Takahiro Okumura

Left ventricular phase entropy: Novel prognostic predictor in patients with dilated cardiomyopathy and narrow QRS

BackgroundThe prognostic impact and pathophysiology of global left ventricular mechanical dyssynchrony (LVMD), namely mechanical dyssynchrony of whole left ventricle, as assessed by phase analysis of electrocardiographically gated (ECG-gated) myocardial perfusion SPECT has not been clearly elucidated in patients with dilated cardiomyopathy (DCM) and narrow QRS complex (<120xa0ms).Methods and ResultsForty-six patients with DCM underwent ECG-gated myocardial 99mTc-sestamibi perfusion SPECT and endomyocardial biopsy. LV phase entropy was automatically calculated using a phase analysis of ECG-gated myocardial perfusion SPECT. The patients were divided into two groups according to the median phase entropy value: low-phase entropy (<0.61) (Nxa0=xa023: LE group) and high-phase entropy (≥0.61) (Nxa0=xa023: HE group). In the Kaplan-Meier survival analysis, the event-free survival rate was significantly lower in the HE group (log-rank Pxa0=xa00.015). Moreover, high-phase entropy was an independent predictor of adverse cardiac events (hazard ratio, 5.77%; 95% confidence interval, 1.02-108.32; Pxa0=xa00.047). Interestingly, the mRNA expression levels of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in endomyocardial biopsy specimens were significantly lower in the HE group (Pxa0=xa00.015).ConclusionLV phase entropy, which may reflect impairment of Ca2+ handling caused by decreased SERCA2a mRNA levels, is a novel prognostic predictor in patients with DCM and narrow QRS complex.

Impact of Renal Functional/Morphological Dynamics on the Calcification of Coronary and Abdominal Arteries in Patients with Chronic Kidney Disease

Aim: Fast-progressing vascular calcification (VC) is accompanied by renal atrophy and functional deterioration along with atherosclerosis in patients with chronic kidney disease (CKD). However, the relationship between VC progression and renal functional and/or morphological changes remains unclear. Methods: We included 70 asymptomatic patients with CKD without hemodialysis in our study. To identify temporal variations, the coronary artery calcification score (CACS), abdominal aortic calcification index (ACI), and renal parenchymal volume index (RPVI) were determined via spiral computed tomography scans taken during the study. We investigated significant factors related to annualized variations of CACS (ΔCACS/y) and ACI (ΔACI/y). Results: During the follow-up period (4.6 years), median values of CACS [in Agatston units (AU)] and ACI increased from 40.2 to 113.3 AU (p = 0.053) and from 13.2 to 21.7% (p = 0.036), respectively. Multivariate analysis revealed that CACS at baseline (p < 0.001) and diabetes mellitus (DM) status (p = 0.037) for ΔCACS/y and ACI at baseline (p = 0.017) and hypertension (HT) status (p = 0.046) for ΔACI/y were significant independent predictors. Furthermore, annualized RPVI variation was significantly related to both ΔCACS/y and ΔACI/y (R = −0.565, p < 0.001, and R = −0.289, p = 0.015, respectively). On the other hand, independent contributions of the estimated glomerular filtration rate (eGFR) and annualized eGFR variation to VC progression were not confirmed. Conclusion: The degree of VC at baseline, DM, HT, and changes in renal volume, but not eGFR, had a strong impact on VC progression in patients with CKD.

Abnormal Circadian Blood Pressure Profile as a Prognostic Marker in Patients with Nonischemic Dilated Cardiomyopathy

