Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes.

BACKGROUND: Unstable angina (UA) is associated with systemic inflammation and with expansion of interferon-gamma-producing T lymphocytes. The cause of T-cell activation and the precise role of activated T cells in plaque instability are not understood. METHODS AND RESULTS: Peripheral blood T cells from 34 patients with stable angina and 34 patients with UA were compared for the distribution of functional T-cell subsets by flow cytometric analysis. Clonality within the T-cell compartment was identified by T-cell receptor spectrotyping and subsequent sequencing. Tissue-infiltrating T cells were examined in extracts from coronary arteries containing stable or unstable plaque. The subset of CD4(+)CD28(null) T cells was expanded in patients with UA and infrequent in patients with stable angina (median frequencies: 10.8% versus 1.5%, P<0.001). CD4(+)CD28(null) T cells included a large monoclonal population, with 59 clonotypes isolated from 20 UA patients. T-cell clonotypes from different UA patients used antigen receptors with similar sequences. T-cell receptor sequences derived from monoclonal T-cell populations were detected in the culprit but not in the nonculprit lesion of a patient with fatal myocardial infarction. CONCLUSIONS: UA is associated with the emergence of monoclonal T-cell populations, analogous to monoclonal gammopathy of unknown significance. Shared T-cell receptor sequences in clonotypes of different patients implicate chronic stimulation by a common antigen, for example, persistent infection. The unstable plaque but not the stable plaque is invaded by clonally expanded T cells, suggesting a direct involvement of these lymphocytes in plaque disruption.

Molecular fingerprint of interferon-gamma signaling in unstable angina.

BACKGROUND: Activation of circulating monocytes in patients with acute coronary syndromes may reflect exposure to bacterial products or stimulation by cytokines such as IFN-gamma. IFN-gamma induces phosphorylation and nuclear translocation of transcription factor STAT-1, which initiates a specific program of gene induction. To explore whether monocyte activation is IFN-gamma driven, patients with unstable (UA) or stable angina (SA) were compared for nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10. METHODS AND RESULTS: Peripheral blood mononuclear cells were stained for expression of CD64 on CD14(+) monocytes and analyzed by PCR for transcription of IP-10. Expression of CD64 was significantly increased in patients with UA. Monocytes from UA patients remained responsive to IFN-gamma in vitro, with accelerated transcriptional competency of CD64. IP-10-specific sequences were spontaneously detectable in 82% of the UA patients and 15% of SA patients (P<0.001). Most importantly, STAT-1 complexes were found in nuclear extracts prepared from freshly isolated monocytes of patients with UA, which provides compelling evidence for IFN-gamma signaling in vivo. CONCLUSIONS: Monocytes from UA patients exhibit a molecular fingerprint of recent IFN-gamma triggering, such as nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10, which suggests that monocytes are activated, at least in part, by IFN-gamma. IFN-gamma may derive from stimulated T lymphocytes, which implicates specific immune responses in the pathogenesis of acute coronary syndromes.

Perturbation of the T-cell repertoire in patients with unstable angina.

BACKGROUND: Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-gamma is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald's class IIIB) and with stable angina (SA). METHODS AND RESULTS: Peripheral blood lymphocytes were collected at the time of hospitalization and after 2 and 12 weeks. Cytokine-producing CD4(+) and CD8(+) T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA was associated with an increased number of CD4(+) and CD8(+) T cells producing IFN-gamma, whereas patients with SA had higher frequencies of IL-2(+) and IL-4(+) CD4(+) T cells. Expansion of the IFN-gamma( +) T-cell population in UA persisted for at least 3 months. Increased production of IFN-gamma in UA could be attributed to the expansion of an unusual subset of T cells, CD4(+)CD28(null) T cells. CONCLUSIONS: Patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFN-gamma production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-gamma is produced by CD4(+)CD28(null) T cells, which are expanded in UA and distinctly low in SA and controls. The emergence of CD4(+)CD28(null) T cells may result from persistent antigenic stimulation.

Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

BACKGROUND: A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. METHODS AND RESULTS: Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase-MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% (P=0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P=0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. CONCLUSIONS: Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.

Mitral regurgitation due to ruptured chordae tendineae in patients with hypertrophic obstructive cardiomyopathy.

