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Biomedical subjects

J S Schroeder

Publications and source records attributed to J S Schroeder.

At least 19 recordsLinked to original sources

Intracoronary ultrasound in cardiac transplant recipients. In vivo evidence of "angiographically silent" intimal thickening.

BACKGROUND: Accelerated coronary atherosclerosis is a major factor limiting allograft longevity in cardiac transplant recipients. Histopathology studies have demonstrated the insensitivity of coronary angiography for detecting early atheromatous disease in this patient population. Intracoronary ultrasound is a new imaging technique that provides characterization of vessel wall morphology. The purpose of this study was to compare in vivo intracoronary ultrasound with angiography in cardiac transplant recipients. METHODS AND RESULTS: The left anterior descending coronary artery was studied with intracoronary ultrasound in 80 cardiac transplant recipients at the time of routine screening coronary angiography 2 weeks to 13 years after transplantation. A mean and index of intimal thickening were obtained at four coronary sites. Intimal proliferation was classified as minimal, mild, moderate, or severe according to thickness and degree of vessel circumference involved. Twenty patients were studied within 1 month of transplantation and had no angiographic evidence of coronary disease. An intimal layer was visualized by ultrasound in only 13 of these 20 presumably normal hearts. The 60 patients studied 1 year or more after transplantation all had at least minimal intimal thickening. Twenty-one patients (35%) showed minimal or mild, 17 (28%) moderate, and 21 (35%) severe thickening. Forty-two of these 60 patients had angiographically normal coronary arteries, 21 (50%) of whom had either moderate or severe thickening. All 18 patients with angiographic evidence of coronary disease had moderate or severe intimal thickening, but there was no statistically significant difference in intimal thickness or index when compared with the patients with moderate or severe proliferation and normal angiograms (thickness, 0.53 +/- 0.35 mm versus 0.64 +/- 0.30 mm, p = NS; index, 0.28 +/- 0.10 versus 0.34 +/- 0.10, p = NS). CONCLUSIONS: The majority of patients 1 or more years after cardiac transplantation have ultrasound evidence of intimal thickening not apparent by angiography. Intracoronary ultrasound offers early detection and quantitation of transplant coronary disease and provides characterization of vessel wall morphology, which may prove to be a prognostic marker of disease.

Coronary Angiography

Characteristics of serial electrocardiograms in heart transplant recipients.

To characterize "normal electrocardiogram patterns" after transplantation, serial surface 12-lead electrocardiograms (ECGs) taken 2 weeks, 1 month, and 1 year postoperatively in a group of 50 heart transplant recipients were analyzed and were correlated with clinical parameters. Some recipient atrial activity was evident in 40% of patients at 2 weeks, but in only 16% at 1 year; donor atrial activity was normal in 90% to 94% of patients at all times. ECG intervals generally were normal and did not change over time. The most prevalent abnormality was the presence of incomplete (IRBBB) or complete right bundle branch block (RBBB) patterns (14% at 2 weeks, 16% at 1 month, and 22% at 1 year). In patients with hemodynamic measurements available approximately at the time of the ECG recording 1 year following transplantation, there was a significant correlation between the presence of IRBBB and RBBB patterns and somewhat higher levels of right atrial mean pressure (6.8 versus 3.9 mm Hg, p = 0.01), pulmonary artery systolic pressure (32.5 versus 24.5 mm Hg, p = 0.001) and diastolic pressure (16.2 versus 11.2 mm Hg, p = 0.004), and right ventricular systolic pressure (31.4 versus 26.9 mm Hg, p = 0.019) and pulmonary artery wedge mean pressure (11.3 versus 7.9 mm Hg, p = 0.010). Repolarization changes were also common but decreased in frequency over time (78% at 2 weeks to 34% at 1 year) and did not correlate with the presence or absence of rejection. We conclude that ECG abnormalities in heart transplant recipients are generally mild and that IRBBB and RBBB patterns correlate with increased right heart pressures.

Atrial Function

Transplant coronary artery disease: histopathologic correlations with angiographic morphology.

