Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverter defibrillators.

INTRODUCTION: Ventricular oversensing (OS) of respirophasic noise transients may cause spurious detections and therapies and pacing inhibition among patients with implantable cardioverter defibrillators (ICDs). The incidence of OS and its relationship to clinical variables and ICD system design are unknown. METHODS AND RESULTS: Three hundred twenty-nine patients performed provocative respiratory maneuvers at rest during intrinsic rhythm and continuous ventricular pacing. OS resulting in spurious ventricular detections was provoked in 3 (0.9%) of 329 patients during intrinsic rhythm and 34 (10.3%) of 329 during pacing. Noise transients not recognized and marked as sensed events, but visually evident on the local endocardial ventricular electrogram, were provoked in an additional 23 (7.0%) of 329 patients. Multivariate logistic regression identified history of spontaneous OS (P < 0.0005, odds ratio 9.7, 95% confidence interval [CI] 1.9 to 50.0), automatic gain control device (P < 0.0005, odds ratio 5.3, 95% CI 2.6 to 10.8) or integrated bipolar lead (P = 0.05, odds ratio 2.6, 95% CI 1.0 to 7.25), and male gender (P = 0.008, odds ratio 3.7, 95% CI 1.2 to 11.1) as predictive of provocable OS. Spontaneous OS resulting in spurious ventricular detections and therapies occurred in 12 (3.6%) patients during follow-up. Eleven of 12 spontaneous episodes occurred in male patients during ventricular pacing; 11 of 12 patients had automatic gain control devices and integrated bipolar leads. CONCLUSION: OS is commonly provoked in ICD patients during ventricular pacing and may occur spontaneously, causing spurious tachyarrhythmia therapies and pacing inhibition. Differences in the incidence of spontaneous and provoked OS between ICD systems can be explained on the basis of unique features of automatic sensing systems and sensing lead design.

Echocardiographic determinants of left ventricular ejection fraction after acute myocardial infarction.

OBJECTIVE: This study was performed to determine if factors other than the size of regional dysfunction influence the global left ventricular ejection fraction after acute myocardial infarction. BACKGROUND: Left ventricular ejection fraction is an important prognostic variable after acute myocardial infarction. Although infarct size is known to affect the subsequent global left ventricular ejection fraction, it remains unclear whether other factors such as site or severity of the wall motion abnormality influence the ejection fraction after acute myocardial infarction. METHODS: Sixty-nine consecutive patients (mean age 61 +/- 14 years, 46 [67%] male) who did not receive thrombolytic therapy or undergo early revascularization were studied by echocardiography 1 week after Q-wave myocardial infarction. The absolute size of the region of abnormal wall motion (AWM) and the percentage of the endocardium involved (%AWM) were quantitated along with the wall motion score. A severity index was then derived as the mean wall motion score within the region of AWM. Site of myocardial infarction was classified as either anterior or inferior from the endocardial map. Left ventricular ejection fraction was measured by Simpson's method with 2 apical views. RESULTS: Twenty-nine (42%) patients had anterior and 40 had inferior myocardial infarction. The mean left ventricular ejection fraction was significantly lower in anterior than in inferior myocardial infarction (44.8% +/- 11.5% vs 53% +/- 8.6%; P =. 001). The mean %AWM was greater in anterior than in inferior myocardial infarction (32.1 +/- 15.5 vs 22.4 +/- 14.1; P =.01). The mean wall motion score was greater in anterior than in inferior myocardial infarction (9.8 +/- 6.4 vs 6.4 +/- 4.4; P =.01). The mean severity index did not differ by site. Multiple regression analysis demonstrated that, in descending order of importance, %AWM, extent of apical involvement, and site of myocardial infarction were independent determinants of global left ventricular ejection fraction. CONCLUSIONS: For myocardial infarctions of similar size, left ventricular ejection fraction is lower when apical involvement is extensive and the site of infarction is anterior. This site-dependent difference may be related to characteristics specific to the apex.

