Cardiovascular risk and thiazolidinediones--what do meta-analyses really tell us?

Meta-analyses of clinical trials suggest that the use of the thiazolidinedione (TZD), rosiglitazone, in patients with type 2 diabetes mellitus may increase the risk of myocardial ischaemic events by 30-40%. Although these controversial data must be interpreted with caution, in the absence of definitive prospective cardiovascular (CV) outcomes data, they represent a prominent source of evidence concerning the CV safety of rosiglitazone. The results of meta-analyses and a large randomized-controlled CV outcomes trial provide strong evidence that pioglitazone does not increase the risk of coronary events. This article clarifies the clinical significance of these meta-analytical findings alongside other sources of evidence and assesses their impact on evolving treatment guidelines and recommendations for the use of TZDs in patients with type 2 diabetes.

Echocardiographic systolic time intervals. Left ventricular performance in coronary artery disease.

The ratio of the preejection period to the left ventricular ejection time (PEP/LVET), obtained from the aortic root echocardiogram, was studied immediately before and after left ventricular (LV) cineangiography in 23 patients with documented coronary artery disease. The initial PEP/LVET ratio was inversely related to LV ejection fraction (r = -.78, P less than or equal to .001). Repeat measurements taken 60 s after angiography showed a significant decrease from a mean value of .36 +/- .13 to .27 +/- .08 (P less than or equal to .005). Furthermore, when patients were divided into those with an initial PEP/LVET value above and below 0.40, those with a higher value showed a significantly greater decrease following contrast left ventriculography (mean decrease, 0.16 vs 0.06, P less than or equal to .01). This study indicates that systolic time intervals derived from echocardiography are a reliable noninvasive measure of LV function, and that ventricular function improves following left ventriculography, with the degree of improvement being inversely related to initial function.

Recent discoveries in assessment of coronary heart disease: impact of vascular mechanisms on development of atherosclerosis.

Until recently, arterial stenosis and occlusion due to buildup of atherosclerotic plaque were recognized as the primary causes of coronary heart disease (CHD). Currently, CHD is viewed as a lifelong process of endothelial inflammation, thrombosis, and plaque instability and rupture. Lifestyle modification is an important first step in prevention of CHD, but even those patients who are the most committed to following a healthy diet and lifestyle frequently require the addition of drug therapy to further reduce risk. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce risk by lowering low-density lipoprotein cholesterol levels, as well as by stabilizing plaques, restoring endothelial function, and counteracting oxidative and inflammatory processes. Angiotensin-converting enzyme inhibitors also have antiatherogenic properties. Early, aggressive lipid intervention is the key to primary and secondary prevention of CHD.

Cardiopulmonary resuscitation: a teaching aid.

Laboratory dogs are used to demonstrate and practice cardiopulmonary resuscitation (CPR) procedures. Cardiovascular collapse, cardiac arrest, and ventricular fibrillation are produced in anesthesized dogs and then managed by the student. The laboratory exercise focuses and emphasizes CPR material taught in the classroom and on mannequins. With the current emphasis on CPR training and certification, we recommend the concept to the dental profession as an added dimension in teaching CPR.

Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade.

Anaphylaxis to known allergens occurred in two patients under treatment for hypertension with propranolol. The clinical course of both cases was similar. Bradycardia associated with an undetectable blood pressure, unusual severity, and sluggish response to treatment were major common factors in which blockade of the beta-adrenergic system may have had a role. Propranolol, a beta-adrenergic antagonist that acts competitively by blocking the adenylate cyclase receptor on efferent cells, is well recognized to cause increased airways resistance in some asthmatic and normal subjects. It is postulated that propranolol potentiated anaphylaxis in these patients by inhibition of adenylate cyclase, resulting in lowered intracellular cyclic AMP and a lowered threshold of mediator release. The bradycardia during profound hypotension is attributed to an unopposed cholinergic action caused by blunting of the normal endogenous beta-adrenergic response by propranolol.

Acute directional coronary atherectomy prior to stenting in complex coronary lesions: ADAPTS Study.

The purpose of this study was to determine the results of directional coronary atherectomy (DCA) combined with stenting in a high-risk patient population. The use of stenting or DCA alone for aorto-ostial lesions, total chronic occlusions, long lesions, and lesions containing thrombus is associated with lowered success and a relatively high restenosis rate. Between July 1993 and October 1996, we treated 89 lesions with the combined approach of DCA and stenting in 60 consecutive patients. Thirty-one (51.7%) patients were treated because of unstable angina, 11 (18.3%) for post-myocardial infarction (MI) angina, 3 (5.0%) for acute MI, and 15 (25.0%) patients for stable angina. A total of 43 (71.7%) patients had multivessel disease, 19 (31.7%) had undergone previous coronary artery bypass graft (CABG), and 17 (28.3%) patients had undergone multivessel revascularization. The procedure was successful in all patients; and no postprocedural deaths or emergent CABG occurred. Two patients (3.3%) had non-Q-wave MI after the procedure and 1 patient (1.7%) experienced Q-wave MI due to subacute stent closure 7 days after the procedure. During follow-up ranging from 6 months to 3 years, 2 (3.3%) patients died, 2 (3.3%) required CABG surgery, 1 (1.7%) patient had an MI, and 6 patients (10.0%) required target vessel revascularization. By the quantitative coronary angiography, the initial minimal luminal diameter (MLD) averaged 0.91+/-0.45 mm (74.7+/-11.8% stenosis) increasing to 3.80+/-0.44 mm (-6.7+/-12.1%) after the combined approach procedure. Thirty patients (50.0%) met criteria for late (> or =6 months) angiographic follow-up. Late MLD loss averaged 1.13+/-1.07 mm, for a mean net gain of 1.61+/-1.23 mm. Available angiographic follow-up evaluation showed a restenosis rate of 13.3%. A combined approach, defined as the use of both DCA and stenting, is safe and yields a low restenosis rate in high-risk patients who have lesions known to respond less favorably to stenting or DCA alone.

Infection of an implantable cardioverter defibrillator: management without removal of the device in selected cases.

A case is presented in which an implantable cardioverter defibrillator (ICD) became infected in the abdominal wall pocket 5 weeks following implantation. There was no evidence clinically or by computed tomographic scan suggesting mediastinal extension of the infection. The infection was treated successfully by debriding the abdominal wall pocket followed by a combination of pocket irrigation with antibiotic solution, parenteral antibiotics, and long-term oral antibiotics. This conservative therapy was successful and avoided removal of the device.