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.

Cyclic variation in heart rate score by holter electrocardiogram as screening for sleep-disordered breathing in subjects with heart failure.

BACKGROUND: Sleep-disordered breathing (SDB) is critically associated with cardiovascular mortality and morbidity, especially in patients with heart failure (HF). However, the majority of SDB patients remain undiagnosed. In contrast, abnormality in heart rate variability has been reported in patients with SDB. To explore an efficient electrocardiogram (ECG)-based screening tool for SDB, we examined the usefulness of cyclic variation in heart rate score (CVHRS) by Holter ECG in subjects with HF. METHODS: In this study, 102 subjects with HF were enrolled. We simultaneously performed Holter ECG with overnight portable sleep monitoring, and we measured the respiratory disturbance index (RDI) and CVHRS. We determined the temporal position of the individual dips comprising the CVHRS using time-domain methods. CVHRS was measured as cyclic and autocorrelated dips in smoothed interbeat interval time series. RESULTS: There were 25 subjects with severe SDB (RDI ≥ 30 events/h) and 77 subjects with none-to-moderate SDB (0 ≤ RDI < 30 events/h). There was a significant positive correlation between CVHRS and RDI (r = 0.60, P < .001). In receiver operating characteristic analysis, CVHRS (cutoff of 30 events/h) identified severe SDB with a sensitivity of 82%, a specificity of 77%, and an area under the curve of 0.83. CONCLUSIONS: CVHRS determined by Holter ECG is a useful screening index for severe SDB in subjects with HF.

Sudden cardiac arrest associated with an anomalous aortic origin of the left coronary artery from the opposite sinus of valsalva.

A 13-year-old boy was brought to our hospital after recovering from ventricular fibrillation that occurred after an episode of chest pain during training with his soccer team. Subsequent 64-slice multidetector computed tomography revealed the left coronary artery arising from the right sinus of Valsalva, which coursed between the ascending aorta and root of the main pulmonary artery. Surgical correction including unroofing of the left coronary ostium and pulmonary artery translocation was performed successfully. One year later, he remained asymptomatic and was back on his soccer team.

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

BACKGROUND: 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. MATERIALS AND METHODS: We researched consecutive 648 patients admitted for HF as follows: underweight (BMI < 18·5 kg/m(2) , n = 86), normal (18·5 ≤ BMI < 25, n = 380), overweight (25 ≤ BMI < 30, n = 147) and obese (30 ≤ BMI, n = 35) and compared the results from their laboratory tests and echocardiography. We also followed cardiac and all-cause mortality. RESULTS: Obese group had a higher prevalence of obesity-related comorbidity (hypertension, diabetes, dyslipidemia); however, tumour necrosis factor-α, adiponectin, troponin T and systolic pulmonary arterial pressure were higher in the underweight group than in the other groups (P < 0·05, respectively). Left and right ventricular systolic function did not differ among the groups. In the Kaplan-Meier analysis, cardiac and all-cause mortality progressively increased from obese to overweight, normal and underweight group. Importantly, in the Cox proportional hazard analyses after adjusting for known risk factors, BMI was an independent predictor of cardiac and all-cause mortality (P < 0·01, respectively) in HF patients. CONCLUSIONS: Body mass index was an independent predictor of cardiac death and all-cause mortality in HF patients. Furthermore, lower BMI was associated with higher circulating levels of tumour necrosis factor-α, adiponectin and troponin T and higher systolic pulmonary arterial pressure.

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.

Phosphodiesterase 3A1 protects the heart against angiotensin II-induced cardiac remodeling through regulation of transforming growth factor-ß expression.

Accumulating evidence suggests that there are direct interactions between ß-adrenergic and angiotensin II signaling pathways, and ß-blockers protect the heart against angiotensin II-induced cardiac remodeling. Phosphodiesterase 3A (PDE3A) regulates ß-adrenergic receptor/protein kinase A signaling by metabolizing cAMP. Therefore, we hypothesized that overexpressed PDE3A has cardioprotective effects against angiotensin II-induced cardiac remodeling by regulating angiotensin II signaling. In the present study, we used transgenic mice with cardiac-specific overexpressed PDE3A1. We showed that continuous administration of angiotensin II caused cardiac hypertrophy in the wild-type mouse heart, but not in the transgenic mouse heart. Angiotensin II induced cardiac fibrosis in both wild-type and transgenic mice, but the extent of fibrosis was less in transgenic mice compared to wild-type mice. Moreover, basal expression levels of transforming growth factor-ß were lower in transgenic mouse hearts, and it remained at lower levels after angiotensin II stimulation. These findings suggest that PDE3A protects the heart from angiotensin II-induced cardiac remodeling through its modulation of the functional connection between angiotensin II and transforming growth factor-ß.

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.

High-sensitivity cardiac troponin T predicts non-cardiac mortality in heart failure.

BACKGROUND: Cardiac troponins are independent predictors of cardiac mortality in patients with heart failure (HF). Recently, elevation of troponins was described in non-cardiac diseases such as stroke and infection, among others, but it remains unclear whether high-sensitivity troponin T (hs-TnT) predicts non-cardiac mortality in HF patients. METHODS AND RESULTS: Four-hundred and forty-four consecutive HF patients admitted to hospital for the treatment of decompensated HF were divided into 2 groups based on median hs-TnT: group L (<0.028ng/ml, n=220) and group H (≥0.028ng/ml, n=224). We compared all-cause mortality and echocardiographic findings between the 2 groups. In the follow-up period (mean 472 days), 77 deaths (49 cardiac deaths and 28 non-cardiac deaths) were observed. The event-free rate was significantly lower in group H than in group L for non-cardiac death (P=0.025), cardiac death (P<0.001), and all-cause mortality (P<0.001). On multivariate Cox proportional hazard analysis, high hs-TnT was found to be an independent predictor of non-cardiac death (P=0.042), cardiac death (P<0.001) and all-cause mortality (P<0.001) in HF patients after adjusting for risk factors. Regarding echocardiographic parameters, left ventricular wall thickness was higher (P<0.001), and ejection fraction was lower (P=0.011) in group H than in group L. CONCLUSIONS: Hs-TnT is an independent predictor not only of cardiac mortality, but also of non-cardiac mortality in HF patients.

Suppressive effects of adaptive servo-ventilation on ventricular premature complexes with attenuation of sympathetic nervous activity in heart failure patients with sleep-disordered breathing.

Ventricular arrhythmias play a critical role in chronic heart failure (CHF) and are associated with adverse clinical outcomes. Sleep-disordered breathing (SDB) is associated with arrhythmias and/or a poor prognosis in CHF. Adaptive servo-ventilation (ASV) is a ventilatory support system designed to normalize ventilation in CHF patients with SDB. However, the effects of ASV on ventricular arrhythmias and sympathetic nervous activity are still unclear. Nineteen CHF patients with SDB were examined. We performed simultaneous overnight polysomnography and 24-h Holter ECG monitoring, and measured levels of daily urinary catecholamines for two consecutive days (baseline and on ASV). ASV significantly improved the apnea-hypopnea index (p < 0.01), arousal index (p < 0.01), and mean SpO(2) (p < 0.01), and decreased daily urinary catecholamines (0.466-0.353 mg/day, p = 0.016) compared to baseline. Furthermore, power in the low to high frequency range as a marker of sympathetic nervous activity decreased across a 24-h period (24-h period: 2.8-1.9, p = 0.017; during daytime: 3.7-2.3, p = 0.013; and during sleep time: 1.5-1.3, p = 0.026). Importantly, ASV significantly decreased ventricular premature complexes not only during sleep time but also across a 24-h period (40.5-21.9 beats/h, p = 0.013). The short-term use of ASV reduced ventricular arrhythmias with the attenuation of sympathetic nervous activity, as demonstrated by urinary catecholamines and heart rate variability. ASV may have anti-sympathetic nervous and anti-arrhythmic effects for CHF with SDB.

A case of acute myocardial infarction during perioperative period of non-cardiac surgery in a patient with antiphospholipid syndrome and a history of coronary artery bypass surgery.

A 65-year-old woman underwent coronary artery bypass surgery and was diagnosed with antiphospholipid syndrome (APS) at the same time in 1985. She was admitted to our hospital to undergo mastectomy for left breast cancer in 2012. She was put on intravenous infusion of heparin and stopped receiving both antiplatelet agents and warfarin. The operation was performed without complications, and antithrombotic therapy was restarted one day after the operation. On day 6 postoperative, she complained of sudden chest pain and on examination she was diagnosed with acute myocardial infarction. The culprit lesion was in a saphenous vein graft and coronary intervention was performed. .

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.

Adaptive servoventilation improves cardiorenal function and prognosis in heart failure patients with chronic kidney disease and sleep-disordered breathing.

BACKGROUND: Chronic kidney disease (CKD) and sleep-disordered breathing (SDB) play critical roles in the progression of chronic heart failure (CHF). However, it still remains unclear whether adaptive servoventilation (ASV) improves cardiorenal function and the prognosis of CHF patients with CKD and SDB. METHODS AND RESULTS: Eighty CHF patients with CKD (estimated glomerular filtration rate of <60 mL min(-1) 1.73 cm(-2)) and SDB (apnea-hypopnea index >15/h) were enrolled and divided into 2 groups: 36 patients were treated with usual care plus ASV (ASV group) and 44 patients were treated with usual care alone (Non-ASV group). Levels of B-type natriuretic peptide, glomerular filtration rate, cystatin C, C-reactive protein, noradrenaline, and left ventricular ejection fraction were measured before treatment and 6 months after treatment. Patients were followed to register cardiac events occurring after enrollment. Six months of ASV therapy reduced levels of B-type natriuretic peptide, cystatin C, C-reactive protein, and noradrenaline and improved the glomerular filtration rate and ejection fraction (all P < .05). However, none of these parameters changed in the Non-ASV group. Thirty-two events (14 deaths and 18 rehospitalizations) occurred during the follow-up period (mean 513 days). Importantly, the event-free rate was significantly higher in the ASV group than in the Non-ASV group (77.8% vs 45.5%; log rank P < .01). CONCLUSIONS: ASV improves the prognosis of CHF patients with CKD and SDB, with favorable effects such as the improvement of cardiorenal function and attenuation of inflammation and sympathetic nervous activity.