Regional myocardial perfusion after experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The pathophysiology of cardiac injury after subarachnoid hemorrhage (SAH) remains controversial. Data from animal models suggest that catecholamine-mediated injury is the most likely cause of cardiac injury after SAH. However, researchers also have proposed myocardial ischemia to be the underlying cause, as a result of coronary artery disease, coronary artery spasm, or hypertension and tachycardia. To test the hypothesis that SAH-induced cardiac injury occurs in the absence of myocardial hypoperfusion, we developed an experimental canine model that reproduces the clinical and pathological cardiac lesions of SAH and defines the epicardial and microvascular coronary circulation. METHODS: Serial ECG, hemodynamic measurements, coronary angiography, regional myocardial blood flow measurements by radiolabeled microspheres, 2D echocardiography, and myocardial contrast echocardiography were performed in 9 dogs with experimental SAH and 5 controls. RESULTS: Regional wall motion abnormalities were identified in 8 of 9 SAH dogs and 1 of 5 controls (Fisher's Exact Test, P=0.02) but no evidence was seen of coronary artery disease or spasm by coronary angiography and of significant myocardial hypoperfusion by either regional myocardial blood flow or myocardial contrast echocardiography. CONCLUSIONS: In this experimental model of SAH, a unique form of regional left ventricular dysfunction occurs in the absence of myocardial hypoperfusion. Future studies are justified to determine the cause of cardiac injury after SAH.

Complications of exercise and pharmacologic stress tests: differences in younger and elderly patients.

BACKGROUND: Age characteristics of patients undergoing various types of stress tests are important because of differences in clinical background and exercise performance between the young and elderly. Adverse effects of pharmacologic agents are known to be more common in the elderly, who are less able to perform vigorous exercise stress testing. We investigated the clinical background, performance characteristics, and complication rate of various stress tests in younger (<75 years old) and elderly (>75 years old) patient populations. METHODS: A total of 3412 patients (2796 younger, 616 elderly) underwent 5 types of stress tests with (1) technetium-99m sestamibi (MIBI) single photon emission computed tomography: symptom-limited exercise (Ex, 1598 younger, 173 elderly), (2) dipyridamole infusion (0.14 mg/kg/min, 4 minutes) without exercise (D, 260 younger, 114 elderly), (3) with exercise (DEx, 339 younger, 112 elderly), (4) adenosine infusion (0.14 mg/kg/min, 5 minutes) without exercise (A, 253 younger, 101 elderly), and (5) with exercise (AEx, 346 younger, 116 elderly). RESULTS: Sixty-seven percent of patients in the younger population were able to achieve 85% of the maximum predicted heart rate, whereas 54% of the elderly reached this level of exercise. No patient had life-threatening complications. In both the younger and elderly groups, chest discomfort, feelings of impending syncope, flushing, and fall in blood pressure occurred less frequently in DEx than D and in AEx than A. Sinus bradycardia occurred less frequently in AEx than A in the younger (1.2% vs 4.3%, P < .05) and elderly groups (0.9% vs 6.9%, P < .05). Atrioventricular block was less frequent in AEx than A in the younger group (3.2% vs 7.9%, P < .05) but not so in the elderly group (13.0% vs 17.8%, not significant). The frequency of ischemic electrocardiographic changes in DEx and AEx was very similar to that of Ex in both the younger and elderly groups, although ischemic electrocardiographic changes in D and A are known to be less frequent. CONCLUSION: Of the elderly group who were judged to be fit to exercise to 85% of maximum predicted heart rate, nearly half failed to reach this level. In contrast, the younger patients were able to achieve this level in 67% of tests. Supplementation with modest exercise reduced most of the pharmacologically related adverse effects. The elderly group was not protected from atrioventricular block as effectively as the younger group by additional exercise in the adenosine stress test. Ischemic electrocardiographic changes in the pharmacologic stress test were as frequent as in the exercise stress test when modest supplementary exercise was added to the pharmacologic protocol. There were no deaths, myocardial infarction, or other major complications. These observations suggest that exercise and pharmacologic stress tests are safe in the elderly, including those patients more than 75 years old.

Cardiac outcome in patients with subarachnoid hemorrhage and electrocardiographic abnormalities.

OBJECTIVE: Approximately 25% of patients with subarachnoid hemorrhage (SAH) have electrocardiographic (ECG) abnormalities consistent with myocardial ischemia or myocardial infarction (MI), and their cardiac prognosis remains unclear. The objective of this study was to determine the cardiac and all-cause mortality rate of a series of patients with SAH with ECG changes consistent with ischemia or MI. METHODS: Using an existing database of patients with SAH and predetermined ECG criteria for ischemia or MI, a study group of patients with abnormal ECG results within 3 days of presentation and before aneurysm surgery was identified. Database patients without abnormal ECG results served as a control group. Cardiac mortality, defined as death resulting from arrhythmia, congestive heart failure, or cardiogenic shock, was assessed by chart review. RESULTS: Of 439 patients with SAH in the database, 58 met the criteria for the study group. Forty-one of these patients were treated neurosurgically. No deaths resulting from cardiac causes occurred, and 20 patients died as a result of noncardiac causes. In a multivariable analysis, age older than 65 years and Hunt and Hess grade of at least 3 were predictive of all-cause mortality. ECG abnormalities, however, were not a statistically significant predictor. CONCLUSION: In patients with SAH and ECG readings consistent with ischemia or MI, the risk of death resulting from cardiac causes is low, with or without aneurysm surgery. The ECG abnormalities are associated with more severe neurological injury but are not independently predictive of all-cause mortality.

