Heterogeneity of hemodynamic parameters in untreated primary hypertension, and individualization of antihypertensive therapy based on noninvasive hemodynamic measurements.

Noninvasive measurement of hemodynamic parameter was undertaken in 240 patients with untreated primary hypertension using impedance cardiography (ICG) in outpatient clinics. High output was defined as a cardiac index (CI) >3.6 L/minute/m(2) and high resistance was defined as the total peripheral resistance index (TPRI) >2700 dyne·s·m(2)/cm(5). Of all patients, 67% had high-resistance hypertension (high TPRI with normal or low CI), and 16% had high-output hypertension (high CI with normal TPRI). Treatment with ß-blockers for high-output hypertension and with calcium channel blockers for high-resistance hypertension reduced blood pressure equally, and restored normal hemodynamic balance, as reported in studies using invasive monitoring methods. These findings suggest that it is appropriate to use noninvasive ICG measurements to guide antihypertensive therapy. Multivariate analysis showed that female gender, tachycardia, and low body mass index (BMI) were associated with high-output hypertension, but age was not. Heterogeneity of hemodynamic parameters is thought to be one of the reasons why the efficacies of antihypertensive agents differ between patients. It may be feasible to predict which antihypertensive agent would be the most effective for a particular patient based on hemodynamic measurements or combination of gender, heart rate, and BMI.

Preliminary study on the development of a system dynamics model: the case of EVAHEART.

The Japanese medical device industry's stagnation over the years can be attributed to the uncertainty related to device development. The purpose of this study is to identify the major factors that impact development. We studied the ventricular assist device EVAHEART through interviews with the persons involved and created a development model using system dynamics. There are at least six stages in the device development process, including interactions with academia and the government. Through a simulation and comparison to Novacor, it was determined that the satisfaction of academia leads to government action in the subsequent measures. Our trial simulation of EVAHEART suggests that it has the potential to clarify unclear relationships in the development of devices.

Landiolol, an ultra-short-acting ß1-blocker, more effectively terminates atrial fibrillation than diltiazem after open heart surgery: prospective, multicenter, randomized, open-label study (JL-KNIGHT study).

BACKGROUND: Recent studies have suggested that esmolol is the first choice for rate control in patients with postoperative atrial fibrillation (AF) after coronary artery bypass surgery, but side-effects of esmolol such as hypotension are problematic. To overcome this problem, landiolol, an ultra-short-acting ß(1)-blocker with a less negative inotropic effect than esmolol, has been developed. The aim of the present study was to investigate whether landiolol was effective for both rate control and conversion to normal sinus rhythm (NSR). METHODS AND RESULTS: A prospective, randomized, open-label comparison between i.v. landiolol and diltiazem in patients with postoperative AF was undertaken between January 2008 and June 2009 in Japan. Of 335 patients included in the analysis, 71 patients went into AF. Among these 71 patients, conversion to NSR within 8h after onset of AF occurred in 19 of 35 patients (54.3%) in the landiolol group vs. 11 of 36 patients (30.6%) in the diltiazem group (P<0.05). The incidence of hypotension was lower in the landiolol group (4/35, 11.4%) compared with the diltiazem group (11/36, 30.6%; P<0.05). The incidence of bradycardia was also lower in the landiolol group (0%) compared with the diltiazem group (4/36, 11.1%; P<0.05). CONCLUSIONS: Landiolol is more effective and safer than diltiazem for patients with postoperative AF after open heart surgery.

Optimal initial diagnostic strategies for the evaluation of stable angina patients: a multicenter, prospective study on myocardial perfusion imaging, computed tomographic angiography, and coronary angiography.

