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Background Leakage of Ca2+ from the sarcoplasmic reticulum (SR) is a critical contributing factor to heart failure pathophysiology. Therefore, reducing SR Ca2+ leaks may provide significant additive benefits when used in combination with conventional therapies. Dantrolene, a drug routinely used to treat malignant hyperthermia, also stabilizes the cardiac isoform of the release channel (RyR2), thus decreasing SR Ca2+ leaks. The purpose of this study is to evaluate the effect of chronic administration of dantrolene on heart failure and lethal arrhythmia in patients with chronic heart failure and reduced ejection fraction in a multicenter, randomized, double-blind, controlled study. Methods Patients with chronic heart failure who had functional status of New York Heart Association class II and III and a left ventricular ejection fraction Results This paper presents the rationale and trial design of the study. Recruitment for the study started on 8 December 2017. Conclusions The results of this trial will clarify the efficacy and safety of dantrolene for ventricular arrhythmia, as well as mortality and morbidity in patients with chronic heart failure and reduced ejection fraction during guideline-directed medical treatment.

We herein report a rare autopsy case of tako-tsubo cardiomyopathy (TTC) presenting ventricular tachycardia after pacemaker implantation. A 69-year-old male received a dual-chamber pacemaker implantation for complete atrioventricular block. He had no chest symptoms after the operation. Three days later, he developed severe chest pain, followed by syncope. Electrocardiogram showed sustained monomorphic ventricular tachycardia. Despite the use of amiodarone and frequent electrical defibrillation, ventricular tachycardia and ventricular fibrillation were repeated incessantly. He died 24 h after the syncope. The autopsy revealed no hemopericardial effusion, or perforation of leads. There were also no obstructive lesions in the coronary arteries. Myocardial necrosis was observed in the entire circumference and the all layers of the left ventricle. Microscopically, myocardial necrosis was plurifocal and contraction band necrosis. We speculate that catecholamine cardiotoxicity caused ventricular tachycardia in this case. Further studies are needed to clarify the heterogeneity of this disease.

Iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy provides useful diagnostic information in differentiating Parkinson's disease (PD) from other neurological diseases. Moreover, a number of studies have reported that 123I-MIBG imaging provides powerful diagnostic and prognostic information in congestive heart failure (HF) patients. The aim of the present study was to investigate the cardiovascular predictive value of cardiac 123I-MIBG imaging in patients with PD.Seventy-eight patients with PD were retrospectively studied. All patients underwent 123I-MIBG imaging at 30 min (early) and 240 min (delayed) after the tracer injection, and clinical parameters were also investigated.During a mean follow-up of 27 ± 12 months, 5 patients required hospitalization for HF. There were no occurrences of myocardial infarction, fatal arrhythmia or sudden death. There was no significant coronary artery stenosis, significant valvular heart disease, or cardiomyopathy in the HF patients. The left ventricular ejection fraction (LVEF) was normal in the HF patients. (123)I-MIBG delayed heart to mediastinal ratio (delayed H/M) was lower and washout rate (WR) was higher in HF patients than non-HF patients (1.62 ± 0.21 vs. 1.34 ± 0.08, p = 0.019; 31.9 ± 5.5 vs. 38.2 ± 3.3, p = 0.005, respectively). Both WR and delayed H/M did not correlate with Hoehn and Yahr stage. The WR showed a weak negative correlation with delayed H/M (R = -0.357, p0.001) upon simple linear regression analysis. A multivariate Cox regression analysis revealed that WR and delayed H/M were independently associated with HF (p = 0.014, p = 0.029, respectively). Kaplan-Meier analysis revealed that patients with abnormal WR (37%) and delayed H/M (1.48) had a higher incidence of HF than those with normal WR and delayed H/M (p = 0.014, p = 0.04, respectively).WR showed stronger predictive power than delayed H/M in Kaplan-Meier analysis. WR has more useful cardiovascular predictive value than delayed H/M in Japanese patients with PD. Further studies are needed to clarify the significance of abnormal MIBG uptake in PD patients.