Hypercholesterolemia exacerbates transplant arteriosclerosis via increased neointimal smooth muscle cell accumulation: studies in apolipoprotein E knockout mice.

BACKGROUND: Hypercholesterolemia is thought to be a significant risk factor for coronary vasculopathy in cardiac transplant recipients. METHODS AND RESULTS: We examined the development of arteriosclerosis in mouse carotid artery loops allografted from B.10A(2R) (H-2h2) donors to normocholesterolemic C57BL/6J (H-2h) recipients and hypercholesterolemic C57BL/6J recipients in which the apolipoprotein (apo) E gene had been knocked out. Luminal occlusion and cross-sectional neointimal area were greater in arteries allografted into hypercholesterolemic recipients at 15 and 30 days after transplantation. We also measured cellular and extracellular matrix components of the neointima by computerized planimetry of the fractional areas subtended by smooth muscle cells (anti-alpha-actin stain), collagen (Masson's trichrome), lipid (oil red O), and leukocytes (anti-CD45). The neointimal area stained for smooth muscle cells was significantly greater in hypercholesterolemic recipients than in normocholesterolemic recipients at 15 and 30 days after allografting. Lipid contributed to neointimal area to a lesser degree, and there was no significant increase in the contribution of collagen or leukocytes. CONCLUSIONS: Smooth muscle cell accumulation appears to be the principal contributor to the increase in neointimal area observed in arteries allografted into hypercholesterolemic mice.

Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy.

BACKGROUND: In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS: Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS: The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968 to 1995.

OBJECTIVES: A total of 4756 cases of intraaortic balloon pump support have been recorded at the Massachusetts General Hospital since the first clinical insertion for cardiogenic shock in 1968. This report describes the patterns of intraaortic balloon use and associated outcomes over this time period. METHODS: A retrospective record review was conducted. RESULTS: Balloon use has increased to more than 300 cases a year at present. The practice of balloon placement for control of ischemia (2453 cases, 11.9% mortality) has become more frequent, whereas support for hemodynamic decompensation (congestive heart failure, hypotension, cardiogenic shock) has been relatively constant (1760 cases, 38.2% mortality). Mean patient age has increased from 54 to 66 years, and mortality has fallen from 41% to 20%. Sixty-five percent (3097/4756) of the total patient population receiving balloon support underwent cardiac surgery. Placement before the operation (2038 patients) was associated with a lower mortality (13.6%) than intraoperative (771 patients, 35.7% mortality) or postoperative use (276 patients, 35.9% mortality). Independent predictors of death with balloon pump support were insertion in the operating room or intensive care unit, transthoracic insertion, age, procedure other than angioplasty or coronary artery bypass, and insertion for cardiogenic shock. Independent predictors of death with intraoperative balloon insertion were age, mitral valve replacement, prolonged cardiopulmonary bypass, urgent or emergency operation, preoperative renal dysfunction, complex ventricular ectopy, right ventricular failure, and emergency reinstitution of cardiopulmonary bypass. CONCLUSIONS: Balloons are being used more frequently for control of ischemia in more patients who are elderly with lower mortality. An institutional bias toward preoperative use of the balloon pump appears to be associated with improved outcomes.

Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina.

BACKGROUND: Restenosis remains the major limitation of percutaneous coronary revascularization. Macrophages release cytokines, metalloproteinases, and growth factors that may induce smooth muscle cell migration and proliferation. We tested the hypothesis that primary lesions that develop restenosis after coronary atherectomy have more macrophages and smooth muscle cells than primary lesions that do not develop restenosis. METHODS AND RESULTS: Fifty patients with unstable angina were identified. Total and segmental areas were quantified on trichrome-stained sections of coronary atherectomy tissue. Macrophages and smooth muscle cells were identified by immunohistochemical staining. Restenosis, defined as > 50% stenosis diameter by quantitative cineangiography, was present in 30 patients. The other 20 patients (< 50% stenosis) constitute the "no restenosis" group. The percentages of smooth muscle cell areas were similar in specimens from patients with and without restenosis (57 +/- 5% and 52 +/- 6%) (P = NS). However, macrophage-rich areas were larger in plaque tissue from patients with restenosis (20.4 +/- 2%) than in tissue from patients without restenosis (9.3 +/- 2%) (P = .0007). Multiple stepwise logistic regression analysis identified macrophages as the only independent predictor for restenosis (P = .006). CONCLUSIONS: Macrophages are increased in coronary atherectomy tissue from primary lesions that develop restenosis, suggesting a possible role for macrophages in the restenotic process after percutaneous coronary intervention.