Mitral valve regurgitation in association with hypertrophic obstructive cardiomyopathy is usually caused by the systolic anterior motion of the anterior mitral leaflet. Recently, five patients were encountered with hypertrophic obstructive cardiomyopathy who had mitral regurgitation due to ruptured chordae tendineae. The diagnosis was confirmed in all patients during operation for left ventricular septal myectomy-myotomy (Morrow procedure). Preoperative identification of ruptured chordae tendineae as the cause of mitral regurgitation was established by transesophageal echocardiography in the three most recent cases. All patients had successful septal myectomy-myotomy for relief of left ventricular outflow obstruction, and mitral valve competence was restored by valve repair rather than by prosthetic valve replacement. The clinical course of these patients illustrates important management considerations as well as the utility of transesophageal echocardiography for diagnosis. Chordal rupture should be considered in the differential diagnosis of mitral regurgitation in patients with hypertrophic obstructive cardiomyopathy, especially in those with acute hemodynamic deterioration.

Lone atrial fibrillation in elderly persons: a marker for cardiovascular risk.

BACKGROUND: The risk of stroke in persons aged 60 years and younger with lone atrial fibrillation (LAF) is no greater than in the general population. The effect of older age on the risk of stroke in persons with LAF is less well established. PARTICIPANTS AND METHODS: The risk of stroke in persons with LAF and without substantial comorbidities was examined in a population-based study at a single institution in Olmsted County, Minnesota, and compared with that in an age- and sex-matched population. The mean age was 74 years (range, 61-97 years). The median duration of follow-up was 9.6 years until death or last follow-up. RESULTS: Of 55 patients, 26 had 31 cardiovascular events during follow-up, occurring a median of 5.1 years after diagnosis (range, 0.7-18 years). Of 11 cerebrovascular events, 6 were transient ischemic attacks and 5 were strokes. The event rates (percentage per person-year) were 0.9% for stroke, 1.1% for transient cerebral ischemia, and 2.6% for myocardial infarction, for a total cardiovascular event rate of 5.0% per person-year. The corresponding rates for the age- and sex-matched control group were 0.2%, 0%, and 1.1%, for a total of 1.3% per person-year. The incidence of total cardiovascular events was significantly greater (P< .01) in those with LAF, although there was no difference in survival. CONCLUSION: Lone atrial fibrillation occurring after age 60 years is a risk marker for a substantial increase in cardiovascular events that warrants consideration for antithrombotic therapy.

Early coronary angiography improves long-term survival in unstable angina.

BACKGROUND: The role of early coronary angiography in the evaluation of patients with unstable angina has been controversial. This study was designed to determine the effect of early coronary angiography on long-term survival in patients with unstable angina. METHODS: We reviewed the Olmsted County Acute Chest Pain Database, a population-based epidemiologic registry that includes all patients residing within Olmsted County who were seen for emergency department evaluation of acute chest pain from 1985 to 1992. Patients with symptoms consistent with myocardial ischemia qualifying as unstable angina were classified as undergoing early (

Percutaneous pericardial catheter drainage: report of 42 consecutive cases.

Test results of 42 consecutive patients with pericardial effusion treated with percutaneous pericardial drainage were analyzed. Intermittent (79%) or continuous (21%) drainage through a 60-cm pigtail catheter (No. 6Fr to 8Fr) was used. Clinical indications were urgent or semiurgent treatment of large (38%), life-threatening (24%), recurrent (21%) or acute (traumatic) (17%) pericardial effusion. Sixteen patients had a malignant cause for the effusion. Mean duration of use of the indwelling pericardial catheter was 3.5 days (range less than 1 day to 19 days). Two of the 9 catheters in patients on continuous drainage but only 1 of 33 catheters in patients on intermittent drainage became occluded. There was only 1 possible infective complication. Six patients had subsequent elective surgical intervention for persistent or recurrent effusion. Placement of an indwelling pericardial catheter guided by 2-dimensional echocardiography is safe and effective for initial treatment of selected pericardial effusions.

Effect of concomitant or very early statin administration on in-hospital mortality and reinfarction in patients with acute myocardial infarction.

