James A. Heinsimer

The impact of aging on adrenergic receptor function: clinical and biochemical aspects.

From this discussion, several conclusions can be drawn. First, with advancing age there is a decrease in cardiovascular responsiveness and, more specifically, there is a decrease in catecholamine-stimulated chronotropic and inotropic responses. This decreased function has its biochemical correlate in the observation that cyclic AMP levels are decreased in response to isoproterenol infusion in cells or tissues derived from aged organisms. Second, although most work on human circulating cells suggests that beta-adrenergic receptor densities are unchanged, measurements of beta-adrenergic receptor concentrations in various cells from various animals (predominantly rats) have yielded conflicting results. Some of this disparity could be due to the observation that local concentrations of norepinephrine, such as those found intramyocardially, may be very different from those in circulating plasma. Indeed, whereas circulating norepinephrine levels tend to rise with age, the intramyocardial norepinephrine levels tend to fall with senescence. Thus, circulating lymphocytes may or may not be an appropriate model to reflect the catecholamine milieu to which other tissues may be exposed. Accordingly, a note of caution must be entered in terms of extrapolating findings regarding the levels of human lymphocyte beta-adrenergic receptors and cyclic AMP activity to those found, for example, in the human heart. Furthermore, it is likely that age-related changes in adrenergic function may be the result of changes in coupling of receptors to the adenylate cyclase system, as suggested by Feldman and co-workers, and/or changes in steps distal to cyclase activation, as suggested by Guarnieri and colleagues.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized factorial trial of reperfusion strategies and aspirin dosing in acute myocardial infarction

The focus of new research efforts to improve the morbidity and mortality associated with acute myocardial infarction (AMI) has turned to adjuvant agents that show promise of improving outcomes following coronary thrombolysis. We enrolled 162 patients with AMI in a randomized trial comparing front-loaded tissue-plasminogen activator (t-PA) plus weight-adjusted heparin with anisoylated plasminogen streptokinase activator complex (APSAC) without heparin as well as standard-dose (325 mg) and low-dose (81 mg) aspirin. The primary end point was an in-hospital morbidity profile; secondary end points were clinical and angiographic potency and hemorrhagic events. Selected sites performed an electrocardiographic substudy to determine the time to 50% ST-segment recovery and the time to steady state. Although the trial was terminated when the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial showed that t-PA had a significant mortality advantage over streptokinase, important trends were evident. Patients given t-PA and heparin were better anticoagulated (p = 0.001), yet AP-SAC-treated patients had more bleeding complications. The primary end point favored t-PA (25.4% vs 31.3%), and the secondary end points were similar in both groups. In the electrocardiographic substudy, the t-PA group achieved both 50% ST-segment recovery and steady-state recovery sooner than the APSAC group. Patients taking low-dose aspirin had lower in-hospital mortality and less recurrent ischemia but more strokes than the standard-dose aspirin group. Thus, this trial demonstrated trends favoring front-loaded t-PA with weight-adjusted heparin over APSAC without heparin in the treatment of AMI. The use of low-dose aspirin did not appear to impose a loss of protection from adverse events, nor did standard-dose aspirin increase serious bleeding.

Influence of underlying coronary artery disease on the natural history and prognosis of exercise-induced left bundle branch block

The long-term prognosis of exercise-induced left bundle branch block (BBB) in patients with and without underlying coronary artery disease (CAD) was examined by following 15 patients (7 with normal coronary arteries and 8 with CAD) for an average of 6.6 years (range 2.2 to 11.2). Over the follow-up interval, permanent left BBB developed in 8 of the 15 patients. Seven of these 8 had underlying CAD, compared to 0 of 6 patients with normal coronary arteries and normal left ventricular function (p less than 0.002). In 1 patient with normal coronary arteries and a left ventricular ejection fraction of 0.34, permanent left BBB developed. During follow-up, 4 patients died; 3 had significant CAD and 1 had depressed left ventricular function. In no patient did high-grade atrioventricular block develop and no patient required pacing. Thus, development of permanent left BBB in patients with exercise-induced left BBB is related to presence or absence of underlying CAD or myocardial disease. When left BBB is found in the absence of underlying heart disease, there does not tend to be progression of the conduction disturbance and the prognosis is excellent.

Echocardiographic detection of perforation of the cardiac ventricular septum by a permanent pacemaker lead

Abstract Previously reported complications of temporary transvenous pacing include perforation of the ventricular septum or ventricular wall. 1–4 Perforation of the ventricular septum by a permanent pacing electrode with long-term left ventricular pacing has not been reported.

Rheumatoid arthritis and coronary arteritis

Abstract Rheumatoid arthritis is associated with a variety of cardiac manifestations, particularly pericarditis, myocarditis and granulomas. Coronary arteritis has been detected in up to 20% of necropsy patients with rheumatoid arthritis, but involvement is usually confined to small arteries. 1 Rheumatoid-associated coronary arteritis rarely causes clinically evident myocardial infarction. We describe findings in a patient with rapidly progressive rheumatoid arthritis who had acute myocardial infarction from severe, generalized rheumatoid-associated coronary arteritis.

