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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

A 69-year-old man underwent repeat percutaneous coronary intervention for in-stent restenosis in the obtuse marginal artery 8 months after biolimus-eluting stent (2.5×28mm Nobori stent, Terumo, Tokyo, Japan) implantation. Coronary angiography showed focal stenosis in the distal part of the stent. Intravascular ultrasound revealed low echoic heterogeneous intimal tissue. Optical coherence tomography also revealed a heterogeneous finding classified as a layered pattern. Coronary angioscopy detected a white mass with a paste-like appearance at the stenosis extending around the in-stent restenosis as a thin membrane where stent strut could be seen transparently. A small part of the mass was swinging in the blood stream. Coronary angioscopic imaging was beneficial for the understanding of the suspected mechanism and feature of the in-stent restenosis after second-generation stent implantation, which was apparently different from neointimal hyperplasia after bare-metal stent implantation.

To investigate whether HDL(2) can inhibit further oxidative modification of partially oxidized LDL (ox-LDL) by interrupting the chain oxidation reaction after lipid hydroperoxides (LOOH) formation.Following incubation of LDL 400 microg protein/mL phosphate-buffered saline with Cu(2+) for 1.75 h (defined as 0 min), incubation was continued after adding HDL(2) 200 microg protein/mL or HDL(2) 800 microg protein/mL to give both ox-LDL+HDL(2) 200 microg protein/mL or ox-LDL+HDL(2) 800 microg protein/mL. As a control, ox-LDL 200 microg protein/mL and native LDL were prepared. Each sample was subjected to agarose gel electrophoresis and the LOOH in each sample was measured.When the electrophoretic mobility of native LDL was designated 1, the relative electrophoretic mobility (REM) of ox-LDL increased significantly over time. The REMs of ox-LDL+HDL(2) 800 microg protein/mL from 10 min to 9 h were significantly lower than the REM of ox-LDL at the respective times (p0.01). LOOH of ox-LDL+HDL(2) 800 microg protein/mL at 1, 3, 6 and 9 h was significantly higher than LOOH in ox-LDL at the respective times (p0.01). The results of ox-LDL+HDL(2) 200 microg protein/mL were almost the same but to a lesser extent than the results of ox-LDL+HDL(2) 800 microg protein/mL.The present findings suggest that HDL(2) can inhibit further oxidative modification of partially oxidized LDL by interrupting the chain oxidation reaction after LOOH formation in a concentration-dependent manner.

Although higher red cell distribution width (RDW) has recently been reported to be associated with increased mortality independent of anemia in patients with heart failure and those with coronary artery disease (CAD), the mechanism underlying this association is unknown. We hypothesized that higher RDW may reflect neurohumoral activation and a chronic inflammatory state that each contribute to adverse clinical outcomes in these populations. We measured RDW and plasma levels of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hs-CRP) in 226 consecutive patients undergoing cardiac catheterization for CAD (age, 67 +/- 8 years; males, 77%; RDW, 45.8 +/- 3.3 fL; hemoglobin, 13.2 +/- 1.4 g/dL; BNP, median [interquartile range], 26.0 [9.0-58.4] pg/mL; hs-CRP, 679 [345-1920] ng/mL). Plasma BNP (r = 0.21, P0.01) but not hs-CRP (r = 0.04, P0.1) levels correlated with RDW. After adjustment for potential confounders including age, gender, body mass index, glomerular filtration rate, hemoglobin, and known hemodynamic determinants of BNP, including elevated left ventricular end-diastolic pressure and volume and slow left ventricular relaxation, RDW was independently predicted by BNP (r(2) = 0.058, P0.001). In conclusion, elevated BNP levels are independently associated with higher RDW in patients with CAD. Neurohumoral activation may be a mechanistic link between increased RDW and adverse clinical outcomes in this population.