Accelerated coronary artery disease is a major cause of morbidity and mortality among cardiac transplant recipients. Ten patients who died or underwent retransplantation within 2 months of coronary angiography had direct correlation of angiographic (normal discrete lesions, diffuse concentric narrowing) with histologic appearance of coronary arteries. Of the 26 angiographically normal segments, 73% showed mild to moderate fibrous intimal thickening by light microscopy. The remainder had intermediate lesions or atheromatous plaques. Discrete stenoses usually corresponded to lipid-rich intermediate or atheromatous disease. In contrast, angiographically diffuse, concentrically narrowed lesions usually were areas of severe fibrous intimal thickening. Fresh or organizing thrombus was most often associated with discrete lesions and accounted for all complete occlusions. Histologic and angiographic comparisons of the degree of luminal narrowing showed generally good correlation for high grade stenoses. Lesions graded as having less than 25% diameter narrowing were often underestimated angiographically as compared with histologic determinations. Transplant coronary artery disease has a heterogeneous histologic and angiographic appearance, with angiographic underestimation of disease in some patients.

Adult

The antiatherogenic effects of calcium antagonists.

Evidence that calcium antagonists can suppress diet-induced atherosclerosis in the thoracic aorta of animals has existed for a decade. Recently, the results of quantitative angiographic trials of calcium antagonists in humans have become available, confirming their beneficial effect on coronary artery disease. Nifedipine treatment reduces the rate of new lesion development in patients with mild-to-moderate coronary artery disease, reduces disease progression, and, in some cases, induces lesion regression. There is evidence that the use of verapamil may be associated with lesion regression and stenosis prevention, and that nicardipine may influence the progression of minimal coronary lesions. Theoretically, a wide range of explanations for an effect of calcium antagonists on atherogenesis is possible. Potential mechanisms include preventing calcium overload, upregulating LDL receptors with enhanced LDL clearance, inhibiting cell migration into the arterial wall, and antiplatelet effects. The exact mechanism remains unclear, but alteration of serum lipid levels and blood pressure does not appear to be the common pathway. Work with humans is still preliminary, and longer follow-up and further trials are required to determine the appropriate clinical application of calcium timing for their introduction.

Animals

The influence of preoperative patient characteristics on early and late survival following cardiac transplantation.

In an attempt to identify the preoperative factors that influence survival following cardiac transplantation, we retrospectively analyzed multiple demographic, clinical, and hemodynamic data of 301 consecutive patients who underwent cardiac transplantation between December 1980 and July 1988 (cyclosporine era). Univariate and multivariate regression analyses revealed that the two most deleterious risk factors for premature death following transplantation were pulmonary hypertension not responsive to vasodilator challenge and preoperative requirement of hemodynamic support (intravenous inotropes or mechanical assistance). The combination of these two independent risk factors was an even stronger predictor of mortality (relative risk, 6:1; p less than 0.0001): the 3-month actuarial survival rate of the 20 patients with this combination was 30.3% versus 78.4% of the 47 patients with only pulmonary hypertension, 87.9% of the 42 patients with only the requirement of hemodynamic support, and 95.3% of the 172 patients with neither of these two risk factors. The difference in postoperative mortality between patients with versus those without these two risk factors is due to a higher rate of fatal infectious complications: six of 20 patients (30%) with both risk factors died from infection within 3 months after transplant compared with three deaths among 172 patients (1.7%) with neither of these risk factors. The majority of fatal infections were pulmonary. There were significantly more fatal and nonfatal infectious episodes in patients with one or both of these risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

A review of calcium antagonists and atherosclerosis.

Many detailed studies have demonstrated that calcium antagonists can suppress development of diet-induced atherosclerosis in the thoracic aorta of animals. A number of possible mechanisms have been proposed based on in vitro work, but the exact mechanism remains unclear. Alteration of serum lipid levels and blood pressure does not appear to be the common pathway. Differing effects between calcium antagonists of different classes indicate that the voltage-dependent calcium channel-blocking action common to all calcium antagonists is not the sole mechanism. Preliminary results of several major quantitative angiographic studies in human coronary artery disease have recently become available and indicate that calcium antagonists are able to retard the progression of existing lesions in humans also. There is also evidence that calcium antagonists may prevent the development of new lesions and, in some cases, induce lesion regression. Longer follow-up and further trials are required to assess the appropriateness of widespread clinical application of these agents in coronary artery disease, to determine the optimal timing for their introduction, and to define their mechanism of action in influencing the natural history of atherosclerosis.

Animals

Arrhythmias and clinical electrophysiology of the transplanted human heart.

