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We report a case of a 24-year-old previously healthy Japanese man who presented to the emergency department due to cardiopulmonary arrest lasting for 4 min. He had complained of chest pain and worsening dyspnea but was well until 3 days before admission. He had no history of alcohol consumption. Marked lactic acidosis, high-output heart failure, and hypotension with widened pulse pressure led to a diagnosis of shoshin beriberi. The patient recovered successfully without any residual symptoms after appropriate thiamine therapy. Because of the complexity of the clinical presentation and the lack of rapid diagnostic tests, thiamine deficiency remains difficult to diagnose. In this patient, we suspected that shoshin beriberi was caused by long-term poor nutritional status secondary to a severe gambling addiction to Japanese pinball games, known as 'pachinko'. Alcoholism, long-term intravenous alimentation, and diuretic use are well-known causes. We should not miss the opportunity for early intervention, even in young non-alcoholic patients such as this case. If left untreated, patients may die from cardiopulmonary collapse within hours of symptom onset. Thiamine should be administered as soon as suspicion for thiamine deficiency arises, such as in conditions of widened pulse pressure in a young patient. Alcoholism, long-term intravenous alimentation, and diuretic use are well-known causes of thiamine deficiency. However the complexity of the clinical presentation and the lack of rapid diagnostic tests make its diagnosis difficult. Shoshin beriberi is a fulminant form of this disease. We should not miss opportunities for early intervention. Thiamine should be administered as soon as its deficiency is suspected, such as in conditions of widened pulse pressure especially in a young patient. [ABSTRACT FROM AUTHOR]

Summary: Background and purpose: The majority of heart transplant (HTx) candidates require left ventricular assist device (LVAD) support for more than 2 years before transplantation in Japan. However, the only currently available device is the extracorporeal pulsatile LVAD. The long-term management of extracorporeal LVAD support has improved remarkably over the years. To determine which post-operative management factors are related to the long-term survival of patients on such LVAD, we retrospectively compared the incidence of complications and their management strategies between the initial and recent eras of LVAD use, classified by the year of LVAD surgery. Methods: Sixty-nine consecutive patients supported by extracorporeal pulsatile LVAD as a bridge to HTx between 1994 and 2007 were reviewed retrospectively. The patients were assigned according to the time of LVAD surgery to either group A (n =30; between 1994 and 2000) or group B (n =39; between 2001 and 2007). Results: Patients in group B survived significantly longer on LVAD support than those in group A (674.6 vs. 369.3 days; p <0.001). The 1- and 2-year survival rates were significantly higher in group B than that in group A (82% vs. 48%, p <0.0001; 68% vs. 23%, p <0.0001, respectively). The proportion of deaths due to cerebrovascular accidents was lower (17% vs. 50%, p <0.001) in group B compared with group A. The incidences of systemic infection were similar in both groups, but the proportions of patients alive and achieving transplant surgery after systemic infection were higher in group B than those in group A (55% vs. 14%, p <0.01; 14% vs. 36%, p <0.05, respectively). Conclusions: The long-term survival of patients even on “first-generation” extracorporeal LVAD has improved significantly in the recent era. Careful management of cerebrovascular accidents and systemic infection will play important roles in the long-term LVAD management. [Copyright &y& Elsevier]

Abstract: Thermal therapy for heart failure is recognized to improve clinical symptoms. We describe our experience with appendicular thermal therapy applied to a patient fitted with an extracorporeal left ventricular assist device (LVAD) who was wait-listed for a heart transplant. A 21-year-old male with end-stage heart failure due to dilated cardiomyopathy was fitted with a LVAD. His general condition stabilized after LVAD placement and the status of his heart failure has remained at NYHA class II for the past 13 months. However, his cardiac function did not sufficiently recover to discontinue LVAD support. We conducted appendicular thermal therapy using a steam foot bath and heated gloves for 2 weeks. Immediately after thermal therapy, his average sublingual temperature increased from 36.3 to 37.0°C and the grade of mitral regurgitation, as well as LV ejection fraction and endothelial function improved. Furthermore, levels of oxidative and anti-oxidative stress markers decreased and increased, respectively, after 2 weeks of therapy. No complications developed. We conclude that appendicular thermal therapy was safe in this patient waiting for a heart transplant and who had an extracorporeal LVAD, and that the procedure might be beneficial for others with end-stage heart failure. [Copyright &y& Elsevier]

