Effectiveness and safety of morphine administration for refractory dyspnoea among hospitalised patients with advanced heart failure: the Morphine-HF study.

Objectives: Morphine is effective in alleviating dyspnoea in patients with cancer. We aimed to investigate the effectiveness and safety of morphine administration for refractory dyspnoea in patients with advanced heart failure (HF).

Methods: We conducted a multicentre, prospective, observational study of hospitalised patients with advanced HF in whom morphine was administered for refractory dyspnoea.

Mode of death in elderly and super-elderly patients with acute heart failure: Insights from Japanese heart failure registry.

Background: In Japan, both the prevalence of the elderly and super-elderly and those of acute heart failure (AHF) have been increasing rapidly.

Methods: This registry was a prospective multicenter cohort, which enrolled a total of 1253 patients with AHF. In this study, 1117 patients' follow-up data were available and were categorized into three groups according to age: <75 years old (nonelderly), 75-84 years old (elderly), and ≥ 85 years old (super-elderly).

Association Between Physical Status and the Effects of Combination Therapy With Renin-Angiotensin System Inhibitors and β-Blockers in Patients With Acute Heart Failure.

This study investigated whether combination therapy (CT) with renin-angiotensin system inhibitors and β-blockers improved endpoints in acute heart failure (AHF). AHF patients were recruited to this prospective multicenter cohort study between April 2015 and August 2017. Patients were divided into 3 categories based on ejection fraction (EF), namely heart failure (HF) with reduced EF (HFrEF), HF with midrange EF (HFmrEF), and HF with preserved EF (HFpEF), and a further into 2 groups according to physical status (those who could walk independently outdoors and those who could not).

Clinical Characteristics and Outcomes of Heart Failure Patients With Long-Term Care Insurance - Insights From the Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

Background: In Japan, the long-term care insurance (LTCI) system has an important role in helping elderly people, but there have been no clinical studies that have examined the relationship between the LTCI and prognosis for patients with acute heart failure (HF).

Methods and results: This registry was a prospective multicenter cohort, 1,253 patients were enrolled and 965 patients with acute HF aged ≥65 years were comprised the study group. The composite endpoint included all-cause death and hospitalization for HF after discharge.

A decline in activities of daily living due to acute heart failure is an independent risk factor of hospitalization for heart failure and mortality.

Background: Although activities of daily living (ADL) are recognized as being pertinent in averting relevant readmission of heart failure (HF) and mortality, little research has been conducted to assess a correlation between a decline in ADL and outcomes in HF patients.

Methods: The Kitakawachi Clinical Background and Outcome of Heart Failure Registry is a prospective, multicenter, community-based cohort of HF patients. We categorized the patients into four types of ADL: independent outdoor walking, independent indoor walking, indoor walking with assistance, and abasia.

A trafficking-deficient KCNQ1 mutation, T587M, causes a severe phenotype of long QT syndrome by interfering with intracellular hERG transport.

Background: KCNQ1-T587M is a C-terminal mutation correlated with severe phenotypes of long QT syndrome (LQTS). However, functional analysis of KCNQ1 channels with the T587M mutation showed a mild genotype in the form of haploinsufficiency in a heterologous expression system. This study sought to explore the molecular mechanism underlying the phenotype-genotype dissociation of LQTS patients carrying the KCNQ1-T587M mutation.

Clinical Characteristics and Social Frailty of Super-Elderly Patients With Heart Failure - The Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

Background: Social background is important in preventing admission/readmission of heart failure (HF) patients. However, few clinical studies have been conducted to assess the social background of these patients, especially elderly patients.Methods and Results:The Kitakawachi Clinical Background and Outcome of Heart Failure (KICKOFF) Registry is a prospective multicenter community-based cohort of HF patients, established in April 2015.

Mechanistic basis for the pathogenesis of long QT syndrome associated with a common splicing mutation in KCNQ1 gene.

Mutations in KCNQ1, the gene encoding the delayed rectifier K(+) channel in cardiac muscle, cause long QT syndrome (LQTS). We studied 3 families with LQTS, in whom a guanine to adenine change in the last base of exon 7 (c.1032G>A), previously reported as a common splice-site mutation, was identified.

High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.

Objectives: We carried out a complete screening of the SCN5A gene in 38 Japanese patients with Brugada syndrome to investigate the genotype-phenotype relationship.

Background: The gene SCN5A encodes the pore-forming alpha-subunit of voltage-gated cardiac sodium (Na) channel, which plays an important role in heart excitation/contraction. Mutations of SCN5A have been identified in 15% of patients with Brugada syndrome.

Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: multicenter study in Japan.

Objectives: We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS).

Background: The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms.

Methods: Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes.

Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome.

Introduction: Beta-blockers are widely used to prevent the lethal cardiac events associated with the long QT syndrome (LQTS), especially in KCNQ1-related LQTS (LQT1) patients. Some LQT1 patients, however, are refractory to this therapy.

Methods And Results: Eighteen symptomatic LQTS patients (12 families) were genetically diagnosed as having heterozygous KCNQ1 variants and received beta-blocker therapy.

Bepridil block of recombinant human cardiac IKs current shows a time-dependent unblock.

Whole-cell patch-clamp techniques were employed to examine the effects of bepridil, a Ca2+ channel blocker with Vaughan Williams class III action, on a slow component of cardiac delayed rectifier K+ current (IKs), which was reconstituted in HEK293 cells by transfecting KCNQ1 and KCNE1. Micromolar bepridil inhibited tail currents carried by KCNQ1/KCNE1 channels in a concentration-dependent manner (IC50 = 5.3 +/- 0.

Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome.

Background: Experimental studies suggest that the interval between peak and end of T wave (Tpe) in transmural ECGs reflects transmural dispersion of repolarization (TDR), which is amplified by beta-adrenergic stimulation in the LQT1 model. In 82 patients with genetically identified long-QT syndrome (LQTS) and 33 control subjects, we examined T-wave morphology and various parameters for repolarization in 12-lead ECGs including corrected QT (QTc; QT/R-R(1/2)) and corrected Tpe (Tpec; Tpe/R-R(1/2)) before and during exercise stress tests.

Methods And Results: Under baseline conditions, LQT1 (n=51) showed 3 cardinal T-wave patterns (broad-based, normal-appearing, late-onset) and LQT2 (n=31) 3 patterns (broad-based, bifid with a small or large notch).