Prevalence and timing of regional myocardial dysfunction after rotational coronary atherectomy.

OBJECTIVES: This study aimed to evaluate the prevalence and time course of wall motion abnormalities associated with rotational coronary atherectomy. BACKGROUND: Although initial clinical studies found evidence of transient wall motion abnormalities after rotational coronary atherectomy, the prevalence and duration of these wall motion abnormalities are unknown. METHODS: Using simultaneous echocardiography, we prospectively evaluated 22 patients undergoing rotational atherectomy and compared their wall motion abnormalities with those of 10 patients undergoing coronary angioplasty alone. The extent of wall motion abnormality was quantified and plotted against time to produce curves of abnormal wall motion development and recovery for the two groups. RESULTS: The cumulative ischemic time was similar for the two groups ([mean +/- SD] 10.3 +/- 6 min for rotational atherectomy vs. 9.6 +/- 4.2 min for coronary angioplasty, p = 0.73). The rate of return to baseline function was significantly lower in the rotational atherectomy group than in the coronary angioplasty group (rotational atherectomy rate constant 0.069 +/- 0.079/min vs. coronary angioplasty rate constant 1.250 +/- 0.47/min, p = 0.0001). The mean time to recovery of baseline wall motion in the rotational atherectomy group (153 min, 95% confidence interval [CI] 6.5 to 3,600) was significantly longer than in the coronary angioplasty group (2.6 min, 95% CI 1.3 to 5.5, p = 0.0001). Rotational atherectomy burr time was longer in the patients who developed myocardial infarction than in those without myocardial infarction (4.7 +/- 2.4 vs. 3 +/- 1.4 min, p = 0.045). CONCLUSIONS: Transient wall motion abnormalities are common after rotational coronary atherectomy and have a longer duration than those observed after coronary angioplasty. This disparity may be a consequence of differences in the mechanisms by which rotational coronary atherectomy and coronary angioplasty produce their effect.

Diagnostic accuracy of antimyosin scintigraphy in suspected myocarditis.

BACKGROUND: Radiolabeled antibody specific for cardiac myosin administered intravenously has been used to define noninvasively regions of myocardial necrosis. Inflammatory heart disorders such as myocarditis and heart transplant rejection demonstrate diffuse and often faint myocardial uptake of antimyosin antibody. This study was undertaken to evaluate the reproducibility and diagnostic accuracy of antimyosin antibody imaging for the detection of patients with suspected myocarditis. METHODS AND RESULTS: Fifty antimyosin scans, performed consecutively in patients with suspected myocarditis, were evaluated by one independent observer and two panels of observers. Antimyosin scan interpretations were compared with endomyocardial biopsy results and also with serial changes in left ventricular function. An independent observer (A) and a panel of five observers (A through E) interpreted the antimyosin scans as positive or negative on the basis of both planar images and tomographic reconstructions. Three of the five observers (A through C) again interpreted the scans but based interpretation only on planar images. Blinded random sequence evaluation of antimyosin scans based on the planar and tomographic interpretations revealed moderate agreement between the independent observer (A) and the group of observers (A through E) (kappa = 0.58). There was also moderate agreement between interpretations based on planar images alone and interpretations based on both planar and tomographic images (kappa [A through E]/[A through C] = 0.57; kappa [A through C]/A = 0.48). Comparison of antimyosin scan results with histologic evidence of myocarditis in endomyocardial biopsy specimens demonstrated that all scan results obtained from the individual or the panels of observers had a very high sensitivity (91% to 100%) and a high negative predictive value (93% to 100%). The specificity (31% to 44%) and positive predictive value (28% to 33%) were less impressive. We also compared the scan and biopsy results with the composite clinical standard of significant left ventricular functional improvement. Endomyocardial biopsy demonstrated poor sensitivity (35%) compared with antimyosin scans (82% to 94%) but had superior specificity (endomyocardial biopsy, 79%; antimyosin scan, 25% to 42%). The specificity of interpretations based on planar and tomographic interpretations (38% to 42%) was better than the planar images alone (25%). If reversible left ventricular dysfunction is considered clinical evidence of myocarditis, this study suggests that a negative endomyocardial biopsy significantly misses the presence of the disease. On the other hand, a negative antimyosin scan almost invariably excludes myocarditis. CONCLUSIONS: This study demonstrates a high degree of interobserver reproducibility of antimyosin interpretation. Comparison of the scintigraphic results with histologic and clinical standards indicates a high sensitivity of antimyosin scans for the detection of myocarditis. The antimyosin scan is also not likely to miss clinically or pathologically diagnosed myocarditis, in contrast to the endomyocardial biopsy, which missed clinically validated myocarditis 65% of time. The combination of high sensitivity and negative predictive value suggests that antimyosin scintigraphy may be an effective screening procedure for obviating biopsies in patients with suspected myocarditis.