In a retrospective analysis, 66 patients identified as having received a statin drug within 24 hours of admission for acute myocardial infarction were matched 3:1 with a control group of 198 patients not treated with a statin agent. End points of in-hospital mortality and in-hospital reinfarction were significantly lower in the statin-treated group, pointing to a benefit from very early statin treatment in acute myocardial infarction.

Characteristics of presenting electrocardiograms of acute myocardial infarction from a community-based population predict short- and long-term mortality.

To investigate the relevance of presenting electrocardiographic (ECG) patterns to short- and long-term mortality in nonreferral patients with acute myocardial infarction (AMI), 6 ECG patterns were analyzed. A consecutive series of 907 patients from Olmsted County, Minnesota, admitted to the Mayo Clinic Cardiac Care Unit from January 1, 1988 to March 31, 1998 for acute myocardial infarction comprised the study population. ECG patterns and distribution in the population were: (1) ST elevation alone (20.8%), (2) ST elevation with ST depression (35.2%), (3) normal or nondiagnostic electrocardiograms (18.5%), (4) ST depression alone (11.8%), (5) T-wave inversion only (10.7%), and (6) new left bundle branch block (LBBB) (3.0%). Seven- and 28-day mortalities varied significantly (p <0.01) among the 6 ECG groups. Respective mortalities were 3.0% and 6.0% for patients with normal or nondiagnostic electrocardiograms, 3.1% and 5.2% for T-wave inversion only, 7.4% and 10.6% for ST elevation alone, 9.4% and 13.1% for ST depression alone, 10.3% and 13.8% for ST elevation with ST depression, and 18.5% and 22.2% for new LBBB. Length of hospital stay (LOS) also varied among the ECG pattern groups (p <0.001) with the longest average LOS being in the new LBBB group (12.5 days). Long-term survival was similar among 5 ECG pattern groups (45% to 55% at 8 years from discharge) with the exception of LBBB (20% at 8 years). Among non-LBBB groups, ST-segment depression with or without ST elevation was associated with increased short-term mortality. Also, in this community-based population, 18.5% of patients had normal or nondiagnostic electrocardiograms.

Bundle branch block as a predictor of long-term survival after acute myocardial infarction.

Using a community-based population of patients with acute myocardial infarction (AMI), we sought to: (1) determine the prevalence of bundle branch block (BBB) on the presenting electrocardiogram (ECG), (2) compare the clinical characteristics and the treatment administered to patients with and without BBB, and (3) determine the association of BBB with mortality. We analyzed the admission ECGs of 894 consecutive patients with AMI from Olmsted County, Minnesota, seen at our institution from January 1988 to March 1998. Of these, 53 had left BBB (LBBB) (5.9%) and 60 had right BBB (RBBB) (6.7%). Patients with BBB were more likely to be older, have a history of AMI or hypertension, and to be in Killip class >I at presentation. They were less likely to receive primary reperfusion therapy, beta blockers, or heparin, but more likely to receive angiotensin-converting enzyme inhibitors. They had lower mean predischarge ejection fractions (38 +/- 16% vs 50 +/- 15%, p <0.0001). In-hospital mortality was 13.3%, 17.0%, and 9.1% for patients with RBBB, LBBB, and no BBB, respectively (p = 0.11). Respective postdischarge survival at 1, 3, and 5 years was 80%, 60%, and 50% in the RBBB group, 78%, 56%, and 51% in the LBBB group, and 92%, 85%, and 76% in the group without BBB (p <0.0001). Although BBB was not an independent predictor of mortality on multivariate analysis, the presence of transient or persistent BBB with AMI is an easily recognized clinical marker of increased mortality. Our conclusion from this study is that in a community-based population, patients who had LBBB or RBBB at the time of AMI had lower predischarge ejection fractions and higher in-hospital and long-term unadjusted mortality.

Management of coronary risk factors by registered nurses versus usual care in patients with unstable angina pectoris (a chest pain evaluation in the emergency room [CHEER] substudy).

