Toshimi Koitabashi

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.

Evaluation of the impact of atrial fibrillation on rehospitalization events in heart failure patients in recent years

BACKGROUND Although we have previously reported that the presence of paroxysmal atrial fibrillation (AF) is an independent risk factor for rehospitalization in patients with congestive heart failure (CHF) in a population from 1996 to 2002, the impact of AF configuration as a risk factor in a more recent population remains to be clarified. METHODS AND RESULTS 319 patients with CHF admitted to our institute in 2006-2007 were retrospectively evaluated. The patients were divided into 3 groups in accordance with their basic cardiac rhythm, i.e. sinus rhythm (n=210), chronic AF (n=68), and paroxysmal AF (n=41). During the follow-up period of 19 ± 17 months, there was no significant difference in mortality or rehospitalization events among the 3 groups (p=0.542). In the multivariate analysis, no administration of β-blockers was the only independent risk factor for rehospitalization due to CHF exacerbation. CONCLUSIONS The clinical impact of AF configuration as a risk factor of rehospitalization due to CHF exacerbation was considered to be decreased in recent years.

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.

Myosin Autoreactive T Cells And Autoimmune Myocarditis. Lessons from the Disease Caused by Cardiac Myosin Peptide CM2

We have proposed a unique animal model of experimental autoimmune myocarditis (EAM). This rat myocarditis is systematically provoked by immunization with cardiac myosin, and evolves toward dilated cardiomyopathy through repetitive immunizations. In this process, myosin epitopes, dendritic cells and myosin autoreactive T cells are the three major elements initiating and promoting this disease. Despite many attempts, we have failed, thus far, to identify myosin autoreactive and myocarditogenic T cells in vitro. However, recently, T cell lines specifically reactive to the cardiac myosin peptide, CM 2 (AA: 1539-1555), and showing myocarditogenecity have been identified. Line characterization of harvested T cells from EAM rats rendered ill by whole cardiac myosin was repetitively and systematically tested. Thus, T cell lines autoreactive to CM 2 and inducing transfer myocarditis were isolated out of many candidates. Acute myocarditis transferred by means of these T cell lines became more severe, and disease transfer with these cell lines caused chronic myocarditis in syngenic Lewis rat. Importantly, the myosin autoreactive and myocarditogenic T cells were also able to transfer the myocarditis into SCID mice beyond the MHC restriction.

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.

Hemodilution after Initial Treatment in Patients with Acute Decompensated Heart Failure

Decongestion is an important goal of heart failure (HF) management. Blood cell concentration is a recognized indicator for guiding decongestive treatment for HF. We aimed to assess the clinical impact of hemodilution and hemoconcentration after initial treatment in acute decompensated HF (ADHF) patients. We retrospectively evaluated hemoglobin levels and body weight obtained before admission, on admission, 3 days after admission, and at discharge in 102 consecutive patients admitted with ADHF. Patients were then stratified into hemodilution (n = 55) and hemoconcentration (n = 47) groups based on whether their hemoglobin levels decreased or increased, respectively, during the first 3 days after admission. From before admission to admission, hemoglobin levels decreased less in the hemodilution group (-0.16 ± 0.98 g/dL) than in the hemoconcentration group (-0.88 ± 1.11 g/dL) (P < 0.001); however, there was no significant difference in body weight (P≥ 0.05). More patients in the hemodilution group (85%) had grade III/IV pulmonary edema (Turners criteria) compared with the hemoconcentration group (63%) (P < 0.01). Rate of readmission for HF within 180 days of discharge was higher in the hemodilution group (34%) compared with the hemoconcentration group (9%) (P < 0.01). Hemodilution after initial treatment for ADHF was associated with severe pulmonary edema at admission and higher readmission rates.