Echocardiography can predict which patients will develop severe mitral regurgitation after percutaneous mitral valvulotomy.

OBJECTIVES: Using two-dimensional echocardiography, we sought to identify features that are associated with severe mitral regurgitation after percutaneous mitral valvulotomy and combine them into a predictive score. BACKGROUND: Severe mitral regurgitation after percutaneous mitral valvulotomy is a major complication carrying an adverse prognosis that, to date, has not been predictable in advance. METHODS: In a consecutive series of 566 patients who underwent percutaneous mitral valvulotomy, 37 (6.5%) developed severe mitral regurgitation (assessed by angiography) after the procedure, 31 of whom had an echocardiogram available before percutaneous mitral valvulotomy. These 31 patients were matched by age, gender, mitral valve area and degree of mitral regurgitation before valvulotomy with 31 randomly selected patients who did not develop severe mitral regurgitation after percutaneous mitral valvulotomy. An echocardiographic score was developed on the basis of the pathologic studies of valves of patients who developed severe regurgitation after percutaneous mitral valvulotomy (leaflet rupture of relatively thin portions of nonhomogeneously thickened leaflets in the presence of commissural and subvalvular calcification) and evaluated uneven distribution of thickness in the anterior and posterior mitral leaflets, degree of commissural disease and subvalvular disease involvement, with each component graded from 0 to 4 (total, 0 to 16). Intraobserver and interobserver variability for score assessment were 6% and 7%, respectively. RESULTS: The total mitral regurgitation echocardiographic score was significantly greater in the severe mitral regurgitation group (11.7 +/- 1.9 [mean +/- SD] vs. 8.0 +/- 1.2, p < 0.001). In addition, the component grades for the anterior leaflet (3.2 +/- 0.7 vs. 2.3 +/- 0.6, p < 0.001), commissures (2.6 +/- 0.7 vs. 1.6 +/- 0.6, p < 0.001) and subvalvular apparatus (3.2 +/- 0.6 vs. 2.3 +/- 0.7, p < 0.001) were also higher in the mitral regurgitation group. With a total score > or = 10 as a cutoff point for predicting severe mitral regurgitation after percutaneous mitral valvulotomy, a sensitivity of 90 +/- 5% and a specificity of 97 +/- 3% were obtained. Stepwise logistic regression analysis identified the mitral regurgitation echocardiographic score as the only independent predictor for developing severe mitral regurgitation after percutaneous mitral valvulotomy (p < 0.0001). CONCLUSIONS: This new mitral regurgitation echocardiographic score can predict the development of severe mitral regurgitation after percutaneous mitral valvulotomy and can be useful in the selection of patients for this technique.

Geriatric patients with acute myocardial infarction: Cardiac risk factor profiles, presentation, thrombolysis, coronary interventions, and prognosis.

