Kenneth Ng

Bromocriptine use and the risk of valvular heart disease

It has been reported that patients on pergolide and carbergoline have an increased risk of developing valvular heart disease. It is uncertain if bromocriptine, an ergot‐derived dopamine agonist (DA) with partial 5‐HT2B activity, is associated with a similar risk. We assessed the frequency of valvular heart disease in Parkinsons disease (PD) patients on bromocriptine compared to pergolide and a control group of PD patients who had not been treated on any DA. Seventy‐two PD patients on bromocriptine, 21 patients on pergolide, and 47 control PD patients were recruited. Transthoracic echocardiographic studies were performed and reviewed by a blinded cardiologist. The risk for the bromocriptine group to develop any abnormal valvular regurgitation was 3.32 (adjusted OR, 95% CI: 1.11–9.92, P = 0.03) compared to controls, whereas the risk for the pergolide group was 3.66 (adjusted OR, 95% CI: 1.22–10.97, P = 0.02). When cumulative dose of bromocriptine was analyzed by quartiles, patients with a greater exposure to bromocriptine had significantly higher risk of developing both mild and moderate‐severe regurgitations (P for trend, 0.005 and 0.019, respectively). This study demonstrated that bromocriptine use was associated with an increased risk of developing valvular heart disease, which occurred in a cumulative dose‐dependent manner.

Impact of race on morbidity and mortality in patients with congestive heart failure: A study of the multiracial population in Singapore

AIM We assessed the impact of race on clinical outcome in the multiracial Singapore congestive heart failure (CHF) population. METHODS 668 CHF patients (Age 66+/-12 years, Ejection fraction 29+/-13%), consisting of Chinese (72%), Malays (17.1%) and Indians (10.9%) were prospectively followed up for 24+/-12 months. Primary outcome measure was the composite end-point of all-cause mortality or CHF readmission. RESULTS Composite end-points occurred in 198 (29.6%) patients (133 deaths, 112 CHF readmissions). Diabetes mellitus (DM), peripheral vascular disease and hyperlipidemia were more prevalent in Indians compared to Malays or Chinese (all p<0.05). Indians and Malays had higher composite end-point rates compared to the Chinese (p=0.01). Although Indians and Malays had higher CHF readmission rates compared to the Chinese (p<0.01), a trend towards a higher all-cause mortality rate was seen in Malays (p=0.12). Malay race was an independent predictor of the composite end-point (OR=1.65, 95% CI=1.04-2.63, p=0.034), as were age, diabetes mellitus, ischemic cardiomyopathy, beta-blocker use, and NYHA class (all p<0.05). CONCLUSIONS In the multiracial Singapore CHF population, Indians and Malays had a worse outcome compared to the Chinese, due to higher CHF readmission rates in Indians and higher mortality and CHF readmission rates in Malays. While the worse outcome in Indians may be due to the greater prevalence of diabetes mellitus and atherosclerotic vascular disease, the cause of the poorer prognosis in Malays is unclear.

Myocardial contractile dysfunction associated with increased 3-month and 1-year mortality in hospitalized patients with heart failure and preserved ejection fraction

BACKGROUND There is a clinical need for a contractility index that reflects myocardial contractile dysfunction even when ejection fraction (EF) is preserved. We used novel relative load-independent global and regional contractility indices to compare left ventricular (LV) contractile function in three groups: heart failure (HF) with preserved ejection fraction (HFPEF), HF with reduced ejection fraction (HFREF) and normal subjects. Also, we determined the associations of these parameters with 3-month and 1-year mortality in HFPEF patients. METHODS 199 HFPEF patients [median age (IQR): 75 (67-80) years] and 327 HFREF patients [69 (59-76) years] were recruited following hospitalization for HF; 22 normal control subjects [65 (54-71) years] were recruited for comparison. All patients underwent standard two-dimensional Doppler and tissue Doppler echocardiography to characterize LV dimension, structure, global and regional contractile function. RESULTS The median (IQR) global LV contractility index, dσ*/dtmax was 4.30s(-1) (3.51-4.57s(-1)) in normal subjects but reduced in HFPEF [2.57 (2.08-3.64)] and HFREF patients [1.77 (1.34-2.30)]. Similarly, median (IQR) regional LV contractility index was 99% (88-104%) in normal subjects and reduced in HFPEF [81% (66-96%)] and HFREF [56% (41-71%)] patients. Multi-variable logistic regression analysis on HFPEF identified sc-mFS <76% as the most consistent predictor of both 3-month (OR=7.15, p<0.05) and 1-year (OR=2.57, p<0.05) mortality after adjusting for medical conditions and other echocardiographic measurements. CONCLUSION Patients with HFPEF exhibited decreased LV global and regional contractility. This population-based study demonstrated that depressed regional contractility index was associated with higher 3-month and 1-year mortality in HFPEF patients.

