Hiroaki Hiraiwa

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.

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

BACKGROUND Little 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). METHODS We 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. RESULTS Median 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. CONCLUSIONS The 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. A 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 (105 868 U/L) and was diagnosed with DMD …

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.

Late-onset Fulminant Myocarditis with Immune Checkpoint Inhibitor Nivolumab

A 60-year-old man was diagnosed with melanoma. After receiving 13 infusions of nivolumab, he had fulminant myocarditis. The myocardial biopsy specimen revealed extensive lymphocytic infiltration, interstitial edema, and myocardial necrosis, with predominant CD4+, CD8+, CD20-, and programmed death-1- markers. Programmed death-1 ligand 1 (PD-L1) was predominantly expressed on the surface of the damaged myocardium. Although it is reported that myocarditis induced by the human anti-programmed death-1 inhibitor nivolumab therapy rarely occurred at > 2 months use in clinical trials, this case showed that even if at a late phase, long-term use of immune checkpoint inhibitors might to lead immune-related adverse events including myocarditis.

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

BACKGROUND Myocardial 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. METHODS We 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. RESULTS At 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). CONCLUSIONS The Selvester QRS score can predict future cardiac events in NIDCM, reflecting myocardial fibrosis assessed by CVF.

Myocardial contractile reserve predicts left ventricular reverse remodeling and cardiac events in dilated cardiomyopathy

BACKGROUND Catecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events. METHODS There was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dtmax), an index of LV contractility, at baseline and following the infusion of dobutamine (10μg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dtmax from the baseline to peak values under dobutamine stress (ΔLVdP/dtmax) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n=15) and who did not receive follow-up echocardiography (n=2), 83 patients were enrolled (52.5±12.3 years). RESULTS During the follow-up period (4.7±2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dtmax (hazard ratio: 1.024, p=0.007) and the symptom duration (hazard ratio: 0.977, p=0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dtmax cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dtmax≥75.1% group (p=0.045). CONCLUSIONS ΔLVdP/dtmax estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM.