Biomedical subjects

Patrick J Commerford

Publications and source records attributed to Patrick J Commerford.

8 recordsLinked to original sources

PubMed2006

Controversies in ventricular remodelling.

Ventricular remodelling describes structural changes in the left ventricle in response to chronic alterations in loading conditions, with three major patterns: concentric remodelling, when a pressure load leads to growth in cardiomyocyte thickness; eccentric hypertrophy, when a volume load produces myocyte lengthening; and myocardial infarction, an amalgam of patterns in which stretched and dilated infarcted tissue increases left-ventricular volume with a combined volume and pressure load on non-infarcted areas. Whether left-ventricular hypertrophy is adaptive or maladaptive is controversial, as suggested by patterns of signalling pathways, transgenic models, and clinical findings in aortic stenosis. The transition from apparently compensated hypertrophy to the failing heart indicates a changing balance between metalloproteinases and their inhibitors, effects of reactive oxygen species, and death-promoting and profibrotic neurohumoral responses. These processes are evasive therapeutic targets. Here, we discuss potential novel therapies for these disorders, including: sildenafil, an unexpected option for anti-transition therapy; surgery for increased sphericity caused by chronic volume overload of mitral regurgitation; an antifibrotic peptide to inhibit the fibrogenic effects of transforming growth factor beta; mechanical intervention in advanced heart failure; and stem-cell therapy.

Animals↗

PubMed2006

Controversies in stable coronary artery disease.

Coronary heart disease is still highly prevalent worldwide, and stable angina pectoris is one of its more common presentations. Three major controversies are risk factor management, drug therapy, and intervention. As well as the major risk factors stated by the Framingham study and European guidelines, other factors include abdominal obesity, metabolic syndrome, and psychological stress. How should these additional factors be rated? With respect to drug therapy, apart from aspirin, all patients with stable angina should be assessed for statin treatment. Although statins will reduce coronary events by about one third in patients with vascular disease, the absolute benefit depends on the absolute risk. Non-controversially, all patients should be considered for angiotensin-converting-enzyme inhibitors. The concept that beta blockers are protective from future coronary events can be disputed. Percutaneous coronary intervention can relieve symptoms without extending lifespan beyond medical therapy. However, strong mortality data favour coronary-artery bypass grafting in individuals with triple-vessel or even double-vessel disease. Thus, effort angina needs comprehensive assessment, lifestyle changes, and treatment tailored to the individual patient.

Adolescent↗

PubMed2006

Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry.

BACKGROUND: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.

Adolescent↗

PubMed2005

Congestive heart failure complicating non-ST segment elevation acute coronary syndrome: incidence, predictors, and clinical outcomes.

There are limited data regarding the incidence and clinical significance of congestive heart failure (CHF) in patients with non-ST segment elevation acute coronary syndromes (ACS). The objectives of this study were to examine the incidence, predictors, and clinical outcomes in patients with ACS without ST elevation who develop CHF. We studied patients with unstable angina or non-ST segment elevation myocardial infarction (NSTEMI) randomized to hirudin or unfractionated heparin in the Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) trial. The diagnosis of CHF was based on a combination of clinical and radiographic features. Patients were followed for 6 months. Of 10 141 randomized patients, 501 (4.9%) developed CHF within the first week and 643 (6.3%) during 6 months of followup. Independent predictors for the development of CHF were older age, female sex, diabetes, prior MI, prior CHF, and NSTEMI at presentation. Compared with patients who did not develop CHF, patients who developed CHF were at increased risk of death (odds ratio (OR) 3.4, 95% CI 2.7-4.3), new MI (OR 2.8, 95% CI 2.2-3.6), and the need for intra-aortic balloon pump insertion (OR 5.4, 95% CI 3.5-8.4) at 7 days and 6 months. There was no increase in use of cardiac catheterization (OR 0.8, 95% CI 0.7-1.0) or revascularization (OR 0.9, 95% CI 0.7-1.1) in patients who developed CHF. CHF is a common complication in patients presenting with non-ST segment elevation ACS and is strongly associated with adverse clinical outcomes including new MI and death. Despite this worse prognosis, patients with ACS developing CHF are less likely to be referred for invasive management.

Acute Disease↗

PubMed2003

Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study.

BACKGROUND: We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome (ACS). METHODS AND RESULTS: In the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, 12 562 patients with ACS using aspirin, 75 to 325 mg daily, were randomized to clopidogrel or placebo for up to 1 year. In this analysis, patients were divided into the following 3 aspirin dose groups: < or =100 mg, 101 through 199 mg, and > or =200 mg. The combined incidence of cardiovascular death, myocardial infarction, or stroke was reduced by clopidogrel regardless of aspirin dose, as follows: < or =100 mg, 10.5% versus 8.6% (relative risk [RR], 0.81 [95% CI, 0.68 to 0.97]); 101 to 199 mg, 9.8% versus 9.5% (RR, 0.97 [95% CI 0.77 to 1.22]); and > or =200 mg, 13.6% versus 9.8% (RR, 0.71 [95% CI, 0.59 to 0.85]). The incidence of major bleeding increased with increasing aspirin dose both in the placebo group (1.9%, 2.8%, and 3.7%, respectively; P=0.0001) and the clopidogrel group (3.0%, 3.4%, and 4.9%, respectively; P=0.0009); thus, the excess risk with clopidogrel was 1.1%, 1.2%, and 1.2%, respectively. The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 (95% CI 1.29 to 2.72) in the placebo group, 1.6 (95% CI 1.19 to 2.23) in the clopidogrel group, and 1.7 (95% CI 1.36 to 2.20) in the combined group. CONCLUSIONS: In patients with ACS, adding clopidogrel to aspirin is beneficial regardless of aspirin dose. Bleeding risks increase with increasing aspirin dose, with or without clopidogrel, without any increase in efficacy. Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg, with or without clopidogrel.

Acute Disease↗

PubMed2003

Early and late effects of clopidogrel in patients with acute coronary syndromes.

BACKGROUND: The risk of ischemic events is high, both early and late after acute coronary syndromes (ACS). We examine the benefits and risks associated with the use of adding clopidogrel to aspirin within the first 30 days and later (31 days to 12 months) in 12 562 patients with ACS. METHODS AND RESULTS: A total of 12 562 ACS patients were randomized to receive clopidogrel (300 mg initially followed by 75 mg/d) or placebo for 3 to 12 months. The proportion of patients experiencing cardiovascular death, myocardial infarction, or strokes (primary outcome) at 30 days was 5.4% in the placebo group and 4.3% in the active group (relative risk 0.79, 95% CI 0.67 to 0.92). Beyond 30 days, the corresponding rates were 6.3% versus 5.2% (relative risk 0.82, 95% CI 0.70 to 0.95). There was no significant excess in life-threatening bleeds in each period (0.97% versus 1.28%, relative risk 1.32, 95% CI 0.95 to 1.84 for 0 to 30 days; 0.83% versus 0.91%, relative risk 1.09, 95% CI 0.75 to 1.59 for 31 days to 12 months). Further subdivision of the early data indicates benefits within 24 hours with consistently lower rates of the primary outcome in combination with refractory or severe ischemia. CONCLUSIONS: Clopidogrel reduces the risk of ischemic vascular events, with the benefits emerging within 24 hours of initiation of treatment and continuing throughout the 12 months (mean 9 months) of the study.

Acute Disease↗

PubMed2002

Antihypertensive effects of angiotensin converting enzyme inhibition by lisinopril in post-transplant patients.

BACKGROUND: It is not known whether strict control of blood pressure (BP) in mild post-transplant hypertension gives any benefit. Our primary objective was to test the antihypertensive effects of lisinopril added to standard therapy on ambulatory BP (ABP) of post-transplant patients. The secondary objective was to monitor echocardiographic and hemodynamic end points. METHODS: Post-transplant patients with an abnormality of the 24-h ABP recording were recruited to this double-blind randomized prospective study that started 2 to 3 months after transplantation. Patients were then evaluated at 6, 12, 18, and 24 months after transplantation. RESULTS: Lisinopril decreased the clinic BP and ABP, the latter from 134/85 to 126/82 mm Hg at 6 months (P =.01 v placebo) and 121/79 mm Hg after 2 years (P =.03 v placebo). Fewer patients in the lisinopril group required added amlodipine to control the BP (P =.01). Data on left ventricular (LV) mass are difficult to interpret because by coincidence in this small study, the lisinopril group had lower initial values than placebo. However, in the lisinopril group mean LV mass decreased by 10% (P =.02) and mass index by 13% (P =.01), whereas placebo LV mass and index did not change. The LV end-diastolic diameter increased only in the placebo group (P =.008). There were no significant changes in any of the other secondary outcomes, including the cardiac index and systemic vascular resistance. CONCLUSIONS: Thus, in these post-transplant patients, stricter BP control to normal levels by the addition of lisinopril to existing therapy, reduced BP and modestly decreased LV mass without altering cardiac hemodynamic function.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Fixed-dose versus adjusted-dose warfarin in patients with prosthetic heart valves in a peri-urban impoverished population.

BACKGROUND AND AIMS OF THE STUDY: Patients with mechanical heart valves are critically dependent upon adequate anticoagulation. The present patients are young, geographically dispersed and socioeconomically deprived. Hospital attendance is erratic, and compliance with conventional anticoagulation difficult. The need exists for an alternative method of anticoagulation that requires neither regular visits nor adjustment of the warfarin dose. METHODS: A five-year prospective randomized double-blind study was undertaken to compare the efficacy and safety of a predetermined, individualized fixed-dose versus adjusted-dose warfarin. Postopoeratively, 296 patients, after an initial dose-finding phase (International Normalized Ratio (INR) 2.0 - 3.5), were randomized to either fixed-dose or adjusted-dose warfarin. RESULTS: For the intention-to-treat analysis, the groups were well-matched with regard to baseline characteristics. Among patients on fixed-dose warfarin, 63% of INRs were in the range 2.0 - 4.5 compared with 64% in patients on adjusted-dose warfarin. The mean follow up period was 2.4 years in both groups; total follow up was 725 patient-years. There were seven deaths in the fixed-dose warfarin group, and five in the adjusted-dose group (p = 0.52). Thirteen major thrombotic events, occurred in the fixed-dose warfarin group, and four in the adjusted-dose group (p = 0.02). Twelve major hemorrhagic events occurred in each group. CONCLUSION: In this predominantly young, impoverished population, despite similar overall INR control, fixed-dose warfarin was associated with an increase in thromboembolic events, but no significant increase in mortality or hemorrhagic events. Fixed-dose warfarin may be an acceptable option where conventional anticoagulation is impracticable. In particular, the study highlighted the difficulties of adequate anticoagulation in a population where compliance is erratic and often non-existent.

Adolescent↗