Development of Severe Heart Failure in a Patient with Squamous Non-small-cell Lung Cancer During Nivolumab Treatment.

Cardiac side effects associated with immune checkpoint inhibitors (ICIs) are an uncommon but serious complication with a relatively high mortality. We experienced a case of cardiomyopathy induced by nivolumab. Echocardiography showed diffuse hypo-kinesis of the left ventricular cardiac wall and a significant decrease in the ejection fraction, like dilated cardiomyopathy. The myocardial biopsy showed non-inflammatory change; cardiac function gradually improved after treatment of acute heart failure without a corticosteroid. Although non-inflammatory left ventricular dysfunction induced by ICIs is rare, it is a reported cardiovascular toxicity. Physicians should consider this complication when treating patients with ICIs for malignant diseases.

Administration of angiotensin-converting enzyme inhibitors is associated with slow progression of mild aortic stenosis in Japanese patients.

It is almost unknown which demographic factors or medications affect the progression of aortic stenosis (AS) in Japanese patients with mild AS. We identified a total of 194 patients with native tricuspid valvular AS, defined as a continuous-wave Doppler determined peak aortic valve jet velocity of ≥ 2.0 m/s, in whom echo Doppler studies were repeated at an interim of at least 6 months. Annualized change in peak jet velocity was calculated, and effects of age, sex, diabetes mellitus, blood pressure, serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels, and use of statins and antihypertensive agents on the progression of AS were retrospectively evaluated. Peak aortic valve jet velocity was 2.36 ± 0.79 m/s (mean ± SD) and annualized increase in peak aortic valve jet velocity was 0.17 ± 0.32 m/s/year for all the studied patients. The increase in peak aortic valve jet velocity was lower in patients taking angiotensin-converting enzyme inhibitors (ACE-Is) than in those not taking ACE-Is (0.04 ± 0.22 vs. 0.20 ± 0.32 m/s/year, P < 0.05). Such protective associations were not observed for other first-line antihypertensive agents and statins. Multiple linear regression analysis revealed that ACE-I treatment, decrease in left ventricular ejection fraction, and higher peak aortic valve jet velocity at the first echocardiogram were associated with slower progression of AS. Administration of ACE-Is was associated with the slow progression of mild AS in Japanese patients. Prospective study to assess this hypothesis is needed.

Decrease in serum adiponectin levels in response to treatment predicts good prognosis in acute decompensated heart failure.

Adiponectin is a cardioprotective adipocytokine. Serum adiponectin concentration decreases in patients who are obese but increases in patients with chronic heart failure (CHF). The aim of this study was to explore the temporal changes in serum adiponectin concentration following treatment for acute decompensated heart failure (ADHF). Serum adiponectin was measured on admission and at discharge in 95 patients who were admitted to our hospital with ADHF. Ten patients without heart failure (HF) served as controls. Serum adiponectin concentration was higher on admission in HF patients than in the controls (22.6±13.3 µg/mL vs 9.3±3.9 µg/mL, P<.01). Serum adiponectin concentration decreased after treatment in HF patients (18.0±11.7 µg/mL vs 22.6±13.3 µg/mL, P<.01). The larger temporal decrease in adiponectin level in ADHF was associated with the lower incidence of cardiac death or HF hospitalizations (log-rank, P<.05). Serum adiponectin concentration was elevated in ADHF and decreased following the treatment. How much serum adiponectin decreases in response to treatment in ADHF is an important determinant of the prognosis.

Matrix metalloproteinase-1 and -2 levels are differently regulated in acute exacerbation of heart failure in patients with and without left ventricular systolic dysfunction.

Matrix metalloproteinases (MMPs) play important roles in progression of chronic heart failure (HF) by regulating cardiac extracellular matrix metabolism. However, there is no report to investigate the difference of circulating MMP-1 and MMP-2 levels between systolic HF (SHF) and diastolic HF (DHF), particularly in light of acute exacerbation of HF. We assessed 110 HF patients who were admitted because of an acute exacerbation. They were divided into two groups: SHF [n = 68, left ventricular ejection fraction (LVEF) <45%] or DHF (n = 42, LVEF > or =45%). Ten patients without HF served as controls. Serum MMP-1 and MMP-2, and plasma brain natriuretic peptide (BNP) levels were examined on admission and at discharge. Serum MMP-1 level was higher on admission in both SHF and DHF than in controls. It was higher in SHF than in DHF and did not change at discharge in both groups. Serum MMP-2 level was equally higher on admission in SHF and DHF than in controls. It decreased in both groups at discharge. Treatment-induced changes in LVEF and BNP level correlated with those in MMP-2 level in SHF but not in DHF. Circulating MMP-1 and MMP-2 levels showed different dynamics between SHF and DHF in acute exacerbation and after treatment. These differences in circulating MMP-1 and MMP-2 levels may be related to the phenotype of HF.

