Fatal Cardiac Events Research Articles

Classification, epidemiology, risk factors, and natural history of peripheral arterial disease.

Peripheral arterial disease (PAD) is a clinical condition that has often been neglected. The clinical diagnosis of PAD may be made on the basis of an accurate history by using the WHO/Rose Questionnaire or the Edinburgh Questionnaire. From a clinical point of view, PAD may be classified into four stages. The PARTNERS Programme (PAD Awareness, Risk and Treatment: NEw Resources for Survival) is a recent study based on a partnership to improve PAD care. In this population, the prevalence of patients who were PAD+/CVD- was approximately 12% in males and 15% in females; PAD+/CVD+ approximately 18% in males and 14% in females; PAD-/CVD+ 28% in males and 17% in females; and finally, patients without vascular disease (PAD-/CVD-) 42% in males and 54% in females. The lessons derived from the PARTNERS Programme Study were informative; PAD is detectable in routine practice, using a simple, inexpensive, always available, clinical test such as calculation of the ankle-brachial pressure index (ABPI). Fewer than half of individuals with PAD are aware of their condition, while physicians are unaware of the presence of PAD in 70% of their patients with the condition. Diabetics and smokers are at high risk for PAD. Diabetes is present in about 41% of patients with PAD and a history of smoking (> 10 pack for year) is present in over 63% of patients with PAD. Antiplatelet therapy is taken by only about half of patients with PAD. Finally, the lack of diagnosis and treatment means that PAD patients remain at elevated risk of heart attack and stroke. Efforts must be made to diffuse this information to improve the diagnosis and treatment of PAD to reduce the risk of future fatal and nonfatal cardiac and cerebrovascular events.

The Time Has Come to Stop Letting the HERS Tale Wag the Dogma

The premise of this commentary is simple. We believe there has been enormous overinterpretation and misinterpretation of recent clinical data (the HERS tale1) with regard to the efficacy of hormone replacement therapy (HRT) in preventing or diminishing the risk of heart disease (the dogma). Both the medical and lay press have focused on obtaining a single yes-or-no answer to the question, “Does postmenopausal HRT reduce the risk of cardiovascular disease (CVD)?” This oversimplified approach has led to unjustified generalizations with regard to the question and to the summary judgment in some circles that HRT is not beneficial for the prevention of heart disease. See p 2300 A brief review of the literature in this area reveals the source of much of the controversy and confusion. In 1992, an elegant meta-analysis by Grady and colleagues2 concluded that “there is extensive and consistent observational evidence that estrogen use reduces risks for CHD [coronary heart disease] about 35%.” This conclusion has since been supported by additional observational studies that together include several hundred thousand woman-years of follow-up. As one example, a recent update from the Nurse’s Health Study (>400 000 woman-years of follow-up) again confirmed a 40% to 60% reduction in cardiovascular events in women taking HRT.3,4 In contrast to this large body of observational data, the recent prospective Heart Estrogen/progestin Replacement Study (HERS) proved negative. HERS, the first prospective, randomized trial of HRT assessing cardiovascular end points, demonstrated that combined HRT (0.625 mg/d conjugated equine estrogens [CEE] and 2.5 mg/d of medroxyprogesterone acetate [MPA]) had no effect on fatal or nonfatal cardiac events.1 The study included 2763 women with established coronary artery disease followed up for an average of 4.1 years. It is largely the discrepancy between the results of HERS and the many prior observational studies that …

Cardiac avoidance in breast radiotherapy: a comparison of simple shielding techniques with intensity-modulated radiotherapy