Abstract: Background: Because plasma levels of adenosine are increased in patients with chronic heart failure (CHF), we examined adenosine concentrations in the plasma and heart and assessed the activity of ecto-5′-nucleotidase in the plasma and ventricular myocardium in patients with CHF. Methods and Results: We studied 36 patients with CHF (New York Heart Association Class I/II/III/IV, 9/8/12/7). Twenty-five subjects without CHF were used as controls. Both plasma adenosine levels and ecto-5′-nucleotidase activity were significantly higher in patients with CHF (219 ± 28 nmol/L and 0.72 ± 0.03 nmoL/mg protein/min, respectively) than in control subjects (71 ± 8 nmol/L and 0.54 ± 0.02 nmoL/mg protein/min, respectively). Plasma adenosine levels sampled from the coronary sinus were significantly higher than from the aorta in patients with CHF, but these differences were not observed in control subjects. Ecto-5′-nucleotidase protein levels were markedly increased in the ventricular myocardium in patients with CHF. Conclusions: These increases in ecto-5′-nucleotidase in the plasma and myocardium may contribute to increased plasma and cardiac adenosine levels. The increased ecto-5′-nucleotidase activity and adenosine levels in blood may become an index of the presence or severity of CHF. [Copyright &y& Elsevier]

Objectives: Phosphodiesterase (PDE) III inhibitor therapy is effective for treatment of acute decompensated heart failure (ADHF). Nevertheless, this drug is expensive than conventional inotropic agent dobutamine. We compared total medication costs of the patients treated with PDE III inhibitor amrinone therapy to that of the patients treated with conventional dobutamine therapy during initial hospitalization. Methods: We analyzed 160 consecutive patients with ADHF admitted to our hospital. Shock, dehydration, severe infection, multiple organ failure, and mild heart failure (New York Heart Association class IIs) were not eligible for the study. Ninety-seven patients were divided into two groups: 1) DOB group treated with dobutamine therapy; and 2) AMR group treated with amrinone therapy. Total medication costs and cost for hospital room charge were calculated based on their usage during the initial hospitalization for each patient. Group comparison was done between the DOB and AMR groups. Results: Length of stay was longer in the DOB group than in the AMR group. Mean calculated cost of intravenous drugs was higher in the DOB group (173,186 ± 239,147 yen) than in the AMR group (63,145 ± 47,223 yen, P < 0.05). Total medication costs were higher in the DOB group than in the AMR group. Cost for hospital room charge was higher in the DOB group than in the AMR group. Conclusions: In the treatment of ADHF, appropriate therapy even with expensive drugs makes total medication costs less expensive comparing with conventional therapy with cheaper drugs during initial hospitalization. [ABSTRACT FROM AUTHOR]

Summary: We report a case of 45-year-old man, who was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) and presented with right ventricular (RV) enlargement with a global decrease in RV contractility accompanied by impairment of left ventricular function. He was placed on the heart transplant waiting list. Endomyocardial biopsy from RV septal wall did not show any evidence of sarcoidosis or inflammatory change. Four years after he was put on the heart transplant waiting list, a computed tomography chest scan for the purpose of anatomical evaluation for coronary sinus prior to biventricular pacing lead implantation incidentally showed bilateral hilar lymphadenopathy, which suggested the possibility of sarcoidosis. Biopsy of the inguinal lymph node pathologically was consistent with sarcoidosis. The 2[18F]fluoro-2-deoxy-d-glucose positron emission tomography scanning (FDG-PET) demonstrated intense uptake in the myocardium, and the patient was finally diagnosed as having cardiac sarcoidosis. After steroid treatment, the abnormal FDG-PET uptake disappeared. The patient therefore represented a case of cardiac sarcoidosis masquerading as ARVC. It should be recognized that RV involvement is one of the manifestations in cardiac sarcoidosis. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to investigate whether liposomal adenosine has stronger cardioprotective effects and fewer side effects than free adenosine. Background: Liposomes are nanoparticles that can deliver various agents to target tissues and delay degradation of these agents. Liposomes coated with polyethylene glycol (PEG) prolong the residence time of drugs in the blood. Although adenosine reduces the myocardial infarct (MI) size in clinical trials, it also causes hypotension and bradycardia. Methods: We prepared PEGylated liposomal adenosine (mean diameter 134 ± 21 nm) by the hydration method. In rats, we evaluated the myocardial accumulation of liposomes and MI size at 3 h after 30 min of ischemia followed by reperfusion. Results: The electron microscopy and ex vivo bioluminescence imaging showed the specific accumulation of liposomes in ischemic/reperfused myocardium. Investigation of radioisotope-labeled adenosine encapsulated in PEGylated liposomes revealed a prolonged blood residence time. An intravenous infusion of PEGylated liposomal adenosine (450 μg/kg/min) had a weaker effect on blood pressure and heart rate than the corresponding dose of free adenosine. An intravenous infusion of PEGylated liposomal adenosine (450 μg/kg/min) for 10 min from 5 min before the onset of reperfusion significantly reduced MI size (29.5 ± 6.5%) compared with an infusion of saline (53.2 ± 3.5%, p < 0.05). The antagonist of adenosine A1, A2a, A2b, or A3 subtype receptor blocked cardioprotection observed in the PEGylated liposomal adenosine-treated group. Conclusions: An infusion as PEGylated liposomes augmented the cardioprotective effects of adenosine against ischemia/reperfusion injury and reduced its unfavorable hemodynamic effects. Liposomes are promising for developing new treatments for acute MI. [Copyright &y& Elsevier]