BACKGROUND: For stable patients suspected of having coronary artery disease (CAD), myocardial perfusion imaging (MPI) or computed tomographic angiography (CT) is used for initial evaluation, while coronary angiography (CAG) is used for confirming the diagnosis. The choice of the initial diagnostic test might influence the treatment strategy. METHODS AND RESULTS: Patients scheduled for MPI, CT, or CAG as the initial diagnostic test were enrolled. The primary and secondary end-points were a major adverse cardiac event (MACE) and revascularization, respectively. Of the 2,878 patients enrolled, 2,825 underwent initial diagnostic tests, and 2,780 were followed up for 1.42±0.49 years. After adjustment for CAD severity, Cox proportional hazard regression analysis showed that the risk of MACE in the MPI and CT groups were similar and significantly less than that in the CAG group (hazard ratio, 0.82 vs. 2.19; 95% confidence interval [CI], 0.43-1.58 vs. 1.40-3.44). Furthermore, the rate of revascularization in the MPI group was less than that of the CT (odds ratio, 1.62; 95% CI, 1.20-2.18) and CAG (odds ratio, 5.36; 95% CI, 4.07-7.05) groups. CONCLUSIONS: These data indicate that for stable patients with suspected CAD, the use of MPI or CT as the initial diagnostic test was associated with better prognosis than the use of CAG, and that initial evaluation with MPI was associated with a lower requirement of coronary intervention.

Risk of sudden death in end-stage hypertrophic cardiomyopathy.

BACKGROUND: It remains unclear whether end-stage hypertrophic cardiomyopathy (HCM) is associated with as high a rate of sudden death as occurs among HCM patients with preserved left ventricular (LV) systolic function. The purpose of this study was to evaluate the incidence of sudden death among patients with end-stage HCM and to identify high-risk end-stage patients. METHODS AND RESULTS: A total of 490 consecutive patients with HCM, who were diagnosed and followed-up at our hospital, were analyzed retrospectively. End-stage HCM was defined by an LV ejection fraction <50% on echocardiography during follow-up. Among the 490 HCM patients, 43 patients (8.8%) were diagnosed as having end-stage HCM during a mean follow-up period of 12 ± 7 years after the initial diagnosis. During a mean follow-up period of 5 ± 3 years after progression to end-stage HCM, sudden death occurred in 21 of 43 patients (47%). Cox proportional hazards analysis identified syncope as an independent predictor of sudden death (hazard ratio = 6.15; 95% confidence interval, 2.40-15.75; P < .001). CONCLUSIONS: This study demonstrated that patients with end-stage HCM have a high incidence of sudden death. Therefore, it is suggested that an aggressive therapeutic strategy to counter sudden death should be considered for patients with end-stage HCM.

Depression and outcomes in hospitalized Japanese patients with cardiovascular disease. - Prospective single-center observational study-.

BACKGROUND: Several studies have suggested that depression poses a risk in cardiovascular patients. The aim of the present study was to evaluate the prevalence of depression and its effect on cardiovascular events and mortality in Japanese inpatients with cardiovascular disease. METHODS AND RESULTS: A total of 505 patients hospitalized with cardiovascular disease (28% female; mean age, 61 ± 14 years; 31% ischemic heart disease; 47% New York Heart Association [NYHA] class II-IV; 25% implantation of pacing devices) were enrolled in the present prospective observational study. The Zung Self-Rating Depression Scale (SDS) was used to screen for depression. The primary outcome was the time to death or cardiovascular event, and the secondary outcome was death. In total, 109 patients (22%) were diagnosed with depression (Zung SDS index score ≥ 60). NYHA class III/IV, defibrillator implantation, and being unmarried were independently associated with depression. During an average follow-up period of 38 ± 15 months, 92 patients (18%) reached the primary outcome. There was a higher incidence of the primary outcome in patients with depression than in those who were not depressed (P<0.01). Depressed patients had a significantly higher rate of mortality than non-depressed patients (P<0.01). Depression was an independent predictor of the primary outcome (hazard ratio, 2.25; 95% confidence interval: 1.30-3.92, P<0.01). CONCLUSIONS: Depression was not uncommon in Japanese inpatients with cardiovascular disease and was associated with cardiovascular outcomes.

