Hyperuricemia predicts adverse outcomes in patients with heart failure.

BACKGROUND: Hyperuricemia is associated with worse outcomes of patients with chronic heart failure (HF). However, it is unknown in an unselected HF patients encountered in routine clinical practice. We thus assessed the impact of hyperuricemia on long-term outcomes including mortality and rehospitalization among patients hospitalized with worsening HF. METHODS: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of hospitalized HF patients and the outcomes were followed for 2.1 years after discharge. Study cohorts (n=1869) were divided into 2 groups according to serum uric acid (UA) at discharge; ≥ 7.4 mg/dL (n=908) and <7.4 mg/dL (n=961). RESULTS: Of the total cohort of HF patients, 56% had hyperuricemia defined as UA ≥ 7.0mg/dl. Patients with UA ≥ 7.4 mg/dL had higher rates of all-cause death, cardiac death, rehospitalization, and all-cause death or rehospitalization due to worsening HF. After multivariable adjustment, higher UA levels were a significant and independent predictor for all-cause death (adjusted hazard ratio [HR] 1.413, 95% confidence interval [CI] 1.094-1.824, P=0.008) and cardiac death (adjusted HR 1.399, 95% CI 1.020-1.920, P=0.037). CONCLUSIONS: Hyperuricemia was common in patients with HF encountered in clinical practice and higher UA was independently associated with long-term adverse outcomes in these patients.

Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure.

BACKGROUND: The RALES trial demonstrated that spironolactone improved the prognosis of patients with heart failure (HF). However, it is unknown whether the discharge use of spironolactone is associated with better long-term outcomes among hospitalized systolic HF patients in routine clinical practice. We examined the effects of spironolactone use at discharge on mortality and rehospitalization by comparing with outcomes in patients who did not receive spironolactone. METHODS: The JCARE-CARD studied prospectively the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed with an average of 2.2 years of follow-up. RESULTS: A total of 946 patients had HF with reduced left ventricular ejection fraction (LVEF) (<40%), among whom spironolactone was prescribed at discharge in 435 patients (46%), but not in 511 patients (54%). The mean age was 66.3 years and 72.2% were male. Etiology was ischemic in 39.7% and mean LVEF was 27.1%. After adjustment for covariates, discharge use of spironolactone was associated with a significant reduction in all-cause death (adjusted hazard ratio 0.612, P=.020) and cardiac death (adjusted hazard ratio 0.524, P=.013). CONCLUSIONS: Among patients with HF hospitalized for systolic dysfunction, spironolactone use at the time of discharge was associated with long-term survival benefit. These findings provide further support for the idea that spironolactone may be useful in patients hospitalized with HF and reduced LVEF.

Body mass index is an independent predictor of long-term outcomes in patients hospitalized with heart failure in Japan.

BACKGROUND: Obesity is a risk factor for cardiovascular disease (CVD) and is also associated with an increased risk of death in subjects without CVD. However, in heart failure (HF), elevated body mass index (BMI) has been shown to be associated with better prognosis, but it is unknown whether this is the case in unselected HF patients encountered in routine clinical practice in Japan. METHODS AND RESULTS: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed for 2.1 years. Study cohort (n=2,488) was classified into 3 groups according to baseline BMI: <20.3kg/m(2) (n=829), 20.3-23.49kg/m(2) (n=832), and ≥23.5kg/m(2) (n=827). The mean BMI was 22.3±4.1kg/m(2). Patients with higher BMI had lower rates of all-cause death, cardiac death, and rehospitalization because of worsening HF. After multivariable adjustment, the risk for all-cause death and cardiac death significantly increased with decreased BMI levels compared with patients with BMI ≥23.5kg/m(2). However, BMI levels were not associated with rehospitalization for worsening HF. CONCLUSIONS: Lower BMI was independently associated with increased long-term all-cause, as well as cardiac, mortality in patients with HF encountered in routine clinical practice in Japan.

