Mohammed Yousufuddin

Incremental changes in QRS duration in serial ECGs over time identify high risk elderly patients with heart failure

Aims: To investigate the hypothesis that changes in the ECG over time may be an important and readily available marker of prognostic value in patients with heart failure. Methods: 112 elderly patients (81 men) with stable heart failure, a mean (SD) age of 73.3 (4.4) years, left ventricular ejection fraction 38 (17)%, and peak oxygen consumption 15.1 (4.7) ml/kg/min had ECG measurements on two occasions a minimum of 12 (5) months apart. Results: During the subsequent follow up period (mean 27 (17) months) 45 patients died. QRS duration (p = 0.001) and heart rate (p = 0.03) at baseline were found by Cox proportional hazard method analysis to predict adverse outcomes in these patients. Of the changes in ECG parameters between the first and second visit, broadening of QRS duration (p = 0.001) predicted mortality. On Kaplan-Meier survival analysis, patients with < 5% change in QRS duration had fewer end points than patients with 5–20% change. A > 20% increase in QRS duration was associated with the worst prognosis. Progressive prolongation of QRS duration correlated closely with deterioration of LV systolic and diastolic function. Conclusion: A single measurement of QRS duration has significant prognostic value in elderly patients with heart failure and the increase in QRS duration over time is an even better predictor of adverse out comes.

Femoral haemostasis after transcatheter therapeutic intervention: a prospective randomised study of the angio-seal device vs. the femostop device

BACKGROUND A number of haemostatic devices are available to facilitate early haemostasis following transfemoral interventional procedures. METHODS AND RESULTS We have prospectively compared 150 patients (age: 57+/-12 years, mean+/-S.D.) who were randomly assigned to either external compression using the FemoStop device or direct closure of the arterial puncture using the Angio-Seal device. The Angio-Seal was deployed in the catheter laboratory after the conclusion of the procedure. Patients, randomised to FemoStop, had their sheath removed when the activated clotting time (ACT) was less than 100 s before applying the device. The primary endpoint was the composite of bleeding, haematoma formation, bruise, requirement for blood transfusion, clinical indication for ultrasound examination at 2 h and 24 h following the procedure and crossover to either method at 2 and 24 h after the device deployment. The 95% of the Angio-Seal and 96% of FemoStop patients were discharged on the day following the procedure. An increased number of patients in the Angio-Seal group reached a clinical end-point within the first 2 h (45% vs. 3%, P<0.0001). This difference became insignificant at 24 h (25% vs. 30%, P=0.6). CONCLUSION Although less comfortable, the overall efficacy of the FemoStop appeared to be higher than that of the Angio-Seal device.

Gender differences in the urinary excretion rates of cortisol and androgen metabolites

Animal studies show significant differences in steroid metabolism between male and female subjects. Similar studies in human subjects are still needed. The aim of this study was to evaluate differences in 24-h urinary excretion of cortisol and androgen metabolites between healthy male and female volunteers to estimate if such differences were significant. Urinary metabolite measurements were performed by gas chromatography. The median urinary excretion of total cortisol metabolites was 6965 μg/day for men and 4595 μg/day for women (P=0·0005). Urinary excretion of 11 β-hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol (5β), allotetrahydrocortisol (5α), α-cortolone, β-cortolone + β-cortol and α-cortol were also significantly different in men compared with women. Total androgen metabolites in men (2660 μg/day) were also higher than in women (1850 μg/day) (P< 0·0003). Similarly, urinary excretion of androsterone (5α), aetiocholanolone (5β) and dehydroepiandrosterone were also significantly greater (all P=0·01). This confirms significant differences in the steroid metabolite excretion profiles between men and women. Laboratories should consider adopting gender-related reference ranges for cortisol and androgen metabolite excretion in 24-h urine samples.