Pharmacokinetics of intravenous amiodarone and its electrocardiographic effects on healthy Japanese subjects.

The aim of this phase I, dose-escalating study was to evaluate the pharmacokinetics, electrocardiographic effect and safety of amiodarone after a single intravenous administration in Japanese subjects. Thirty-two healthy Japanese male volunteers (20-32 years) were randomized to three single-dose groups (1.25, 2.5 and 5.0 mg/kg). In each group, six (1.25 mg/kg) or ten (2.5 and 5.0 mg/kg) subjects received a single 15-min infusion of intravenous amiodarone, and two subjects received glucose solution as control. The pharmacokinetic profile, blood pressure and electrocardiographic analyses were obtained on a timely basis after up to 77 days. The maximum plasma concentration (C (max)) and area under the concentration-time curve (AUC(0-96)) for amiodarone 1.25, 2.5 and 5.0 mg/kg displayed dose-dependent characteristics: mean C (max) was 2,920 ± 610, 7,140 ± 1,480 and 13,660 ± 3,410 ng/ml, respectively; the mean AUC(0-96) was 3,600 ± 700, 8,100 ± 1,600 and 16,600 ± 4,300 ng h/ml, respectively. A long serum half-life (>14 days) was observed for amiodarone and desethylamiodarone. PR intervals were prolonged at 15 min (0.16 ± 0.0.1 vs. 0.15 ± 0.01 s, p = 0.03) and 18 min (0.17 ± 0.01 vs. 0.15 ± 0.01 s, p = 0.03) with the 5.0 mg/kg dose compared with baseline. No other significant changes in electrocardiographic parameters, pulse rate or blood pressure were observed. A needle-pain-induced vasovagal effect appeared in a volunteer, and three volunteers experienced pain at the drug infusion site. After a single infusion of amiodarone at doses of 1.25-5.0 mg/kg, serum concentrations increased in a dose-dependent manner. A single intravenous amiodarone dose barely affected the electrocardiographic parameters and was well tolerated.

Novel algorithm for identifying T-wave current density alternans using synthesized 187-channel vector-projected body surface mapping.

The noninvasive evaluation of ventricular T-wave alternans (TWA) in patients with lethal ventricular arrhythmias is an important issue. In this study, we propose a novel algorithm to identify T-wave current density alternans (TWCA) using synthesized 187-channel vector-projected body surface mapping (187-ch SAVP-ECG). We recorded 10 min of 187-ch SAVP-ECG using a Mason-Likar lead system in the supine position. A recovery time (RT) dispersion map was obtained by averaging the 187-ch SAVP-ECG. The TWCA value was determined from the relative changes in the averaged current density in the T-wave zone (Tpeak ± 50 ms) for two T-wave types. We registered 20 ECG recordings from normal controls and 11 ECG recordings from nine subjects with long QT syndrome (LQT). We divided LQT syndrome subjects into two groups: group 1 provided 9 ECG recordings without visually apparent TWAs, and group 2 provided 2 ECG recordings with visually apparent TWAs. The QTc interval values in the LQT groups were higher than those in the control (515 ± 60 ms in LQT G-1, 600 ± 27 ms in LQT G-2 vs. 415 ± 19 ms in control, P < 0.001). The RTendc dispersion values among the LQT subjects were higher than those of the control subjects (48 ± 19 ms in LQT G-1, 65 ± 30 ms in LQT G-2 vs. 24 ± 10 ms in control, P < 0.01). The mean TWCA value was significantly higher in the LQT G-2 group with visually apparent TWCAs (0.5 ± 0.2% in control, 2.1 ± 1.2% in LQT G-1, and 32.3 ± 6.9% in LQT G-2). Interestingly, the two-dimensional distribution of TWCA in LQT was inhomogeneous and correlated with the distribution of increased RT dispersion. We conclude that a novel algorithm using 187-ch SAVP-ECG might provide new insights into body surface TWCA.