Beta-blocker use at discharge in patients hospitalized for heart failure is associated with improved survival.

BACKGROUND: Previous studies demonstrated that beta-blocker use at the time of hospital discharge significantly increased postdischarge treatment rates, associated with an early (60- to 90-day) survival benefit in patients with heart failure (HF). However, it is unknown whether this therapeutic approach can also improve the long-term survival. We thus examined the long-term effects of beta-blocker use at discharge on outcomes in patients hospitalized for HF and left ventricular systolic dysfunction (LVSD) (ejection fraction <40%). METHODS AND RESULTS: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) enrolled HF patients hospitalized with worsening symptoms and they were followed during an average of 2.2 years. A total of 947 patients had LVSD, among whom 624 (66%) were eligible to receive a beta-blocker at discharge. After adjustment for covariate and propensity score, discharge use of beta-blocker, when compared to no beta-blocker use, was associated with a significant reduced risk of all-cause mortality (hazard ratio (HR) 0.564, 95% confidence interval (CI) 0.358-0.889, P=0.014) and cardiac mortality (HR 0.489, 95%CI 0.279-0.859, P=0.013) after hospital discharge. CONCLUSIONS: Beta-blocker use at the time of discharge was associated with a long-term survival benefit in a diverse cohort of patients hospitalized with HF.

Discharge use of angiotensin receptor blockers provides comparable effects with angiotensin-converting enzyme inhibitors on outcomes in patients hospitalized for heart failure.

Large-scale, placebo-controlled, randomized clinical trials have shown that angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) reduce mortality and hospitalization in patients with heart failure (HF) caused by left ventricular systolic dysfunction (LVSD). However, it is unknown whether ACE inhibitors and ARBs have similar effects on the long-term outcomes in HF patients encountered in routine clinical practice. The Japanese Cardiac Registry of Heart Failure in Cardiology enrolled HF patients hospitalized with worsening symptoms and they were followed during an average of 2.2 years. The outcome data were compared in patients with LVSD by echocardiography (ejection fraction, EF <40%) according to the predischarge use of ACE inhibitors (n=356) or ARBs (n=372). The clinical characteristics were similar between patients with ACE inhibitor and ARB use, except for higher prevalence of hypertensive etiology and diabetes mellitus. There was no significant difference between ACE inhibitor and ARB use in all-cause death (adjusted hazard ratio 0.958, 95% confidence interval 0.601-1.527, P=0.858) and rehospitalization (adjusted hazard ratio 0.964, 95% confidence interval 0.683-1.362, P=0.836). The effects of ACE inhibitor and ARB use on the outcomes were generally consistent across all clinically relevant subgroups examined, including age, sex, etiology, EF, hypertension, diabetes mellitus, and beta-blocker use. Discharge use of ARBs provided comparable effects with ACE inhibitors on outcomes in patients hospitalized for HF. These findings provide further support for guideline recommendations that ARBs can be used in patients with HF and LVSD as an alternative of ACE inhibitors.

Role of left ventricular regional diastolic abnormalities for global diastolic dysfunction in patients with hypertrophic cardiomyopathy.

BACKGROUND: The usefulness of Doppler strain rate imaging for assessment of left ventricular regional diastolic function has not been fully determined. OBJECTIVE: We aimed to clarify the relationships between diastolic strain rates and global diastolic function and find a useful index for regional diastolic function in patients with hypertrophic cardiomyopathy (HCM). METHODS: Strain rate curves were obtained using an apical approach at 12 different sites of the left ventricular myocardium in 25 patients with HCM and 20 control subjects, and peak early diastolic strain rate (ESR), peak late diastolic strain rate, and the time from QRS to ESR were measured. The flow propagation velocity was measured using color M-mode Doppler echocardiography as a global diastolic index. RESULTS: Each of the spatially averaged values of ESR and ESR/peak late diastolic strain rate and the coefficients of variation of time from QRS to ESR was significantly correlated with flow propagation velocity, but the best correlation was observed in ESR. Although both ESR and peak late diastolic strain rate of each myocardial segment of patients with HCM tended to decrease as the wall thickness increased, only ESR significantly decreased even in the segments without apparent hypertrophy. CONCLUSIONS: In patients with HCM, the reduction of ESR was more closely associated with global diastolic dysfunction than asynchrony, and ESR may be a useful and sensitive index for regional diastolic function.

