Takashi Owada

Liver Dysfunction Assessed by Model for End-Stage Liver Disease Excluding INR (MELD-XI) Scoring System Predicts Adverse Prognosis in Heart Failure

Aims Liver dysfunction due to heart failure (HF) is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI) is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. Methods and Results We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, n = 289) and Group H (MELD-XI ≥10, n = 273). We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days), 104 deaths (62 cardiac deaths and 42 non-cardiac deaths) were observed. The event (cardiac death, non-cardiac death, all-cause death)-free rate was significantly higher in group L than in group H (logrank P<0.05, respectively). In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L (P<0.05, respectively). Conclusions The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF.

Clinical features of patients with decompensated heart failure after the Great East Japan Earthquake.

The occurrence of heart failure (HF) and its clinical features after a great disaster have not been rigorously examined. We retrospectively examined the effect of the Great East Japan Earthquake on the occurrence of decompensated HF. The number of patients admitted for treatment of decompensated HF and their clinical features were compared between 2 periods, March 11, 2011 to September 10, 2011 (after the earthquake) and the same period in the previous year. The number of admissions increased from 55 in 2010 to 84 in 2011. A comparison of the clinical features showed that the patients admitted after the earthquake had (1) older age (p = 0.031), (2) greater systolic blood pressure (p = 0.039), (3) a greater incidence of new-onset HF due to valvular heart disease (p = 0.040), (4) interruption of drugs (p = 0.001), (5) a greater incidence of infection (p = 0.019), (6) greater B-type natriuretic peptide (p = 0.005) and C-reactive protein (p = 0.003) levels, (7) a lower estimated glomerular filtration rate (p = 0.048) and lower albumin levels (p = 0.021), and (8) a larger diameter of the inferior vena cava (p = 0.008). In conclusion, these results suggest that the earthquake increased the incidence of HF in association with high blood pressure, interruption of drugs, inflammation, malnutrition, and fluid retention. Taking appropriate measures to control blood pressure, nutritional status, and hygiene environment might decrease the occurrence of HF in future disasters.

Impact of body mass index on mortality in heart failure patients.

Higher body mass index (BMI) is associated with incident heart failure (HF), but paradoxically associated with better prognosis, recognized as the obesity paradox in HF. However, the impact of BMI on detailed prognosis on HF and the mechanism of obesity paradox remain still unclear.

Cardiovascular function and prognosis of patients with heart failure coexistent with chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease (COPD) often coexists with heart failure (HF), and is considered to be associated with adverse outcomes in HF patients. However, the features of cardiovascular function and the detailed all-cause mortality of HF with COPD remain unclear. METHODS AND RESULTS Consecutive 378 patients admitted for HF who underwent spirometry were divided into three groups: HF without COPD (non-COPD group, n=272), HF with mild COPD (GOLD I group, n=82), and HF with moderate COPD (GOLD II group, n=24). The GOLD II group, as compared to non-COPD group, had (1) higher troponin T (p=0.009); (2) greater cardio-ankle vascular index (p=0.032); and (3) similar cardiac systolic and diastolic function of the right and left ventricle. In addition, rates of cardiac (p=0.049), non-cardiac (p=0.001), and all-cause mortality (p=0.002) were higher in GOLD II group than in non-COPD and GOLD I groups. Importantly, in the Cox proportional hazard analyses, the GOLD stage II was an independent predictor of cardiac (p=0.038), non-cardiac (p=0.036), and all-cause mortality (p=0.015) in HF patients. CONCLUSIONS HF patients with coexistent moderate COPD (GOLD stage II) have greater myocardial damage, greater arterial stiffness, and higher cardiac and non-cardiac mortality.