New Visualization Models of Designation Pathway and Group Categorization of Cell-Device and Protein-Device Combination Products in the United States.

PURPOSE: The developer and sponsor of new cell-device and protein-device combination products in the United States needs to forecast which classification and designation to the regulatory scheme of biological products or devices would be required for the new products by the Food and Drug Administration (FDA). To improve the predictability and acceptability of the designation of new cell-device and protein-device combination products for innovators, developers, and sponsors, and to encourage the development and early access of new combination products, we proposed new visualization models of the designation pathway and group categorization. METHODS: We searched the website of the FDA and the Alliance for Regenerative Medicine (ARM) on May 3, 2021 to identify the regulatory scheme of the FDA's capsular decision cases of cell-device and protein-device combination products, and of the tissue-engineered products approved by the FDA. RESULTS: By introducing a new definition of the primary intended use (PIU) of developers and sponsors extracted from the classification factors of primary mode of action (PMOA), as well as drug-device and biologic-device combination products, we developed new visualization models of the designation pathway and the two-dimensional model of group categorization, and proposed a new group categorization of cell-device and protein-device combination products, focusing on the device component function. DISCUSSION: The new visualization models and the group categorization proposed in this study may increase the predictability and acceptability of the classification of newly developed cell-device and protein-device combination products to regulatory schemes in the US for innovators, developers, and sponsors.

New Visualization Models of Designation Pathway and Group Categorization of Device-Drug and Device-Biologic Combination Products Classification in the United States: Analysis of FDA Capsular Decisions.

OBJECTIVE: The developer and sponsor of new combination products in US needs to forecast which classification and designation to the regulatory scheme of drug, biological product, or device would be required for the new products by the Food and Drug Administration (FDA). To improve the predictability and acceptability of the designation of new combination products for innovators, developers, and sponsors, and to encourage the development and early access of new combination products, we proposed new visualization models of the designation pathway and group categorization. METHOD: We searched the website of the FDA on 15 November, 2020 to identify the regulatory scheme of the FDA's 129 capsular decision cases of device-drug and device-biologics combination products and other publicly available cases the FDA designated to the drug/biologic or device regulatory scheme. RESULTS: By introducing a new definition for primary intended use (PIU) by developers and sponsors extracted from the classification factors of primary mode of action (PMOA), we developed new visualization models of the designation pathway and two-dimensional group categorization. And applying these models to the cases the FDA designated, we proposed a new group categorization of combination products while focusing on the device component function. CONCLUSIONS: The new visualization models with PIU and PMOA and the new group categorization focusing on the device component function proposed in this study may increase predictability and acceptability of the classification of newly developed combination products into the regulatory scheme of drug, biological product, and device, for innovators, developers, and sponsors.

Acute decompensated heart failure syndromes (ATTEND) registry. A prospective observational multicenter cohort study: rationale, design, and preliminary data.

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

Long-term prognosis of diabetic patients with acute myocardial infarction in the era of acute revascularization.

