Takashi Naruke

Prognostic Utility of B-Type Natriuretic Peptide Assessment in Stable Low-Risk Outpatients With Nonischemic Cardiomyopathy After Decompensated Heart Failure

OBJECTIVES We investigated the clinical utility of B-type natriuretic peptide (BNP) assay in stable outpatients with nonischemic dilated cardiomyopathy (NICM) after decompensated heart failure (HF). BACKGROUND Patients with NICM admitted for decompensated HF frequently experience sudden death or redecompensation after hospital discharge. The prognostic value of BNP during hospitalization has been demonstrated. However, clinical utility of BNP in stable outpatient setting has been poorly investigated. METHODS Eighty-three NICM outpatients who were clinically stable in New York Heart Association functional class 1 to 2 for 6 months after discharge for decompensated HF were enrolled, and then followed for an additional 18 months. The main end point was first readmission for decompensated HF or death. B-type natriuretic peptide levels were measured at 3-month intervals from discharge to enrollment, and echocardiographic dimensions at discharge and enrollment. RESULTS Mean discharge BNP level was 210 +/- 148 pg/ml. Twenty-eight patients were readmitted for decompensated HF or suddenly died at a median time of 11 months from the time of discharge. Among various variables including BNP measurements, clinical parameters and echocardiographic dimensions, a 6-month post-discharge BNP of >190 pg/ml was most closely associated with combined event in the Cox proportional hazards model (hazard ratio 2.29; 95% confidence interval 1.42 to 3.56; p = 0.0005), and had the best discriminatory power (area under the receiver operating characteristic curve 0.91, sensitivity 96%; specificity 76%). CONCLUSIONS Even in stable low-risk outpatients with NICM at 6 months after hospital discharge for decompensated HF, BNP assessment predicts a long-term risk of redecompensation.

Baseline cardiac magnetic resonance imaging versus baseline endomyocardial biopsy for the prediction of left ventricular reverse remodeling and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy.

Endomyocardial biopsy (EMB) and late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging performed at baseline are both used to evaluate the extent of myocardial fibrosis. However, no study has directly compared the effectiveness of these diagnostic tools in the prediction of left ventricular reverse remodeling (LVRR) and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Seventy-five patients with newly diagnosed IDCM who were undergoing optimal therapy were assessed at baseline using LGE-CMR imaging and EMB; the former measured LGE area and the latter measured collagen volume fraction (CVF) as possible predictive indices of LVRR and cardiac event-free survival. Among all the baseline primary candidate factors with P < 0.2 as per univariate analysis, multivariate analysis indicated that only LGE area was an independent predictor of subsequent LVRR (β = 0.44; 95 % confidence interval (CI) 0.87–2.53; P < 0.001), as indicated by decreasing left ventricular end-systolic volume index over the 1-year follow-up. Kaplan–Meier curves indicated significantly lower cardiac event-free survival rates in patients with LGE at baseline than in patients without (P < 0.01). By contrast, there was no significant difference in prognosis between patients with CVF values above (severe fibrosis) and below (mild fibrosis) the median of 4.9 %. Cox proportional hazard analysis showed that LGE area was an independent predictor of subsequent cardiac events (hazard ratio 1.06; 95 % CI 1.02–1.10; P ≤ 0.01). The degree of myocardial fibrosis estimated by baseline LGE-CMR imaging, but not that estimated by baseline EMB, can predict LVRR and cardiac event-free survival in response to therapy in patients with newly diagnosed IDCM.