Elderly patients have a higher mortality after acute myocardial infarction (MI) yet are treated less aggressively than younger patients. To determine (l) the risk-factor profiles, (2) presentation, (3) management, and (4) hospital outcomes for the elderly (> or = 75 years) compared with middle aged (66 to 74 years) and younger (< or = 65 years) patients in the 1990s, we studied 561 consecutive patients with acute MI. Compared with younger patients, the elderly more frequently had congestive heart failure (40 percent vs 14 percent; p < 0.00001) and non-Q wave infarctions (76 percent vs 56 percent; p < 0.005), received thrombolysis (9 percent vs 34 percent; p < 0.0001), and underwent catheterization (35 percent vs 73 percent; p < 0.00001), percutaneous transluminal coronary angioplasty (9 percent vs 31 percent; p < 0.0002), and coronary artery bypass grafting (5 percent vs 15 percent; p < 0.03) less frequently. Those who did not receive thrombolysis all had contraindications. Mortality was higher in the elderly (19 percent vs 5 percent; p < 0.004), especially among those who did not receive thrombolysis (20 percent vs 7 percent; p < 0.03). Multivariate predictors of mortality included age, and congestive heart failure. In addition, when clinical course and management variables were considered, use of the intraaortic balloon pump was a predictor of mortality, whereas undergoing coronary angiography was a negative predictor (relative risk, 0.3; 95 percent confidence intervals, 0.1 to 0.6).

Immunologic basis of transplant-associated arteriosclerosis.

Although immunosuppressive therapy minimizes the risk of graft failure due to acute rejection, transplant-associated arteriosclerosis of the coronary arteries remains a significant obstacle to the long-term survival of heart transplant recipients. The participation of specific inflammatory cell types in the genesis of this lesion was examined in a mouse model in which carotid arteries were transplanted across multiple histocompatibility barriers into seven mutant strains with immunologic defects. An acquired immune response--with the participation of CD4+ (helper) T cells, humoral antibody, and macrophages--was essential to the development of the concentric neointimal proliferation and luminal narrowing characteristic of transplant arteriosclerosis. CD8+ (cytotoxic) T cells and natural killer cells were not involved in the process. Arteries allografted into mice deficient in both T-cell receptors and humoral antibody showed almost no neointimal proliferation, whereas those grafted into mice deficient only in helper T cells, humoral antibody, or macrophages developed small neointimas. These small neointimas and the large neointimas of arteries grafted into control animals contained a similar number of inflammatory cells; however, smooth muscle cell number and collagen deposition were diminished in the small neointimas. Also, the degree of inflammatory reaction in the adventitia did not correlate with the size of the neointima. Thus, the reduction in neointimal size in arteries allografted into mice deficient in helper T cells, humoral antibody, or macrophages may be accounted for by a decrease in smooth muscle cell migration or proliferation.

Sex differences in cardiac arrest survivors.

BACKGROUND: Important sex differences in the epidemiology of sudden death and in the results of electrophysiological testing in survivors of cardiac arrest have been identified. These differences are currently poorly understood. METHODS AND RESULTS: Three hundred fifty-five consecutive survivors of out-of-hospital cardiac arrest (84 women and 271 men) referred for electrophysiologically guided therapy were analyzed retrospectively for sex differences in underlying pathology and predictors of outcome. Women were significantly less likely to have underlying coronary artery disease than men (45% versus 80%) and more likely to have other forms of heart disease or structurally normal hearts (P<.0001). The mean left ventricular ejection fraction was higher in women (0.46+/-0.18 versus 0.41+/-0.18, P<.05), and women were more likely to have no inducible arrhythmia at baseline electrophysiological testing (46% versus 27%, P=.002), although when the patients were stratified by coronary artery disease status, these sex differences were no longer present. The independent predictors of outcome differed between men and women. In men, a left ventricular ejection fraction of <0.40 was the most powerful independent predictor of total (relative risk, 2.8; 95% CI, 1.6 to 5.0; P<.0001) and cardiac (relative risk, 6.3; 95% CI, 2.9 to 13.5; P<.0001) mortality. In contrast, the presence of coronary artery disease was the only independent predictor of total (relative risk, 4.5; 95% CI, 1.5 to 13.4; P=.003) and cardiac (relative risk, 4.4; 95% CI, 1.2 to 15.6; P=.012) mortality in women. CONCLUSIONS: Females survivors of cardiac arrest are less likely to have underlying coronary artery disease. The predictors of total and cardiac mortality differ between male and female survivors. Coronary artery disease status is the most important predictor in women, and impaired left ventricular function is the most important predictor in men.

Influence of the implantable cardioverter/defibrillator on sudden death and total mortality in patients evaluated for cardiac transplantation.