Objectives: The goal of this work was to determine whether the blockade of histamine H2 receptors is beneficial for the pathophysiology of chronic heart failure (CHF). Background: Because CHF is one of the major life-threatening diseases, we need to find a novel effective therapy. Intriguingly, our previous study, which predicts the involvement of histamine in CHF, suggests that we should test this hypothesis in patients with CHF. Methods: We selected 159 patients who received famotidine among symptomatic CHF patients for the retrospective study. We blindly selected age- and gender-matched CHF patients receiving drugs for gastritis other than histamine H2 receptor blockers as a control group. For the prospective study, 50 symptomatic CHF patients were randomly divided into 2 groups. One group received famotidine of 30 mg/day for 6 months, and the other group received teprenone. Results: In the retrospective study, famotidine of 20 to 40 mg decreased both left ventricular end-diastolic and end-systolic lengths (LVDd and LVDs, respectively) and the plasma B-type natriuretic peptide (BNP) levels (182 ± 21 vs. 259 ± 25 pg/ml, p < 0.05) with unaltered fractional shortening (FS). In a randomized, open-label study, compared with teprenone, famotidine of 30 mg prospectively decreased both New York Heart Association functional class (p < 0.05) and plasma BNP levels (183 ± 26 pg/ml vs. 285 ± 41 pg/ml, p < 0.05); this corresponded to decreasing both LVDd (57 ± 2 mm vs. 64 ± 2 mm, p < 0.05) and LVDs (47 ± 2 mm vs. 55 ± 2 mm, p < 0.05) with unaltered FS (15 ± 1% vs. 17 ± 1%). The frequency of readmission because of worsening of CHF was lower in the famotidine group (4% and 24%, p < 0.05). On the other hand, teprenone had no effects on CHF. Conclusions: Famotidine improved both cardiac symptoms and ventricular remodeling associated with CHF. Histamine H2 receptor blockers may have therapeutic benefits for CHF. [Copyright &y& Elsevier]

Objectives: We investigated the effects of erythropoietin (EPO) on neovascularization and cardiac function after myocardial infarction (MI). Background: Erythropoietin exerts antiapoptotic effects and mobilizes endothelial progenitor cells (EPCs). Methods: We intravenously administered EPO (1,000 IU/kg) immediately [EPO(0) group], 6 h [EPO(6h) group], or 1 week [EPO(1wk) group] after the permanent ligation of the coronary artery in dogs. Control animals received saline immediately after the ligation. Results: The infarct size 6 h after MI was significantly smaller in the EPO(0) group than in the control group (61.5 ± 6.0% vs. 22.9 ± 2.2%). One week after MI, the circulating CD34-positive mononuclear cell numbers in both the EPO(0) and the EPO(6h) groups were significantly higher than in the control group. In the ischemic region, the capillary density and myocardial blood flow 4 weeks after MI was significantly higher in both the EPO(0) and the EPO(6h) groups than in the control group. Four weeks after MI, left ventricular (LV) ejection fraction in the EPO(6h) (48.6 ± 1.9%) group was significantly higher than that in either the control (41.9 ± 0.9%) or the EPO(1wk) (42.6 ± 1.2%) group but significantly lower than that in the EPO(0) group (56.1 ± 2.3%). The LV end-diastolic pressure 4 weeks after MI in both the EPO(0) and the EPO(6h) groups was significantly lower than either the control or the EPO(1wk) group. Hematologic parameters did not differ among the groups. Conclusions: In addition to its acute infarct size-limiting effect, EPO enhances neovascularization, likely via EPC mobilization, and improves cardiac dysfunction in the chronic phase, although it has time-window limitations. [Copyright &y& Elsevier]

This article reports changes in tacrolimus (FK506) blood levels connected with carbamazepine (CBZ). A drug interaction between FK506 and CBZ was investigated in a woman, who was in her 40s, who underwent heart transplantation. Pharmacokinetic parameters were measured, including dose and trough blood levels (C0), area under the serum concentration-time curve from 0 to 12 hours (AUC0–12h), and apparent clearance of oral FK506 (CL/F) for FK506 alone (about 3 months before starting CBZ) and combined with CBZ (11 days and about 3 months after starting CBZ). FK506 C0 levels were decreased within 7 days of CBZ treatment. FK506 dosing required a 1.3- to 1.4-fold increase to maintain adequate blood levels while taking 200 mg CBZ daily. The AUC0–12h/dose 11 days after CBZ treatment was about 50% of the value before CBZ, and was about 70% at 3 months after CBZ treatment. The CL/F at 11 days and about 3 months after starting CBZ treatment was about 2 times higher than before CBZ therapy. FK506 C0 levels are decreased by CBZ treatment, and blood levels should be closely monitored. [Copyright &y& Elsevier]