Clinical significance of heart rate during acute decompensated heart failure to predict left ventricular reverse remodeling and prognosis in response to therapies in nonischemic dilated cardiomyopathy

Although an increased heart rate (HR) is a strong predictor of poor prognosis in cases of chronic heart failure (HF), the clinical value of HR as a predictor in acute decompensated HF (ADHF) is unclear. Seventy-eight patients with nonischemic dilated cardiomyopathy (NIDCM) with sinus rhythm who were first hospitalized for ADHF from 2002 to 2010 were retrospectively investigated after exclusion of patients with tachycardia-induced cardiomyopathy. The patients were divided into two groups stratified by HR on admission with a median value of 113 beats/min (Group H with HR ≥ 113 beats/min; Group L with HR < 113 beats/min). Despite similar backgrounds, including pharmacotherapy for HF, HR changes responding to titration of β-blocker (BB) therapy and myocardial interstitial fibrosis, left ventricular (LV) ejection fractions improved more significantly 1 year later in Group H than in Group L (57 % ± 11 % vs. 46 % ± 12 %, P < 0.001). Cardiac event-free survival rates were also significantly improved in Group H (P = 0.038). Multiple regression analysis revealed that only the peak HR on admission was an independent predictor of LV reverse remodeling (LVRR) 1 year later (β = 0.396, P = 0.005). High HR on first admission for ADHF is a strong predictor of LVRR, with a better prognosis in the event of NIDCM in response to optimal pharmacotherapy, independent of pre-existing myocardial damage and subsequent HR reduction by BB therapy.

β2-Adrenergic Agonists Suppress Rat Autoimmune Myocarditis Potential Role of β2-Adrenergic Stimulants as New Therapeutic Agents for Myocarditis

Background— The therapeutic potential of β2-adrenergic receptor (AR) agonists in the treatment of autoimmune diseases has been reported. However, the role of these drugs in the myocardial structure–induced autoimmune process, which is thought to play a crucial role in the progression of myocarditis to subsequent complications, has not been elucidated. Methods and Results— Experimental autoimmune myocarditis (EAM) was induced in rats by immunization with cardiac myosin. On daily administration from day 0 after immunization, the β2-selective AR agonists formoterol or salbutamol ameliorated EAM on day 21 and increased myocardial interleukin-10/interferon-γ mRNA levels. Propranolol, a nonselective β-AR antagonist, aggravated EAM on day 21 and decreased mRNA levels, whereas metoprolol, a β1-selective AR antagonist, showed no effect. These results were reflected in vivo by the proliferation of cardiac myosin–primed lymph node cells from drug-treated rats. In vitro addition of β2-selective AR agonists inhibited the activation of cardiac myosin fragment–specific myocarditogenic T lymphocytes, and this effect was reversed by ICI118,551, a β2-selective AR antagonist. Furthermore, treatment with 2 different β2-selective AR agonists starting on day 14 also ameliorated EAM on day 21. Conclusions— β2-AR stimulation suppressed the development of EAM by inhibiting cardiac myosin–specific T-lymphocyte activation in lymphoid organs and by shifting the imbalance in Th1/Th2 cytokine toward Th2 cytokine. Furthermore, it also ameliorated established myocardial inflammation. β2-AR–stimulating agents may represent important immunomodulators of the cardiac myosin–induced autoimmune process and have potential as a new therapy for myocarditis.

Morphological changes in mitochondria during mechanical unloading observed on electron microscopy: a case report of a bridge to complete recovery in a patient with idiopathic dilated cardiomyopathy

The recovery of the cardiac function under mechanical support has not been well documented from a histopathological point of view. We herein report a case of idiopathic dilated cardiomyopathy in which the patient showed a complete recovery of the systolic function following treatment with a left ventricular assist device (LVAD) for deteriorated heart failure. A light microscopic observation showed marked regression of hypertrophic myocytes with significant intracellular vacuolization and scarcity at the time of LVAD implantation after the administration of mechanical support. Furthermore, an electron microscopic observation revealed that these findings were regulated primarily by volumetric regression and morphometric improvements in cardiomyocytic mitochondria.

