Cardiac troponin is associated with cardiac outcomes in men and women with atrial fibrillation, insights from the ARISTOTLE trial.

BACKGROUND: Cardiac troponin T (cTnT) and I (cTnI) concentrations provide strong prognostic information in anticoagulated patients with atrial fibrillation (AF). Whether the associations between cardiac troponin concentrations and mortality and morbidity differ by sex is not known. OBJECTIVES: To assess whether men and women have different concentrations and prognostic value of cTnT and cTnI measurements in anticoagulated patients with AF. METHODS: cTnT and cTnI concentrations were measured with high-sensitivity (hs) assays in EDTA plasma samples obtained from the multicentre ARISTOTLE trial, which randomized patients with AF and at least one risk factor for stroke or systemic embolic event to warfarin or apixaban. Patients were stratified according to sex and the associations between hs-troponin concentrations, and all-cause death, cardiac death, myocardial infarction, stroke or systemic embolic event and major bleeding were assessed in multivariable regression models. RESULTS: We found higher cardiac troponin concentrations in men (n = 9649) compared to women (n = 5331), both for hs-cTnT (median 11.8 [Q1-3 8.1-18.0] vs. 9.6 [6.7-14.3] ng L-1 , P < 0.001) and hs-cTnI (5.8 [3.4-10.8] vs. 4.9 [3.1-8.8] ng L-1 , P < 0.001). Adjusting for baseline demographics, comorbidities and medications, men still had significantly higher hs-troponin concentrations than women. C-reactive protein and N-terminal pro-B-type natriuretic peptide concentrations were higher in female patients. Both hs-cTnT and hs-cTnI concentrations were associated with all clinical outcomes similarly in men and women (p-value for interaction >0.05 for all end-points). CONCLUSION: Men have higher hs-troponin concentrations than women in AF. Regardless of sex, hs-troponin concentrations remain similarly associated with adverse clinical outcomes in anticoagulated patients with AF.

The prognostic implications of lack of palpitations in patients hospitalised with atrial fibrillation: observations from a 20-year registry.

OBJECTIVES: It is well recognised that patients differ in the clinical presentation of atrial fibrillation (AF), ranging from the typical symptom of palpitations, atypical symptoms in others and a substantial that are asymptomatic. Whether the different patterns of presentation are associated with differences in outcomes is not known. The aim of this study was to evaluate the prevalence and the prognostic implications of lack of palpitations among patients hospitalised with AF in a large prospective registry. METHODS: Retrospective analysis of all patients hospitalised with AF in Qatar from 1991 to 2010 was made. Patients were divided into two groups according to the presence or absence of palpitations on presentation. Clinical characteristics and outcome were analysed. RESULTS: During the 20-year period, 3850 patients were hospitalised for AF; 1724 (44.8%) had palpitations on presentation while 2126 (55.2%) had no palpitations. Patients who lacked palpitations were 9 years older, had a higher prevalence of diabetes mellitus (64.7% vs. 35.3%), underlying coronary artery disease (CAD; 14.6% vs. 6.2%) and severe left ventricular dysfunction on echocardiography (25.5% vs. 6.6%), (all, p = 0.001). There were 141 deaths among the group with no palpitations compared with 19 among the group with palpitations (6.6% vs. 1.1%). Multivariate analysis of mortality predictors identified 'lack of palpitations' as an independent predictor of in-hospital mortality (relative risk 5.56; 95% confidence interval 1.20-25.0, p = 0.03). CONCLUSIONS: Our study demonstrates for the first time that lack of palpitations as the presenting symptom of patients with AF is associated with worse in-hospital outcome independent of other risk factors or therapy. The underlying mechanisms and the role of confounders warrant further investigation.

Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study.

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Time to presentation with acute myocardial infarction in the elderly: associations with race, sex, and socioeconomic characteristics.