Background and purpose: Adjuvant breast radiotherapy (RT) is now part of the routine care of patients with early breast cancer. However, analysis of the Early Breast Cancer Trialists’ Collaborative suggests that patients with the lowest risk of dying of breast cancer are at significant risk of cardiac mortality due to longer relapse-free survival. Patients with a significant amount of heart in the high-dose volume have been shown to be at risk of fatal cardiac events. This study was designed to assess whether conformal planning or intensity-modulated radiotherapy (IMRT) techniques allow reduced cardiac irradiation whilst maintaining full target coverage. Material and methods: Ten patients with early breast cancer were available for computed tomography (CT) planning. Each had at least 1 cm maximum heart depth within the posterior border of conventional tangents. For each patient, plans were generated and compared using dose volume histograms for planning target volume (PTV) and organs at risk. The plans included conventional tangents with and without shielding. The shielding was designed to either completely spare the heart or to shield as much heart as possible without compromising PTV coverage. IMRT plans were also prepared using two- and four-field tangential and six-field arc-like beam arrangements. Results: PTV homogeneity was better for the tangential IMRT techniques. For all patients, cardiac irradiation was reduced by the addition of partial cardiac shielding to conventional tangents, without compromise of PTV coverage. The two- and four-field IMRT techniques also reduced heart doses. The average percentage volume of heart receiving >60% of the prescription dose was 4.4% (range 1.0-7.1%) for conventional tangents, 1.5% (0.2–3.9%) for partial shielding, 2.3% (0.5–4.6%) for the two-field IMRT technique and 2.2% (0.4–5.6%) for the four-field IMRT technique. For patients with larger maximum heart depths the four-field IMRT plan achieved greater heart sparing than the partial shielding, although irradiation of the contralateral breast was increased. Full cardiac shielding resulted in the most complete heart sparing but with compromise of the PTV coverage; the mean volume receiving less than 95% of the prescription dose was 4% (range 1.5–8.7%). Conclusion: All patients undergoing adjuvant tangential breast RT in whom the heart is seen to be in the high-dose volume should be considered for the addition of cardiac-sparing lead blocks. Three-dimensional CT planning and alternative beam arrangements with IMRT optimization enables more complete cardiac sparing without compromise of PTV coverage in certain patients.

Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease.

The number of infectious pathogens to which an individual has been exposed (infectious burden) may correlate with coronary artery disease (CAD). In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the risk for future fatal cardiac events among patients with angiographically documented CAD. Methods and Results-In 1018 patients, IgG or IgA antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were determined. Moreover, highly sensitive C-reactive protein was measured. Follow-up information on cardiovascular events was obtained (mean 3.1 years, maximum 4.3 years). Seropositivities to Epstein-Barr virus (P=0.001), H pylori (P=0.002), and herpes simplex virus type 2 (P=0.045) were independently associated with the future risk of cardiovascular death. An increasing number for pathogen burden was significantly predictive of the long-term prognosis (P<0.0001). Infectious burden divided into 0 to 3, 4 or 5, and 6 to 8 seropositivities was associated with an increasing mortality of 3.7%, 7.2%, and 12.6%, respectively. Patients seropositive to >5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1.4 to 18.3) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpesviridae (P<0.0001). The prognostic impact of total or viral pathogen burden was independent of the C-reactive protein level. These results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the long-term prognosis in patients with documented CAD.

Different prognostic impact of 24-hour mean blood pressure and pulse pressure on stroke and coronary artery disease in essential hypertension.

We tested the hypothesis that the steady and pulsatile components of blood pressure (BP) exert a different influence on coronary artery disease and stroke in subjects with hypertension. We analyzed data on 2311 subjects with essential hypertension. All subjects (mean age 51 years, 47% women) underwent off-therapy 24-hour ambulatory BP monitoring. Over a follow-up period of up to 14 years (mean 4.7 years), there were 132 major cardiac events (1.20 per 100 person-years) and 105 cerebrovascular events (0.90 per 100 person-years). After adjustment for age, sex, diabetes, serum cholesterol, and cigarette smoking (all P<0.01), for each 10 mm Hg increase in 24-hour pulse pressure (PP), there was an independent 35% increase in the risk of cardiac events (95% CI 17% to 55%). Twenty-four-hour mean BP was not a significant predictor of cardiac events after controlling for PP. After adjustment for age, sex, and diabetes (all P<0.05), for every 10 mm Hg increase in 24-hour mean BP, the risk of cerebrovascular events increased by 42% (95% CI 19% to 69%), and 24-hour PP did not yield significance after controlling for 24-hour mean BP. Twenty-four-hour PP was also an independent predictor of fatal cardiac events, and 24-hour mean BP was an independent predictor of fatal cerebrovascular events. In subjects with predominantly systolic and diastolic hypertension, ambulatory mean BP and PP exert a different predictive effect on the cardiac and cerebrovascular complications. Although PP is the dominant predictor of cardiac events, mean BP is the major independent predictor of cerebrovascular events.