This study examined whether nurses could manage coronary risk factors in patients with unstable angina more effectively than physicians practicing usual care. Three hundred twenty-six patients were randomized in the emergency room to a 6-month program of risk factor management by a registered nurse versus participation in usual care. The nurse intervention consisted of a 30-minute counseling visit at 6 to 10 days after the chest pain episode and a second 30-minute session 1 month later. Multiple risk factors were assessed and addressed: smoking, blood lipids, blood pressure, blood glucose, physical inactivity, weight, psychological stress, and social isolation. Compared with usual care, nurse intervention patients significantly reduced both triglycerides (-29 +/- 8 vs 5 +/- 6 mg/dl; p <0.0004) and weight (-0.9 +/- 3.3 vs +0.1 +/- 2.1 kg; p = 0.0071), and had corresponding improvements in self-reported diet compliance and exercise (+34 +/- 106 vs +9 +/- 98 minutes, p = 0.0491). No significant differences between groups were observed in terms of 6-month changes in total, high-density lipoprotein, or low-density lipoprotein cholesterol, blood pressure, fasting blood glucose, percent body fat or waist-hip ratio, or psychological distress scores. The 6-month rate of recurrent events (cardiac death, out-of-hospital cardiac arrest, myocardial infarction) and/or revascularizations (coronary artery bypass surgery or coronary angioplasty) was lower in the nurse intervention group (1% vs 9%; p = 0.002). We conclude that a nurse-delivered risk factor intervention program for patients with chest pain is feasible and more effective than usual care in terms of fostering lifestyle changes that may lower coronary risk.

An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study).

Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI) with ST-segment elevation may be attenuated by neutrophil-mediated reperfusion injury. Inflammatory mediators released from potentially viable myocytes cause activation of neutrophils, which traverse the endothelium and enter the myocardium. This process involves interaction between the neutrophil-expressed CD11/CD18 and endothelial-expressed intercellular adhesion molecule-1 (ICAM-1). Preclinical studies have shown that monoclonal antibodies (MAb) to CD18 can limit infarct size and preserve left ventricular function. We sought to determine the initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb to CD11/CD18, in patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA). Sixty patients with AMI were randomized to low- (0.3 mg/kg) or high-dose (1.0 mg/kg) Hu23F2G or to placebo immediately before PTCA. We found no clinically significant differences in vital signs, physical examination, laboratory evaluation, or need for subsequent cardiac interventions. In Hu23F2G treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/- 1,298 microg/L (low-dose group) and 15,558 +/- 4409 microg/L (high-dose group) between 5 and 60 minutes, then declined over 72 hours to near-baseline values. Myocardial single-photon emission computed tomographic imaging 120 to 260 hours after PTCA showed no statistically significant differences in final left ventricular defect size. Hu23F2G was well tolerated, with no increase in adverse events, including infections. Thus, Hu23F2G appears safe and well tolerated in patients undergoing PTCA for AMI.

Comparison of two aspirin doses on ischemic stroke in post-myocardial infarction patients in the warfarin (Coumadin) Aspirin Reinfarction Study (CARS).

The Coumadin Aspirin Reinfarction Study demonstrated that combination treatment with fixed dose warfarin (1 or 3 mg) + aspirin 80 mg was not superior to aspirin 160 mg alone after myocardial infarction for reducing nonfatal reinfarction, nonfatal stroke, and cardiovascular death. In this analysis, we examined the importance of aspirin dose in the protection against the secondary end point of ischemic stroke. The comparison arms for this analysis were warfarin 1 mg + aspirin 80 mg versus aspirin 160 mg. In the Coumadin Aspirin Reinfarction Study, 2,028 patients were randomized to aspirin 80 mg plus warfarin 1 mg, and 3,393 were randomized to aspirin 160 mg alone. A predictive model for ischemic stroke was developed using the Cox proportional-hazards model. A reduced Cox proportional-hazards model was developed to test for the effect of aspirin dose on ischemic stroke in predefined subgroups. The incidence of ischemic stroke was lower in patients treated with aspirin 160 mg than in patients treated with aspirin 80 mg + warfarin 1 mg (0.6% vs 1.1%; p = 0.0534). Age, previous stroke or transient ischemic attack, and aspirin dose were independent predictors of ischemic stroke. In addition, the highest risk patients, those with Q-wave myocardial infarction and male patients, appeared to receive greater benefit from aspirin 160 mg than from aspirin 80 mg + warfarin 1 mg. The results of this secondary analysis suggest that aspirin 160 mg is more effective than aspirin 80 mg + warfarin 1 mg in preventing ischemic stroke in post-myocardial infarction patients.