[Dilation of the brachial artery in response to sublingual nitroglycerin can predict the antihypertensive effects of valsartan: a study using novel high-frequency high-frame-rate ultrasound imaging].

OBJECTIVES: The efficacy of antihypertensive agents can vary in patients. Four to 8 weeks may be required before antihypertensive agents become fully effective. Predicting the efficacy can help agent selection and dose setting. This study determined whether nitroglycerin-induced vasodilation of brachial arteries can predict the antihypertensive action of angiotensin II receptor antagonist. METHODS: Untreated uncomplicated patients with essential hypertension, who gave informed consent, were studied (n = 20, mean age 55 years). Before antihypertensive treatment, nitroglycerin-induced vasodilation of the brachial arteries was measured using a novel method of 15 MHz high-frequency high-frame-rate ultrasound imaging (Hitachi EUB8000). Diameter of the brachial artery at the end-systolic phase was measured before and after 0.3 mg nitroglycerin sublingual spray and percentage vasodilation (%D-N) was calculated. The reduction of mean blood pressure after nitroglycerin (%BP-N) was calculated. Valsartan monotherapy (40-80 mg/day)was administered for 3-6 months (mean 132 days). Reduction of mean blood pressure after valsartan monotherapy (%BP-V) was calculated. RESULTS: Valsartan decreased systolic blood pressure from 138 +/- 13 to 130 +/- 17 mmHg, and diastolic blood pressure from 83 +/- 11 to 78 +/- 11 mmHg (p < 0.05). %D-N was correlated closely with %BP-V (r = - 0.70, p < 0.001). %BP-N had no correlation with %BP-V (r = 0.13, p = 0.58). CONCLUSIONS: Direct vasodilatory action of nitroglycerin on vascular smooth muscle cells may predict the chronic antihypertensive effect of angiotensin II receptor antagonist.

Increased plasma concentrations of N-terminal pro-brain natriuretic peptide reflect the presence of mildly reduced left ventricular diastolic function in hypertension.

BACKGROUND: The potential use of assays of N-terminal pro-brain natriuretic peptide for detection of diastolic abnormalities associated with alterations in blood pressure has not been elucidated. This study was designed to determine whether increased plasma concentrations of N-terminal pro-brain natriuretic peptide sensitively reflect abnormal diastolic function associated with hypertension. METHODS: Concentrations of N-terminal pro-brain natriuretic peptide in plasma were assayed in 40 previously untreated hypertensive patients without overt congestive heart failure and in 20 age and sex-matched controls. Hypertensive patients were studied with the use of pulsed Doppler and color M-mode Doppler echocardiography for the evaluation of left ventricular diastolic function. RESULTS: Concentrations of N-terminal pro-brain natriuretic peptide were elevated in hypertensive patients [75.1+/-75.2 (SD) pg/ml compared with 37.9+/-38.5 in controls, P<0.05]. In hypertensive patients, concentrations of N-terminal pro-brain natriuretic peptide were negatively correlated with the ratio of color M-mode flow propagation velocity to transmitral E velocity consistent with the view that increased concentrations of N-terminal pro-brain natriuretic peptide are indicative of alterations in diastolic function. Hypertensive patients with N-terminal pro-brain natriuretic peptide values above the mean value in the control group exhibited significantly increased brachial intimal-medial thickness and reduced wall stress, consistent with the view that increased N-terminal pro-brain natriuretic peptide was associated with favorable peripheral arterial remodeling. CONCLUSIONS: Elevated concentrations of N-terminal pro-brain natriuretic peptide in plasma reflect the presence of left ventricular diastolic abnormalities and peripheral arterial remodeling in asymptomatic patients with hypertension.