BACKGROUND: Although prompt treatment is a cornerstone of the management of acute myocardial infarction (AMI), prior studies have shown that one fourth of AMI patients arrive at the hospital >6 hours after symptom onset. It would be valuable to identify individuals at highest risk for late arrival, but predisposing factors have yet to be fully characterized. METHODS AND RESULTS: Data from the Cooperative Cardiovascular Project, involving Medicare beneficiaries aged >65 years hospitalized between January 1994 and February 1996 with confirmed AMI, were used to identify patients who presented "late" (>/=6 hours after symptom onset). Patient characteristics were tested for associations with late presentation by use of backward stepwise logistic regression. Among 102 339 subjects, 29.4% arrived late. Significant predictors of late arrival (odds ratio, 95% CI) included diabetes (1.11, 1.07 to 1.14) and a history of angina (1.32, 1.28 to 1.35), whereas prior MI (0.82, 0.79 to 0.85), prior angioplasty (0.80, 0.75 to 0.85), prior bypass surgery (0.93, 0.89 to 0.98), and cardiac arrest (0.52, 0.46 to 0. 58) predicted early presentation. Additionally, initial evaluation at an outpatient clinic (2.63, 2.51 to 2.75) and daytime presentation (1.67, 1.59 to 1.72) predicted late arrival. Finally, female sex, black race, and poverty, which were evaluated with an 8-level race-sex-socioeconomic status interaction term, were also risk factors for delay. CONCLUSIONS: Delayed hospital presentation is a common problem among Medicare beneficiaries with AMI. Factors associated with delay include not only clinical and logistical issues but also race, sex, and socioeconomic characteristics. Education efforts designed to hasten AMI treatment should be directed at individuals with risk factors for late arrival.

Race, sex, poverty, and the medical treatment of acute myocardial infarction in the elderly.

BACKGROUND: Race, sex, and poverty are associated with the use of diagnostic cardiac catheterization and coronary revascularization during treatment of acute myocardial infarction (AMI). However, the association of sociodemographic characteristics with the use of less costly, more readily available medical therapies remains poorly characterized. METHODS AND RESULTS: We evaluated 169 079 Medicare beneficiaries >/=65 years of age treated for AMI between January 1994 and February 1996 to determine the association of patient race, sex, and poverty with the use of medical therapy. Multivariable regression models were constructed to evaluate the unadjusted and adjusted influence of sociodemographic characteristics on the use of 2 admission (aspirin, reperfusion) and 2 discharge therapies (aspirin, beta-blockers) indicated during the treatment of AMI. Therapy use varied by patient race, sex, and poverty status. Black patients were less likely to undergo reperfusion (RR 0.84, 95% CI 0. 78, 0.91) or receive aspirin on admission (RR 0.97, 95% CI 0.96, 0. 99) and beta-blockers (RR 0.94, 95% CI 0.88, 1.00) at discharge. Female patients were less likely to receive aspirin on admission (RR 0.98, 95% CI 0.97, 0.99) and discharge (RR 0.98, 95% CI 0.96, 0.99). Poor patients were less likely to receive aspirin (RR 0.97, 95% CI 0. 96, 0.98) or reperfusion (RR 0.97, 95% CI 0.93, 1.00) on admission and aspirin (RR 0.98, 95% CI 0.96, 1.00), or beta-blockers (RR 0.95, 95% CI 0.91, 0.99) on discharge. CONCLUSIONS: Medical therapies are currently underused in the treatment of black, female, and poor patients with AMI.

Acute myocardial infarction complicated by atrial fibrillation in the elderly: prevalence and outcomes.

BACKGROUND: Although atrial fibrillation (AF) is a common complication of acute myocardial infarction (MI), patient characteristics and association with outcomes remain poorly defined in the elderly. METHODS AND RESULTS: We evaluated 106 780 Medicare beneficiaries > or =65 years of age from the Cooperative Cardiovascular Project treated for acute MI between January 1994 and February 1996 to determine the prevalence and prognostic significance of AF complicating acute MI in elderly patients. Patients were categorized on the basis of the presence of AF, and those with AF were further subdivided by time of AF (present on arrival versus developing during hospitalization). AF and non-AF patients were compared by univariate analysis, and logistic regression modeling was used to identify clinical predictors of AF. The influence of AF on outcomes was evaluated by unadjusted Kaplan-Meier survival curves and logistic regression models. AF was documented in 23 565 patients (22. 1%): 11 510 presented with AF and 12,055 developed AF during hospitalization. AF patients were older, had more advanced heart failure, and were more likely to have had a prior MI and undergone coronary revascularization. AF patients had poorer outcomes, including higher in-hospital (25.3% versus 16.0%), 30-day (29.3% versus 19.1%), and 1-year (48.3% versus 32.7%) mortality. AF remained an independent predictor of in-hospital (odds ratio [OR], 1. 21), 30-day (OR, 1.20), and 1-year (OR, 1.34) mortality after multivariate adjustment. Patients developing AF during hospitalization had a worse prognosis than patients who presented with AF. CONCLUSIONS: AF is a common complication of acute MI in elderly patients and independently influences mortality, particularly when it develops during hospitalization.