Variation of the platelet glycoprotein IIIa PIA1/A2 allele frequencies in the three ethnic groups of Singapore

BACKGROUND Polymorphisms of the glycoprotein IIIa receptor have been shown to be associated with differences in platelet aggregability. The PI(A2) variant of the polymorphism has been reported to be an inherited risk factor for acute coronary events. Although the allele frequency of this polymorphism is well documented in Caucasian populations, studies involving Asian Indians, Malays and Chinese are lacking. We studied 706 random male individuals to determine the genotypic distribution of this polymorphism in Singapore. METHODS Male subjects included in this study were drawn from those undergoing routine annual medical examinations offered by their employers. Venous blood was obtained from these patients after an overnight fast and from which genomic DNA was extracted. Genotyping was carried out by polymerase chain reaction (PCR) followed by digestion with restriction enzyme NciI. Personal and family medical history of the subjects were also taken. RESULTS The genotype distribution of the individuals studied was in accordance to a population at Hardy Weinberg equilibrium. The frequency of the PI(A2) allele was 0.1, 0.01 and 0.01 in the Indians, Malays and Chinese, respectively. The differences in frequencies of the PI(A2) variant are significant among different ethnic groups (P<0.001 for Indians vs. Chinese and Indians vs. Malays). CONCLUSIONS We observed a significantly higher frequency of the PI(A2) allele among Indians relative to the Chinese and Malays in Singapore. The effect of this genotype may partially explain the higher rate of ischaemic heart disease seen among Indians compared to the Chinese and Malay ethnic groups.

Comprehensive noninvasive evaluation of bypass grafts and native coronary arteries in patients after coronary bypass surgery: accuracy of 64-slice multidetector computed tomography compared to invasive coronary angiography.

Aims We assessed the accuracy of 64-slice multidetector computed tomography (MDCT) compared with that of invasive coronary angiography (ICA) in the evaluation of symptomatic postcoronary artery bypass graft (post-CABG) patients. Methods MDCT and ICA were performed in 44 consecutive post-CABG patients with chest pain (mean age 66 ± 10 years, mean duration post-CABG 9 ± 5 years). MDCT findings were compared with the corresponding ICA, which was read by an interventional cardiologist blinded to the MDCT findings. Significant stenosis was defined as at least 50% luminal stenosis. Results One hundred and thirty-seven grafts (31 arterial and 106 venous), all evaluable by MDCT, were assessed. In a ‘per graft’ analysis, MDCT could detect significant disease in bypass grafts (graft occlusion or stenosis) with a sensitivity of 98% and specificity of 98%. In a ‘per segment’ analysis, MDCT could detect significant disease in all native coronary arteries with a sensitivity of 91% and specificity of 79% and in clinically relevant native coronary arteries with a sensitivity of 92% and specificity of 84%. In a ‘per vessel’ analysis, MDCT could differentiate native arterial occlusion from nonocclusive stenosis with a sensitivity of 68% and specificity of 70%. In a ‘per patient’ analysis, MDCT could detect significant disease in bypass grafts or clinically relevant native coronary arteries with a sensitivity of 100%, specificity of 40% and accuracy of 93%. Conclusion Sixty-four-slice MDCT allows evaluation of bypass grafts and native coronary arteries in post-CABG patients. Although accurate for detecting bypass graft disease, 64-slice MDCT has significant limitations when evaluating native arteries in post-CABG patients.

Impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure due to left ventricular systolic dysfunction

OBJECTIVE We assessed the impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure. METHODS 1668 consecutive patients with chronic heart failure (age 65+/-13 years, ejection fraction 28+/-12%, 67% male) were followed up for 36+/-12 months. 837 patients (50.2%) were diabetic and 1076 patients (65%) had ischemic cardiomyopathy. Primary outcome measure was all-cause mortality. Secondary outcome measures were heart failure readmission and the composite end-point. RESULTS There were 223 (13.4%) deaths and 112 (7%) heart failure readmissions. Ischemic cardiomyopathy, renal failure, hypertension, cerebrovascular disease, peripheral vascular disease, and hyperlipidemia were more prevalent in diabetics (all p<0.01). All-cause mortality (17.3% vs 9.4%), heart failure readmission (8.1% vs 5.3%) and the composite end-point (21.9% vs 12.6%) occurred more frequently in diabetics (all p<0.05). Diabetes was an independent predictor of all-cause mortality (OR=1.70, p=0.01), as were ischemic cardiomyopathy (OR=1.85, p=0.01), hypertension (OR=1.78, p=0.01), GFR (OR=0.98, p<0.01), and beta-blocker use (OR=0.55, p<0.01). CONCLUSIONS In spite of advances in heart failure treatment, the presence of diabetes mellitus significantly worsens survival in South East Asian patients with congestive heart failure.