Objectives: An abnormal circadian blood pressure (BP) profile is considered a risk factor for cardiovascular disease. However, its significance in heart failure patients with nonischemic etiology is unknown. Herein, we investigated the prognostic value of a circadian BP profile in patients with nonischemic dilated cardiomyopathy (NIDCM). Methods: We enrolled 114 NIDCM patients (76 males, mean age 53.1 years). The percent nighttime BP fall (%NBPF) was defined using ambulatory BP monitoring as a percent decrease in mean systolic BP in nighttime from daytime. All patients were divided into three groups: dipper (%NBPF ≥10), non-dipper (0 ≤ %NBPF < 10), and riser (%NBPF <0). Results: Riser patients had the highest serum creatinine levels (dipper, 0.78 ± 0.20 mg/dl; non-dipper, 0.85 ± 0.21 mg/dl; riser, 0.99 ± 0.23 mg/dl; p = 0.006). In survival analysis, riser patients had the highest cumulative cardiac-related deaths (log-rank, p = 0.001), which was an independent predictor of cardiac-related deaths (hazard ratio, 12.6; 95% confidence interval, 1.76-253; p = 0.01). Multivariate analysis revealed that the norepinephrine level at 24-hour collected urine (24 h U-NE) and the serum creatinine level were independent determinants of %NBPF (adjusted R2 = 0.20; 24 h U-NE, p = 0.0001; serum creatinine, p = 0.04). Conclusions: The riser profile was associated with poor prognosis of NIDCM, which may reflect impaired sympathetic nervous system activity. Evaluating the circadian BP profile may be useful for risk stratification in NIDCM patients.

Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy

BACKGROUNDnLittle is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM).nnnMETHODSnWe enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6μg/mL, lathosterol 1.4μg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia.nnnRESULTSnMedian brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol <153mg/dL was a best cut-off value for discrimination of the D-subset.nnnCONCLUSIONSnThe combined reduction of campesterol and lathosterol that indicated intestinal cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM.

Long-Term Pathological Follow-Up of Myocardium in a Carrier of Duchenne Muscular Dystrophy With Dilated Cardiomyopathy

Duchenne muscular dystrophy (DMD) is a fatal X-linked disorder, with an incidence of ≈1 in 3600 to 6000 male births. DMD is caused by mutations in the dystrophin gene located at Xp21.2 and is clinically characterized by progressive muscle degeneration and dilated cardiomyopathy (DCM). Some female DMD carriers show a variety of clinical manifestations, ranging from creatine kinase elevation to severe muscle weakness. DCM has been reported in 8% to 18% of female DMD carriers and sometimes results in a lethal course. Here, we describe long-term follow-up observations of myocardial changes in a DMD carrier with DCM.nnA 29-year-old female presented with progressive shortness of breath, increasing ankle edema, and orthopnea after a full-term normal delivery. A chest X ray showed cardiomegaly and bilateral pleural effusions, and echocardiography showed a severely reduced left ventricular ejection fraction of 24%, with a markedly increased left ventricular end-diastolic diameter of 71 mm. She was admitted for heart failure, and her symptoms improved with furosemide and inotropes. There were no symptoms to suggest myopathy, and blood analysis revealed no elevation of creatine kinase (60 U/L). Her newborn boy showed extreme elevation of creatine kinase (105u2009868 U/L) and was diagnosed with DMD …

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

BACKGROUNDnThe 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).Methodsu2004andu2004Results: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.nnnCONCLUSIONSnThe FFR reflects latent myocardial abnormalities and predicts cardiac events in the setting of HCM, even during the asymptomatic stages of the disease.

Early Prediction Model for Successful Bridge to Recovery in Patients With Fulminant Myocarditis Supported With Percutaneous Venoarterial Extracorporeal Membrane Oxygenation ― Insights From the CHANGE PUMP Study ―

BACKGROUNDnCardiac recovery and prevention of end-organ damage are the cornerstones of establishing successful bridge to recovery (BTR) in patients with fulminant myocarditis (FM) supported with percutaneous venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, the timing and method of successful BTR prediction still remain unclear. We aimed to develop a prediction model for successful BTR in patients with FM supported with percutaneous VA-ECMO.Methodsu2004andu2004Results:This was a retrospective multicenter chart review enrolling 99 patients (52±16 years; female, 42%) with FM treated with percutaneous VA-ECMO. The S-group comprised patients who experienced percutaneous VA-ECMO decannulation and subsequent discharge (n=46), and the F-group comprised patients who either died in hospital or required conversion to other forms of mechanical circulatory support (n=53). At VA-ECMO initiation (0-h), the S-group had significantly higher left ventricular ejection fraction (LVEF) and lower aspartate aminotransferase (AST) concentration than the F-group. At 48 h, the LVEF, increase in the LVEF, and reduction of AST from 0-h were identified as independent predictors in the S-group. Finally, we developed an S-group prediction model comprising these 3 variables (area under the curve, 0.844; 95% confidence interval, 0.745-0.944).nnnCONCLUSIONSnWe developed a model for use 48 h after VA-ECMO initiation to predict successful BTR in patients with FM.