Update on intravenous fibrinolytic therapy for acute myocardial infarction.

Intravenous fibrinolytic therapy is used widely in the treatment of ST-elevation acute myocardial infarction. Advances in this therapeutic modality during the past 5 years include new third-generation fibrinolytic agents and creative strategies to enhance administration and efficacy of fibrinolytic therapy. Several of the new agents allow for single- or double-bolus injection. A number of ongoing large randomized trials are attempting to determine whether the combination of fibrinolytic therapy with low-molecular-weight heparin or a glycoprotein IIb/IIIa antagonist enhances coronary reperfusion and reduces mortality and late reocclusion. One large prospective trial is investigating the potential benefit of prehospital administration of fibrinolytic therapy. This article summarizes recent safety and efficacy data on fibrinolytic therapy, with particular emphasis on the new third-generation fibrin-specific agents; reviews the preliminary data on facilitated fibrinolysis; and discusses the rationale for prehospital administration of fibrinolytic therapy.

Management of atrial fibrillation in adults: prevention of thromboembolism and symptomatic treatment.

Because of its prevalence in the population and its associated underlying diseases and morbidity, atrial fibrillation (AF) is an important and costly health problem. Advancing age, diabetes, heart failure, valvular disease, hypertension, and myocardial infarction predict the occurrence of AF within a population. The management of AF is complex and involves prevention of thromboembolic complications and treatment of arrhythmia-related symptoms. Stroke occurs in 4.5% of untreated patients with AF per year. Independent risk factors for stroke in nonrheumatic patients with AF are advanced age; a history of prior embolism, hypertension, or diabetes; and echocardiographic findings of left atrial enlargement and left ventricular dysfunction. Warfarin decreases stroke by two-thirds and death by one-third; aspirin is only about half as effective overall and is insufficient therapy for those with risk factors for stroke. Options for thromboembolic prophylaxis are use of warfarin for all in whom it is safe or, alternatively, warfarin for those with risk factors and aspirin for those without risk factors. One-half of the patients with AF are 75 years of age or older. The uniform applicability and relative safety of warfarin therapy in this age-group are controversial. Specific therapy for the arrhythmia should be dictated by the need to control symptoms. Symptomatic treatments include rate-control medications and strategies designed to terminate and prevent arrhythmia recurrence. Digoxin, beta-adrenergic blockers, verapamil, and diltiazem slow excessive ventricular rates in patients with AF and may favorably manage comorbid conditions. The efficacy of anti-arrhythmic medications is only 40 to 70% per year in preventing recurrences of AF, and these agents, except amiodarone, may increase the risk of sudden death in patients with certain types of organic heart disease and AF. The use of nonpharmacologic symptomatic therapies such as atrioventricular node modification or ablation with a rate-response pacemaker or surgical intervention is increasing.

T-cell immunity in acute coronary syndromes.

Acute coronary syndromes (ACS) are complications of atherosclerotic vascular disease that are triggered by the sudden rupture of an atheroma. Atherosclerotic plaque stability is determined by multiple factors, of which immune and inflammatory pathways are critical. Unstable plaque is characterized by an infiltrate of T cells and macrophages, thereby resembling a delayed hypersensitivity reaction. On activation, T cells secrete cytokines that regulate the activity of macrophages, or the T cells may differentiate into effector cells with tissue-damaging potential. Constitutive stimulation of T cells and macrophages in ACS is not limited to the vascular lesion but also involves peripheral immune cells, suggesting fundamental abnormalities in homeostatic mechanisms that control the assembly, turnover, and diversity of the immune system as a whole. This review gives particular attention to the emergence of a specialized T-cell subset, natural killer T cells, in patients with ACS. Natural killer T cells have proinflammatory properties and the capability of directly contributing to vascular injury.

Intercessory prayer and cardiovascular disease progression in a coronary care unit population: a randomized controlled trial.

