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Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.

The safety and efficacy of an empiric superior vena cava isolation (SVCI) in addition to circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF) have not been clarified. A total of 186 consecutive patients who underwent catheter ablation of PAF were included. All patients underwent a CPVI. Patients in the first half underwent an additional SVCI only if SVC-triggered AF or rapid SVC activity was observed during the procedure (n = 93, as-needed SVCI, group I), and those in the second half underwent an empirical SVCI after the CPVI (n = 93, empiric SVCI, group II). The CPVI was successfully performed in all patients. An SVCI was performed in 8 of 93 patients (9%) in group I and 81 of the 93 patients (87%) in group II. In the remaining 12 patients in group II, an SVCI was not performed because of the lack of SVC potentials. During a mean follow-up of 27 ± 12 months, the atrial tachyarrhythmia recurrence rate after a single ablation procedure in the patients in group II was lower than that in group I (44% vs 23%, p = 0.035). A Cox regression multivariate analysis demonstrated that an empiric SVCI was an independent predictor of an atrial tachyarrhythmia recurrence after a single ablation procedure (odds ratio: 0.57, 95% confidence interval 0.31 to 0.999; p = 0.049). Neither sinus node injury nor any injury to the phrenic nerve was observed. In conclusion, an empiric SVCI in addition to the CPVI improved the outcome of AF ablation in patients with PAF without any additional adverse effects.

Background Conventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention. Methods We retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions. Results Thirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan–Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P  = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36–29.25, P  = 0.02). Five patients experienced ICD implant-related complications. Conclusions Our findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.

Objective Atrial tachyarrhythmias (ATAs) lead to clinical deterioration and worsening heart failure (HF) in patients with acute decompensated HF (ADHF). We evaluated the effects of the ultrashort-acting intravenous β1-blocker landiolol on the heart rate, hemodynamics, and outcome in patients with ATAs and ADHF. Methods A total of 67 consecutive hospitalized patients with ATAs and ADHF who were treated with landiolol (36 males, 67 ± 12 years) were included in this single-center retrospective study. The primary endpoints were changes in heart rate and systolic blood pressure from baseline during intravenous landiolol administration. The secondary endpoints included restoration of sinus rhythm and outcomes. Results The median maintenance dose of intravenous landiolol was 3.0 (range 1.0–12.0) μg/kg/min and the median treatment duration was 5 (range 1–24) days. Intravenous landiolol reduced heart rate (141 ± 17 beats/min at baseline to 99 ± 20 beats/min at 6 h, P  < 0.001) without a marked reduction in blood pressure or deterioration of HF. During landiolol treatment, 15 (22%) patients had spontaneously restored sinus rhythm. Eight patients experienced in-hospital death, and 41 (69%) were discharged with sinus rhythm. During the follow-up of 16 ± 12 months, patients with sinus rhythm showed a lower frequency of rehospitalization due to worsening HF than patients with ATAs (5/41 vs. 7/18, P  = 0.019). Conclusions Our results showed that intravenous landiolol reduces the heart rate without markedly decreasing blood pressure in patients with ATAs and ADHF. Approximately 70% of the discharged patients were in sinus rhythm, and these patients showed a lower frequency of rehospitalization due to worsening HF (UMIN-CTR no. UMIN000033650).

Regional myocardial ischemia is thought to be characterized by diastolic dysfunction. We aimed to clarify whether temporal analysis of strain rate (SR) index derived from two-dimensional speckle-tracking echocardiography (2DTE) can assess the regional myocardial ischemia or not. Forty-two patients with significant coronary stenoses were referred for percutaneous coronary intervention (PCI). 2DTE was performed before and a day after PCI. Time from aortic valve closure to peak early diastolic longitudinal SR ∆(TAVC- E SR ) was measured both at baseline and during adenosine triphosphate (ATP) infusion. TAVC- E SR was calculated as TAVC- E SR during ATP infusion subtracted by TAVC- E SR at baseline. In forty-five target ischemic regions, TAVC- E SR at baseline was significantly longer than that of control regions (166 ± 28 vs. 136 ± 32 ms, P  < 0.0001). TAVC- E SR in target ischemic regions significantly prolonged during ATP stress to 221 ± 37 ms ( P  < 0.0001), while it did not change in control regions. Immediately after PCI, TAVC- E SR in target regions significantly decreased to 135 ± 27 ms, P  < 0.0001 without prolongation during ATP stress. Receiver operating characteristic curves demonstrated that ∆TAVC- E SR could assess regional myocardial ischemia by a cutoff criterion of 14 ms with sensitivity of 93 % and specificity of 95 %. 2DTE-derived TAVC- E SR significantly increased during ATP stress only in ischemic myocardium. This phenomenon disappeared immediately after PCI. Temporal analysis of TAVC- E SR appeared to be useful to assess the regional myocardial ischemia.