Short-term use of adaptive servo ventilation improves renal function in heart failure patients with sleep-disordered breathing.

Sleep-disordered breathing (SDB) deteriorates the prognosis of patients with chronic heart failure (CHF). Adaptive servo ventilation (ASV) is a new therapeutic modality to treat SDB including Cheyne-Stokes respiration associated with central sleep apnea. Renal function plays critical roles in the progression of CHF and is a strong predictor of clinical outcomes. Cystatin C is a marker of renal function, and more sensitive than serum creatinine. The purpose of the present study was to examine whether ASV is effective for cardiac overload and renal dysfunction in CHF patients with SDB. Fifty patients with CHF and SDB (mean left ventricular ejection fraction 34.0 %, estimated glomerular filtration rate (eGFR) 62.8 ml/min/1.73 cm(2)) were examined. We performed polysomnography for two consecutive days (baseline and on ASV), and measured levels of serum N terminal-pro B-type natriuretic peptide (NT-pro BNP), cystatin C, and estimated glomerular filtration rate based on cystatin C (eGFR Cyst C). ASV significantly improved the apnea hypopnea index, central apnea index, obstructive apnea index, arousal index, mean SPO2, and lowest SPO2 compared to baseline. ASV decreased NT-pro BNP (1,109.0 (2,173.2) to 912.8 (1,576.7) pg/ml, p < 0.05), cystatin C (1.391 ± 0.550-1.348 ± 0.489 mg/l, p < 0.05), and increased eGFR Cyst C (61.9 ± 30.8-65.7 ± 33.8 ml/min/1.73 cm(2), p < 0.01). ASV improved SDB, reduced cardiac overload, and ameliorated renal function in CHF patients with SDB. ASV has short-term beneficial effects on not only SDB but also cardio-renal function. ASV might be a promising useful tool for CHF as an important non-pharmacotherapy with cardio-renal protection.

A reduction of coronary flow reserve is associated with chronic kidney disease and long-term cardio-cerebrovascular events in patients with non-obstructive coronary artery disease and vasospasm.

BACKGROUND: Coronary flow reserve (CFR) provides essential information about the coronary microvasculature. Chronic kidney disease (CKD) is a risk factor for cardio-cerebrovascular diseases. We hypothesized that low CFR is associated with CKD and long-term cardio-cerebrovascular events in the patients without obstructive coronary artery diseases and vasospasm. METHOD AND RESULTS: In this study, 73 patients suspected with coronary artery disease but had no epicardial coronary stenosis and vasospasm were enrolled. There were 13 CKD patients and CFR was measured using the Doppler flow wire methods in the left anterior descending artery. CFR was significantly lower in CKD group than non-CKD group (3.13 ± 0.6 vs. 4.00 ± 1.1, P = 0.007). From multivariate logistic regression analysis, the independent factor associated with the presence of CKD was only CFR (odds ratio 3.85, 95% confidence interval 1.27-11.70, P = 0.017). In the patients with low CFR (≤ 2.8), cardio-cerebrovascular events were more common than those with normal CFR (CFR > 2.8). Besides, in the patients who had both low CFR and CKD, long-term cardio-cerebrovascular events were more likely to occur than those with normal CFR or non-CKD. CONCLUSIONS: Our data suggest that low CFR is associated with CKD and cardio-cerebrovascular events in the patients without coronary stenosis and vasospasm.

Adaptive servo ventilation improves cardiac dysfunction and prognosis in chronic heart failure patients with Cheyne-Stokes respiration.

Cheyne-Stokes respiration (CSR) is often observed in patients with chronic heart failure (CHF). Although adaptive servo ventilation (ASV) is effective for CSR, it remains unclear whether ASV improves the cardiac function and prognosis of patients with CHF and CSR.Sixty patients with CHF and CSR (mean left ventricular ejection fraction 38.7%, mean apnea hypopnea index 36.8 times/hour, mean central apnea index 19.1 times/hour) were enrolled in this study. Patients were divided into two groups: 23 patients treated with ASV (ASV group) and 37 patients treated without ASV (Non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels and echocardiography were performed before, 3 and 6 months after treatments in each group. Patients were followed-up for cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, NYHA functional class, BNP levels, cardiac systolic and diastolic function were significantly improved with ASV treatment for 6 months. In contrast, none of these parameters changed in the Non-ASV group. Importantly, Kaplan-Meier analysis clearly demonstrated that the event-free rate was significantly higher in the ASV group than in the Non-ASV group.Adaptive servo ventilation improves cardiac function and prognosis in patients with chronic heart failure and Cheyne-Stokes respiration.