Contrast-induced nephropathy (CIN) is one of the important complications of coronary angiography (CAG) and percutaneous coronary intervention (PCI), especially in patients with chronic kidney disease (CKD). Prophylactic administration of N-acetylcysteine (NAC) and aminophylline has been reported to be effective in some trials, but the results still remain controversial. We investigated the efficacy of NAC or aminophylline in preventing CIN.Forty-five consecutive patients undergoing CAG and/or PCI were randomly assigned to receive hydration and NAC (704 mg orally twice daily; NAC group, n=15), hydration and aminophylline (250 mg intraveneously 30 min before CAG and/or PCI; aminophylline group, n=15), or hydration alone (control group, n=15). We compared serum creatinine (SCr), creatinine clearance (Ccr), blood beta-2 microglobulin, and urinary beta-2 microglobulin levels at baseline and 48h after CAG and/or PCI. In the NAC group, SCr decreased from 1.00 + or - 0.36 to 0.67 + or - 0.16 mg/dl (p0.01), and Ccr significantly increased from 62.4 + or - 15.6 to 80.4 + or - 8.39 ml/min (p0.01). In the aminophylline group, SCr and Ccr were unchanged. In the control group, SCr significantly increased from 0.94 + or - 0.21 to 1.28 + or - 0.21 mg/dl (p0.01), and Ccr significantly decreased from 63.7 + or - 16.1 to 46.1 + or - 10.6 ml/min (p0.01) after CAG and/or PCI. In the NAC group, mean blood beta-2 microglobulin significantly decreased from 2.38 + or - 0.58 to 1.71 + or - 0.38 mg/dl (p0.01), and in the aminophylline group, mean urinary beta-2 microglobulin concentration significantly decreased from 337 + or - 31.0 to 239 + or - 34 microg/ml (p0.01).These results suggest that both prophylactic NAC and aminophylline administration are effective in preventing CIN, but not with hydration alone. It appears that the two compounds work in different ways against CIN.

Contributions of rapid filling, slow filling and atrial systole to the left ventricular (LV) filling volume were analyzed with the use of radionuclide ventriculography at rest, both globally and regionally, in 34 patients with isolated disease of the left anterior descending coronary artery. The patients included 17 with a normal ejection fraction (EF greater than or equal to 50%; group 1) and 17 with a depressed EF (less than 50%; group 2), and the data were compared with those obtained from 13 normal subjects. A computer program subdivided the LV image into 4 regions, and time-activity curves were constructed globally and regionally by reverse-gating from the R wave. In both groups the contribution of rapid filling to the LV filling volume was decreased significantly in the affected septal and apical regions, and in the global left ventricle compared with that in normal subjects. In group 1, the contribution of atrial systole showed an increase in these affected regions and in the global left ventricle. In contrast, in group 2, the atrial contribution was not increased globally or regionally as much as was expected. However, the contribution of slow filling was either increased significantly or tended to increase in the affected regions and in the global left ventricle. There were negative correlations between the contribution of rapid filling and that of slow filling in the global left ventricle (r = -0.73, p less than 0.001) and in each of the septal, apical and lateral regions (r greater than or equal to -0.60, p less than 0.001), which suggested that the contribution of slow filling as well as of atrial systole undergoes an increase as rapid filling is impaired. Thus, in patients with coronary artery disease, the left ventricle relies on slow filling as well as atrial systole to affect diastolic LV filling in the affected regions and in the global left ventricle in the presence of LV systolic dysfunction.

The aim of the study was to assess the relationship between changes in heart rate variability (HRV) and parameters of neuroendocrine activation in patients with various levels of left ventricular dysfunction. Measurements of HRV, plasma norepinephrine (PNE), and plasma atrial natriuretic peptide (ANP) were performed in 17 age- and gender-matched control subjects (group C) and in 39 patients with ischemic heart disease or cardiomyopathy who were subdivided into 3 equal groups according to their left ventricular ejection fraction: group N (normal); group M (mildly impaired); and group S (severely impaired). Spectral analysis of HRV (from 10-min electrocardiograms) was analyzed by the method of coarse-graining spectral analysis. PNE and ANP were significantly elevated in group S only (p

Many invasive and noninvasive methods have been used to study the cardiac atria; however, few allow quantitative measurement of atrial function. To determine the interaction between left ventricular (LV) contraction and left atrial (LA) filling, gated radionuclide angiography was conducted in 30 normal subjects (24 men and 6 women, mean age 58 +/- 10 years, range 26-68). LV and LA time-activity curves and their first-derivative curves were obtained simultaneously by using the method of Bough et al. The LV ejection fraction (64 +/- 18%) and LV peak ejection rate (LVPER; 3.42 +/- 0.27 EDV/s) were computed from these curves. As indices of LA filling, LA fractional emptying (38 +/- 12%) and LA peak filling rate (LAPFR; 2.86 +/- 0.17 LAVmax/s)--the latter being defined as the peak rate of LA filling during the LA filling phase--were also computed from these curves. In all subjects, the timing of the LVPER coincided with the occurrence of LAPFR, and there was a significant positive correlation between the LVPER and LAPFR (r = 0.81, p < 0.001), indicating that the LAPFR was strongly affected by the degree of LVPER. Thus, these results indicate that LV contractile performance plays an important role in determining LA passive filling during ventricular systole.