Sokolow-Lyon voltage is suitable for monitoring improvement in cardiac function and prognosis of patients with idiopathic dilated cardiomyopathy

The clinical significance of electrocardiogram in the assessment of patients with idiopathic dilated cardiomyopathy (IDCM) is currently unknown. The aim of this study was to determine the feasibility of recording serial changes in Sokolow–Lyon voltage (∆%QRS‐voltage) in one year to estimate left ventricular reverse remodeling (LVRR) and predict a prognosis of IDCM patients under tailored medical therapy.

Usefulness of the Combination of In-Hospital Poor Diuretic Response and Systemic Congestion to Predict Future Cardiac Events in Patients With Acute Decompensated Heart Failure

We aimed to (1) investigate the relation between diuretic response (DR) with or without systemic congestion and prognosis and (2) explore the potential predictors of poor DR for risk stratification in patients with acute decompensated heart failure (ADHF). We enrolled 186 consecutive patients hospitalized for ADHF. The DR was defined as (body weight at dischargexa0- body weight at admission)/40xa0mg furosemide or equivalent loop diuretic dose. Systemic congestion on admission was simply evaluated by the presence of leg edema or jugular venous distention. All patients were divided into 4 groups based on the median of DR (-0.50xa0kg/40xa0mg) and the status of systemic congestion; GR/C (good DR with systemic congestion, nxa0= 66), GR/N (good DR without systemic congestion, nxa0= 27), PR/C (poor DR with systemic congestion, nxa0= 48); and PR/N (poor DR without systemic congestion, nxa0= 45). The composite outcome was defined as cardiac death and rehospitalization for worsening heart failure. In survival analysis, the cardiac event-free rate in PR/C was significantly lower than that in any other groups (log-rank, p <0.001), and PR/C was an independent predictor of cardiac events (hazard ratio 2.17, pxa0= 0.016). In conclusion, the combination of in-hospital poor DR, characterized by previous ischemic heart disease, and prehospital dose of daily loop diuretics, and systemic congestion provides a risk stratification for future cardiac events in patients with ADHF.

The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy

BACKGROUNDnMyocardial fibrosis is associated with poor prognosis in nonischemic dilated cardiomyopathy (NIDCM) patients. The Selvester QRS score on 12-lead electrocardiogram is associated with both the amount of myocardial scar and poor prognosis in myocardial infarction patients. However, its use in NIDCM patients is limited. We investigated the prognostic value of the QRS score and its association with collagen volume fraction (CVF) in NIDCM patients.nnnMETHODSnWe enrolled 91 consecutive NIDCM patients (66 men, 53±13 years) without permanent pacemakers or cardiac resynchronization therapy devices. The Selvester QRS score was calculated by two expert cardiologists at NIDCM diagnosis. All patients were followed up over 4.5±3.2 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening heart failure, and lethal arrhythmia. We also evaluated CVF using endomyocardial biopsy samples.nnnRESULTSnAt baseline, the left ventricular ejection fraction was 32±9%, plasma brain natriuretic peptide level was 80 [43-237] pg/mL, and mean Selvester QRS score was 4.1 points. Twenty cardiac events were observed (cardiac death, n=1; hospitalization for worsening heart failure, n=16; lethal arrhythmia, n=3). Cox proportional hazard regression analysis revealed that the Selvester QRS score was an independent determinant of cardiac events (hazard ratio, 1.32; 95% confidence interval, 1.05-1.67; p=0.02). The best cut-off value was determined as 3 points, with 85% sensitivity and 47% specificity (area under the curve, 0.688, p=0.011). In Kaplan-Meier survival analysis, the QRS score ≥3 group had more cardiac events than the QRS score <3 group (log-rank, p=0.007). Further, there was a significant positive correlation of Selvester QRS score with CVF (r=0.46, p<0.001).nnnCONCLUSIONSnThe Selvester QRS score can predict future cardiac events in NIDCM, reflecting myocardial fibrosis assessed by CVF.