A multicenter observational study of the effectiveness of antiarrhythmic agents in ventricular arrhythmias: A propensity-score adjusted analysis.

BACKGROUND: Ventricular tachyarrhythmias (VTs) are life-threatening events that result in hemodynamic compromise. Recurrence is common and may worsen a patient׳s clinical course despite appropriate treatment. This study aimed to examine the effectiveness of antiarrhythmic drugs for suppression of VTs. METHODS: In this cohort study, eligible patients were those who were admitted to one of the nine cardiovascular care centers and treated with continuous infusion of an antiarrhythmic drug for at least 1 h to prevent recurrence of VTs after return of spontaneous circulation. To adjust for differences in baseline characteristics among treatment groups, propensity scores for administered agents were generated and used as covariates in regression analyses. RESULTS: Seventy-two patients were enrolled and 67 patients were included in the final analysis. Amiodarone (n=21, 31.3%), nifekalant (n=24, 35.8%), and lidocaine (n=22, 32.8%) were administered as first-line therapy for suppression of VTs. In the adjusted analyses, the odds ratio (OR) of switching to a different drug was significantly higher in the lidocaine group (OR 37.6, 95% CI 5.1-279, p<0.001) than in the amiodarone group, but not in the nifekalant group (OR 4.1, 95% CI 0.72-23.2, p=0.11). There was no significant difference in mortality rate in the lidocaine group (OR 1.67, 95% CI 0.40-6.95, p=0.48) or the nifekalant group (OR 1.11, 95% CI 0.15-4.85, p=0.89) compared with the amiodarone group. CONCLUSION: Amiodarone and nifekalant are similarly effective in preventing VT recurrence, but their impact on survival rate is minimal. These data indicate that both nifekalant and amiodarone can be used for treatment of refractory VT.

Peripheral microvascular dysfunction predicts residual risk in coronary artery disease patients on statin therapy.

OBJECTIVE: Although lowering of low-density lipoprotein cholesterol (LDL-C) by statins is essential in treatment of coronary artery disease (CAD) patients, there is considerable residual risk of secondary coronary artery events (CAE). We examined whether microvascular dysfunction (MiD), measured by peripheral artery tonometry (PAT), can predict prognosis of CAD patients previously treated with statins. METHODS: We measured log-transformed reactive hyperemia index (L_RHI) in 213 CAD patients who had already achieved LDL-C <100 by statin therapy. Patients were followed-up for secondary CAE for a median of 2.7 years. Patients were divided into two groups: L_RHI ≥ 0.54 (n = 99) and L_RHI < 0.54 (n = 114). RESULTS: During follow-up, CAE occurred in 4 (4.0%) patients in the L_RHI ≥ 0.54 group and 18 (15.8%) patients in the L_RHI < 0.54 group (P = 0.006). Cox regression analysis indicated that L_RHI was an independent predictor for CAE even after adjustment by Framingham traditional risk factors (FRF; age, T-C/HDL-C ratio, systolic blood pressure, diabetes, current smoker, and gender) and estimated glomerular filtration rate (eGFR) for secondary CAE (HR 0.79, 95% CI: 0.66-0.95). ROC analysis for CAE prediction showed that the AUC for models including FRF only, FRF + eGFR, and FRF + eGFR + L_RHI were 0.60, 0.71, and 0.77, respectively. Moreover, adding eGFR to FRF only (0.63, P = 0.003) and adding L_RHI to the FRF + eGFR model were associated with significant improvement of net reclassification improvement (0.79, P = 0.007). CONCLUSION: MiD measured by non-invasive PAT adds incremental predictive ability to traditional risk factors for prognosis of CAD patients successfully treated with statins.

Clinical effectiveness of tolvaptan in patients with acute decompensated heart failure and renal failure: design and rationale of the AQUAMARINE study.

