Association with left atrial volume index and long-term prognosis in patients without systolic dysfunction nor atrial fibrillation: an observational study.

The prognostic impact of left atrial size in patients without systolic dysfunction nor atrial fibrillation (AF) has not been fully elucidated in Japan. We retrospectively analyzed data obtained from 4444 consecutive patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in our hospital. Those who presented with a history of myocardial infarctions, severe and moderate valvular diseases, low ejection fraction (< 50%), and documented AF, and without data on LA volume index (LAVI) or tissue Doppler early diastolic mitral annular velocity were excluded. We defined high LAVI as a value > 34 ml/m2. The primary outcome measure was a composite of all-cause death and major adverse cardiac events. A total of 2792 patients were categorized into two groups: 2627 with normal LAVI (94.1%), 165 with high LAVI (5.9%). The median age of patients in the normal and high LAVI groups were 67, and 77 years, respectively (p < 0.001). Prevalence of diabetes mellitus, hypertension, and chronic kidney disease, and left ventricular mass index was higher in the high-LAVI group than normal-LAVI group. After adjusting for confounders, the excess 3-year risk of primary outcome of high-LAVI related to normal-LAVI was significant (hazard ratio 1.44; 95% confidence interval 1.03-1.97, p = 0.032). High-LAVI should be considered a marker of a worse long-term follow-up in patients without systolic dysfunction nor AF.

Thirty-Day Readmission After Infective Endocarditis: Analysis From a Nationwide Readmission Database.

Background The contemporary incidence of and reasons for early readmission after infective endocarditis ( IE ) are not well known. Therefore, we analyzed 30-day readmission demographics after IE from the US Nationwide Readmission Database. Methods and Results We examined the 2010 to 2014 Nationwide Readmission Database to identify index admissions for a primary diagnosis of IE with survival at discharge. Incidence, reasons, and independent predictors of 30-day unplanned readmissions were analyzed. In total, 11 217 patients (24.8%) were nonelectively readmitted within 30 days among the 45 214 index admissions discharged after IE . The most common causes of readmission were IE (20.5%), sepsis (8.7%), complications of device/graft (8.1%), and congestive heart failure (7.6%). In-hospital mortality and the valvular surgery rates during the readmissions were 8.1% and 9.1%, respectively. Discharge to home or self-care, undergoing valvular surgery, aged ≥60 years, and having private insurance were independently associated with lower rates of 30-day readmission. Length of stay of ≥10 days, congestive heart failure, diabetes mellitus, renal failure, chronic pulmonary disease, peripheral artery disease, and depression were associated with higher risk. The total hospital costs of readmission were $48.7 million per year (median, $11 267; interquartile range, $6021-$25 073), which accounted for 38.6% of the total episodes of care (index+readmission). Conclusions Almost 1 in 4 patients was readmitted within 30 days of admission for IE . The most common reasons were IE , other infectious causes, and cardiac causes. A multidisciplinary approach to determine the surgical indications and close monitoring are necessary to improve outcomes and reduce complications in in-hospital and postdischarge settings.

Outcome From a Randomized Controlled Clinical Trial　- Improvement of Peripheral Arterial Disease by Granulocyte Colony-Stimulating Factor-Mobilized Autologous Peripheral-Blood-Mononuclear Cell Transplantation (IMPACT).

BACKGROUND: The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. CONCLUSIONS: In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

Impact of the left ventricular mass index on the outcomes of severe aortic stenosis.

OBJECTIVE: To elucidate the factors associated with high left ventricular mass index (LVMI) and to test the hypothesis that high LVMI is associated with worse outcome in severe aortic stenosis (AS). METHODS: We analysed 3282 patients with LVMI data in a retrospective multicentre registry enrolling consecutive patients with severe AS in Japan. The management strategy, conservative or initial aortic valve replacement (AVR), was decided by the attending physician. High LVMI was defined as LVMI >115 g/m2 for males and >95 g/m2 for females. We compared the risk between normal and high LVMI in the primary outcome measures compromising aortic valve-related death and heart failure hospitalisation. RESULTS: Age was mean 77 (SD 9.6) years and peak aortic jet velocity (Vmax) was 4.1 (0.9) m/s. The factors associated with high LVMI (n=2374) included female, body mass index ≥22, absence of dyslipidemia, left ventricular ejection fraction <50%, Vmax ≥4 m/s, regurgitant valvular disease, hypertension, anaemia and end-stage renal disease. In the conservative management cohort (normal LVMI: n=691, high LVMI: n=1480), the excess adjusted 5-year risk of high LVMI was significant (HR: 1.53, 95% CI 1.26 to 1.85, p<0.001). In the initial AVR cohort (normal LVMI: n=217, high LVMI: n=894), the risk did not differ significantly between the two groups (HR: 0.96, 95% CI 0.60 to 1.55, p=0.88). There was a significant interaction between the initial treatment strategy and the risk of high LVMI (p=0.016). CONCLUSIONS: The deleterious impact of high LVMI on outcome was observed in patients managed conservatively, but not observed in patients managed with initial AVR. TRIAL REGISTRATION NUMBER: UMIN000012140; Post-results.

Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial.

AIMS: Most of recurrent atrial tachyarrhythmias after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are due to reconnection of PVs. The aim of the present study was to evaluate whether elimination of adenosine triphosphate (ATP)-induced dormant PV conduction by additional energy applications during the first ablation procedure could reduce the incidence of recurrent atrial tachyarrhythmias. METHODS AND RESULTS: We randomly assigned 2113 patients with paroxysmal, persistent, or long-lasting AF to either ATP-guided PVI (1112 patients) or conventional PVI (1001 patients). The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of Vaughan Williams class I or III antiarrhythmic drugs at 1 year with the blanking period of 90 days post ablation. Among patients assigned to ATP-guided PVI, 0.4 mg/kg body weight of ATP provoked dormant PV conduction in 307 patients (27.6%). Additional radiofrequency energy applications successfully eliminated dormant conduction in 302 patients (98.4%). At 1 year, 68.7% of patients in the ATP-guided PVI group and 67.1% of patients in the conventional PVI group were free from the primary endpoint, with no significant difference (adjusted hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.74-1.09; P = 0.25). The results were consistent across all the prespecified subgroups. Also, there was no significant difference in the 1-year event-free rates from repeat ablation for any atrial tachyarrhythmia between the groups (adjusted HR 0.83; 95% CI 0.65-1.08; P = 0.16). CONCLUSION: In the catheter ablation for AF, we found no significant reduction in the 1-year incidence of recurrent atrial tachyarrhythmias by ATP-guided PVI compared with conventional PVI.

Effect on treadmill exercise capacity, myocardial ischemia, and left ventricular function as a result of repeated whole-body periodic acceleration with heparin pretreatment in patients with angina pectoris and mild left ventricular dysfunction.

Whole-body periodic acceleration (WBPA) has been developed as a passive exercise device capable of improving endothelial function by applying pulsatile shear stress to vascular endothelium. We hypothesized that treatment with WBPA improves exercise capacity, myocardial ischemia, and left ventricular (LV) function because of increased coronary and peripheral vasodilatory reserves in patients with angina. Twenty-six patients with angina who were not indicated for percutaneous coronary intervention and/or coronary artery bypass grafting were randomly assigned to remain sedentary (sedentary group) or undergo 20 sessions of WBPA with the motion platform for 4 weeks (WBPA group) in addition to conventional medical treatment. WBPA was applied at 2 to 3 Hz and approximately ±2.2 m/s² for 45 minutes. We repeated the symptom-limited treadmill exercise test and adenosine sestamibi myocardial scintigraphy. In the WBPA group, the exercise time until 0.1-mV ST-segment depression increased by 53% (p <0.01) and the double product at 0.1-mV ST-segment depression by 23% (p <0.001). Severity score of myocardial scintigraphy during adenosine infusion decreased from 20 ± 10 to 14 ± 8 (p <0.001) and severity score at rest also decreased from 13 ± 10 to 8 ± 10 (p <0.01). On scintigraphic images at rest, LV end-diastolic volume index decreased by 18% (p <0.01) with an augmentation of LV ejection fraction from 50 ± 16% to 55 ± 16% (p <0.01). In contrast, all studied parameters remained unchanged in the sedentary group. In conclusion, treatment with WBPA for patients with angina ameliorates exercise capacity, myocardial ischemia, and LV function.

[Clinical analysis of precaution against atrial fibrillation following cardiac surgery: landiolol or amiodarone?].