Left ventricular diastolic filling has been reported to be impaired with advancing age in normal subjects. To investigate the influence of regional ventricular diastolic asynchrony on global ventricular filling as a function of age and to assess the location of asynchronous regions within the left ventricle, radionuclide ventriculography was conducted in 48 normal subjects aged 15 to 73 years. Left ventricular regional filling was assessed by dividing the left ventricular region of interest into 4 quadrants, from which global, septal, apical and lateral time-activity curves and first-derivative curves were derived. Indexes of global left ventricular systolic function at rest did not correlate with age. However, indexes of global early diastolic filling declined significantly with age; peak filling rate normalized to end-diastolic volume (r = -0.42; p < 0.01), to stroke volume (r = -0.48; p < 0.001) and to peak ejection rate (r = -0.47; p < 0.001) decreased with advancing age. Global time to peak filling rate also increased with aging (r = 0.41; p < 0.01). Early diastolic asynchrony was measured as the sum of the absolute values of the time differences from global peak filling rate to that in each of three quadrants (delta TPFR). delta TPFR increased with age (r = 0.37; p < 0.01). Global peak filling rate normalized to end-diastolic volume (r = -0.40; p < 0.01), to stroke volume (r = -0.45; p < 0.01) and to peak ejection rate (r = -0.51; p < 0.001) decreased significantly with increasing delta TPFR. Time to peak filling rate of the lateral region occurred first (163 +/- 33 ms), followed by the apical (184 +/- 38 ms) and finally the septal region (195 +/- 35 ms). With regard to the sequence of regional filling, this suggests that a physiologic asynchrony exists in resting condition in normal subjects. Times to peak filling rate in the septal and apical regions were modestly correlated with age (r = 0.29; p < 0.05, r = 0.30; p < 0.05 respectively), but that in the lateral region did not show significant correlation with age. This may indicated that the effects of advancing age on the regional filling differ in regions within the left ventricle. These results suggest that aging alters left ventricular early diastolic filling in association with the increase in physiologic asynchrony.

To assess the degree of collateral vessels after myocardial infarction, coronary angiograms, left ventriculograms, and exercise thallium-201 myocardial scintigrams of 36 patients with previous myocardial infarction were reviewed. All 36 patients had total occlusion of infarct-related coronary artery and no more than 70% stenosis in other coronary arteries. In 19 of 36 patients with transient reduction of thallium-201 uptake in the infarcted area during exercise (Group A), good collaterals were observed in 10 patients, intermediate collaterals in 7 patients, and poor collaterals in 2 patients. In 17 of 36 patients without transient reduction of thallium-201 uptake in the infarcted area during exercise (Group B), good collaterals were seen in 2 patients, intermediate collaterals in 7 patients, and poor collaterals in 8 patients (p less than 0.025). Left ventricular contractions in the infarcted area were normal or hypokinetic in 10 patients and akinetic or dyskinetic in 9 patients in Group A. In Group B, 1 patient had hypokinetic contraction and 16 patients had akinetic or dyskinetic contraction (p less than 0.005). Thus, patients with transient reduction of thallium-201 uptake in the infarcted area during exercise had well developed collaterals and preserved left ventricular contraction, compared to those in patients without transient reduction of thallium-201 uptake in the infarcted area during exercise. These results suggest that the presence of viable myocardium in the infarcted area might be related to the degree of collateral vessels.

Contributions of late diastolic filling (slow filling and atrial systolic phases) to total filling volume in both global and regional left ventricle were analyzed using radionuclide techniques in 21 patients with isolated left anterior descending coronary artery disease without previous myocardial infarction. A computer program subdivided the image of the left ventricle into four regions at a geometric center of the area. The time-activity and its first-derivative curves of the global and regional left ventricles were computed. In the global left ventricle, the percent contributions of late diastolic filling to total filling volume were significantly increased in patients with one-vessel disease than in control subjects (20 +/- 5%, 28 +/- 4%; p less than 0.001). In the regional left ventricle, in patients with one-vessel disease, the percent contributions of late diastolic filling to total filling volume were significantly increased in the septal (25 +/- 5%, 34 +/- 8%; p less than 0.001) and in the apical regions (21 +/- 4%, 28 +/- 4%; p less than 0.001) which were perfused by stenosed vessel. In contrast, there were no significant differences in this value between the two groups in the normally perfused lateral region (22 +/- 6%, 25 +/- 5%; p = NS). These results indicate that the late diastolic filing makes a larger contribution to the left ventricular filling in the affected regions than in the normally perfused regions, and that the increased late diastolic filling in the affected regions are the cause for the increased late diastolic filling in the global left ventricle in patients with one-vessel disease.

