Long-term prognosis of patients undergoing radiofrequency catheter ablation for atrial fibrillation: comparison between heart failure subtypes based on left ventricular ejection fraction.

AIMS: Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). METHODS AND RESULTS: Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced (<40%), mid-range (40-49%), and preserved (≥50%) LVEF were 98 (14.9%), 107 (16.3%), and 451 (68.8%) patients, respectively. The prevalence of ischaemic heart disease and cardiomyopathies was higher among patients with reduced as compared with preserved LVEF (27.6% vs. 10.0%, P < 0.05 and 36.7% vs. 15.3%, P < 0.05, respectively). The median follow-up period was 2.9 years. The 3-year cumulative risk for the primary endpoint was higher in patients with reduced LVEF (32.7%) compared to those with mid-range (11.7%) or preserved (11.6%) LVEF (P < 0.001). Reduced LVEF was the most significant independent risk factor for primary endpoint (hazard ratio, 2.83; 95% confidence interval 1.74-4.61, P < 0.001). The 3-year arrhythmia recurrence rate was similar among the groups (48.2%, 42.8%, and 47.3%, respectively, P = 0.75). CONCLUSION: This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.

Reverse Remodeling and Non-Contrast T1 Hypointense Infarct Core in Patients With Reperfused Acute Myocardial Infarction.

BACKGROUND: Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it.Methods and Results: We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P<0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month follow-up (hazard ratio: 0.087, 95% confidence interval: 0.017-0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs. CONCLUSIONS: ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.

Catheter ablation of ganglionated plexi in patients with adenosine triphosphate-induced atrial fibrillation after pulmonary vein isolation.

Intravenous ATP may induce atrial fibrillation (AF). ATP shares similar receptor-effector coupling systems with acetylcholine. However, the association between an ATP injection and the hyperactivity of the intrinsic cardiac autonomic nervous system, known as ganglionated plexi (GPs), is not well understood. We describe a series of patients with non-pulmonary vein (PV) trigger sites provoked by an ATP injection, and assess the feasibility of a ganglionated plexus (GP) ablation. We retrospectively analyzed 547 patients (69% male; mean age 67.4 ± 10.4 years; 38.5% non-paroxysmal AF) who underwent a total of 604 ablation procedures. Intravenous ATP was administered with an isoproterenol infusion during sinus rhythm after a pulmonary vein isolation in 21.3%, Box isolation in 78.6%, and SVC isolation in 52.0% of the procedures, respectively. We reviewed the incidence, the distribution of the foci, and the ablation outcomes in patients with ATP-induced AF. A total of seven patients (1.3%) had ATP-induced AF. Foci were identified in the coronary sinus (CS) in six patients, right atrial posterior wall (RAPW) adjacent to the interatrial groove in two, mitral annulus in two, ligament of Marshall in one, right septum below the foramen ovale in one and left atrial posterior wall in one, respectively. Among these trigger foci, we confirmed the vagal response by high-frequency stimulation in the CS and RAPW in six and two patients, respectively. After a median RF time of 2.9 min (range 2.5-11.3) targeting these foci, in five of six patients who received a repeat ATP injection, the AF became non-inducible. ATP-provoked trigger foci were distributed among certain sites that overlapped with the distribution of the GPs. The GP ablation was effective for this rare, but challenging situation.

Incidence and Clinical Significance of 30-Day and 90-Day Rehospitalization for Heart Failure Among Patients With Acute Decompensated Heart Failure in Japan　- From the NARA-HF Study.

BACKGROUND: Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.Methods and Results:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654-3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153-5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF. CONCLUSIONS: The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.

Impact of Atrial Fibrillation on the Prognosis of Acute Decompensated Heart Failure With and Without Mitral Regurgitation.