PURPOSE: Over half of all admitted acute decompensated heart failure (ADHF) patients have renal failure. Although diuretics represent the mainstay of treatment strategy even in this population, there are unmet needs for safer and more effective treatment. Tolvaptan is a vasopressin-2 receptor antagonist, and we hypothesized that adding tolvaptan to standard diuretic therapy would be more effective in ADHF patients with renal function impairment. METHODS: The Answering question on tolvaptan's efficacy for patients with acute decompensated heart failure and renal failure (AQUAMARINE) is a multicenter, randomized controlled clinical trial, which will enroll 220 patients from 17 hospitals in Japan. ADHF patients whose estimated glomerular filtration rate is above 15 and below 60 mL/min/1.72 m(2) will be randomly assigned within 6 h after admission to usual care with furosemide or tolvaptan add-on therapy. Primary endpoint is achieved urine output within 48 h. Secondary endpoints include dyspnea relief measured by 7-points Likert scale, incidence of worsening renal function, dose of furosemide used within 48 h, and changes of brain natriuretic peptide. CONCLUSION: This study is the first multicenter study in Japan to evaluate clinical effectiveness of tolvaptan add-on therapy in ADHF patients with renal failure. The results of this study address the treatment strategy of this high-risk population (UMIN Clinical Trial Registry Number: UMIN000007109).

Prognostic implications of chronic kidney disease and anemia after percutaneous coronary intervention in acute myocardial infarction patients.

Anemia is a common complication of chronic kidney disease (CKD), and a few studies suggest that both CKD and anemia have a marked impact on the prognosis of patients with cardiovascular disease. We retrospectively analyzed the prevalence of CKD and anemia in 312 patients with acute myocardial infarction (AMI). The patients were divided into four groups according to the presence of CKD and anemia. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2), and anemia was defined according to the World Health Organization definition. Of 312 AMI patients, 166 (53.2%) had CKD and 87 (27.8%) had anemia. A powerful relationship was observed between both CKD and anemia and major adverse cardiac and cerebrovascular events (MACCE) or death by any cause. After adjustment for comorbidities, the hazard ratio (HR) for MACCE was significantly higher in the anemia-only group (HR 5.42, 95% confidence interval (CI) 1.38-21.27, P = 0.015), the CKD-only group (HR 6.4, 95% CI 2.09-19.58, P = 0.001), and the CKD and anemia group (HR 11.61, 95% CI 3.65-36.89, P < 0.001). With respect to death by any cause, the HR was significantly higher in the CKD-only group (HR 2.68, 95% CI 1.02-7.02, P = 0.045) and the CKD and anemia group (HR 4.40, 95% CI 1.56-12.43, P = 0.005). One-half of the patients with AMI had CKD as well. Furthermore, when anemia coexisted with CKD, these conditions had a multiplicative amplification effect on the risk of MACCE and death by any cause in patients with AMI.

Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure in high-risk population.

BACKGROUND: Although tolvaptan is a recently approved drug for heart failure and causes aquaresis without affecting renal function, its clinical efficacy for patients with acute decompensated heart failure (ADHF) is yet to be elucidated. METHODS AND RESULTS: We conducted a prospective observational study in patients with ADHF and high risk for worsening renal function (WRF). Risk stratification for WRF was done by scoring system. Of 174 patients, 114 patients were included as high-risk population for WRF. Incidence of WRF, urine output within 24h and 48 h, and changes in brain natriuretic peptide (BNP) were recorded in 44 patients treated with tolvaptan plus conventional therapy, and 70 patients with only conventional therapy. Urine output at 24h and 48 h after admission were both significantly higher in the tolvaptan group (p=0.001 and <0.001, respectively), and changes in BNP were not significantly different (p=0.351). However, the incidence of WRF was significantly lower in the tolvaptan group compared to the conventional group (22.7% vs 41.4%, p=0.045). Logistic regression analysis showed that treatment with tolvaptan was an independent factor for reducing WRF (hazard ratio 0.28, 95% confidence interval; 0.10-0.84; p=0.023). CONCLUSION: In patients with ADHF with high risk of WRF, treatment with tolvaptan could prevent WRF compared to conventional therapy.

Endothelial dysfunction measured by peripheral arterial tonometry predicts prognosis in patients with heart failure with preserved ejection fraction.