Prognostic value of impaired myocardial fatty acid uptake in patients with acute myocardial infarction

Impaired cardiac fatty acid uptake, assessed by the radiolabelled fatty acid analogue beta-methyl-p-iodophenyl pentadecanoic acid (I-123-BMIPP), is observed in the myocardium following acute ischaemic events, but the long-term prognostic implication has not been established. This study aimed to determine the prognostic value of cardiac BMIPP uptake in patients with acute myocardial infarction. Following the assessment of thallium-201 and I-123-BMIPP uptake, 101 post-infarct patients were prospectively followed up with primary end points of cardiac death, heart failure and non-fatal infarction. During a mean follow-up of 28 months, three cardiac deaths, three non-fatal infarctions, 23 revascularizations and four recurrences of angina pectoris were observed. Multivariate analysis identified reduced uptake of BMIPP and perfusion, no beta-blocking treatment and greater thallium-BMIPP mismatch (i.e. larger BMIPP defect than thallium defect) as significant predictors for overall cardiac events. Prior myocardial infarction, reduced left ventricular ejection fraction and greater thallium-BMIPP mismatch were selected as independent predictors of harder cardiac events. Female patients, those with greater BMIPP defect or greater thallium-BMIPP mismatch showed worse clinical outcomes. The inclusion of BMIPP data improved the prognostic values of conventional significant predictors. In conclusion, impaired myocardial I-123-BMIPP uptake and perfusion-BMIPP mismatch are related to a high probability of fatal and non-fatal cardiac events, suggesting the aetiological relevance and prognostic value of impaired cardiac fatty acid metabolism in viable, but jeopardized, myocardium following acute myocardial infarction.

7110 Rectal or rectosigmoid cancer diagnoses made secondary to anticoagulation with resultant lower gastrointestinal (gi) bleeding.

Patients without GI signs or symptoms that are anticoagulated for cardiac or cardiovascular disease that have new lower GI bleeding are often watched for lengthy periods of time, with bleeding being ascribed to anticoagulation, prior to being referred for endoscopy. We present 3 cases in which new lower GI bleeding after anticoagulation resulted in new diagnoses of rectal or rectosigmoid cancer. The first patient is a 63 year old white male with atherosclerotic heart disease who underwent his second percutaneous transthoracic coronary angioplasty after a positive stress test. He subsequently developed bright red, lower GI bleeding, initially felt to be secondary to anticoagulation. Rectal exam revealed heme positive stool only, however; colonoscopy was performed, revealing a rectosigmoid junction mass that was biopsy positive for adenocarcinoma. Low anterior resection revealed a T3N2M0 lesion measuring 2.7 x 2.6 x 1.0 cm with 4/7 regional lymph nodes involved with tumor. He received postoperative chemo-radiation and is doing well. The second patient is a 66 year old white male who developed right-sided weakness, paresthesias and facial droop secondary to a cardiovascular accident and was placed on anticoagulant therapy. During his hospitalization, he developed a small amount of rectal bleeding. Rectal exam revealed a mass. Colonoscopy revealed an ulcerated rectal mass, measuring 4 cm, involving 1/4 of the rectal wall that was biopsy positive for adenocarcinoma. Additionally, 4 polyps were removed. Upon deep questioning, patient noted a recent decrease in stool caliber and occasional constipation. EUS revealed a T3N1 tumor, CEA was 4.2 (0-2.5). The patient underwent pre-operative chemo-radiation, followed by complete resection of a 1.9 x 1.1 x 0.5 cm tumor with 0/10 positive lymph nodes, followed by further chemotherapy and is doing well. The third patient is a 73 year old white female with a history of chronic atrial fibrillation, who was recently anticoagulated. She developed rectal bleeding and flexible sigmoidoscopy revealed a 3 x 2 cm mass 4 cm from the anal verge, biopsy positive for adenocarcinoma. Colonoscopy was confirmatory. CT revealed only rectal wall thickening. The patient had a fatal cardiac event less than a week later. Patients who experience new GI bleeding after being placed on anticoagulation can indeed harbor neoplasm. They should undergo prompt endoscopic evaluation to prevent a delay in diagnosis.

