Background: The existence of atypical fast-slow (F/S) atrioventricular (AV) nodal reentrant tachycardias (NRT) using slow pathway (SP) variants connected to the right atrial (RA) inferolateral (inf) free wall (FW) along the tricuspid annulus (TA), has been neither confirmed nor precisely characterized.

Methods and Results: We studied 7 patients (mean age, 48±16 years; 5 men) with F/S-AVNRT with long RP intervals and an earliest atrial activation at the RA inf-FW along the TA (inf-F/S-AVNRT). AV reentrant tachycardia was excluded on observation of the transition zone criteria in all 7 patients. Atrial tachycardia was excluded on the observation of a V-A-V activation sequence after the induction or entrainment of the tachycardia from the right ventricle in all. During the tachycardia, low-frequency, fractionated potentials (LP) preceding the local atrial electrogram were recorded near the site of the earliest atrial activation in 6 patients. Observations of conduction delay and block of the LP during ventricular entrainment or ablation of the tachycardia indicated that LP reflect retrograde activation via the inf-SP. Retrograde SP conduction was interrupted at the site of earliest atrial activation in 3 patients, and in the right posterior septum in 4 patients.

Conclusions: inf-F/S-AVNRT are distinct supraventricular tachycardia incorporating an SP variant connected to the RA inf-FW along the TA in the retrograde direction, which were eliminated by ablation.

Background: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) with ventricular dyssynchrony, but not all patients respond to a similar extent. We investigated the efficacy and safety of exercise training (ET) in patients without response to CRT.

Methods and Results: Thirty-four patients who participated in a 3-month ET program and underwent cardiopulmonary exercise testing at baseline and after the program were divided into 17 responders and 17 non-responders based on echocardiographic response criteria: either an increase in ejection fraction (EF) ≥10% or a reduction in left ventricular (LV) end-systolic volume ≥10%. Baseline characteristics including peak oxygen uptake (V̇O₂) and isometric knee extensor muscle strength (IKEMS) were similar in both groups, but non-responders had lower EF and larger LV. During the ET program, neither group had exercise-related adverse event including life-threatening ventricular arrhythmia. Peak V̇O₂and IKEMS were significantly improved in both groups and there was no significant difference in change in peak V̇O₂or IKEMS between responders and non-responders. On multiple regression analysis, change in IKEMS was an independent predictor of change in peak V̇O₂, whereas the response to CRT was not.

Conclusions: In HF patients undergoing CRT implantation, ET safely improved exercise capacity regardless of response to CRT, suggesting that even advanced HF patients without response to CRT can possibly benefit from ET.

Background: The features of sleep-associated acute heart failure (AHF) patients admitted at midnight or early morning (M/E) are unclear.

Methods and Results: Of 1,268 AHF patients screened, 932 were analyzed, and divided into 2 groups by admission time (M/E group, 23:00–06:59, n=399; daytime group, 07:00–22:59, n=533). Those in the M/E group were further divided by the presence of a prodrome: with (n=176; prodrome group) or without (n=223; sudden onset group). The median time from symptom onset to hospitalization was significantly shorter in the M/E group (98 min; range, 65–170 min) than in the daytime group (123 min; range, 68–246 min). The 365-day HF event rate in the M/E group was significantly lower than that of the daytime group. On multivariate logistic regression modeling the M/E group was independently associated with a better outcome than the daytime group (OR, 0.673; 95% CI: 0.500–0.905). In the M/E group, the 365-day HF event rate was significantly lower in the prodrome group than in the sudden onset group. On multivariate logistic regression modeling, inclusion in the prodrome group was independently associated with a better outcome (OR, 0.544; 95% CI: 0.338–0.877).

Conclusions: AHF patients admitted during sleeping hours were not sicker than those admitted during the daytime. The absence of a prodrome, however, might be associated with future repeated HF events.

Background: Cardio-renal anemia syndrome (CRAS) is a growing health problem, with a high mortality rate. Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are well-established diagnostic and prognostic biomarkers of heart failure (HF). The difference in the clinical significance of these biomarkers, however, has not yet been completely elucidated in HF. The aim of the present study was to compare the prognostic ability of BNP and NT-proBNP in HF patients with CRAS.