BACKGROUND: Implantable cardioverter/defibrillators (ICDs) may reduce sudden tachyarrhythmic death in patients with severe left ventricular dysfunction. It is uncertain whether this improves survival, particularly in patients awaiting cardiac transplantation. METHODS AND RESULTS: The effect of treatment for spontaneous ventricular arrhythmias (ICD [n = 59], antiarrhythmic drugs [n = 53], or no antiarrhythmic treatment [n = 179]) on total mortality and mode of cardiac death was analyzed in 291 consecutive patients evaluated for cardiac transplantation between January 1986 and January 1995. There were 109 deaths (37.4%) (63 [21.6%] sudden, 40 [13.7%] nonsudden, and 6 [2.1%] noncardiac) during mean follow-up of 15 months (range, 1 to 118 months). Baseline clinical variables, medical therapies for heart failure, and actuarial rates of transplantation were similar between treatment groups. Kaplan-Meier sudden death rates were lowest in the ICD group, intermediate in the no antiarrhythmic treatment group, and highest in the drug treatment group throughout follow-up (12-month sudden death rates, 9.2%, 16.0%, and 34.7%, respectively; P = .004). Total mortality and nonsudden death rates did not differ. Cox proportional-hazards model revealed that antiarrhythmic drug treatment was associated with sudden death (relative risk, 2.1; 95% CI, 1.04 to 3.39; P = .04) and ICD was associated with nonsudden death (relative risk, 2.26; 95% CI, 1.12 to 4.62; P = .02). CONCLUSIONS: Sudden death rates were lowest in patients treated with ICDs compared with drug treatment or no antiarrhythmic treatment. However, although ICDs reduced sudden death in selected high-risk patients with severe left ventricular dysfunction, the effect on long-term survival was limited, principally by high nonsudden death rates.

Do gender-based differences in presentation and management influence predictors of hospitalization costs and length of stay after an acute myocardial infarction?

Previous studies have reported conflicting results on gender differences in the management of acute myocardial infarction (AMI) and have not evaluated hospital length of stay or costs. To determine gender-based differences in presentation, management, length of stay, costs, and prognosis after AMI, we studied 561 patients with AMI. Women were older, had systemic hypertension, diabetes mellitus, and a non-Q-wave AMI more frequently, whereas more men smoked cigarettes. Predictors of coronary angiography were: male gender (RR 1.9; 95% CI 1.2 to 3.1), chest pain at presentation (RR 1.8; 95% CI 1.0 to 3.3), recurrent angina (RR 4.1; 95% CI 2.5 to 6.8), admission via the emergency room (RR 0.2; 95% CI 0.1 to 0.3), and younger age. Gender did not predict mortality. Among presenting features, the predictors of length of stay were diabetes, prior coronary bypass and prior coronary angioplasty in men, and age alone in women. Pulmonary edema and need for coronary bypass during the hospital course were predictors of length of stay in men only. Among presenting features, predictors of cost were diabetes in men and congestive heart failure in women. Predictors of cost during hospitalization for men were pulmonary edema, coronary angiography, intraaortic balloon pump use, and coronary bypass; for women, they were peak levels of creatine kinase and coronary bypass. Thus, predictors of length of stay and hospitalization costs differ based on gender. Efforts at cost containment may need to be gender-specific.

Antimyosin uptake and myofibrillarlysis in dilated cardiomyopathy.

BACKGROUND: Although antimyosin scintigraphy detects myocyte necrosis associated with myocarditis, it has also been reported to yield positive results in a large number of patients with clinical dilated cardiomyopathy without histologic evidence of myocarditis. The question to be resolved is whether this discordance represents false-positive results of antimyosin scans or whether antimyosin scintigraphy more accurately identifies the presence of myocyte necrosis than does endomyocardial biopsy testing. METHODS AND RESULTS: Forty patients with the acute onset of dilated cardiomyopathy (left ventricular ejection fraction < 45%; mean 27% +/- 11%) but no endomyocardial biopsy evidence of myocarditis, were identified from a consecutive series of 50 patients who had undergone indium 111 antimyosin antibody scintigraphy and endomyocardial biopsy for suspected myocarditis. The endomyocardial biopsy specimens were analyzed to identify features correlating with antimyosin uptake or improvement in left ventricular ejection fraction (LVEF) over time. Twenty-five patients showed left ventricular myocardial uptake of radiolabeled antimyosin antibody by both planar and tomographic imaging. The remaining 15 patients had no antimyosin uptake. Of the 25, 22 (88%) patients with positive findings on antimyosin scans had degenerated, myofibrillarlytic myocytes in their biopsy specimens. Of the 15 patients with negative findings on antimyosin scans, only 6 (40%) had similar myofibrillarlytic myocytes (chi 2 = 8.13; p < 0.0047). No other histological feature correlated with the antimyosin positivity. Stepwise multiple regression analysis was performed for identification of predictors of short-term improvement in LVEF. Patients with positive findings on antimyosin scans showed a trend toward improvement with time (F = 3.97; p > 0.05). None of the histologic features predicted improvement in the LVEF. However, the combination of positive findings on an antimyosin scan and myofibrillarlysis did correlate significantly with spontaneous improvement in ejection fraction (F = 4.53; 0.01; < p < 0.05). CONCLUSIONS: This study identifies myofibrillarlysis as a common pathologic alteration in patients with recent onset of dilated cardiomyopathy and positive findings on antimyosin scan, who lack right ventricular biopsy evidence of myocarditis. Because myofibrillarlytic cell population may represent a histologic spectrum of viable to necrotic myocytes, it appears that antimyosin uptake detects necrotic myofibrillarlytic myocytes that are not identified by light microscopy.