Long-term effects of clinical outcome with low and high dose in the Captopril in Heart Insufficient Patients Study (CHIPS)

Background — Although angiotensin-converting enzyme inhibitors are recommended as first line therapy in patients with chronic heart failure, the target doses proven to be effective in major morbidity and mortality trials (e.g. captopril 50 mg b.i.d), are generally not used in daily practice in Belgium.Aim — The objective of this study (CHIPS, Captopril in Heart Insufficient Patients Study) was to compare the long-term effects of a low dose (25 mg b.i.d.) and a high dose (50 mg b.i.d.) of captopril in mild to moderate heart failure.After a titration period of at least 10 days, patients who tolerated 50 mg b.i.d., were randomly assigned to receive either the low dose or the high dose of captopril and followed up to 2 years.Results — 298 patients were included and were followed up for a mean of 12 months. Progression in heart failure seems to be favourably influenced by therapy with high dose in comparison to low dose; a relative difference of 29% in the rates of heart failure worsening was observed between the two doses, 31.5% and 22.4% for low and high dose (p = 0.088), respectively. Treatment with high dose showed also a trend to benefit as compared to low dose in reducing the number of hospitalizations for all causes from 22.4 to 14.5% (p = 0.1) and for congestive heart failure from 14.7 to 7.2% (p = 0.06); moreover, the incidence of fatal and nonfatal cardiac events showed a trend in favour of the high dose of 22% (p = 0.142). The total number of adverse events was comparable for both doses, but dizziness and hypotension were a little more frequently reported in the high-dose group. Serum creatinine values showed no significant changes either in the low-dose or in the high-dose group.Conclusion — In the CHIPS-study, in comparison to a low dose, therapy with a high dose of captopril tends to improve the long-term clinical outcome of patients with mild to moderate heart failure without significantly more toxicity.

T axis as an indicator of risk of cardiac events in elderly people

The T axis was postulated to be a general marker of repolarisation abnormality, indicative of subclinical myocardial damage. The aim of this investigation was to assess the prognostic importance of the T axis for fatal and non-fatal cardiac events, in a prospective cohort study of men and women aged 55 years and older. 2352 men and 3429 women from the population-based Rotterdam Study took part in the study. Electrocardiograms were done, and T axes were categorised as normal, borderline, or abnormal. Data were analysed with Cox's proportional-hazards models; adjustment for age and sex was done where appropriate. During 3-6 (mean 4) years of follow-up of the 5781 participants, 165 (2.9%) fatal and 192 (3.3%) non-fatal cardiac events occurred. Participants with an abnormal T axis (n=609) had an increased risk of cardiac death (hazard ratio 3.9 [95% CI 2.8-5.6]), sudden cardiac death (4.4 [2.6-7.4]), non-fatal cardiac events (2.7 [1.9-3.9]), and combined fatal or non-fatal cardiac events (3.2 [2.5-4.1]); p<0.001 for each. Additional adjustment for established cardiovascular risk factors resulted in lower, but still significant risk for all endpoints. The risk associated with an abnormal T axis was higher than those for any other cardiovascular risk factor. Additional subgroup analyses indicated that the risk of cardiac death was not substantially modified by age, sex, or history of myocardial infarction. The T axis is a strong and independent risk indicator of fatal and non-fatal cardiac events in the elderly.

Long term survival effect of metoprolol in dilated cardiomyopathy

ObjectiveTo evaluate the additive effect of metoprolol treatment on long term incidence of fatal and non-fatal cardiac events in idiopathic dilated cardiomyopathy.Design586 patients with idiopathic dilated cardiomyopathy were prospectively enrolled...