BACKGROUND: The long-term prognosis of diabetic patients with acute myocardial infarction (AMI) treated by acute revascularization is uncertain, and the optimal pharmacotherapy for such cases has not been fully evaluated. METHODS: To elucidate the long-term prognosis and prognostic factors in diabetic patients with AMI, a prospective, cohort study involving 3021 consecutive AMI patients was conducted. All patients discharged alive from hospital were followed to monitor their prognosis every year. The primary endpoint of the study was all-cause mortality, and the secondary endpoint was the occurrence of major cardiovascular events. To elucidate the effect of various factors on the long-term prognosis of AMI patients with diabetes, the patients were divided into two groups matched by propensity scores and analyzed retrospectively. RESULTS: Diabetes was diagnosed in 1102 patients (36.5%). During the index hospitalization, coronary angioplasty and coronary thrombolysis were performed in 58.1% and 16.3% of patients, respectively. In-hospital mortality of diabetic patients with AMI was comparable to that of non-diabetic AMI patients (9.2% and 9.3%, respectively). In total, 2736 patients (90.6%) were discharged alive and followed for a median of 4.2 years (follow-up rate, 96.0%). The long-term survival rate was worse in the diabetic group than in the non-diabetic group, but not significantly different (hazard ratio, 1.20 [0.97-1.49], p = 0.09). On the other hand, AMI patients with diabetes showed a significantly higher incidence of cardiovascular events than the non-diabetic group (1.40 [1.20-1.64], p < 0.0001). Multivariate analysis revealed that three factors were significantly associated with favorable late outcomes in diabetic AMI patients: acute revascularization (HR, 0.62); prescribing aspirin (HR, 0.27); and prescribing renin-angiotensin system (RAS) inhibitors (HR, 0.53). There was no significant correlation between late outcome and prescription of beta-blockers (HR, 0.97) or calcium channel blockers (HR, 1.27). Although standard Japanese-approved doses of statins were associated with favorable outcome in AMI patients with diabetes, this was not statistically significant (0.67 [0.39-1.06], p = 0.11). CONCLUSIONS: Although diabetic patients with AMI have more frequent adverse events than non-diabetic patients with AMI, the present results suggest that acute revascularization and standard therapy with aspirin and RAS inhibitors may improve their prognosis.

Prevalence and persistence of depression in patients with implantable cardioverter defibrillator: a 2-year longitudinal study.

BACKGROUND: It is unclear whether depression persists in patients with implantable cardioverter defibrillators (ICDs). We evaluated the prevalence and persistence of depression in ICD patients over a 2-year period. METHODS: The study included 90 consecutively hospitalized patients. Patients underlying heart disease was 24% coronary artery disease, 29% idiopathic dilated cardiomyopathy, 24% hypertrophic cardiomyopathy, 13% idiopathic VF/long QT syndrome and miscellaneous conditions 11%. A secondary indication for ICD implantation was present in 20 patients. All patients completed the Zung Self-Rating Depression Scale (SDS) at study baseline and at the their routine follow-up visit 2 years after the baseline questionnaire. Delivery of ICD therapies was tracked throughout the 2 years. RESULTS: Depression, indicated by a Zung SDS index score exceeding 60, was present in 29 (32%) of patients at study baseline. Depression was present in 11/51 (21%) patients scheduled to undergo ICD implantation, 2/2 (100%) patients whose device was upgraded to a CRT-D, 3/14 (21%) patients who had undergone pulse generator replacement, 7/14 (50%) patients who experienced electrical storm and 6/9 (66%) patients hospitalized with acute decompensated heart failure. NYHA functional class III was significantly associated with depression at baseline (HR 6.7, 95% CI 1.68-27.2, p = 0.0007). No differences were noted for female gender, demographics, ß-blocker use, or LVEF ≤35% (p = ns). Depression was present in 25 (28%) of patients at 2 years follow-up, persisting in 21 (72%) of patients whose Zung SDS scores were elevated at baseline. The median time from ICD shock therapy to completion of the 2 year questionnaire was 9 months (range, 1-22). Patients who were depressed (9/25, 36%) experienced more shocks than non-depressed patients (6/65, 9%) after 2 years (p = 0.002). CONCLUSIONS: Depression is not uncommon among patients who meet criteria for ICD implantation and persists over time particularly when functional status is impaired. Depression is associated with a higher incidence shock therapy.

Gender difference in arrhythmic occurrences in patients with nonischemic dilated cardiomyopathy and implantable cardioverter-defibrillator.

Previous studies indicated that women were less likely to experience ventricular arrhythmia recurrence than men among patients with coronary artery disease and implantable cardioverter defibrillator (ICD). However, it is not clear whether the risk for ventricular tachyarrhythmia is gender-dependent in patients with nonischemic dilated cardiomyopathy. This study included 173 consecutive nonischemic dilated cardiomyopathy patients with a left ventricular ejection fraction of <45% (122 men and 51 women), who received ICD therapy between 1990 and 2008. The average follow-up period was 33 +/- 28 months. There was no significant difference in event-free rates of appropriate ICD therapy between genders for all patients (P = 0.15) and by indication of ICD (primary prevention: P = 0.43, secondary prevention: P = 0.24). There was also no significant difference in event-free rates of electrical storm between genders (P = 0.17). In high-risk patients with nonischemic dilated cardiomyopathy who received ICD, there was no gender difference in the incidence of appropriate ICD therapy or electrical storm.

Angiotensin receptor blocker-based therapy and cardiovascular events in hypertensive patients with coronary artery disease and impaired renal function.

The aim of this study was to assess the effects of angiotensin receptor blocker (ARB)-based therapy on cardiovascular events in high-risk hypertensive patients with coronary artery disease (CAD) and impaired renal function in post hoc analysis of HIJ-CREATE (Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease). Patients (n=2049) were randomly assigned to candesartan-based or non-ARB treatment arms; 1022 patients (age 70 ± 6 years, 28% female) with impaired renal function, defined as creatinine clearance <60 ml/min at baseline. There was no difference in major adverse cardiac event (MACE), a composite of cardiovascular death, non-fatal myocardial infarction, unstable angina, heart failure, stroke and other cardiovascular events requiring hospitalization between the two arms in patients without impaired renal function. However, there was a lower incidence of MACE in the candesartan-based treatment arm than in the non-ARB treatment arm (HR=0.79, 95% CI 0.63-0.99, p=0.039) in patients with impaired renal function. Among the MACE, candesartan-based treatment reduced hospitalization for unstable angina (HR=0.71, 95% CI 0.52-0.96, p=0.028). Although candesartan-based treatment was not superior to non-ARB treatment in prevention of cardiac mortality, ARB-based therapy may be beneficial in reducing risk of coronary events in hypertensive patients with CAD and impaired renal function.

Interlead difference between T-peak to T-end intervals in resynchronization patients with an implantable cardioverter-defibrillator.

BACKGROUND: The effectiveness of cardiac resynchronization therapy (CRT) in preventing sudden cardiac death is controversial. Epicardial left ventricular pacing reverses the direction of activation of the left ventricular wall from the epicardium to the endocardium. We evaluated whether the interlead difference between T-peak to T-end (Tp-e) intervals determined by a 187-channel repolarization interval-difference mapping electrocardiograph (187-ch RIDM-ECG) is related to the occurrence of ventricular tachyarrhythmia requiring implantable cardioverter-defibrillator (ICD) therapy in heart failure patients receiving CRT with a defibrillator (CRT-D). METHODS AND RESULTS: Repolarization interval-difference mapping electrocardiograph (187-channel) was performed on 61 patients who received CRT-D. Twenty-one patients experienced appropriate ICD therapy. The interlead difference between corrected recovery time intervals was not significantly different between patients with and without appropriate ICD therapy (98 ± 24 milliseconds versus 88 ± 24 milliseconds). The interlead difference between corrected Tp-e intervals was significantly higher in patients with appropriate ICD therapy than in those without (88 ± 22 milliseconds versus 59 ± 23 milliseconds, P < .001). CONCLUSION: The interlead difference between corrected Tp-e intervals determined by 187-ch RIDM-ECG may be related to appropriate ICD therapy in heart failure patients receiving CRT-D.

Angiotensin II receptor blocker-based vs. non-angiotensin II receptor blocker-based therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE).