Effect of beta-adrenergic receptor blockade on the physiologic response to dobutamine stress echocardiography.

Dobutamine is an effective pharmacologic stress agent because of its beta-adrenergic receptor agonist properties. Theoretically, concurrent beta-adrenergic receptor blockade might alter this effectiveness, but clinical experience has been variable. Before assessing the relative effectiveness and implications of dobutamine stress echocardiography (DSE) to detect myocardial ischemia in the presence of beta-blockade the physiologic and hemodynamic effects of dobutamine with simultaneous beta-blockade must be understood in a controlled setting. Therefore the purpose of this study was to determine if beta-blocking agents alter the timing and magnitude of the physiologic response to graded doses of dobutamine during a standard DSE. Paired DSEs were performed in seven instrumented open-chest dogs with and without beta-blockade (esmolol 500 micrograms/kg initial bolus and 100 micrograms/kg/min infusion). Heart rate, systolic pressure, proximal left anterior descending coronary artery flow, myocardial thickening, and percentage left ventricular area change (% AC) were monitored. The data for each parameter were fit to linear or exponential functions. With graded doses of dobutamine, the rate of increase in coronary flow was greater than that in %AC, which in turn was greater than that in heart rate (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Upregulation and modulation of inducible nitric oxide synthase in rat cardiac allografts with chronic rejection and transplant arteriosclerosis.

BACKGROUND: The Lewis-F344 rat cardiac transplantation model produces cardiac allografts with chronic rejection characterized by arteriosclerotic lesions composed of macrophages and smooth muscle cells. Modulation of the inflammatory response with a diet deficient in essential fatty acids protects against the development of intimal thickening. Little is known about the components of the inflammatory response mediating this process. The cytokine-inducible isoform of nitric oxide synthase (iNOS) regulates the high-output nitric oxide pathway that confers activation properties to macrophages and regulates vasomotion, monocyte adherence, and smooth muscle cell proliferation in the vasculature. The purpose of the present study was to determine whether the iNOS pathway was upregulated during the course of chronic cardiac rejection. METHODS AND RESULTS: We studied iNOS mRNA and protein expression patterns in a series of Lewis-F344 cardiac allografts with early and late chronic rejection and after modulation of the inflammatory response (in an effort to attenuate arteriosclerosis). Relative gene transcript levels were measured with a 32P-dCTP reverse-transcriptase polymerase chain reaction assay designed to amplify iNOS mRNA. The distribution of the iNOS gene product was examined by immunocytochemistry with a polyclonal antibody against iNOS. NOS transcript levels increased significantly in cardiac allografts (days 7, 14, 28, and 75) compared with paired host hearts (exposed to the same circulation) and syngrafts (P < .003). Immunostaining localized the iNOS antigen within subpopulations of mononuclear inflammatory cells in cardiac allografts--presumably, activated macrophages. The number of iNOS-positive mononuclear cells was 25-fold higher in cardiac allografts compared with paired host hearts and syngrafts (P < .009). In cardiac allografts of 75 days or older, there also was striking iNOS staining within some medial and intimal smooth muscle cells in various vessels. Modulation of the inflammatory response (with a diet deficient in essential fatty acids) produced significant decreases in the intimal thickening score and in the percentage of diseased vessels in 28-day cardiac allografts compared with allografts from rats fed a control diet. There was a correlate decrease in iNOS transcript levels and in the number of iNOS-positive mononuclear cells in the 28-day cardiac allografts from rats fed the essential fatty acid-deficient diet. CONCLUSIONS: The early and persistent upregulation of iNOS in chronic cardiac rejection and the coincident reduction in arteriosclerosis and downregulation of iNOS suggest that this inducible regulator may contribute to the inflammatory response mediating transplant arteriosclerosis.