Symptomatic ventricular tachyarrhythmia is associated with delayed gadolinium enhancement in cardiac magnetic resonance imaging and with elevated plasma brain natriuretic peptide level in hypertrophic cardiomyopathy.

BACKGROUND: Delayed gadolinium enhancement (DGE) in cardiac magnetic resonance (CMR) imaging indicates the areas with myocardial fibrosis, which are suggested to be arrhythmogenic substrate in hypertrophic cardiomyopathy (HCM). Elevated brain natriuretic peptide (BNP) is associated with cardiovascular events in HCM. We investigated the grade of DGE in CMR and plasma BNP levels in HCM patients with or without symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF). METHODS AND RESULTS: We recruited 26 consecutive untreated HCM patients without any symptoms of heart failure. They were divided into 2 groups: (1) patients with symptomatic VT/VF [VT/VF(+) group, n=6]; (2) patients without symptomatic VT/VF [VT/VF(-) group, n=20]. CMR was performed to evaluate left ventricular geometry and the grade of DGE. Plasma BNP levels, left ventricular mass index, and the number of segments with positive DGE were greater in the VT/VF(+) group than in the VT/VF(-) group (698.1+/-387.6 vs. 226.9+/-256.8 pg/ml, p=0.006; 152.3+/-49.5 vs. 89.5+/-24.1 g/m(2), p=0.003; 9.7+/-5.7 vs. 3.5+/-3.3, p=0.013). On logistic regression, adjusted odds ratio for symptomatic VT/VF was 214 for logBNP (95% confidence interval [CI] 1.2-37,043, p=0.04) and 1.54 for DGE score (95% CI 1.01-2.34, p=0.04). CONCLUSIONS: High plasma BNP levels and the enlarged area of DGE in CMR were associated with symptomatic ventricular tachyarrhythmia. These factors may be useful markers for detecting high-risk patients of sudden cardiac death in HCM.

Anemia as a factor that elevates plasma brain natriuretic peptide concentration in apparently healthy subjects.

Plasma brain natriuretic peptide (BNP) is widely used as a biomarker of heart failure (HF); however, its concentration is often found to be high even in apparently healthy subjects and little is known about which factors contribute to physiological change in plasma BNP concentration in subjects without HF. We examined the effects of gender, age, and anemia on plasma BNP concentration in apparently healthy subjects. The study population consisted of 1036 healthy subjects who underwent an annual health examination at their company in 2005. There were 874 women, ranging in age from 30 to 63 years (mean, 41 years). Plasma BNP concentration was abnormal (> 18.4 pg/mL) in 292 subjects. The incidence was significantly higher in women than in men (31% versus 14%, P < 0.01). Mean plasma BNP concentration was higher in women than in men. The difference in plasma BNP concentration was associated with the difference in blood hemoglobin and age. Logarithmically transformed BNP concentration correlated inversely with blood hemoglobin (r = -0.30, P < 0.01 for all; r = -0.21, P < 0.01 for women; r = -0.20, P < 0.01 for men). By multiple regression analysis, logarithmically transformed BNP concentration correlated with hemoglobin, age, and gender. In conclusion, anemia is likely a critical determinant that elevates plasma BNP concentration in apparently healthy subjects.

Predictors of length of hospital stay after acute myocardial infarction in Japan.

BACKGROUND: In Western countries, the length of hospital stay after acute myocardial infarction (AMI) has decreased dramatically during the past 3 decades and is now approximately 1 week. However, epidemiological data concerning the length of hospital stay, its predictors and trends based on a large-scale sample are still limited in Japan. METHODS AND RESULTS: The study group comprised 4,113 surviving AMI patients who were enrolled in the Osaka Acute Coronary Insufficiency Study from April 1998 to March 2003. The mean length of hospital stay was 31.2 days. Clinical factors (patient characteristics, severity of infarction, therapy, and in-hospital complications) only explained 26% of the variation in hospital stay. The mean hospital stay was significantly longer in 1998 than in 2002. In 2002, occupational status and admission to a high-volume hospital were independent predictors of a shorter hospital stay, but this association was not observed in 1998. CONCLUSIONS: The hospital stay is still extremely long in Japan and clinical factors do not provide an explanation. The findings of the present study suggest that the hospital stay could be reduced in some patients with AMI, but randomized studies are needed to examine the feasibility of early discharge.