Outcomes of patients with chronic renal insufficiency in the bypass angioplasty revascularization investigation.

BACKGROUND: Although severe chronic kidney disease (CKD) is an independent predictor of mortality among patients with coronary artery disease, the impact of mild CKD on morbidity and mortality has not been fully defined. METHODS AND RESULTS: Morbidity and mortality for the 3608 patients with multivessel coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation randomized trial and registry were compared on the basis of the presence and absence of CKD, defined as a preprocedure serum creatinine level of >1.5 mg/dL. Seventy-six patients had CKD. Patients with renal insufficiency were older and more likely to have a history of diabetes, hypertension, and other comorbidities. Among patients undergoing PTCA, patients with CKD had a greater frequency of in-hospital death and cardiogenic shock (P<0.05 and 0.01, respectively). There was a trend toward a larger proportion of patients with CKD experiencing angina at 5 years (P=0.079). Patients with CKD had more cardiac admissions (P=0.003 and <0.0001 for patients undergoing PTCA and CABG, respectively) and a shorter time to subsequent CABG after initial revascularization than patients without CKD (P=0.01). CKD was associated with a higher risk of death at 7 years, both of all causes (relative risk 2.2, P<0.001) and of cardiac causes (relative risk 2.8, P<0.001). CONCLUSIONS: CKD is associated with an increased risk of recurrent hospitalization, subsequent CABG, and mortality. This increased risk of death is independent of and additive to the risk associated with diabetes.

Effect of infarct location on myocardial salvage assessed by technetium-99m isonitrile.

To investigate the influence of infarct location on myocardial salvage, technetium-99m isonitrile was injected into 43 patients with a first myocardial infarction before early reperfusion therapy. Primary coronary angioplasty was performed in 22 patients and successful intravenous thrombolytic therapy was given to 15 patients, both within 6 h of the onset of chest pain. Patency of the infarct-related artery was confirmed by angiography in all 37 patients. In the remaining six patients (three with and three without early thrombolytic therapy) the infarct-related artery remained occluded. Single photon emission computed tomography was performed within 6 h of the administration of technetium-99m isonitrile and repeated at the time of hospital discharge. Radionuclide ejection fraction at discharge was significantly lower for patients with anterior infarction (0.41 +/- 0.12) than for those with inferior infarction (0.56 +/- 0.09, p less than 0.001). Early perfusion defect size, a measure of myocardium at risk, was greater in patients with anterior than in those with inferior infarction (52 +/- 9% vs. 18 +/- 10% of the left ventricle, p = 0.0001) as was final defect size (30 +/- 20% vs. 9 +/- 8%, p less than 0.01). The change in myocardial perfusion, an estimate of myocardial salvage, was also greater in patients with anterior infarction (24 +/- 16% vs. 10 +/- 7%, p less than 0.01). However, the proportion of jeopardized myocardium salvaged (salvage index) was not significantly different between patients with anterior or inferior infarction (0.49 +/- 0.34 vs. 0.59 +/- 0.35, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation and management of patients with both peripheral vascular and coronary artery disease.

The prevalence of serious angiographic coronary artery disease ranges from 37% to 78% in patients undergoing operation for peripheral vascular disease. Clinical studies have demonstrated that cardiac outcome after peripheral vascular surgery is not adequately predicted by the standard criteria of history, physical findings and rest electrocardiogram. An adequate exercise work load, left ventricular function and thallium redistribution have proved important in perioperative risk stratification. The choice of a perioperative functional cardiac test depends on patient-related factors and the nature of the peripheral vascular operation. Although procedures involving aortic cross-clamping exert a greater hemodynamic stress than do carotid endarterectomy and femoral popliteal surgery, late cardiac morbidity and mortality are significant in all patients with atherosclerotic disease. The decision to proceed with preoperative coronary angiography and myocardial revascularization should be based primarily on indications independent of the peripheral vascular procedure. However, peripheral vascular surgery may influence the timing of myocardial revascularization. Patients with high risk or unstable coronary artery disease may benefit from preoperative coronary revascularization, although this hypothesis remains unproved. In all patients, careful monitoring during and after operation is essential. All patients with peripheral vascular disease should be considered to be at lifelong risk for fatal and nonfatal cardiac events and should undergo appropriate clinical and laboratory evaluation and be treated accordingly.

Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994) and dobutamine echocardiography (1991 to 1994) for risk stratification before vascular surgery.

OBJECTIVES: This study evaluated the prognostic value of abnormal test results with pharmacologic stress with regard to perioperative and long-term outcomes in a large population of candidates for vascular surgery. BACKGROUND: Although numerous studies have demonstrated the prognostic value of dipyridamole-thallium-201 myocardial perfusion and dobutamine echocardiography in vascular surgery candidates, a synopsis of predictive estimates is difficult because of individual study variability in pretest clinical risk, sample size and study design. METHODS: A systematic review of published reports on preoperative pharmacologic stress risk stratification from the MEDLINE data base (1985 to 1994) identified 10 reports on dipyridamole-thallium-201 myocardial perfusion (1,994 patients) and 5 on dobutamine stress echocardiography (446 patients). Random effects models were used to calculate summary odds ratios and 95% confidence intervals. RESULTS: Summary odds ratios for death or myocardial infarction and secondary cardiac end points were greater for dobutamine echocardiographic dyssynergy (14- to 27-fold) than for dipyridamole-thallium-201 redistribution (4-fold); wider confidence intervals were noted with dobutamine echocardiography. Pretest coronary disease probability was correlated with the positive predictive value of a reversible thallium-201 defect (r=0.70), increasing sixfold from low to high risk patient subsets. Cardiac event rates were low in patients without a history of coronary artery disease (1% in 176 patients) compared with patients with coronary disease and a normal or fixed-defect pattern (4.8% in 83 patients) and one or more thallium-201 redistribution abnormality (18.6% in 97 patients, p=0.0001). CONCLUSIONS: Meta-analysis of 15 studies demonstrated that the prognostic value of noninvasive stress imaging abnormalities for perioperative ischemic events is comparable between available techniques but that the accuracy varies with coronary artery disease prevalence.

Severity and response of chest pain during thrombolytic therapy for acute myocardial infarction: a useful indicator of myocardial salvage and infarct size.

OBJECTIVES: The purpose of this study was to determine noninvasively whether chest pain severity is predictive of the amount of myocardium at risk and whether the response of pain during thrombolysis is associated with myocardial salvage during acute myocardial infarction. BACKGROUND: The perception of chest pain and response to reperfusion therapy during acute myocardial infarction may provide important information for treatment benefit. Previous studies have been limited by the inability to measure myocardium at risk and myocardial salvage. METHODS: Sixty-two patients with acute myocardial infarction received an injection of technetium-99m sestamibi before thrombolysis and again at hospital discharge. Tomographic imaging was performed 1 to 6 h later. Myocardium at risk, infarct size and absolute myocardial salvage were derived from these images using previously described techniques and were expressed as a percent of the left ventricle. Salvage index was calculated by dividing myocardial salvage by the myocardium at risk. Chest pain severity was graded before thrombolysis as none, mild, moderate or severe. Chest pain response during thrombolytic therapy was graded as none, partial or completely resolved. RESULTS: There was no association between chest pain severity and myocardium at risk, but there was a weak trend toward greater myocardial salvage and salvage index (p = 0.09 and p = 0.12, respectively) for patients with more severe symptoms. Patients without chest pain at the start of thrombolysis still demonstrated significant salvage (11 +/- 11% of the left ventricle, p = 0.009). There was a significant association between chest pain response to therapy and both myocardial salvage (p = 0.03) and salvage index (p = 0.01). By multivariate analysis, chest pain severity and response of chest pain during thrombolysis were significant independent predictors of myocardial salvage, salvage index and infarct size. Thrombolysis was most effective in the 20 patients (32%) with moderate or severe chest pain and complete resolution of symptoms during thrombolysis (salvage of 79% to 89% of the area at risk). In the remaining 32 patients with chest pain, salvage of the area at risk was only 32%. CONCLUSIONS: These findings suggest that the assessment of chest pain before and after thrombolytic therapy is a readily available, useful indicator of the efficacy of the therapy.

Cardiomyopathies in the elderly.