Case Report: Rate-Related Left Bundle Branch Block with Chest Pain and Normal Coronary Arteriograms Treated by Exercise Training

A clinical observation of chest pain associated with the onset of rate-related left bundle branch block has been described in patients with normal coronary arteriograms. The authors used standard cardiac rehabilitation techniques for exercise training in a 47-year-old woman with these manifestations. Serial treadmill tests revealed that during the course of 3 months of exercise training, the heart rate at onset of LBBB gradually rose from 133 to 175 beats per minute, and she no longer developed symptoms during her routine daily activities or exercises. Exercise training was a successful nonpharmacologic strategy that delayed the onset of rate-related LBBB and chest pain in this patient and avoided the need for beta blocker therapy.

The Beta-Adrenergic Receptor in Heart Failure

Although the role of the autonomic nervous system in the pathophysiology of heart failure has been studied for decades, only within the past few years have adrenergic receptors and their alterations occupied center stage. There is now considerable evidence linking such receptors to many of the phenomena of heart failure; recent work appears to have significant therapeutic implications.

Improving Cardiac Rehabilitation Referral Patterns Using Computerized Physician Order Entry Systems

Much of the immense burden of cardiovascular disease is ultimately a consequence of unhealthy lifestyle choices, such as physical inactivity, caloric over-consumption, and tobacco use. Unfortunately, clinicians rarely have sufficient time or resources to meaningfully address these issues. Cardiac rehabilitation is a comprehensive program for the secondary prevention of cardiovascular events for a wide spectrum of patients and is designed to address the lifestyle factors related to cardiovascular disease. While cardiac rehabilitation initially focused on exercise training, it has expanded over time to include cardiovascular education, nutritional counseling, behavioral interventions, and pharmacologic therapy. A large body of literature on cardiac rehabilitation has accrued demonstrating its robust health benefits, 1,2 including a survival benefit among patients with coronary artery disease, 2 and now it is advocated by professional clinical organizations for several cardiovascular conditions. 1 Despite its clinical need, cardiac rehabilitation remains vastly underutilized in the US, with 30% of eligible patients enrolling nationwide. 2 While several reasons exist for this poor utilization, the most critical and potentially most correctable reason is widely acknowledged to be the referral process, as only 1 in 2 patients eligible for cardiac rehabilitation are currently being referred. 3 Opportunities for referral often present themselves during the chaotic hospital discharge process or the first outpatient clinic visit after hospitalization, when busy practitioners are in the midst of dealing with symptoms, further testing, medication titration, and other clinical issues. As a result, cardiac rehabilitation generally lies at the bottom of practitioners’ priority lists for ongoing therapy. Also, it is oftentimes unclear which provider should take responsibility for the referral. Further complicating the referral process, many insurance companies require preauthorization. Finally, even if a referral is eventually made, they are often ineffective, being delayed weeks to months after a cardiovascular event, well past the point when patients may be motivated, willing, or able to attend cardiac rehabilitation.

The Use of Exercise Cross-Sectional Echocardiography and Exercise Doppler Echocardiography for the Assessment of Coronary Disease

Echocardiography has been successfully employed to diagnose myocardial infarction (1,2), assess infarct size (3), and quantitate ischemic damage (3,4), as well as to diagnose the presence of coronary artery disease (CAD) (5) and predict its distribution (6). Echocardiography has also proved to be a valuable modality for the assessment of global left ventricular function with a high degree of correlation with invasive techniques. Kisslo and co-workers (7) compared biplane cineangiography against real-time, phased-array, two-dimensional (2-D) echocardiography to assess left ventricular wall motion in patients with suspected ischemic heart disease. Eighteen percent of wall regions could not be visualized echocardiographically; however, in the regions that were assessable, wall motion characteristics were correctly identified in 87% of analyses.

Roentgenograms in Pericardial Effusion-Reply

In Reply.— We heartily agree with Dunn and colleagues that echocardiography is the gold standard for the diagnosis of pericardial effusion. The SCTL chest roentgenogram is intended to increase the sensitivity and specificity of the epicardial fat stripe sign—a radiological finding of pericardial effusion that is commonly cited in the radiological literature and employed in clinical practice. In our patients, the SCTL roentgenogram demonstrated the epicardial fat stripe sign in 86% of patients with a large pericardial effusion, as opposed to a 36% demonstration of the epicardial fat stripe sign by conventional lateral roentgenogram. Thus, while the SCTL roentgenogram was not perfect, it afforded a significant improvement for the detection of pericardial effusion over the conventional roentgenographic indicator. Since the inconvenience and cost of this additional roentgenogram view are minimal, the SCTL technique is recommended to improve the roentgenographic assessment of an enlarged cardiac silhouette or suspected pericardial effusion, especially