Cardiac risk after mediastinal irradiation for Hodgkin's disease

Purpose: To evaluate the risk of cardiac lesions after conventionally fractionated irradiation (Rt) of the mediastine with or without chemotherapy (Ct) in patients with Hodgkin's disease (HD) and to relate them to known cardiovascular risk factors. Patients and methods: Between 1964 and 1992, 352 (total group) patients with HD were treated with curative intention using Rt with or without Ct including the mediastine and had a follow-up of at least 1 year. More than 96% of the patients had a complete follow-up. One hundred forty-four patients (64% of the living patients, heart study group) have regular follow-up in our department and had a special heart examination including rest and exercise ECG, echocardiography and myocardial perfusion scintigraphy (112 patients). Doses per fraction in the anterior heart region were between 1.3 and 2.1 Gy. Total doses were between 30.0 and 42.0 Gy in 93% of cases. The mean length of follow-up was 11.2 years (range 1.0–31.5 years). Other cardiovascular risk factors evaluated were body mass index, blood pressure, smoking history, diabetes mellitus, hypercholesterolemia and history of coronary artery disease before Rt. Results: In the total group, the risk of fatal cardiac ischemic events and/or of sudden unexpected death was significantly higher than expected with a relative risk of 4.2 for myocardial infarction and 6.7 for myocardial infarction or sudden death. In female patients and in patients without other cardiovascular risk factors, the risk of fatal or non-fatal ischemic cardiac events was not significantly different from the expected value. In the subgroup with no cardiovascular risk factors and treatment without Ct, there was no ischemic or other major cardiac event. Echocardiography showed valvular thickenings in a large amount of the patients (the cumulative risk after 30-year follow-up was above 60%) but mostly without hemodynamic disturbance. In patients without hypertension and without coronary artery disease, findings of perfusion scintigraphy and echocardiographic evaluation of systolic and diastolic function were normal. Treatment with Ct was not a significant risk factor for cardiac events but the number of patients whose treatment included adriamycin and with a follow-up exceeding 10 years is to low for a definitive evaluation. Conclusions: In patients without the usual cardiovascular risk factors (smoking, hypertension, obesity, hypercholesterolemia, diabetes mellitus) the risk of serious cardiac lesions after conventionally fractionated irradiation of the mediastinum with an intermediate total dose between 30 and 40 Gy is low. Also the cardiac risk of the combination of this irradiation with Ct including adriamycin with a total dose between 200 and 300 mg/m 2 seems low but further long-term observation is necessary.

T-loop morphology as a marker of cardiac events in the elderly

ST-T wave changes of electrocardiographic (ECG) leads have long been recognized as predictors of future cardiac events, but they only imperfectly characterize T-loop morphology. Using vectorcardiographic (VCG) parameters, we investigated the predictive value of T-loop abnormality for fatal and nonfatal cardiac events in a prospective cohort study among 5,815 elderly. Separately, the predictive value of an easily obtainable T-loop parameter, the T axis, was also assessed. Measurements were determined by a computer program, using VCGs reconstructed from the standard 12-lead ECGs. During the 3 to 6 (mean 4) years of follow-up, 166 fatal and 193 nonfatal cardiac events occurred. Subjects with an abnormal T-loop morphology had increased risks for fatal cardiac events (hazard ratio 4.3; 95% CI 3.0–6.4) and nonfatal cardiac events (3.0; 1.9–4.8). Risks associated with an abnormal T axis alone were only slightly lower. Additional adjustment for established cardiovascular risk indicators resulted in lower, but still highly significant risks. Both T-loop and T-axis abnormalities appear to be strong, independent risk indicators of cardiac events in the elderly.

Lipid modifying agents: mechanisms of action and reduction of cardiovascular disease.