Cardiomyopathies in the elderly have certain characteristic features. The dilated form appears to be less common than in younger patients. Hypertrophic cardiomyopathy is more often associated with severe and concentric hypertrophy. The prognosis of hypertrophic cardiomyopathy seems to be better in the elderly, because they appear to have a lower incidence of sudden death. Restrictive cardiomyopathies are not common in the elderly, and senile amyloid heart disease rarely, if ever, results in congestive heart failure. A syndrome of clinical heart failure with reduced diastolic compliance and preserved systolic function is more common in elderly patients.

Risk factor profiles of patients with sudden cardiac death and death from other cardiac causes: a report from the Coronary Artery Surgery Study (CASS).

Identification of patients at risk of sudden death is essential if optimal preventive treatment strategies are to be developed. In the Coronary Artery Surgery Study (CASS) Registry, 19,946 patients were analyzed to characterize baseline clinical, hemodynamic and angiographic features of patients dying from sudden cardiac death and to compare them with features of patients dying from other cardiac causes, of those dying from noncardiac causes and of survivors. Of the 11,843 medically treated patients, 1,621 died during a mean follow-up period of 5.0 years: death was sudden in 557 (34%), nonsudden but cardiac in 813 (50%) and noncardiac in 251 (16%). In 8,103 surgically treated patients, 824 deaths occurred during a mean follow-up period of 5.1 years: death was sudden in 204 (25%), nonsudden but cardiac in 390 (47%) and noncardiac in 230 (28%). In general, the patients (both medically and surgically treated) who died of cardiac causes, either suddenly or nonsuddenly, were similar to each other but significantly different from patients who either survived or died of noncardiac causes. Although patients with an increased risk of any type of cardiac death could be identified, there were no measures of angiographic or hemodynamic characteristics that were significantly different between patients with sudden cardiac death and those with nonsudden cardiac death. Identification of patients at high risk for sudden cardiac death will require approaches in addition to clinical, angiographic and hemodynamic assessment, such as electrophysiologic assessment or monitoring techniques to identify triggering mechanisms.

Cardiac iron deposition in idiopathic hemochromatosis: histologic and analytic assessment of 14 hearts from autopsy.

In each heart taken from autopsies of 14 men with idiopathic hemochromatosis, the conduction system, atria and 10 sites in the ventricles were histologically graded for stainable iron. Stainable iron was exclusively sarcoplasmic; none was observed in the interstitium. The histologic grade for the same anatomic site varied among hearts and among different anatomic sites in the same heart. Ten hearts had stainable iron in all ventricular sites; one of the three hearts from patients who had undergone therapeutic phlebotomy had no iron at any site. Seven hearts had iron in the atria but at a lesser grade than that found in the ventricles; six hearts had mild focal iron deposition in the atrioventricular conduction system. None of the 14 hearts had stainable iron in the sinus node. Elemental iron was quantitated by atomic absorption spectroscopy in ventricular specimens contiguous to those studied histologically and also in age-matched control hearts. Elemental iron content was markedly increased in hearts with idiopathic hemochromatosis compared with control hearts (p less than 0.01). The quantity of elemental iron varied greatly, similar to stainable iron, but was highest subepicardially. Among the hearts from the 11 patients without prior phlebotomy, three had no stainable iron in the right ventricular septal subendocardium, suggesting that sampling error may be a problem in the evaluation of hemochromatosis by endomyocardial biopsy. The sarcoplasmic location of the iron indicates that cardiac involvement in idiopathic hemochromatosis represents a storage disease and not an infiltrative process; this finding is consistent with the normal ventricular wall thicknesses observed.

Primary angioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99m isonitrile.

Technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (technetium-99m isonitrile) is a new radiopharmaceutical compound that reflects myocardial perfusion. Its kinetics, especially its lack of redistribution after intravenous administration, permits the assessment of changes in myocardial perfusion without delay of therapy. Tomographic images at rest were obtained immediately and 6 to 10 days later in 17 consecutive patients undergoing successful primary angioplasty during their first transmural myocardial infarction. Thirteen patients had anterior infarction. The initial (acute) defect size before angioplasty of 48 +/- 17% of the left ventricle decreased significantly (p less than 0.0001) to 29 +/- 19% on the late scans. There was no correlation between the time to therapy and the reduction in defect size. Twelve of the 17 patients, including 7 of the 11 patients treated after 4 h, demonstrated a definite reduction in the initial defect size. Eight patients with angiographically proved persistent coronary occlusion underwent a similar imaging sequence. The initial defect size in this group remained unchanged on the late scans (24 +/- 16% versus 26 +/- 18%, p = NS). Primary angioplasty is an effective approach toward salvaging myocardium; comparison with thrombolytic drug therapy must await the results of controlled clinical trials.

Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry.

The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term survival in patients with coronary artery disease: importance of peripheral vascular disease. The Coronary Artery Surgery Study (CASS) Investigators.

OBJECTIVES: The purpose of this study was to determine the importance of peripheral arterial disease in predicting long-term survival in patients with clinically evident coronary artery disease. BACKGROUND: Patients in the Coronary Artery Surgery Study (CASS) Registry were followed up for > 10 years. METHODS: Survival in 2,296 patients with peripheral arterial disease was compared with that of 13,953 patients without peripheral arterial disease using Kaplan-Meier survival curves. All patients had known stable coronary artery disease. Clinical, electrocardiographic (ECG), chest X-ray film and catheterization variables of the two groups were compared using the chi-square statistic or the two-sample t test. The independent effect of peripheral arterial disease (as well as other variables) on mortality was determined utilizing a Cox proportional hazards model. RESULTS: Patients with peripheral vascular disease were more likely to have hypertension, diabetes, family history of coronary artery disease, previous angina or myocardial infarction, previous coronary bypass surgery or to have smoked. They also had a higher incidence of congestive heart failure, ECG abnormality and modestly increased frequency of three-vessel disease. Independent correlates of long-term mortality for the entire cohort included age, smoking, diabetes, number of diseased coronary vessels, left ventricular function, hypertension, pulmonary disease, anginal class, previous myocardial infarction and peripheral vascular disease (all p < 0.001). At any point in time, patients with peripheral vascular disease had a 25% greater likelihood of mortality than patients without peripheral vascular disease (multivariate chi-square 25.83, hazard ratio 1.25, 95% confidence interval 1.15 to 1.36, p < 0.001). CONCLUSIONS: Peripheral vascular disease is a strong, independent predictor of long-term mortality in patients with stable coronary artery disease. Aggressive attempts at secondary disease prevention are warranted in this high risk group.

Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction.

This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery.

Percutaneous transluminal coronary angioplasty in the elderly: early and long-term results.

The immediate and long-term efficacy of coronary angioplasty in the elderly was determined by studying 752 patients greater than or equal to 65 years old and comparing patients greater than or equal to 75 years old with those 65 to 74 years old. The oldest patients were more highly symptomatic, were more likely to be in heart failure, had more multivessel disease and were more likely to undergo multivessel dilation. The immediate success rate of angioplasty was higher in the oldest patients (92.8% versus 82%) (p = 0.0003). The hospital mortality rate was also higher (6.2% versus 1.6%) (p less than 0.001). Long-term overall survival was high. However, long-term event-free survival was lowest in the oldest patients, and recurrent severe angina was particularly common. Thus, in very elderly patients, coronary angioplasty is usually successful, but extra caution is warranted; also, long-term relief from angina is less common than in younger patients.

Epidemiology and natural history of atrial fibrillation: clinical implications.

With a substantial impact on morbidity and mortality, the growing "epidemic" of atrial fibrillation (AF) intersects with a number of conditions, including aging, thromboembolism, hemorrhage, hypertension and left ventricular dysfunction. Currently, the epidemiology and natural history of AF govern all aspects of its clinical management. The ongoing global investigative efforts toward understanding AF are also driven by epidemiologic findings. New developments, by affecting the natural history of the disease, could eventually alter the nature of decision making in patients with AF. The crucial issue of rate versus rhythm control awaits completion of the AF Follow-up Investigation of Rhythm Management trial. The processes of electrical and structural remodeling that perpetuate AF appear to be reversible. In the era of functional genomics, the molecular basis of this ubiquitous arrhythmia is in the process of being defined. Unraveling the molecular genetics of AF might provide new insights into the structural and electrical phenotypes resulting from genetic mutations and, as such, new approaches to treatment of this arrhythmia at the ion channel and cellular levels. Thus, current adverse trends are superimposed on a background of a rapidly developing knowledge base and potentially exciting new therapeutic options. Consequently, an understanding of the epidemiology and natural history of AF is crucial to the future allocation of resources and the utilization of an expanding range of therapies aimed at reducing the impact of this disease on a changing patient population.