The denervated transplanted heart has given us numerous opportunities to assess normal and abnormal electrophysiology and the influence of the autonomic system on these parameters. Observation of baseline electrophysiology of the denervated heart and its response to various physiologic and pharmacologic stimuli has emphasized the role of the parasympathetic system on heart rate and arrhythmia modulation in the normal population. In the transplant patients, the denervated hearts lack the full spectrum of physiologic responses due to the absence of vagally mediated neurostimuli. This results in a higher resting heart rate, sluggish rate response to exercise, and perhaps inadequate response to some commonly used drugs such as atropine and digitalis. Nevertheless, the heart's overall response to physiologic demands and various pharmacologic maneuvers including beta-antagonists and antagonists remains relatively normal and the patient's overall cardiac performance appears to be quite adequate. Thus, despite its shortcomings, the denervated heart provides near normal functional integrity and overall improved quality of life. Arrhythmias are generally a minor problem in these patients. Although there appears to be a high prevalence of various forms of arrhythmias, most present as isolated and insignificant problems. The more severe arrhythmias consist primarily of atrial tachyarrhythmias that are usually associated with acute rejection, and treatment for these arrhythmias never pose serious difficulty. However, sudden death remains an intriguing issue. Clearly, serious ventricular tachyarrhythmias can occur in these patients, arguing against the concept of a primary role of an intact autonomic nervous system for the generation of arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac

Progressive coronary luminal narrowing after cardiac transplantation.

Accelerated coronary disease is a major factor limiting long-term survival in cardiac transplant recipients. Coronary angiography was obtained a mean of 5.1 weeks posttransplantation and annually thereafter. Replicate projections recorded after nitroglycerine administration were quantitated using computer-assisted edge detection. Five hundred and fifteen coronary segments in 25 patients having 1-year follow-up and 353 segments in 18 patients reaching 2-year follow-up were compared with baseline angiograms. Significant change was defined as +/- 0.10 mm, equal to 3.8% change in diameter based on three standard deviations obtained from estimation of measurement error. Mean coronary diameter fell from 2.44 +/- 0.26 mm at baseline to 2.21 +/- 0.34 mm (p less than 0.001) at 1-year follow-up. This rate of diameter decline was 20-fold more rapid during the initial posttransplantation year than the rate of change of visually normal segments in nontransplant patients with coronary atherosclerosis elsewhere. There was no significant drop in mean diameter between the first and second year in those patients who had second-year studies. Decrease in absolute diameter for vessels greater than 2.9 mm significantly exceeded diameter reduction for smaller vessels but did not differ when considered as a ratio of vessel diameter. In 21 of 25 patients, mean coronary diameter reduction exceeded the three-standard deviation threshold at their last angiogram, but only two of these patients had visually detectable transplant coronary disease.

Cineangiography

Prodromal characteristics as indicators of cardiac events in patients hospitalized for chest pain.

In an effort to determine the usefulness of prodromata for predicting a myocardial infarction, a prospective analysis was made of 211 consecutive patients with chest pain who were admitted to the Stanford University Medical Center Coronary Care Unit. In their subsequent course, 91 patients had a myocardial infarction, 102 had a myocardial infarction ruled-out, and 18 had a noncardiac etiology for their chest pain. Prodromal chest pain in the previous six months had occurred in 65% of patients and unstable angina in 61%. Infarction versus noninfarction patient groups could not be identified on the basis of prodromal ill health, chest pain, unstable angina, typical versus atypical nature of the chest pain, or activity at the onset of pain. Complaints of preceding fatigue and increased perceived stress were common in both groups. Activity at the onset of the admission chest pain was strenuous in 15% of the infarction patients and 12% of the noninfarction patients. We conclude that prodromal symptoms are common in both infarction and noninfarction patients. Although chest pain probably remains the single most frequent identifier of a new cardiac event, it is common in noninfarction patients and cannot be used alone to predict infarction or death.

Adult

Tracheostomy and hemodynamic changes in sleep-inducing apnea.

Because pulmonary hypertension and systemic hypertension occur during sleep-induced obstructive apnea, six patients underwent overnight hemodynamic monitoring before and after tracheostomy. Variables studied included heart rate, pulmonary artery pressure, femoral artery pressure, and arterial oxygen tension (Po2). After tracheostomy, significant reductions were noted during sleep in mean pulmonary artery pressure from 45 +/- 6 mm Hg (mean +/- SEM) to 22 +/- 2 mm Hg (P less than 0.05) and in mean femoral artery pressure from 137 +/- 6 mm Hg to 97 +/- 3 mm Hg (P less than 0.005). There was also a significant increase for the group in arterial Po2 recorded during the apneic episodes from 38 +/- 3 mm Hg before tracheostomy to 71 +/- 2 mm Hg (P less than 0.001) after tracheostomy. We conclude that tracheostomy improves the hemodynamic abnormalities and hypoxemia that occur during sleep in patients with sleep-induced obstructive apnea.

Adult