Little is known about the outcome of catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) and a severely reduced left ventricular ejection fraction (LVEF). We aimed to clarify the effectiveness of catheter ablation of AF in patients with a severely low LVEF. This retrospective study included 18 consecutive patients with HF and an LVEF of ≤35 % who underwent catheter ablation of AF. We investigated the clinical parameters, echocardiographic parameters and the incidence of hospitalizations for HF. During a median follow-up of 21 months (IQR, 13–40) after the final procedure (9 with repeat procedures), 11 patients (61 %) maintained sinus rhythm (SR) (6 with amiodarone). The LVEF and NYHA class significantly improved at 6 months after the CA in 12 patients (67 %) who were in SR or had recurrent paroxysmal AF (from 25.8 ± 6.3 to 37.0 ± 11.7 %, P  = 0.02, and from 2.3 ± 0.5 to 1.5 ± 0.7, P  < 0.01, respectively) but not in patients who experienced recurrent persistent AF. The patients with SR or recurrent paroxysmal AF had significantly fewer hospitalizations for HF than those with recurrent persistent AF after the AF ablation (log-rank test; P  < 0.01). Catheter ablation of AF improved the clinical status in patients with an LVEF of ≤35 %. A repeat ablation procedure and amiodarone were often necessary to obtain a favorable outcome.

Tachycardia-induced cardiomyopathy (TIC) is a reversible form of the left ventricular (LV) systolic dysfunction and is believed to be a relatively acute process. We report a TIC case with a 30-year history of long-lasting persistent atrial tachycardia involving a 44-year-old man previously diagnosed with dilated cardiomyopathy and a low LV ejection fraction (LVEF) of 20%. ECG revealed atrial tachycardia at 110–120 bpm. He was hospitalised with a worsening heart failure. His clinical status was New York Heart Association functional class III, and echocardiography revealed LV dilation and an LVEF of 9%. A two-dimensional speckle-tracking strain measurement revealed LV mechanical dyssynchrony. He underwent radiofrequency ablation for atrial tachycardia. After restoring sinus rhythm, his cardiac symptoms improved immediately. The LV mechanical dyssynchrony decreased a week after ablation, without changes in the LV dilation or LVEF. Thereafter, the LV dilation and systolic function gradually improved, and atrial tachycardia and heart failure remained absent.

A mitral L-wave indicates advanced diastolic dysfunction with elevated left ventricular filling pressure. Previous studies have reported that the presence of a mitral L-wave is associated with a poor prognosis in patients with heart failure. However, whether the L-wave can predict adverse events in patients with hypertrophic cardiomyopathy (HC) is still unclear. Therefore, we aimed to investigate the prevalence of a mitral L-wave in patients with HC, and the prognosis of patients with or without an L-wave. We analyzed 445 patients with HC. The end points of this study were HC-related death, such as sudden death or potentially lethal arrhythmic events, heart failure-related death, and stroke-related death. A mitral L-wave was defined as a distinct mid-diastolic flow velocity after the E wave with a peak velocity >20 cm/s. The prevalence of an L-wave was 32.4% in patients with HC. Patients with an L-wave were significantly younger, more likely to be women, had higher New York Heart Association functional class, and had a higher prevalence of atrial fibrillation than did patients without an L-wave. Patients with an L-wave had a significantly higher incidence of HC-related death compared with those without an L-wave (log-rank, p < 0.001). The L-wave was an independent determinant of HC-related death in multivariate analysis adjusted for imbalanced baseline variables (adjusted hazard ratio 2.38; 95% confidence interval 1.42 to 4.01; p = 0.001). In conclusion, the presence of a mitral L-wave may be associated with adverse outcome in patients with HC.

The effect of the left ventricular ejection fraction (LVEF) on the prognostic impact of the right atrial pressure (RAP) in patients with heart failure (HF) requires clarification. We aimed to investigate whether LVEF affects the prognostic impact of RAP estimated from inferior vena cava (IVC) measurements in patients hospitalized with HF. Initially, this observational study included 1349 consecutive patients urgently hospitalized with HF. After patient exclusions, 506 and 484 patients with reduced (< 40%) and with non-reduced (≥ 40%) LVEF, respectively, were assigned according to maximum IVC diameter and its collapsibility, to the Normal-RAP (diameter ≤ 2.1 cm; collapsibility ≥ 50%), High-RAP (diameter > 2.1 cm; collapsibility < 50%), and Intermediate-RAP (others) groups. The endpoint comprised cardiovascular death after discharge and hospitalization for HF recurrence. During the observation period, 247 (49%) patients with LVEF < 40% and 178 (37%) patients with LVEF ≥ 40% experienced the endpoint. The patient subgroups with LVEF < 40% had comparable event rates (ptrend = 0.10). The High-RAP subgroup with LVEF ≥40% had a higher event rate than the other subgroups (p < 0.001). The RAP independently predicted the endpoint in patients with LVEF ≥ 40% (hazard ratio: 1.26; 95% confidence interval: 1.01–1.59). The interaction between the RAP groups and LVEF regarding the primary endpoint was significant (pinteraction = 0.007). Stratifying patients with HF according to IVC measurements may predict the post-discharge cardiovascular prognoses of patients with non-reduced LVEF, but not that of patients with reduced LVEF.