Febuxostat (Feburic tablet) in the management of hyperuricemia in a general practice cohort of Japanese patients with a high prevalence of cardiovascular problems.

Hyperuricemia is increasing in prevalence and this is paralleled by an increased incidence of acute gout. In addition, there is growing evidence of an association between high serum levels of uric acid (sUA) and cardiovascular disease (CVD). In this preliminary report, we present 12-16 week results from a multicenter, general practice study in which we evaluated the usefulness of febuxostat in a cohort of untreated patients with hyperuricemia with a high prevalence of CVD. Febuxostat titrated from 10 mg/day up to 40 mg/day resulted in statistically significant and clinically relevant reductions in sUA after 12-16 weeks. A "responder" level of 6.0 mg/dL or lower was achieved in 95 of 100 (95%) patients. Significant reductions in sUA were achieved regardless of the presence/absence of coexisting diseases (e.g. CVD, renal insufficiency, diabetes and obesity) or the class of antihypertensive agent being used by the patient. No serious adverse reactions were noted with febuxostat. Although allopurinol has been used generally for hyperuricemia/gout, it is excreted fully via the kidneys, restricting its use in patients with reduced renal function, and its three-times-daily administration leads to poor adherence. Based on the results of this study, febuxostat may provide an easier option than allopurinol for clinicians specializing in CVDs.

Prognostic significance of T-wave amplitude in lead aVR in heart failure patients with narrow QRS complexes.

BACKGROUND: Prolonged duration of the QRS complex is a prognostic marker in patients with heart failure (HF), whereas electrocadiographic markers in HF with narrow QRS complex remain unclear. We evaluated the prognostic value of the T-wave amplitude in lead aVR in HF patients with narrow QRS complexes. METHODS: We examined 331 patients who were admitted to our hospital for worsening HF (68 ± 15 years, mean ± standard deviation) from January 2000 to October 2004 who had sinus rhythm and QRS complex <120 ms. The patients were categorized into three groups according to the peak T-wave amplitude from baseline in lead aVR: negative (<-0.1 mV; n = 209, 63%), flat (-0.1-0.1 mV; n = 64, 19%), and positive (>0.1 mV; n = 58, 18%). RESULTS: During a mean follow-up of 33 months, 113 (34%) patients had all-cause death, the primary end point. After adjusting for clinical covariates, flat T wave (hazard ratio [HR] 1.86, 95% confidence interval [CI] 1.42-2.46), and positive T wave (HR 6.76, 95% CI 3.92-11.8) were independent predictors of mortality, when negative T wave was considered a reference. CONCLUSIONS: As the peak T-wave amplitude in lead aVR becomes less negative, there was a progressive increase in mortality. The T wave in lead aVR provides prognostic information for risk stratification in HF patients with narrow QRS complexes.

Prognostic significance of circadian variability of RR and QT intervals and QT dynamicity in patients with chronic heart failure.

BACKGROUND: In patients with chronic heart failure (CHF), circadian variability of RR and QT intervals may be altered because of neurohumoral activation and functional and structural remodeling of the heart. OBJECTIVE: The aim of this study was to evaluate the prognostic significance of circadian variability of the RR and QT intervals and QT dynamicity (QT/RR slope) in CHF patients. METHODS: We prospectively enrolled 121 patients with stable CHF in sinus rhythm (age 67 +/- 14 years, mean +/- SD; range 34 to 87 years). The RR, QT, and rate-corrected QT (QTc) intervals and the QT/RR slope measured from 24-hour Holter electrocardiogram were fitted by cosine curves. RESULTS: During the follow-up period of 34 +/- 17 months, 40 (33%) patients died of cardiac causes, 10 of which were sudden. All patients showed significant circadian rhythms in the RR, QT, and QTc intervals and the QT/RR slope by cosine-curve fitting. In addition to the expected higher heart rate, longer QT interval, and steeper QT/RR slope, we found that patient who died of cardiac causes had reduced circadian variability of QT interval (10 +/- 10 ms vs 21 +/- 13 ms) and a later maximum RR interval (4.1 +/- 0.9 AM vs 2.3 +/- 2.1 AM) compared with survivors, among many other statistically significant circadian parameter differences. These 2 parameters were independent predictors of cardiac death in multivariate Cox proportional hazards regression analysis. CONCLUSION: Circadian variability analyses of Holter-derived RR and QT intervals may provide prognostic information beyond that provided by 24-hour averages of these parameters.