Incremental importance of peak-exercise plasma levels of endothelin-1 and natriuretic peptides in chronic heart failure

&NA; Chronic heart failure (CHF) studies investigating the clinical, hemodynamic, and therapeutic importance of endothelin‐1 (ET‐1), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) are largely based on resting plasma levels, which may vary with prior exertion and postprandial status. This study investigated the importance of peak‐exercise plasma levels of ET‐1, ANP, and BNP in the assessment of left ventricular (LV) systolic function. Thirty‐six male‐patients ages 58 ± 10 (mean ± SD ) with NYHA class I‐IV CHF due to coronary artery disease or idiopathic dilated cardiomyopathy were enrolled. LV systolic function was assessed by echocardiography and radionuclide ventriculography. Resting and peak cardiopulmonary exercise venous blood sampling and treadmill exercise testing were performed in the fasting state. Resting plasma levels of ET‐1, ANP, and BNP were elevated compared with reference laboratory normal values. Exercise induced significant (p < 0.0001) increase in plasma levels of ET‐1, ANP, and BNP. On univariate analysis peak‐exercise plasma levels of ET‐1, ANP, and BNP were more closely related to echocardiographically determined LV end‐diastolic diameter and end‐systolic diameter than their resting values. Multiple step‐wise regression models identified resting and peak‐exercise plasma levels of ET‐1 and ANP but only the resting BNP as independent predictors of LV dimensions and systolic function. Peak exercise plasma levels of ANP and ET‐1 are potentially more reliable and important than their resting levels as markers of LV systolic dysfunction and LV dimensions in patients with heart failure.

Raised urinary glucocorticoid and adrenal androgen precursors in the urine of young hypertensive patients: possible evidence for partial glucocorticoid resistance

OBJECTIVE To evaluate urinary glucocorticoid excretion profiles in a cohort of recently diagnosed young hypertensive patients. METHODS After excluding patients with secondary causes, 60 individuals with premature hypertension were recruited (diagnosed by ambulatory blood pressure monitoring before the age of 36 years). In addition, 30 older hypertensive controls (age of onset > 36 years, “middle aged hypertensive controls”), and 30 normal controls (age matched to the young hypertensive group) were studied. All provided 24 hour urine collections for mass spectrometry for total cortisol metabolites and total androgen metabolites by gas chromatography. RESULTS Among male patients, those with premature hypertension had higher total urinary excretion of cortisol metabolites (mean (SD), 13 332 (6472) μg/day) than age matched normal controls (7270 (1788) μg/day; p = 0.00001) or middle aged hypertensive controls (8315 (3565) μg/day; p = 0.002). A similar increase was seen among the female patients, although the absolute concentrations were lower. There was no significant difference between middle aged hypertensive patients and normal controls. Urinary total androgen excretion profiles in female patients also showed an unusual increase in the premature hypertension group (2958 (1672) μg/day) compared with the other groups (middle aged hypertensive controls, 1373 (748) μg/day, p = 0.0003; normal controls, 1687 (636) μg/day, p = 0.002). In all subjects, serum sodium and creatinine concentrations were within the normal range; serum potassium concentrations were found to be low before the start of treatment. CONCLUSIONS Individuals presenting with premature hypertension have an abnormally high excretion of glucocorticoid metabolites in the urine. While the mechanism remains uncertain, these findings are compatible with partial resistance of the glucocorticoid receptors, with a compensatory increase in cortisol and androgen metabolites. The mineralocorticoid effects of the latter (sodium and water retention) may contribute to an abnormally high blood pressure and may have implications for targeted selection of first line treatment in young hypertensive patients.

Risk factors of coronary heart disease: A Bayesian model averaging approach

To analyse the risk factors of coronary heart disease (CHD), we apply the Bayesian model averaging approach that formalizes the model selection process and deals with model uncertainty in a discrete-time survival model to the data from the Framingham Heart Study. We also use the Alternating Conditional Expectation algorithm to transform the risk factors, such that their relationships with CHD are best described, overcoming the problem of coding such variables subjectively. For the Framingham Study, the Bayesian model averaging approach, which makes inferences about the effects of covariates on CHD based on an average of the posterior distributions of the set of identified models, outperforms the stepwise method in predictive performance. We also show that age, cholesterol, and smoking are nonlinearly associated with the occurrence of CHD and that P-values from models selected from stepwise methods tend to overestimate the evidence for the predictive value of a risk factor and ignore model uncertainty.