ObjectivesWe investigated whether a lack of inertia force of late systolic aortic flow and/or apical asynergy provoke early diastolic dysfunction in patients with coronary artery disease (CAD).BackgroundLeft ventricular (LV) isolated diastolic dysfunction is a well-recognized cause of heart failure.MethodsWe evaluated LV apical wall motion and obtained left ventricular ejection fraction (LVEF) by left ventriculography in 101 patients who underwent cardiac catheterization to assess CAD. We also computed the LV relaxation time constant (Tp) and the inertia force of late systolic aortic flow from the LV pressure (P)–first derivative of left ventricular pressure (dP/dt) relation. Using color Doppler echocardiography, we measured the propagation velocity of LV early diastolic filling flow (Vp). Patients with LVEF ≥50% (preserved systolic function [PSF], n = 83) were divided into 2 subgroups: patients with inertia force (n = 53) and without inertia force (n = 30). No patient with systolic dysfunction (SDF) (LVEF

Aim: A patient with severe type III hyperlipoproteinemia and familial hypercholesterolemia (FH) was previously reported (Metabolism, 44,1995:460-465). In the current study, the patient’s apolipoprotein (apo) E gene was analyzed. Methods: An apo E isoform analysis was performed using isoelectric focusing and immunoblotting. In addition, after DNA preparation, a restriction fragment length polymorphism analysis and DNA sequence analysis were performed. Results: The patient’s apo E phenotype was E2/E1, and the genotype was e2/e2. The sequence analysis of the patient’s DNA revealed a new variant of apo E, which involves a single substitution of one serine (AGC) for one arginine (CGC) at position 142, thereby adding one negatively charged unit to apo E2. Therefore, the patient was compound heterozygous for apo E1 (Arg142Ser) and apo E2 (Arg158Cys). Conclusions: A novel mutation, apo E1 Nagoya (Arg142Ser) in a patient with severe type III hyperlipoproteinemia with heterozygous FH was characterized. Since the presence of arginine at the amino acid residue 142 of apo E is considered to play an important role in binding to LDL receptors, the mutation apo E1 Nagoya (Arg142Ser) likely contributed to the expression of severe type III hyperlipoproteinemia in this patient.

To investigate the presence of opioid receptors and their physiological role in cardiac pacemaker cells, we studied electrophysiological effects of fentanyl citrate, an activator of the mu-opioid receptors, on the spontaneous action potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1 mm) of rabbit sinoatrial (SA) node (SAN). Fentanyl (0.1-3 microM) progressively decreased the AP amplitude (APA), maximal rate of depolarization (MRD), and spontaneous firing frequency (SFF) and prolonged the AP duration (APD) and diastolic interval in a concentration-dependent manner. At 1 microM, the spontaneous activity ceased in two of the eight preparations. These actions were blocked by a mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), but were not modified by either kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI), or delta-opioid receptor antagonist ICI-174864. In voltage-clamp experiments using double microelectrode techniques, 1 microM fentanyl reduced the Ca2+ current (ICa) obtained on step depolarization from -40 to 0 mV by 19.9 +/- 9.3% (p < 0.05, n = 5), the fast and slow components of the delayed rectifying K+ current (IKfast, IKslow) tail obtained on repolarization from 10 to -60 mV by 54.7 +/- 4.7 and 41.4 +/- 2.4% (p < 0.05, n = 4), and the hyperpolarization-activated inward current at -90 mV by 12.6 +/- 0.5% (p < 0.05, n = 7), respectively. The gating kinetics of ICa and IKslow were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Even in the era of thrombus aspiration and distal protection for ST-segment elevation acute myocardial infarction (STEMI), microvascular dysfunction does exist and improvement of microvascular dysfunction can improve the prognosis and/or left ventricular dysfunction. We evaluated the acute effects of nitroprusside (NTP) on coronary microvascular injury that occurred after primary percutaneous coronary intervention (PCI) for STEMI in 18 patients. The final Thrombolysis in Myocardial Infarction trial (TIMI) flow grade after PCI was 3 in 17 patients and 2 in 1 patient. The index of microcirculatory resistance (IMR) was improved significantly from 76 ± 42 to 45 ± 37 (P = 0.0006) by intracoronary NTP administration. IMR improved to the normal range (IMR < 30) in 9 patients (50%). Higher TIMI flow grade and lower IMR at baseline were observed more frequently in patients whose IMR recovered to normal range after NTP administration. NTP improved the microcirculatory dysfunction at the acute phase in patients who underwent PCI for STEMI and had final TIMI 3 flow in almost all cases.