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) are frequently combined in patients with heart failure (HF). However, the effect of AF on the prognosis of patients with HF and MR remains unknown. Methods and Results: We studied 867 patients (mean age 73 years; 42.7% female) with acute decompensated HF (ADHF) in the NARA-HF registry. Patients were divided into 4 groups based on the presence or absence of AF and MR at discharge. Patients with severe MR were excluded. The primary endpoint was the composite of cardiovascular (CV) death and HF-related readmission. During the median follow-up of 621 days, 398 patients (45.9%) reached the primary endpoint. In patients with MR, AF was associated with a higher incidence of the primary endpoint regardless of left ventricular function; however, in patients without MR, AF was not associated with CV events. Cox multivariate analyses showed that the incidence of CV events was significantly higher in patients with AF and MR than in patients with MR but without AF (hazard ratio 1.381, P=0.036). Similar findings were obtained in subgroup analysis of patients with AF and only mild MR. Conclusions: The present study demonstrated that AF is associated with poor prognosis in patients with ADHF with mild to moderate MR, but not in those without MR.

Low Insulin Is an Independent Predictor of All-Cause and Cardiovascular Death in Acute Decompensated Heart Failure Patients Without Diabetes Mellitus.

Background Insulin beneficially affects myocardial functions during myocardial ischemia. It increases glucose-derived ATP production, decreases oxygen consumption, suppresses apoptosis of cardiomyocytes, and promotes the survival of cardiomyocytes. Patients with chronic heart failure generally have high insulin resistance, which is correlated with poor outcomes. The role of insulin in acute decompensated heart failure (ADHF) remains unclear. This study aimed to investigate the prognostic value of serum insulin level at the time of admission for long-term outcomes in patients with ADHF. Methods and Results We enrolled 1074 consecutive patients who were admitted to our department for ADHF. Of these 1074 patients, we studied the impact of insulin on the prognosis of ADHF in 241 patients without diabetes mellitus. The patients were divided into groups according to low, intermediate, and high tertiles of serum insulin levels. Primary end points were all-cause death and cardiovascular death. During a mean follow-up of 21.8 months, 71 all-cause deaths and 38 cardiovascular deaths occurred. Kaplan-Meier analysis showed that all-cause and cardiovascular mortality was significantly higher in the low-insulin group than those in the intermediate- and high-insulin groups (log-rank P=0.0046 and P=0.038, respectively). Moreover, according to the multivariable analysis, low serum insulin was an independent predictor of all-cause and cardiovascular mortality (hazard ratio, 2.37 [95% CI, 1.24-4.65; P=0.009] and 2.94 [95% CI, 1.12-8.19; P=0.028], respectively). Conclusions Low serum insulin levels were associated with increased risk of all-cause and cardiovascular death in ADHF patients without diabetes mellitus.

Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice.

Heme oxygenase (HO)-1 is a key player reducing cytotoxicity and enhancing protumoral effects of nitric oxide (NO). We examined zinc protoporphyrin (ZnPP) IX, an HO-1 inhibitor, to affect tumor growth of LL/2 mouse lung cancer cells. ZnPPIX reduced HO-1 expression and HO activity in LL/2 cells, whereas cobalt PPIX (CoPPIX), an HO-1 activator, increased both. LL/2 cells treated with sodium nitropurusside, an NO donor, showed growth inhibition dose-dependently, which was enhanced by ZnPPIX cotreatment, but was reduced by CoPPIX. In mice tumors, ZnPPIX decreased HO-1 expression. LL/2-tumors were found in 88% (7/8) vehicle-treated mice, whereas tumors were found in 38% (3/8) and 25% (2/8) mice treated with 5 and 20 microg/mouse ZnPPIX, respectively (p = 0.0302). Tumor growth was inhibited dose-dependently by ZnPPIX. Vascular endothealial growth factor concentration in tumors was reduced by ZnPPIX (p = 0.0341). Microvessel density (MVD) in ZnPPIX-treated tumors was lower than that in vehicle-treated tumors (p = 0.0362). Apoptotic cell count in ZnPPIX-treated tumors was higher than that in vehicle-treated tumors (p = 0.0003). In contrast, CoPPIX treatment increased HO-1 expression, enhanced tumorigenicity and MVD and reduced apoptosis. From these findings, inhibition of HO-1 by ZnPPIX provides relevant antitumoral effects.