OBJECTIVE: To determine the effect of intercessory prayer, a widely practiced complementary therapy, on cardiovascular disease progression after hospital discharge. PATIENTS AND METHODS: In this randomized controlled trial conducted between 1997 and 1999, a total of 799 coronary care unit patients were randomized at hospital discharge to the intercessory prayer group or to the control group. Intercessory prayer, ie, prayer by 1 or more persons on behalf of another, was administered at least once a week for 26 weeks by 5 intercessors per patient. The primary end point after 26 weeks was any of the following: death, cardiac arrest, rehospitalization for cardiovascular disease, coronary revascularization, or an emergency department visit for cardiovascular disease. Patients were divided into a high-risk group based on the presence of any of 5 risk factors (age = or >70 years, diabetes mellitus, prior myocardial infarction, cerebrovascular disease, or peripheral vascular disease) or a low-risk group (absence of risk factors) for subsequent primary events. RESULTS: At 26 weeks, a primary end point had occurred in 25.6% of the intercessory prayer group and 29.3% of the control group (odds ratio [OR], 0.83 [95% confidence interval (CI), 0.60-1.14]; P=.25). Among high-risk patients, 31.0% in the prayer group vs 33.3% in the control group (OR, 0.90 [95% CI, 0.60-1.34]; P=.60) experienced a primary end point. Among low-risk patients, a primary end point occurred in 17.0% in the prayer group vs 24.1% in the control group (OR, 0.65 [95% CI, 0.20-1.36]; P=.12). CONCLUSIONS: As delivered in this study, intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit.

Dilated cardiomyopathy and myocarditis: natural history, etiology, clinical manifestations, and management.

This monograph begins and ends with a statement of uncertainty regarding many aspects of dilated cardiomyopathy. Natural history studies identify patients with widely differing outcomes. A host of prognostic factors have emerged, yet it would appear that the major determinants of survival are as yet unrecognized. The diagnosis remains primarily one of exclusion, and management is largely nonspecific and supportive. The frequency of sudden cardiac death is well documented, but the ability to accurately identify patients at risk and the efficacy of antiarrhythmic therapy is unestablished. The emerging success of cardiac transplantation is a source of encouragement. The causes of dilated cardiomyopathy remain a source of intense investigation. Accumulating evidence (much of it circumstantial) does, however, implicate a viral etiology and perhaps altered function of the immunoregulatory system. However, the disparity between the severity of functional disturbance with the relative lack of histologic markers of cellular necrosis implies a disturbance at a cellular level. The etiology or etiologies remain elusive. Future investigation directed at fundamental aspects of cardiac cellular biology may provide the answers.

Outcome of valve repair and the Cox maze procedure for mitral regurgitation and associated atrial fibrillation.

OBJECTIVE: The objective was to determine whether the Cox maze procedure provides adjunctive benefit in patients with atrial fibrillation undergoing mitral valve repair. METHODS: We compared the outcome of 39 patients who had the Cox maze procedure plus mitral valve repair between January 1993 and December 1996 (maze group) with that of 58 patients with preoperative atrial fibrillation who had mitral valve repair during the same interval by the same surgeons (control group). Patients in the 2 cohorts were similar for age, gender, preoperative New York Heart Association class III or IV, and duration of preoperative atrial fibrillation. The control group had a higher incidence of previous heart surgery and coronary artery disease. RESULTS: No operative deaths occurred, and 1 patient in each group required pacemaker implantation after the operation. Duration of cardiopulmonary bypass (122 +/- 40 minutes vs 58 +/- 27 minutes, P <.0001) and hospitalization (12.6 +/- 6.4 vs 9.3 +/- 3.4 days, P <.0025) were prolonged in patients having the Cox maze procedure. Overall, 2-year survival was similar (92% +/- 5% for maze patients and 96% +/- 3% for controls). Freedom from atrial fibrillation in the maze group was 74% +/- 8% 2 years after the operation compared with 27% +/- 7% for the control group (P <.0001). Freedom from stroke or anticoagulant-associated bleeding in the maze group was 100% 2 years after the operation compared with 90% +/- 8% in the control group (P =.04). At most recent follow-up, 82% of maze patients were in normal sinus rhythm (53% in control group). CONCLUSION: The addition of the Cox maze procedure to mitral valve repair is safe and effective for selected patients, and elimination of atrial fibrillation decreased late complications.