Association of Hypocalcemia With Mortality in Hospitalized Patients With Heart Failure and Chronic Kidney Disease

BACKGROUND Chronic kidney disease--mineral and bone disorders (CKD-MBD) are associated with vascular calcification and abnormal electrolytes that lead to cardiovascular disease and mortality. CKD-MBD is identified by imbalances in serum calcium (Ca), phosphate, and parathyroid hormone (PTH). Although the relation of phosphate and PTH with the prognosis of HF patients has been reported, the association of Ca with prognosis in patients with heart failure (HF) and CKD remains unclear. METHODS AND RESULTS We examined 191 patients admitted for HF and CKD (estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2)), and they were divided into 2 groups based on levels of corrected Ca: low Ca (Ca <8.4 mg/dL; n = 32) and normal-high Ca (8.4 ≤Ca; n = 159). We compared laboratory and echocardiographic findings, as well as followed cardiac and all-cause mortality. The low-Ca group had 1) higher levels of alkaline phosphatase (308.9 vs. 261.0 U/L; P = .026), 2) lower levels of 1,25-dihydroxy vitamin D (26.1 vs. 45.0 pg/mL; P = .011) and hydrogen carbonate (22.4 vs. 24.5 mmol/L; P = .031), and 3) a tendency to have a higher PTH level (87.5 vs. 58.6 pg/mL; P = .084). In contrast, left and right ventricular systolic function, estimated glomerular filtration rate, urine protein, phosphate, sodium, potassium, magnesium, and zinc did not differ between the 2 groups. In the Kaplan-Meier analysis, cardiac and all-cause mortality were significantly higher in the low-Ca group than in the normal-high-Ca group (P < .05). In the multivariable Cox proportional hazard analyses, hypocalcemia was an independent predictor of all-cause mortality in HF and CKD patients (P < .05). CONCLUSIONS Hypocalcemia was an independent predictor of all-cause mortality in HF and CKD patients.

Impact of Peripheral Artery Disease on Prognosis in Hospitalized Heart Failure Patients

BACKGROUND The impact of peripheral artery disease (PAD) on heart failure (HF) prognosis remains unclear. METHODS AND RESULTS A total of 388 consecutive decompensated HF patients were divided into 2 groups based on the presence of PAD: HF with PAD (PAD group, n=101, 26.0%) and HF without PAD (non-PAD group, n=287, 74.0%). We compared clinical features, echocardiographic parameters, cardiopulmonary exercise testing results, laboratory findings, as well as cardiac, non-cardiac, and all-cause mortality between the 2 groups. The PAD group, as compared with the non-PAD group, had (1) higher prevalence of coronary artery disease (40.6 vs. 27.5%, P=0.011) and cerebrovascular disease (34.7 vs. 18.2%, P=0.001); (2) higher tumor necrosis factor-α (1.82 vs. 1.49 pg/ml, P=0.023), C-reactive protein (0.32 vs. 0.19 mg/dl, P=0.045), and troponin T (0.039 vs. 0.021 ng/ml, P=0.019); (3) lower LVEF (42.4 vs. 48.5%, P<0.001); (4) lower peak V̇O2(13.4 vs. 15.9 ml·kg(-1)·min(-1), P=0.001); and (5) higher V̇E/V̇CO2slope (38.8 vs. 33.7, P<0.001). On Kaplan-Meier analysis, cardiac, non-cardiac, and all-cause mortality were significantly higher in the PAD group than in the non-PAD group (P<0.05, respectively). On Cox proportional hazard analysis after adjusting for confounding factors, PAD was an independent predictor of cardiac and all-cause mortality (P<0.05, respectively) in HF patients. CONCLUSIONS PAD was common and an independent predictor of cardiac and all-cause mortality in HF patients.

Epicardial Adipose Tissue Reflects the Presence of Coronary Artery Disease: Comparison with Abdominal Visceral Adipose Tissue

Accumulation of visceral adipose tissue is associated with a risk of coronary artery disease (CAD). The aim of this study was to examine whether different types of adipose tissue depot may play differential roles in the progression of CAD. Consecutive 174 patients who underwent both computed tomography (CT) and echocardiography were analyzed. Cardiac and abdominal CT scans were performed to measure epicardial and abdominal visceral adipose tissue (EAT and abdominal VAT, resp.). Out of 174 patients, 109 and 113 patients, respectively, presented coronary calcification (CC) and coronary atheromatous plaque (CP). The EAT and abdominal VAT areas were larger in patients with CP compared to those without it. Interestingly, the EAT area was larger in patients with CC compared to those without CC, whereas no difference was observed in the abdominal VAT area between patients with CC and those without. Multivariable logistic regression analysis revealed that the presence of echocardiographic EAT was an independent predictor of CP and CC, but the abdominal VAT area was not. These results suggest that EAT and abdominal VAT may play differential pathological roles in CAD. Given the importance of CC and CP, we should consider the precise assessment of CAD when echocardiographic EAT is detected.

Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction.

Serum uric acid is a predictor of cardiovascular mortality in heart failure with reduced ejection fraction. However, the impact of uric acid on heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we investigated the association between hyperuricemia and mortality in HFpEF patients. Consecutive 424 patients, who were admitted to our hospital for decompensated heart failure and diagnosed as having HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥7 mg/dl or taking antihyperuricemic agents). We compared patient characteristics, echocardiographic data, cardio-ankle vascular index, and cardiopulmonary exercise test findings between the two groups and prospectively followed cardiac and all-cause mortality. Compared with the non-hyperuricemia group (n = 170), the hyperuricemia group (n = 254) had a higher prevalence of hypertension (P = 0.013), diabetes mellitus (P = 0.01), dyslipidemia (P = 0.038), atrial fibrillation (P = 0.001), and use of diuretics (P < 0.001). Cardio-ankle vascular index (8.7 vs. 7.5, P < 0.001) and V̇e/V̇co2 slope (34.9 vs. 31.9, P = 0.02) were also higher. In addition, peak V̇o2 (14.9 vs. 17.9 ml·kg(-1)·min(-1), P < 0.001) was lower. In the follow-up period (mean 897 days), cardiac and all-cause mortalities were significantly higher in those with hyperuricemia (P = 0.006 and P = 0.004, respectively). In the multivariable Cox proportional hazard analyses after adjustment for several confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.036-3.793, P = 0.039). Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF.

Associations of dipeptidyl peptidase-4 inhibitors with mortality in hospitalized heart failure patients with diabetes mellitus

Heart failure (HF) and diabetes mellitus (DM) often co‐exist. Treatment of DM in HF patients is challenging because some therapies for DM are contraindicated in HF. Although previous experimental studies have reported that dipeptidyl peptidase‐4 (DPP‐4) inhibitors improve cardiovascular function, whether DPP‐4 inhibition improves mortality of HF patients with DM remains unclear. Therefore, we examined the impact of DPP‐4 inhibition on mortality in hospitalized HF patients using propensity score analyses.

Mitochondrial-Targeted Antioxidant Maintains Blood Flow, Mitochondrial Function, and Redox Balance in Old Mice Following Prolonged Limb Ischemia

Aging is a major factor in the decline of limb blood flow with ischemia. However, the underlying mechanism remains unclear. We investigated the role of mitochondrial reactive oxygen species (ROS) with regard to limb perfusion recovery in aging during ischemia. We performed femoral artery ligation in young and old mice with or without treatment with a scavenger of mitochondrial superoxide, MitoTEMPO (180 μg/kg/day, from pre-operative day 7 to post-operative day (POD) 21) infusion using an implanted mini-pump. The recoveries of cutaneous blood flow in the ischemic hind limb were lower in old mice than in young mice but were improved in MitoTEMPO-treated old mice. Mitochondrial DNA damage appeared in ischemic aged muscles but was eliminated by MitoTEMPO treatment. For POD 2, MitoTEMPO treatment suppressed the expression of p53 and the ratio of Bax/Bcl2 and upregulated the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in ischemic aged skeletal muscles. For POD 21, MitoTEMPO treatment preserved the expression of PGC-1α in ischemic aged skeletal muscle. The ischemic soleus of old mice showed a lower mitochondrial respiratory control ratio in POD 21 compared to young mice, which was recovered in MitoTEMPO-treated old mice. Scavenging of mitochondrial superoxide attenuated mitochondrial DNA damage and preserved the mitochondrial respiration, in addition to suppression of the expression of p53 and preservation of the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in ischemic skeletal muscles with aging. Resolution of excessive mitochondrial superoxide could be an effective therapy to recover blood flow of skeletal muscle during ischemia in senescence.