To assess left ventricular (LV) systolic and diastolic function globally and regionally and to study the relationship between regional asynchrony and global LV function in patients with stable effort angina pectoris (AP) without previous myocardial infarction, we conducted a resting gated radionuclide ventriculographic study in 15 control subjects (N group) and 22 AP patients with isolated disease of the left anterior descending coronary artery (LAD). In nine of these 22 AP patients, LV systolic and diastolic function before surgical revascularization (Aorto-Coronary Bypass) were compared with those after surgical revascularization. A computer program subdivided the image of the LV into four regions (septal, basal, lateral and apical) by our previously reported method.1, 2 The time-activity and first-derivative curves of the global LV and three regions (septal, lateral, apical; the basal region was not computed) LV were computed. In the global LV, the peak filling rate (PFR) normalized to LV end-diastolic volume (EDV) and the ratio of increment of filling volume at 100 msec from global end-systole (ES) to the EDV (%EFV), which was correlated with the time constant of LV pressure decay during isovolumic relaxation, 3 decreased (p

To study the relationship between global and regional filling of the left ventricle, we conducted resting gated radionuclide ventriculographic studies in 15 control subjects (group 1) and 22 patients with isolated disease of the left anterior descending coronary artery (group 2). None had had a previous myocardial infarction. A computer program subdivided the image of the left ventricle into four regions. The time-activity and first-derivative curves of the global and regional left ventricles were computed. In the global left ventricle, the normalized peak filling rate (PFR) was decreased (p less than .01) and the ratio of the time to PFR (time interval from global end-systole to PFR) to the diastolic time, TPFR/DT, was greater (p less than .02) in group 2 than in group 1. In the regional left ventricle, in the side perfused by the stenosed vessel (septal and apical), PFR was slightly decreased in the apical (p less than .05), but not the septal region (p = NS); TPFR/DT was greater in the apical (p less than .02) and in the septal region (p less than .01) in group 2. In the normally perfused lateral side, there were no significant differences in PFR or in TPFR/DT between group 1 and group 2. Total delta t/DT, which was defined as the ratio of the sum of the absolute values of the time differences from global PFR to regional PFR (septal, apical, and lateral) to the diastolic time, was significantly greater in group 2 (0.09 +/- 0.05 vs 0.16 +/- 0.05; p less than .001). This indicates the existence of asynchronous diastolic filling in the different regions of the left ventricle in group 2. A negative correlation existed between total delta t/DT and global PFR (r = -.64, p less than .001). Thus, in patients with one-vessel disease, asynchronous diastolic filling occurs due to the filling disturbance in the affected regions, which may cause impairment of the filling of the global left ventricle.

To determine the presence and prevalence of regional contraction abnormalities in patients with angina pectoris, radionuclide ventriculography gated to an electrocardiogram was carried out in 22 control subjects (group 1) and in 22 patients with angina pectoris (group 2) with isolated stenosis of the left anterior descending coronary artery. No patients had had previous myocardial infarctions. A computer program subdivided the left ventricle into four regions at a geometric centre, and time-activity curves (30-40 ms/frame) of the global, septal, apical, and lateral regions were computed. There was no significant difference in the ejection fraction in the global or in any of the regions between the two groups. End systole in each region occurred close to global end systole in both groups. In the global region the percentage stroke volume ejected during the first third of systole was not significantly less in group 2 than in group 1. Regional analysis of the segments perfused by the stenosed vessel showed that the percentage stroke volume ejected during the first third of systole in group 2 was significantly less in the septal region and in the apical region compared with that in group 1. In contrast, in the normally perfused lateral region, there was no significant difference in the percentage stroke volume at the first third of systole between the two groups. This indicates that early contraction abnormalities are present in the region perfused by the stenosed vessel in patients with angina pectoris without previous myocardial infarction. Thus analysing the regional change in left ventricular volume during ejection in patients with coronary artery disease can show localised areas of contraction abnormalities during early systole that are not apparent when ventricular contraction is assessed as a whole.