1. Recent studies (4S, CARE, WOSCOPS) with the HMG CoA reductase inhibitors have shown that reductions of total cholesterol and LDL cholesterol reduce the risk for a new fatal or non-fatal cardiac event by approximately 30-35%, providing LDL is decreased by 25-35%. 2. Preliminary data also suggest that achieved LDL levels around 3.2 mmol/L results in no greater reduction in new events than when LDL is lowered even further. 3. There is considerable debate, nonetheless, as to whether these reduction in cardiovascular events are entirely a consequence of LDL reduction or whether the lipid-modifying agents have effects on lipoprotein structure, endothelial cell function, clotting and haemorrheological pathways. 4. The study results achieved with statins have obscured the role of fibrates as useful agents for reducing cardiovascular disease. Fibrates have a different mode of action to stains by reducing triglyceride-rich lipoprotein precursors and favourably altering LDL and HDL composition. 5. The practising clinician needs to consider the lipoprotein phenotype and to choose whether the ideal treatment is stain alone, fibrate alone or perhaps a combination.

Fatal Cardiac Event following Initiation of Risperidone Therapy

To describe a patient who developed fatal pulseless electrical activity following treatment with risperidone. A 34-year-old white woman with no history of cardiac disease was initiated on risperidone therapy for an acute exacerbation of chronic schizophrenia. The patient developed postural hypotension and the risperidone dosage was held at 2 mg bid. On day 5 of risperidone therapy, the patient developed cardiac arrest and was treated for pulseless electrical activity. Her electrocardiogram revealed a prolonged QRS interval of 160 msec and an abnormal QTc interval of 480 msec. Despite resuscitative efforts, the patient became asystolic and was pronounced dead. Adverse cardiac events are rarely associated with risperidone therapy. Prolongation of the QRS and QTc intervals have been reported to occur following two cases of presumed risperidone overdose and also in 8 of 380 patients in a double-blind study reported by the manufacturer. Although other possibilities exists, risperidone cannot be ruled out as the cause of the patient's fatal episode of pulseless electrical activity. Prolongation of the QTc interval with severe adverse effects remains a possibility with the use of risperidone.

Sustained prognostic value of dobutamine stress echocardiography for late cardiac events after major noncardiac vascular surgery.

Late cardiac events after major noncardiac vascular surgery are an important cause of morbidity and mortality. We studied the prognostic value of preoperative dobutamine stress echocardiography, relative to clinical risk assessment, in predicting late cardiac events. Three hundred sixteen patients undergoing major vascular surgery were studied. All patients underwent clinical evaluation for the presence of cardiac risk factors (smoking, hypertension, angina, diabetes, history of heart failure, previous infarction, and age > 70 years) and dobutamine stress echocardiography. Left ventricular wall motion was evaluated at rest, and the extent and severity of stress-induced new wall motion abnormalities were quantified. The heart rate threshold at which new wall motion abnormalities occurred was noted. Patients were followed perioperatively and for 19 +/- 11 months postoperatively, and the occurrence of cardiac events was noted. Univariate and multivariate Cox proportional hazards regression models were used to identify predictors of late cardiac events. Thirty-two cardiac events occurred (11 cardiac deaths, 11 nonfatal myocardial infarctions, and 10 incidents of unstable angina). By multivariate regression analysis, the occurrence of extensive (three or more segments) or limited (one or two segments) stress-induced new wall motion abnormalities and previous infarction independently predicted late cardiac events, elevating the risk by 6.5-, 2.9-, and 3.8-fold, respectively. The severity of ischemia during stress and the heart rate threshold for ischemia were not independently predictive. Patients with a history of myocardial infarction or stress-induced ischemia have a high risk of fatal and nonfatal cardiac events after vascular surgery. Patients with both a history of infarction and extensive stress-induced ischemia are at especially high risk and deserve intensive management.

Diagnosis and management of coronary artery disease in patients with end-stage renal disease on hemodialysis.