AIMS: To test whether angiotensin II receptor blockers (ARBs) therapy can reduce the incidence of cardiovascular events compared with non-ARB-based standard pharmacotherapy in coronary artery disease (CAD) patients with hypertension. METHODS AND RESULTS: Angiographically documented CAD patients with hypertension were randomly assigned to receive either candesartan-based (n= 1024) or non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors (n = 1025). The primary endpoint was the occurrence of a first major adverse cardiovascular event (MACE). There were 552 primary events during a median follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (hazard ratio, 0.89; 95% confidence interval, 0.76-1.06). No significant differences existed between groups in terms of cardiovascular death (2.7 vs. 2.4%, 1.14; 0.66-1.95), non-fatal myocardial infarction (2.8 vs. 2.5%, 1.12; 0.66-1.88), or heart failure (3.9 vs. 4.3%, 0.91; 0.59-1.40). New-onset diabetes was diagnosed significantly less frequently with candesartan than with non-ARBs (0.37; 0.16-0.89). Incidence of study drug discontinuation due to adverse events was lower with candesartan than with non-ARBs (5.7 vs. 12.2%, P < 0.001). CONCLUSION: Although candesartan showed no significant differences in MACE compared with the non-ARB treatment group, the drug significantly reduced the incidence of new-onset diabetes and was better tolerated. This study is registered as International Standard Randomised Controlled Trial No. UMIN000000790.

Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle.

The concept of the plasticity or transdifferentiation of adult stem cells has been challenged by the phenomenon of cell fusion. In this work, we examined whether neonatal cardiomyocytes fuse with various somatic cells including endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial cells or skeletal muscle-derived cells fused with adult cardiomyocytes in vivo. In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins. These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes.

Systolic blood pressure at admission as a predictor of the response to initial carperitide therapy in patients hospitalized for acute decompensated heart failure with left ventricular systolic dysfunction.

PURPOSE: In patients with acute decompensated heart failure (ADHF) and left ventricular systolic dysfunction (LVSD), the role of initial vasodilator therapy remains uncertain. The present study aimed to evaluate the acute efficacy of initial carperitide therapy and to predict its response in ADHF patients with LVSD. METHODS: Twenty-four consecutive patients with ADHF and LVSD were enrolled. Inclusion criteria were a left ventricular ejection fraction < 40%, systolic blood pressure (BP) > 90 mm Hg, and pulmonary capillary wedge pressure >or=18 mm Hg at baseline. Hemodynamic parameters were evaluated by right heart catheterization before and after carperitide infusion. Responders were defined as a >or=30% reduction of pulmonary capillary wedge pressure (PCWP) or a decrease to < 16 mm Hg within 6 h after carperitide infusion. RESULTS: Seventeen (71%) of the 24 patients were responders for initial carperitide therapy. The responders had significantly higher systolic BP and cardiac index at baseline compared with nonresponders. The area under the curve (AUC) for systolic BP was 0.93 and a cut-off value of 120 mm Hg had a sensitivity of 94% and specificity of 86% for predicting the efficacy of carperitide. The AUC for the cardiac index was 0.88 and a cut-off value of 2.30 L/min/m(2) had a sensitivity of 65% and a specificity of 100% for predicting the response to carperitide. CONCLUSIONS: The initial use of carperitide therapy safely reduces PCWP in ADHF patients with LVSD and baseline systolic BP may be useful for predicting the response to initial carperitide therapy for ADHF with LVSD.

Transverse shifting of the esophagus according to the patient's position helped achieve a safe and successful pulmonary vein isolation procedure.

Although the incidence of causing an atrioesophageal fistula during pulmonary vein isolation is very low, this type of injury results in a very high mortality rate. To prevent this complication, keeping a safe distance from the esophagus to the ablation lesion is a simple but safe method. We report a case in which we were able to shift the position of the esophagus by positioning the patient in a lateral posture in order to keep the esophagus at a safe distance from the pulmonary vein antrum, resulting in performance of a safe and successful pulmonary vein antrum isolation.