Sensitive detection of myocardial viability in chronic coronary artery disease by ultrasonic integrated backscatter analysis.

BACKGROUND: Myocardial viability is not synonymous with contractile reserve and identifiable in a significant percentage of dysfunctional myocardial segments without contractile reserve. The usefulness of ultrasonic tissue characterization by the phase-corrected magnitude of cyclic variation of integrated backscatter (MVIB) in chronic coronary artery disease is not fully validated. Thus, whether MVIB predominantly reflects the contractile reserve or myocardial viability of chronically dysfunctional myocardium was determined. METHODS: The MVIB of severely dysfunctional interventricular septum or posterior wall was measured in 34 consecutive patients with previous myocardial infarction. Dobutamine stress echocardiography and fluorine-18 fluorodeoxyglucose positron emission tomography were used as the standards of contractile reserve and myocardial viability, respectively. RESULTS: Among 44 dysfunctional segments, only 15 were judged as having contractile reserve and 29 were judged as not by dobutamine stress echocardiography, whereas 26 segments showed myocardial viability using fluorine-18 fluorodeoxyglucose positron emission tomography and 18 did not. MVIB was greater in segments with than in those without contractile reserve (4.7 +/- 2.2 vs -1.4 +/- 4.9 dB, P < .0001), but there was considerable overlap between the groups. On the other hand, MVIB of segments with and without myocardial viability (4.1 +/- 2.6 vs -4.3 +/- 3.3 dB, P < .0001) was distinctly different and predicted myocardial viability with a sensitivity of 92% and a specificity of 94%. CONCLUSIONS: For patients with chronic coronary artery disease, MVIB better reflects myocardial viability than it does contractile reserve. Ultrasonic tissue characterization, in concordance with fluorine-18 fluorodeoxyglucose positron emission tomography, is a sensitive method for detecting myocardial viability.

Maladaptive arterial remodeling with systemic hypertension associated with increased concentrations in blood of plasminogen activator inhibitor type-1 (PAI-1).

Increased carotid artery intima-media thickness (IMT), but not necessarily peripheral vessel IMT, accompanies atherosclerosis. We hypothesized that IMT in a peripheral, muscular artery known to be resistant to atherosclerotic changes would increase with hypertension, thereby limiting increases in wall stress and potentially preserving endothelial cell function reflected by flow-mediated dilation (FMD). Plasminogen activator inhibitor type-1 (PAI-1) can inhibit vascular smooth muscle cell migration contributing to increased IMT. Thus, increased PAI-1 may attenuate the mural adaptive response. A high-resolution scanner designed to delineate brachial artery FMD and IMT was used in studies of previously untreated patients with essential hypertension (n = 18) and age- and gender-matched normotensive subjects (n = 15). Brachial IMT was increased with hypertension (0.36 +/- 0.07 vs 0.27 +/- 0.03 mm in controls, p <0.01), and FMD was lower (3.6 +/- 1.5% vs 7.8 +/- 3.6, p <0.01). PAI-1 antigen in blood was increased (40.5 +/- 31.8 vs 26.3 +/- 11.6 ng/ml, p <0.05). IMT and FMD correlated positively (r = 0.63, p <0.05) in hypertensive patients. FMD correlated inversely with wall stress (r = -0.57, p <0.05). IMT correlated inversely with PAI-1 (r = -0.61, p <0.05). These observations support the hypothesis that increased PAI-1 attenuated increases in neointimal vascular smooth muscle cell cellularity. Thus, increased PAI-1 may attenuate a mural, adaptive response to hypertension associated with preservation of endothelial cell function.