Methods and Results: We measured BNP and NT-proBNP in 492 consecutive HF patients and in 17 control subjects. All patients were prospectively followed up during a median follow-up period of 1,034 days. NT-proBNP/BNP ratio was elevated in HF patients with CRAS compared with those without CRAS and the control subjects. There was no significant difference in the prognostic abilities of BNP and NT-proBNP in all HF patients. The C-index for NT-proBNP for predicting cardiovascular events and mortality, however, was significantly higher than that for BNP in HF patients with CRAS. On multivariate Cox proportional hazards-regression analysis, NT-proBNP, but not BNP, was an independent predictor for clinical outcome in HF with CRAS.

Conclusions: The difference in the prognostic abilities of BNP and NT-proBNP was high in HF patients with CRAS. NT-proBNP had a superior prognostic ability to BNP in HF patients with CRAS.

Background: Left ventricular (LV) torsion by contraction of inner and outer oblique muscles contributes to EF. Outer muscle plays a predominant role in torsion. We evaluated the impact of LV remodeling by hypertension (HTN) on torsion using 3-dimensional speckle tracking echocardiography (3D-STE).

Methods and Results: LV strain, strain rate during systole (SR-S) and torsion at endocardium, mid-wall and epicardium were assessed on 3D-STE in 53 controls and 186 HTN patients. Torsion was defined as the difference between apical and basal rotation divided by long axis length. LVEF and strain, SR-S and torsion in all 3 layers in HTN without LV hypertrophy (LVH) were similar to those in controls. LV longitudinal strain at endocardium in HTN with LVH decreased, whereas LVEF was similar to that in controls and, which was associated with increased torsion at epicardium. Reduced LVEF in hypertensive HF was associated with reduced strain, SR-S and torsion in all layers and with LV dilation. On multivariate analysis, epicardial torsion was an independent determinant of LVEF. At epicardial torsion cut-off 0.41, the sensitivity and specificity for the identification of HFrEF were 88% and 68%.

Conclusions: Torsion on 3D-STE may represent a compensatory mechanism to maintain LVEF despite reduced endocardial function, suggesting that the deterioration of torsion caused by insult to outer muscle and dilation may lead to HFrEF.

Background: The purpose of the study was to evaluate the impact of nutritional status on 1-year mortality in hospitalized patients with acute decompensated heart failure (ADHF).

Methods and Results: We enrolled 457 hospitalized ADHF patients. Previously established objective nutritional indexes (controlling nutritional status [CONUT], prognostic nutritional index [PNI], geriatric nutritional risk index [GNRI], and subjective global assessment [SGA]) were evaluated at hospital admission. Malnutrition was defined as CONUT score ≥5, PNI score <38, GNRI score <92, and SGA scores B and C. The frequencies of malnutrition based on CONUT, PNI, GNRI, and SGA were 31.5%, 21.4%, 44.9%, and 27.8%, respectively. All indexes were related to the occurrence of 1-year mortality on univariate Cox regression analysis (P<0.05). We constructed a reference model using age, body mass index, systolic blood pressure, sodium concentration, and renal function on multivariable Cox regression analysis. Adding SGA to the reference model significantly improved both net reclassification improvement (NRI) and integrated discrimination improvement (0.344, P=0.002; 0.012, P=0.049; respectively). Other indexes (CONUT, PNI, and GNRI scores) significantly improved NRI (0.254, P=0.019; 0.273, P=0.013; 0.306, P=0.006; respectively).

Conclusions: Nutritional screening assessed at hospital admission was appropriate for the prediction of 1-year mortality in hospitalized patients with ADHF.

Background: Little is known about the superiority of balloon angioplasty vs. stent implantation for femoropopliteal (FP) lesions according to subgroup.

Methods and Results: This study involved 1,018 de novo (balloon angioplasty, n=462; stent implantation, n=556) and 114 in-stent restenosis (ISR) FP lesions (balloon angioplasty, n=69; stent implantation, n=45) treated with endovascular therapy. For de novo FP lesions, the 3-year primary patency rate was significantly better with stent implantation than with balloon angioplasty (61% vs. 69%, log-rank P=0.001), but it was similar for ISR FP lesions (40% vs. 43%, log-rank P=0.83). For de novo FP lesions, stent implantation was favorable in all subgroups except for female sex (hazard ratio [HR], 0.92; 95% CI: 0.65–1.31, P=0.66), critical limb ischemia (CLI; HR, 0.70; 95% CI: 0.46–1.06, P=0.10), calcified lesion (HR, 0.81; 95% CI: 0.46–1.39, P=0.44), and poor tibial run-off (HR, 0.86; 95% CI: 0.59–1.25, P=0.42) subgroups. No difference was found between the 2 treatment strategies for ISR FP lesions in the majority of subgroups. Stent implantation, however, was favorable in totally occluded ISR FP lesions (HR, 0.45; 95% CI: 0.21–1.01, P=0.05).