Atrial fibrillation following cardiac surgery remains as a most common complication. Tachycardia with atrial fibrillation just after the operation could lead to cardiac deterioration. Although we have to control tachycardia, we often have great difficulties in managing these arrhythmias. Many reports have showed landiolol, ultra short-acting beta1 blocker, and amiodarone were effective against postoperative atrial fibrillation. However there has been no report on comparison between these 2 drugs. As excessively sympathetic activity might cause atrial fibrillation, landiolol was introduced into our therapy concomitant with the sedative. Our investigation confirmed that both landiolol and amiodarone were effective in preventing atrial fibrillation, and that the timing of transition from intravenous administration to oral intake was acceptable. When landiolol was administered, enough attention should be paid to the patients whose left ventricular function was low. The patients in whom atrial fibrillation occurred under landiolol therapy showed tendency of lower heart rate in comparison with the patients under amiodarone therapy.

Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome.

BACKGROUND: Drugs with I(Kr)-blocking action cause secondary long-QT syndrome. Several cases have been associated with mutations of genes coding cardiac ion channels, but their frequency among patients affected by drug-induced long-QT syndrome (dLQTS) and the resultant molecular effects remain unknown. METHODS AND RESULTS: Genetic testing was carried out for long-QT syndrome-related genes in 20 subjects with dLQTS and 176 subjects with congenital long-QT syndrome (cLQTS); electrophysiological characteristics of dLQTS-associated mutations were analyzed using a heterologous expression system with Chinese hamster ovary cells together with a computer simulation model. The positive mutation rate in dLQTS was similar to cLQTS (dLQTS versus cLQTS, 8 of 20 [40%] versus 91 of 176 [52%] subjects, P=0.32). The incidence of mutations was higher in patients with torsades de pointes induced by nonantiarrhythmic drugs than by antiarrhythmic drugs (antiarrhythmic versus others, 3 of 14 [21%] versus 5 of 6 [83%] subjects, P<0.05). When reconstituted in Chinese hamster ovary cells, KCNQ1 and KCNH2 mutant channels showed complex gating defects without dominant negative effects or a relatively mild decreased current density. Drug sensitivity for mutant channels was similar to that of the wild-type channel. With the Luo-Rudy simulation model of action potentials, action potential durations of most mutant channels were between those of wild-type and cLQTS. CONCLUSIONS: dLQTS had a similar positive mutation rate compared with cLQTS, whereas the functional changes of these mutations identified in dLQTS were mild. When I(Kr)-blocking agents produce excessive QT prolongation (dLQTS), the underlying genetic background of the dLQTS subject should also be taken into consideration, as would be the case with cLQTS; dLQTS can be regarded as a latent form of long-QT syndrome.

Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes.

Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates ATP-sensitive K+ (K(ATP)) channel activity. Because phospholipase C (PLC) hydrolyzes membrane-bound PIP2, which in turn may potentially decrease K(ATP) channel activity, we investigated the effects of the alpha1-adrenoceptor-G(q)-PLC signal transduction axis on pinacidil-activated K(ATP) channel activity in adult rat and neonatal mouse ventricular myocytes. The alpha1-adrenoceptor agonist methoxamine (MTX) reversibly inhibited the pinacidil-activated K(ATP) current in a concentration-dependent manner (IC50 20.9+/-6.6 micromol/L). This inhibition did not occur when the specific alpha1-adrenoceptor antagonist, prazosin, was present. An involvement of G proteins is suggested by the ability of GDPbetaS to prevent this response. Blockade of PLC by U-73122 (2 micromol/L) or neomycin (2 mmol/L) attenuated the MTX-induced inhibition of K(ATP) channel activity. In contrast, the MTX response was unaffected by protein kinase C inhibition or stimulation by H-7 (100 micro mol/L) or phorbol 12,13-didecanoate. The MTX-induced inhibition became irreversible in the presence of wortmannin (20 micro mol/L), an inhibitor of phosphatidylinositol-4 kinase, which is expected to prevent membrane PIP2 replenishment. In excised inside-out patch membranes, pinacidil induced a significantly rightward shift of ATP sensitivity of the channel. This phenomenon was reversed by pretreatment of myocytes with MTX. Direct visualization of PIP2 subcellular distribution using a PLCdelta pleckstrin homology domain-green fluorescent protein fusion constructs revealed reversible translocation of green fluorescent protein fluorescence from the membrane to the cytosol after alpha1-adrenoceptor stimulation. Our data demonstrate that alpha1-adrenoceptor stimulation reduces the membrane PIP2 level, which in turn inhibits pinacidil-activated K(ATP) channels.