BACKGROUND: There is need for risk stratification of adverse events in patients with heart failure with HFpEF as the number of patients is increasing and prognosis of this population is poor. This study was performed to determine whether endothelial dysfunction measured by peripheral artery tonometry (PAT) can predict prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We included 159 patients with HFpEF, and log-transformed reactive hyperemia index (L_RHI) was measured. Patients were followed-up for HF-related events, which including HF-related death and re-hospitalization due to congestive heart failure for 300 days. RESULTS: A total of 32 HF-related events occurred during follow-up, including 4 deaths due to HF and 28 cases of re-hospitalization due to acute decompensated HF. Cox regression analysis indicated that L_RHI (HR 0.56, 95% CI: 0.39-0.80 for an increase of 0.1) was an independent predictor of HF-related events. Receiver operating characteristic analysis was performed for L_RHI, and the area under the curve was 0.73 (95% CI: 0.62-0.83). Moreover, a value of 0.49 was suggested as the optimal cut-off value for prediction of adverse events in this population. CONCLUSION: L_RHI measured by non-invasive PAT is a predictor of poor prognosis in patients with HFpEF.

ß-blocker prevents sudden cardiac death in patients with hemodialysis.

BACKGROUND: Beta blockers were shown to prevent SCD in cardiomyopathy or coronary artery disease patients. Dialysis patients show elevated mortality rates, predominantly due to cardiovascular disease. SCD is now one of the leading causes of death in this population. However, the prevention of SCD remains to be elucidated. METHODS: We conducted a retrospective study of 316 patients from a database of all patients undergoing maintenance hemodialysis and followed up for 4.9 years. All patients were followed-up until death. Cox regression analysis was used to adjust the hazard ratio for beta blocker use with time until death. RESULTS: SCD occurred during the study period in 3 (3.8%) patients in the beta blocker group and in 27 (11.4%) patients in the non-beta blocker group (P=0.047). Death from all causes occurred in 15 (18.8%) patients in the beta blocker group and in 97 (41.3%) patients in the non-beta blocker group (P<0.001). Kaplan-Meier curve showed that the rates of both SCD and all-cause death were lower in the beta blocker group (log-rank test, P=0.028 and P<0.001, respectively). In the Cox regression model, beta blocker use was significantly associated with lower adjusted risk of SCD (multivariate adjusted hazard ratio, 0.201; 95% confidence interval, 0.058-0.693; P=0.011). CONCLUSION: In hemodialysis patients, beta blocker use was associated with lower risks of SCD and death from all causes. Thus, beta blocker use in this high-risk population may substantially improve outcome.

Prevalence and prognostic implications of pre-diabetic state in patients with heart failure.

BACKGROUND: Diabetes mellitus (DM) is a risk factor of poor prognosis in patients with heart failure (HF). The prevalence and prognostic impact of the pre-diabetic state, however, are not well understood. METHODS AND RESULTS: One hundred and thirty-six consecutive patients admitted due to HF were included in this prospective study. The 75-g oral glucose tolerance test (OGTT) was performed in all patients without known DM, and patients were classified into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM groups. Forty-two of the 136 patients had previously been diagnosed with diabetes. Of the remaining 94 patients without known diabetes, 35 (37.2%) patients were classified as NGT, 9 (9.6%) as having IFG, 37 (39.4%) were classified as having IGT, and 13 (13.8%) were newly diagnosed with DM. During follow-up, patients with DM or IGT had significantly lower major adverse cardiac and cerebrovascular event (MACCE)-free rates than NGT patients (P=0.006, P=0.036, respectively). IFG, however, was not significantly related to increased MACCE risk. The presence of IGT (hazard ratio [HR], 4.51; P=0.011) and DM (HR, 4.74; P=0.005) were independent predictors of MACCE even after multivariate analysis. CONCLUSIONS: IGT and DM contribute to adverse prognosis in patients with HF. It is feasible to perform diabetes screening using OGTT in patients with HF for risk stratification.

A case of giant cell arteritis with massive pericardial effusion.

Giant cell arteritis (GCA) is a chronic inflammatory disease of the medium and large blood vessels. The early symptoms of this disease are nonspecific, and pericardial effusion is a rare manifestation of GCA. Recently, we investigated a case of GCA in which massive pericardial effusion was the initial symptom, and active aortitis was observed on positron emission tomography with fluorine-18 fluorodeoxyglucose. These observations indicated that pericardial effusion could occur in patients with GCA.

