Shuzo Shimazu

Relationship of myocardial fibrosis to left ventricular and mitochondrial function in nonischemic dilated cardiomyopathy--a comparison of focal and interstitial fibrosis.

BACKGROUND Mitochondrial damage is associated with histologic myocardial fibrosis. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) can be used to identify focal fibrosis. We examined whether myocardial fibrosis on CMR and collagen volume fraction (CVF) from biopsies correlated with left ventricular (LV) and mitochondrial function in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS Fifty-nine DCM patients underwent CMR, cardiac catheterization, and endomyocardial biopsy. Minimum first derivative of LV pressure (LVdP/dt(min)) was measured as an index of LV relaxation. Mitochondrial RNA expression was also analyzed. For quantitative analysis of myocardial fibrosis, percentage LGE (%LGE) and CVF were calculated. Patients were divided into 2 groups on the basis of the presence (LGE group; n = 27) or absence (non-LGE group; n = 32) of LGE. Mean CVF and absolute value of LVdP/dt(min) were significantly higher and lower, respectively, in the LGE group than in the non-LGE group. Multivariate analysis revealed that %LGE was an independent determinant of LVdP/dt(min). The abundance of mitochondrial enzyme mRNA was significantly lower in the LGE group. CONCLUSIONS Noninvasive CMR imaging is more useful in predicting diastolic dysfunction than invasive histologic assessments. In addition, it might indicate mitochondrial dysfunction in DCM.

Prognostic Impact of Combined Late Gadolinium Enhancement on Cardiovascular Magnetic Resonance and Peak Oxygen Consumption in Ambulatory Patients With Nonischemic Dilated Cardiomyopathy

BACKGROUND Peak oxygen consumption (peak VO₂) and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) are prognostic in heart failure. We investigated whether LGE-CMR and peak VO₂combined had additive value in risk stratifying patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS Fifty-seven DCM patients underwent CMR and cardiopulmonary exercise testing. Cardiac events were cardiac death, hospitalization for decompensated heart failure, or lethal arrhythmia. Twenty-five (44%) were LGE-positive. The median peak VO₂was 18.5 mL·kg(-1)·min(-1). On multivariate analysis, positive LGE (P = .048) and peak VO₂(P = .003) were independent cardiac event predictors. Cardiac event risk was significantly higher with positive LGE and peak VO₂< 18.5 mL ·kg⁻¹ ·min⁻¹ than with negative LGE and peak VO₂≥ 18.5 mL · kg⁻¹ · min⁻¹ (hazard ratio 12.5; 95% CI 1.57-100; P = .017). In 3 patient groups (group A: no LGE, peak VO₂≥ 18.5 mL · kg⁻¹ · min⁻¹, n = 18; group B: positive LGE or peak VO₂< 18.5 mL · kg⁻¹ · min⁻¹, n = 24; group C: positive LGE and peak VO₂< 18.5 mL · kg⁻¹ · min⁻¹, n = 15) during follow-up (71 ± 32 months), group C had higher cardiac event rates than the others. CONCLUSIONS Combined assessment of LGE-CMR and peak VO₂provides additive prognostic information in ambulatory DCM.

Cardiopulmonary exercise testing to evaluate the exercise capacity of patients with inoperable chronic thromboembolic pulmonary hypertension: an endothelin receptor antagonist improves the peak PETCO2.