Seasonal variation in paroxysmal atrial fibrillation documented by 24-hour Holter electrocardiogram.

BACKGROUND: The incidence of various cardiovascular diseases is known to exhibit seasonal variations, but seasonal patterns of paroxysmal atrial fibrillation (AF) have not been well characterized. OBJECTIVE: The objective of this study was to determine whether seasonal variation affects the incidence of paroxysmal AF and whether this pattern is affected by patient age. METHODS: We identified 258 paroxysmal AF episodes in 237 patients (age 65 +/- 14 years, mean +/- standard deviation; age range 16-95 years) among 12,390 consecutive 24-hour Holter electrocardiogram recordings obtained from 2001 to 2005 at our institute. Seasonal variations were analyzed by both month and by season. The relative risk (RR) of AF for each period was determined as being high or low in relation to the overall mean incidence. The association among clinical covariates and risk of paroxysmal AF was tested by logistic regression analysis. RESULTS: The incidence of paroxysmal AF was highest in September (RR = 1.40, 95% confidence interval [CI] 1.36-1.44) and lowest in June (RR = 0.52, 95% CI 0.50-0.54), with an RR difference of 63% (P < .001) among all patients. Patients aged > or =65 years demonstrated a peak incidence in September (RR = 1.46, 95% CI 1.41-1.51) and a minimum in June (RR = 0.55, 95% CI 0.52-0.58), while those aged <65 years showed a peak incidence in December (RR = 1.33, 95% CI 1.27-1.39) and a minimum in June (RR = 0.49, 95% CI 0.45-0.53). The incidence of paroxysmal AF also showed an autumn peak (RR = 1.21, 95% CI 1.16-1.27) and a summer minimum (RR = 0.66, 95% CI 0.62-0.70), with an RR difference of 53% (P < .001) among all patients. This seasonal variation in paroxysmal AF did not differ between patients of different age ranges. Clinical covariates including underlying disease or medications did not influence the monthly or seasonal variation in paroxysmal AF. There was a significant inverse relationship between the incidence of paroxysmal AF and the length of daylight in patients aged <65 years (r = -0.57, P < .05). CONCLUSION: There was a significant seasonal variation in paroxysmal AF, with maximum and minimum incidences in autumn and summer, respectively, and this pattern was not age dependent.

High-sensitivity C-reactive protein is predictive of successful cardioversion for atrial fibrillation and maintenance of sinus rhythm after conversion.

BACKGROUND: Cardioversion for atrial fibrillation (AF) is the most effective treatment for the restoration of sinus rhythm (SR). Recently, an elevated level of hs-CRP has been shown to be associated with AF burden, suggesting that inflammation increases the propensity for persistence of AF. We examined whether the level of high-sensitivity C-reactive protein (hs-CRP) was predictive of the outcome of cardioversion for AF. METHODS AND RESULTS: One hundred and six patients with a history of symptomatic AF lasting > or =1 day (age 63+/-14 years, mean+/-S.D.) underwent cardioversion. Echocardiography and hs-CRP assay were performed immediately prior to cardioversion. SR was restored in 84 patients (79%). By using selected cutoff values, multiple discriminant analysis revealed significant associations between successful cardioversion and a shorter duration of AF (AF duration< or =36 days, odds ratio (OR), 0.98; 95% confidence interval (CI), 0.97-0.99), smaller left atrial diameter (left atrial diameter< or =40 mm, OR 0.82, 95% CI 0.71-0.94), better-preserved left ventricular ejection fraction (left ventricular ejection fraction> or =60%, OR 0.92, 95% CI 0.86-0.99), and lower hs-CRP level (hs-CRP< or =0.12 mg/dL, OR 0.33, 95% CI 0.21-0.51). During a follow-up period of 140+/-144 days, AF recurred in 64 patients (76%). By using a cutoff value of hs-CRP> or =0.06 mg/dL, Cox proportional-hazards regression model found that only hs-CRP level was an independent predictor of AF recurrence (OR 5.30, 95% CI 2.46-11.5) after adjustment for coexisting cardiovascular risks. When patients were divided by the hs-CRP level of 0.06 mg/dL, percentage of maintenance of SR below and above the cutoff was 53% and 4%, respectively (log-rank test, p<0.0001). CONCLUSIONS: hs-CRP level determined prior to cardioversion represents an independent predictor of both successful cardioversion for AF and the maintenance of SR after conversion.