Electrophysiological actions of MS-551, a novel class III antiarrhythmic agent, were studied using small preparations (0.2 × 0.2 × 0.1mm) of the rabbit sinoatrial (SA) node. MS-551 (0.1–3 µM) exerted a negative chronotropic action by prolonging the action potential duration and diastolic interval. Automaticity was completely suppressed in 5 of 6 preparations at 1–3 µM. Voltage clamp experiments using double microelectrode techniques revealed that MS-551 (0.1–10µM) blocked the delayed rectifying K+ current (IK) in a concentration-dependent manner, and the block was almost saturated at >1 µM, attaining 60% ± 10% at 10 µM (n = 5). The MS-551-sensitive IK tail (Kd = 0.4µM, Hill r = 1.4,n = 5) had fast and slow components of deactivation. MS-551 (1 µM) reduced the amplitudes of control IK fast and IK slow from 20 ± 4 and 11 ± 4 nA to 8 ± 3 and 5 ± 3 nA, respectively (P < 0.01,n = 4). Although the fast deactivation time constant at −60mV remained unaltered (127 ± 12 vs 113 ± 13ms), the slow deactivation time constant was prolonged from 1,117 ± 130 to 1,555 ± 407ms by 1µM MS-551 (P < 0.05). This agent shifted the steady-state activation curve for IK from −21 ± 2 to −26 ± 4mV and increased the slope factor from 8 ± 1 to 9 ± 1mV (P < 0.05,n = 4). The fully-activated IK exhibited prominent inward rectification and was reduced by MS-551. These results suggest that (1) MS-551 prolongs the action potential duration and diastolic interval, and exerts a negative chronotropic action by blocking IK, (2) MS-551 has a higher affinity for the activated than the resting state K+ channel, and (3) this agent may either preferentially block one type of IK, or stabilize a single population of IK in a subconductance state in the rabbit SA node.

AIM The effect of statins in preventing cardiac events in Japanese coronary artery disease (CAD) patients was studied in a retrospective investigation of 148 patients diagnosed with CAD by coronary angiography (CAG). METHODS Sixty-five patients received statins within 2 weeks after CAG, and 83 patients did not receive statins after CAG. RESULTS In the statin group, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced significantly with statin administration (p

It is unknown whether the association of anemia with elevated plasma levels of B-type and atrial natriuretic peptides (BNP and ANP) is mediated by the hemodynamic effects of anemia.The study group comprised 237 consecutive patients (BNP, median [interquartile range], 28.3 [9.5-77.1] pg/ml; ANP, 17.8 [8.5-39.0] pg/ml) undergoing determination of hemoglobin (Hb) and natriuretic peptide levels and cardiac catheterization for evaluation of coronary artery disease (CAD). Hb correlated with BNP (r=-0.36, p0.001) and ANP (r=-0.35, p0.001). Patients with anemia (Hb12 g/dl for females;13 g/dl for males, n=63) were more likely to be older with reduced body mass index and renal function, greater severity of CAD and to have higher heart rate, mean pulmonary capillary wedge pressure, and cardiac output. Anemia was a significant predictor for elevated (third quartile value) natriuretic peptide levels and the predictive value remained significant after adjustment for other predictors, including increased left ventricular end-diastolic pressure and differences in clinical and hemodynamic variables between patients with and without anemia (adjusted odds ratio [95% confidence interval] for elevated BNP and ANP levels, 7.39 [2.76-19.8] and 2.56 [1.08-6.07], respectively).Anemia is an independent predictor for elevated natriuretic peptide levels in patients with known or suspected CAD.

Recently, the importance of central blood pressure for cardiovascular risk stratification has been emphasized. Accordingly, the differences in peak systolic and bottom diastolic pressures between the ascending aorta and the brachial artery should be clarified. Study subjects consisted of 82 consecutive patients with suspected coronary artery disease who underwent cardiac catheterization, and in whom ascending aortic pressure waveform was obtained using a catheter-tipped micromanometer, and at the same time systolic and diastolic pressures were measured (single measurement) from the right upper arm with a cuff-type sphygmomanometer based on the oscillometric technique. No significant systematic difference (bias) was found between the peak pressure obtained in the ascending aorta and the systolic pressure from the right upper arm (133.6 +/- 25.1 vs 131.8 +/- 21.5 mmHg, not significant). Bland-Altman analysis showed only a small bias of +1.8 mmHg, and the limits of agreement were 25.4 mmHg and -21.8 mmHg. In contrast, the bottom pressure in the ascending aorta was significantly lower compared with the diastolic pressure from the upper arm (68.5 +/- 10.7 vs 73.0 +/- 12.4 mmHg, P0.0001). Bland-Altman analysis showed a small but significant bias of -4.5 mmHg, and the limits of agreement were 14.1 mmHg and -23.1 mmHg. The observed biases seemed to remain within practical range. However, random variation in the two measurements was rather large. This is considered to be caused by the random error in the single measurement with the cuff-type sphygmomanometer.