AIMS The 6-min walking distance is often used for assessing the exercise capacity under the treatment with an endothelin receptor antagonist (ERA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The cardiopulmonary exercise testing (CPX) was reported to be more useful for the patients with pulmonary arterial hypertension (PAH), however, few reports exist in patients with inoperable CTEPH. The aim of this study was to investigate the effects of an oral dual ERA, bosentan, on exercise capacity using CPX in patients with PAH and inoperable CTEPH. MAIN METHODS This study included all patients diagnosed with 17 PAH and 12 CTEPH in the World Health Organization functional classes II-IV who started treatment with bosentan therapy. They underwent CPX, which was performed before bosentan therapy and at 3 to 6 months of the treatment. KEY FINDINGS In PAH patients, peak VO2 significantly increased after the bosentan treatment (p=0.009). On the other hand, in CTEPH patients, there were no significant differences in the peak VO2. However, the peak PETCO2 was significantly increased from 23.9±5.2 mm Hg at baseline to 29.3±10.7 mm Hg after the bosentan treatment (p=0.040). In addition, peak heart rate during exercise tended to decrease after the bosentan therapy (p=0.089). SIGNIFICANCE Bosentan therapy improved peak PETCO2 but not peak VO2 in patients with inoperable CTEPH. These findings demonstrated that CPX is useful for assessing the exercise capacity of patients with PAH and inoperable CTEPH under the treatment with an ERA.

Assessment of respiratory disturbance index determined with a non-restrictive monitor and of autonomic nervous system parameters in heart failure patients: A pilot study

BACKGROUND There is a link between sympathetic overactivity and sleep-disordered breathing (SDB), and both of which are important indicators of the development of heart failure. To manage the increasing numbers of heart failure patients, any method used to check for them needs to be as non-invasive, simple, and cost-effective as possible. The purpose of this study is to assess screening of SDB with a non-restrictive monitor and the autonomic nervous system in heart failure patients. METHODS The subjects were 49 patients (mean age: 67 years; male: 78%) hospitalized for worsening heart failure. After stabilization with appropriate medical therapy, each patient simultaneously underwent sleep apnea syndrome (SAS) screening with the SD-101 (Kenzmedico Co. Ltd., Saitama, Japan), which is a novel, non-restrictive, sheet-like monitor for SAS screening, and assessment of heart rate variability (HRV) with a Holter monitor. In addition, we assessed daytime sleepiness by using the Epworth Sleepiness Scale. RESULTS The mean respiratory disturbance index (RDI) was 21.9 events/h. Males had significantly greater RDI values than females (24.5±11.2 events/h vs. 13.0±6.2 events/h, p<0.001). RDI on SD-101 testing was closely correlated with cyclic variation of heart rate index obtained with a Holter electrocardiogram scanner (r=0.843). Although plasma brain natriuretic peptide level was not correlated with HRV, plasma norepinephrine level was moderately well correlated with the total low- to high-frequency ratio of HRV (r=0.529). CONCLUSIONS SAS screening is important for heart failure patients, because absence of subjective sleepiness is not reliable in ruling out SDB. The SAS screening with SD-101 might apply for managing heart failure.

Biphasic Force-Frequency Relation Predicts Primary Cardiac Events in Patients With Hypertrophic Cardiomyopathy

BACKGROUND The force-frequency relation (FFR) is a hemodynamic index of the chronotropic relationship between left ventricular (LV) systolic function (percent change in dP/dtmax) and elevation of heart rate. FFR is a marker of myocardial contractile reserve and follows an upward slope in healthy myocardium [monophasic FFR (MoF)], a pattern that becomes biphasic (BiF) under pathological conditions. However, it remains uncertain whether the FFR determines a patients prognosis. We investigated the promising role of the FFR as a predictor of cardiac events in the setting of hypertrophic cardiomyopathy (HCM).Methods and Results:A total of 113 consecutive patients with HCM (New York Heart Association (NYHA) class I-II) were retrospectively evaluated; 27 (23.9%) had a BiF pattern and they experienced a higher incidence of cardiac events compared with those showing an MoF pattern (median follow-up, 4.7 years; P<0.001). Furthermore, Cox proportional hazard regression analysis revealed that the LV end-diastolic volume index (hazard ratio: 1.051, P=0.014) and BiF pattern (hazard ratio: 15.260, P=0.001) were independent predictors of primary cardiac events. Interestingly, abnormal reductions in myocardial regulatory molecules related to contractility (SERCA2α) were observed exclusively in the patients exhibiting a BiF pattern. CONCLUSIONS The FFR reflects latent myocardial abnormalities and predicts cardiac events in the setting of HCM, even during the asymptomatic stages of the disease.