Endothelial dysfunction in paroxysmal atrial fibrillation as a prothrombotic state. Comparison with permanent/persistent atrial fibrillation.

AIM: Atrial fibrillation (AF), regardless of subtype, is associated with a prothrombotic state, which is related to endothelial dysfunction (ED).We hypothesized that paroxysmal atrial fibrillation (PAF) patients have endothelial dysfunction, and this may partially explain the high thromboembolic risk and poorer outcome in this category of patients. METHODS: The study population consisted of 100 consecutive outpatients with AF (mean age 65.9±7.9 years; 68 (68%) male) and 21 characteristics and comorbidity matched control subjects (mean age 64.8±7.0 years; 13 (61.9%) male). AF patients were divided into the PAF group (n=50) and permanent/persistent AF (PeAF) group (n=50).Reactive hyperemia pulse amplitude tonometry index (RHI) was measured to evaluate endothelial function. RESULTS: RHI was significantly lower in the PAF (1.67±0.30) and PeAF (1.63±0.28) groups in comparison with control subjects (2.12±0.40, both p< 0.001). There was no significant difference in RHI between the PAF and PeAF groups (p= 0.88). On linear regression analysis, both PeAF and PAF are significant independent predictors of RHI. CONCLUSIONS: In conclusion, ED in PAF patients was comparable to PeAF patients, and the presence of PAF itself is a contributing factor for ED independent of other coexisting comorbidities. This may provide a mechanism explaining why the risk of thromboembolism in PAF is comparable with PeAF patients.

A case of fulminant myocarditis with three recurrences and recoveries.

Fulminant myocarditis is characterised by acute onset with severe haemodynamic deterioration. With intensive and appropriate bridging management, the prognosis is better than classic forms of myocarditis. Here, we report a patient who suffered from fulminant myocarditis 3 times over the last 8 years with recovery each time.

Effectiveness of risk stratification according to CHADS2 score in Japanese patients with nonvalvular atrial fibrillation.

Cerebrovascular events increase with additional risk factors in patients with nonvalvular atrial fibrillation (NVAF). The relative risk proportional to the number of risk factors in Japanese patients has not been reported. The prevalence of risk factors was investigated for over 2 years in a prospective cohort study of 265 patients with NVAF. The CHADS2 score is a widely used risk stratification scheme that includes age, hypertension, diabetes mellitus, previous stroke, and heart failure. Cerebral infarction occurred in 23 patients. This group was significantly older and had a significantly higher prevalence of hypertension. The ratio of a CHADS2 score of 0 - 2 was 77% among patients without stroke, but 44% in the cerebral infarction group. Univariate logistic regression analysis showed that the predictive factors of cerebral infarction were: age (odds ratio (OR) 1.087 (confidence interval (CI) 1.032 - 1.145, P = 0.002), hypertension (OR 3.288 (CI 1.086 - 9.962, P = 0.03) and CHADS2 score (OR 1.762 (CI 1.222 - 2.543, P = 0.002). Furthermore, a CHADS2 score of 3 - 6 was associated with a greater risk of cerebral infarction (OR 4.420 (CI 1.838 - 10.631, P < 0.001). The CHADS2 score was a useful marker of stroke risk in this Japanese population. An increased CHADS2 score was associated with an approximate 1.8-fold increase in risk.

Three-dimensional echocardiography could distinguish a ventricular septal defect adjacent to asymptomatic ruptured sinus of valsalva aneurysm.

Sinus of Valsalva aneurysm (SVA) arises frequently in the right coronary sinus, and ventricular septal defect (VSD) is a prevalent coexistent cardiac abnormality. A 38-year-old asymptomatic male diagnosed with VSD on cardiac catheterization in his childhood, was referred to our hospital for the change in intensity of his cardiac murmur pointed out by his family physician. A grade V continuous murmur was auscultated with a thrill loudest at the forth left sternal border. Although, transthoracic and transesophageal echocardiography and cardiac catheterization have showed the ruptured right coronary sinus aneurysm, it was difficult to demonstrate coexistence of a doubly committed subarterial VSD. Three-dimensional echocardiography could provide clear images for diagnosis of the VSD closely adjacent to the ruptured SVA. The defect was confirmed at surgery.