Conclusions: The primary patency rate in de novo FP lesions for the 2 treatment strategies was similar in the female, calcified lesion, CLI, and poor tibial run-off subgroups. Stent implantation was superior to balloon angioplasty for totally occluded ISR FP lesions.

Background: The valve-in-valve (VIV) procedure is being increasingly performed in high-risk patients with a degenerated bioprosthesis in an aortic position in Western countries. The early safety and efficacy of the VIV procedure, however, remain unclear in Japanese patients with a small aortic annulus. We present the protocol for a study designed to evaluate the early safety and efficacy of the VIV procedure in the aortic position in Japanese patients.

Methods and Results: The prospective, single-center, non-comparative, clinical study of the VIV procedure for the aortic position (AORTIC VIV study) commenced in August 2016 and will end in March 2020. Patients will be monitored for ≥1 month after the VIV procedure. The targeted number of patients is 11. Eligible patients are those who have undergone transcatheter aortic valve replacement for a surgical valve (including stented or stentless bioprosthetic valves), or for a transcatheter heart valve. The VIV procedure is performed in high-operative-risk patients with substantial prosthetic valve stenosis, and regurgitation and heart failure resistant to medical treatment (unless the patient meets an exclusion criterion). The safety and efficacy of the VIV procedure will be evaluated in accordance with the Valve Academic Research Consortium-2 initiative.

Conclusions: The AORTIC VIV study will clarify the early safety and efficacy of the VIV procedure in Japanese patients.

Background: Despite evidence of the effects of alirocumab on the incidence of acute coronary events, its impact on plaque stabilization remains uncertain. The present study will investigate the effect of alirocumab on fibroatheroma in patients who underwent recent percutaneous coronary intervention (PCI).

Methods and Results: This phase IV, open-label, randomized, blinded near-infrared spectroscopy plus intravascular ultrasound (NIRS-IVUS) analysis, parallel-group, single-center study will enroll Japanese adults recently hospitalized for PCI with suboptimal low-density lipoprotein cholesterol (LDL-C) control (>70 mg/dL) despite stable statin therapy. Thirty patients will be randomized to receive either alirocumab or standard of care. The alirocumab group will receive alirocumab 75 mg every 2 weeks plus 10 mg rosuvastatin per day. The standard-of-care group will receive 10 mg rosuvastatin per day with dose adjustment to achieve LDL-C <70 mg/dL. Post-treatment NIRS-IVUS will be performed at week 36. The primary endpoint is the change in maximum lipid core burden index in 4-mm pullback compartments (maxLCBI[4 mm]) between baseline and week 36. Secondary endpoints include change in LCBI (lesion), angle of lipid core, plaque burden, and serum lipids and biomarkers related to atherosclerosis and inflammation.

Conclusions: The study will clarify the effects of alirocumab on thin-cap fibroatheroma in patients who underwent recent PCI and who have suboptimal LDL-C control with stable statin therapy.

Background: Information regarding current medical and social conditions and outcome of Japanese heart failure (HF) patients is needed.

Methods and Results: The registry and follow-up study regarding the medical and social conditions and outcomes of hospitalized heart failure patients (REAL-HF) is maintained by 8 regional core hospitals, which provide an interprofessional team approach for HF patients, in Hiroshima Prefecture. We planned to enroll all adult patients hospitalized with symptomatic HF (congestive HF and/or low output syndrome) in 1 year from March 2017. We registered the clinical characteristics of each patient, including physical activity (able to walk independently), during the indexed hospitalization. Information regarding living circumstances, cognitive function test, questionnaire for quality of life (QOL), and interprofessional team approaches was also collected. For patients discharged home, we planned to follow all-cause death, all-cause unscheduled readmission, and the conditions of outpatient cardiac rehabilitation and home nursing-care services at 3 and 12 months after discharge. A total of 1,218 patients has been registered initially. Follow-up is ongoing, and data analysis is expected to be completed in 2019.

Conclusions: The REAL-HF will provide a significant database on the current real conditions of hospitalized HF patients in a local district of Japan, elucidating medical and social risk factors of worsened QOL and prognosis.