Objective: We studied the effects of intracellularly applied inositol-1,4,5-trisphosphate (InsP3) to test the hypothesis that InsP3 is a messenger for stimulation of L-type calcium current ( I Ca(L)) and contractions by muscarinic agonists. Methods: Voltage clamp pulses elicited I Ca(L) that evoked contractions recorded with an edge detector in single guinea pig ventricular myocytes superfused with Tyrode’s solution (36°C). InsP3 or cyclic AMP (cAMP) was dialyzed into the cell at selected times via the patch electrode. Results: InsP3 (1–10 μM) transiently increased isotonic contractions when applied for 4–5 min; higher concentrations (50–300 μM) caused a sustained decrease in contractions. InsP3 had no effect on I Ca(L) at any concentration tested. Caffeine (10 mM)-induced contractures were increased and decreased, respectively, at 3 and 100 μM InsP3. Pentosan polysulfate (50 μg/ml), an InsP3 receptor antagonist, opposed the increased contractions by InsP3. Intrapipette cyclic AMP (10–300 μM) caused sustained increases of I Ca(L) and contractions. Cyclic AMP, but not InsP3, also increased I Ca(L) when intrapipette Cs+ suppressed K+ currents. Conclusions: Increased myocyte shortening at low InsP3 concentrations accords with receptor-initiated sarcoplasmic reticulum Ca2+ release. The transient stimulation of contractions at low concentrations and the sustained reduction of contractions at high concentrations are not consistent with a role for InsP3 in the persistent increase of contractions by muscarinic agonist in ventricular muscle and myocytes. The failure of InsP3 to change I Ca(L) when contractions were increased or decreased militates against the L-type calcium channel being an effector of InsP3.

The effect of carbachol (CCh) on the Na/Ca exchange current ( I Na/Ca) was studied in voltage-clamped ventricular myocytes isolated from guinea pig hearts and superfused with Tyrode solution at 35°C. CCh (100 μM) increased outward current during depolarizations (10–200 ms) from −45 mV and tail current amplitude on repolarization; CCh had no effect on the L-type Ca2+current. Amplitudes of the outward and tail currents declined with increasing duration of the depolarizing clamp pulse. Ouabain produced similar current changes that are suppressed by intrapipette ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid and are characteristic of I Na/Ca. Depolarization from −80 to −30 mV elicited the rapid Na+ current followed by a slowly decaying inward I Na/Ca (J. C. Gilbert, T. Shirayama, and A. J. Pappano. Circ. Res. 69: 1632–1639, 1991.) that was reversibly increased by CCh. Atropine (1–3 μM) prevented the CCh effect. All procedures that suppressed I Na/Caalso suppressed the CCh effect. Sarcoplasmic reticulum (SR) Ca2+ release participated in generating I Na/Cabecause 10 mM caffeine or 1 μM ryanodine blocked I Na/Ca and the effect of CCh. Rapid superfusion of 10 mM caffeine induced inward I Na/Ca at −75 mV; a caffeine-induced charge transfer gives an SR Ca2+ content of 67 μM. CCh increased caffeine-induced current; SR Ca2+ content rose to 98 μM. CCh also augmented the amplitude of steady-state intracellular Ca2+ transients and contractions during a train of voltage-clamp pulses (−75 to 30 mV for 200 ms) at 1 Hz. CCh elevated intracellular Na+ (M. Korth and V. Kühlkamp. Pflügers Arch.403: 266–272, 1985) by inducing a background Na+ current [K. Matsumoto and A. J. Pappano. J. Physiol. (Lond.)415: 487–502, 1989]. Together with these data, the present results are consistent with the hypothesis that CCh, via muscarinic receptors, eventually promotes I Na/Ca at the sarcolemma through a mechanism that requires the SR and that this action accounts for the increased contractions.