renal function on the efficacy and safety of landiolol using data from the J-Land II study, which evaluated landiolol in patients with hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) who were refractory to Class III antiarrhythmic drugs.

Methods and Results:Patient data from the J-Land II study (n=29) were stratified by renal function (estimated glomerular filtration rate [eGFR] <45 and ≥45 mL/min/1.73 m²) and analyzed. Continuous landiolol infusion (1 μg/kg/min, i.v.) was initiated after VT/VF was suppressed with electrical defibrillation; subsequent dose adjustments were made (1–40 μg/kg/min). The primary efficacy endpoint was the proportion of patients free from recurrent VT/VF during the assessment period. Safety endpoints were also assessed. In the eGFR <45 and ≥45 mL/min/1.73 m²groups, the median doses of landiolol during the assessment period were 9.44 and 8.97 μg/kg/min, the proportions of patients free from recurrent VT/VF were 69.2% and 81.8%, and adverse events occurred in 9 and 10 of 13 patients in each group, respectively. There were no apparent differences in the efficacy or safety of landiolol between the 2 groups.

Conclusions:The data suggest that renal function may not affect the efficacy and safety of landiolol for hemodynamically unstable VT or VF.

Background:The term “takotsubo cardiomyopathy” is commonly used in clinical practice. However, there is conceptual problem with the term “cardiomyopathy” in this context because “cardiomyopathy” implies a primary and chronic myocardial disease of unknown etiology. In this study we reviewed the literature related to takotsubo cardiomyopathy to investigate whether it is appropriate to use the term “cardiomyopathy” for this condition.

Methods and Results:A literature review revealed that this condition was originally described in 1990 in Japan as postischemic myocardial stunning with unique left ventricular apical ballooning and that it gradually gained global attention thereafter. Subsequently, the term “takotsubo cardiomyopathy” was introduced to describe this heart failure phenotype. However, this term has been called into question because several recent studies investigating the mechanism underlying this condition have provided evidence of myocardial ischemia possibly due to microvascular dysfunction. The term “takotsubo syndrome” was suggested to describe this microvascular acute coronary syndrome, which is in agreement with the original description of the condition as myocardial stunning following acute myocardial ischemia.

Conclusions:Based on the accumulating evidence of acute myocardial ischemia due to microvascular dysfunction as the mechanism underlying this condition, in addition to the fact that the term “cardiomyopathy” literally implies a primary and chronic myocardial disease, it is advisable that the term “takotsubo syndrome” is used until the etiology and underlying mechanism of this condition are fully clarified.

Background:Endovascular treatment with balloon angioplasty plays a major role in revascularization of below-the-knee (BTK) arteries in patients with critical limb ischemia (CLI). However, with severely calcified lesions, achieving optimal revascularization with balloon angioplasty alone is difficult. Therefore, we are evaluating the safety and effectiveness of the Rotablator atherectomy system as an adjunctive device in the treatment of severely calcified lesions in BTK arteries in the RESCUE-BTK trial, a multicenter, single-arm, open-label, exploratory investigator-initiated clinical study of medical devices. In this paper we describe the design of the trial.

Methods and Results:Seventeen patients with CLI in whom balloon angioplasty has failed are enrolled in the study. The primary endpoint is the procedural success rate of balloon angioplasty after rotational atherectomy. Success is defined as the fulfillment of 3 requirements upon assessment by the core laboratory: (1) final residual diameter stenosis <50%; (2) the absence of a delay in flow or vessel perforation in the target artery, or both; and (3) brisk antegrade flow to the foot. Key secondary endpoints are the number of complications associated with the trial procedures and the limb salvage rate. Participants are followed-up for 6 months after the trial procedures.

Conclusions:The RESCUE-BTK trial will clarify the safety and effectiveness of the adjunctive use of the Rotablator system in severely calcified lesions of BTK arteries in patients with CLI.