Temporal change of myocardial tissue character is associated with left ventricular reverse remodeling in patients with dilated cardiomyopathy: A cardiovascular magnetic resonance study

BACKGROUND Prognostic significance of temporal change in myocardial tissue characterization by cardiovascular magnetic resonance (CMR) has not been elucidated in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS Sixty-eight patients with newly-diagnosed DCM who underwent CMR including late gadolinium enhancement (LGE) both at baseline and during follow-up period were enrolled. LGE score was defined by a signal intensity of ≥5 standard deviations above the remote reference myocardium mean. Left ventricular reverse remodeling (LVRR) defined as a LV ejection fraction increase of ≥10% and a decrease in indexed LV end-diastolic diameter of ≥10% compared to those at baseline was detected in 38% of the patients. There was no significant difference in LGE score between baseline and follow-up (5.8% vs. 7.3%; p=0.38). The change in LGE area (delta-LGE) was significantly lower in patients with LVRR than those without (-0.5%±3.4% vs. 3.0±7.4%; p=0.02). On the other hand, T2 ratio during the follow-up significantly reduced (1.95±0.48 vs. 1.67±0.56; p<0.01); however, there was no significant difference in the change in T2 ratio between patients with LVRR and those without (-0.29±0.73 vs. -0.27±0.66; p=0.88). Multivariate logistic analysis indicated that baseline LGE score [odds ratio; 0.78; 95% confidence interval (CI) 0.66 to 0.90; p<0.01] together with delta-LGE (odds ratio; 0.77; 95% CI 0.61 to 0.92; p=0.01) were independently associated with subsequent LVRR (p<0.01). CONCLUSIONS The temporal change of LGE-CMR score during the clinical course was significantly correlated with following LVRR.

Tafamidis for the Treatment of Hereditary Transthyretin Amyloid Cardiomyopathy: A Case Report

Tafamidis meglumine is a novel medicine that has been shown to slow the progression of peripheral neurological impairment in patients with hereditary transthyretin amyloidosis (ATTR). However, the efficacy of tafamidis against ATTR-related cardiac amyloidosis remains unclear. A 72-year-old woman had cardiac hypertrophy and axonopathy in her lower legs. Endomyocardial biopsy revealed an infiltrative cardiomyopathy consistent with amyloidosis. Immunostaining and genetic studies confirmed the diagnosis of ATTR, and tafamidis was started subsequently. Two years after the initiation of tafamidis treatment, electromyography demonstrated no change in the axonopathy in her lower legs; however, electrocardiography displayed QRS prolongation, and echocardiography disclosed an increase in interventricular septal thickness. Endomyocardial biopsy indicated that transthyretin amyloid infiltration of the myocardium was not reduced. In this case, there was no apparent progression of axonopathy, although there were signs of worsening amyloid cardiomyopathy during the treatment with tafamidis.

Importance of Early Diagnosis of Cardiac Sarcoidosis in Patients with Complete Atrioventricular Block

Our aim is to clarify the factors for early diagnosis of cardiac sarcoidosis (CS) in patients with complete atrioventricular block (CAVB) and its impact on cardiac function after corticosteroid therapy.A total of 15 CS patients with CAVB who underwent corticosteroid therapy were retrospectively analyzed. Patients were divided into two groups according to the time from the first CAVB onset to the diagnosis of CS. Clinical characteristics and outcomes were compared between the early diagnosis group (within 1 year; group E, n = 10) and the late diagnosis group (over 1 year; group L, n = 5).The history of extracardiac sarcoidosis (60 versus 0%, P = 0.0440) and abnormal findings on echocardiography (70 versus 0%, P = 0.0256) at the CAVB onset were significantly more frequent in group E than in group L. The change of left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) levels was significantly better in group E than in group L (0.8 ± 2.8 versus -32.4 ± 3.9%, P < 0.0001; -11.1 ± 16.0 versus 161.8 ± 35.8 pg/mL, P = 0.0013, respectively). After corticosteroid therapy, the LVEF and BNP levels were also significantly better in group E than in group L (53.3 ± 10.7 versus 37.0 ± 9.3%, P = 0.0128; 63.0 ± 46.4 versus 458.8 ± 352.0 pg/mL, P = 0.0027).The diagnosis may be delayed in CS patients with CAVB without history of extracardiac sarcoidosis. Abnormal findings on echocardiography contributed to the early diagnosis of CS. Therefore, the diagnosis of CS may be missed or delayed in patients without them. Time delay from the CAVB onset to the CS diagnosis may exacerbate the cardiac function.