Cardiovascular disease accounts for almost half of the total mortality in patients with ESRD. Ischemic heart disease is responsible for many cardiovascular deaths, with myocardial infarction accounting for approximately 15% and sudden cardiac death or severe left ventricular dysfunction accounting for much of the remainder. The markedly increased prevalence of atherosclerotic cardiovascular disease in patients with ESRD is influenced, at least in part, by numerous risk factors for atherosclerosis, with hypertension, diabetes mellitus, and hypercholesterolemia being particularly important. Because atherosclerotic coronary artery disease (CAD), whether symptomatic or asymptomatic, is associated with an increased incidence of allograft failure and mortality, the results of this study suggest the need for careful evaluation for the presence of CAD in those persons who are under consideration for renal transplantation. Candidates with angina pectoris, previous myocardial infarction, or congestive heart failure are at particularly high risk of a cardiac event, and, therefore, should routinely undergo pretransplant coronary angiography and subsequent surgical revascularization if angina is refractory to medical therapy or CAD is extensive. In contrast, although young, nondiabetic transplant candidates without symptoms or electrocardiographic evidence of CAD have an increased relative risk of cardiac death when compared with age-matched control subjects, their absolute risk of such an event is very low. As a result, they do not require a cardiac evaluation before transplantation. For the remaining transplant candidates at neither low nor high risk of a fatal or nonfatal cardiac event (i.e., those at intermediate risk), the authors of this study routinely perform (1) thallium imaging with dipyridamole or (2) two-dimensional echocardiography with intravenous dobutamine. If the result of these investigations are normal, transplantation proceeds; if abnormal, coronary angiography is performed, followed by surgical revascularization if CAD is extensive. Percutaneous transluminal coronary angioplasty is not recommended in patients with ESRD because it appears to be accompanied by a high likelihood of acute and chronic complications. Although it is hoped that surgical revascularization before renal transplantation improves allograft and patient survival, prospectively obtained data proving that this, in fact, is true do not exist.

Intensity of Testing and Invasive Procedures-Reply

In Reply. —Whether patients with known or suspected noncardiac vascular disease should have evaluation for coronary artery disease is an important clinical question. Patients with peripheral vascular disease are at a high risk for fatal and nonfatal cardiac events. 1 While significant work has been done concerning the preoperative cardiac evaluation in patients undergoing noncardiac vascular surgery, 2 debate continues about how to manage these patients even after the extent of their disease is known. 3 Finally, there is no consensus about whether case finding and risk stratification is either appropriate or costeffective in the population being evaluated in a vascular laboratory. Thus, the question of the use of exercise testing raised by Dr Crouse and colleagues is relevant. Unfortunately, our data could not allow us to discern between those undergoing testing for symptoms and those undergoing testing for case finding and stratification. However, the use of exercise testing in the setting

Causes of coronary events after successful coronary angioplasty.

To determine the causes and incidence of coronary events after successful coronary angioplasty. We evaluated retrospectively follow-up angiograms of 60 patients with coronary events (27 with myocardial infarction, 33 with new-onset angina pectoris) from among 930 consecutive patients who underwent successful elective angioplasty between February 1985 and April 1994. Patients who had undergone percutaneous transluminal coronary angioplasty to bypass grafts were excluded. No fatal cardiac events occurred within 6 months of percutaneous transluminal angioplasty; 10 occurred thereafter. Fifteen patients who developed early (3.9 +/- 1.8 months) restenosis showed non-Q-wave infarction resulting from severe restenosis at the previously dilated site. In patients without early restenosis, cardiac events developed not from the previously dilated site, but from previously undilated, non-obstructive sites. Furthermore, it was found that the patency of the previously dilated site remained good for a long period of time (41 +/- 23 months) in 96% (43 of 45) of these patients. These findings indicate that the vast majority of cardiac events in patients without early restenosis resulted from new lesions distant from the previous angioplasty site. Fatal cardiac events resulting from early restenosis were rare. In patients with no evidence of restenosis, long-term patency remained good. However, a proportion of these patients developed cardiac events resulting from lesions distant from the previous angioplasty site and hence careful long-term follow-up is essential.

Mental stress--induced myocardial ischemia and cardiac events.

To assess the clinical significance of mental stress-induced myocardial ischemia in patients with coronary artery disease (CAD). Cohort study in outpatients in a tertiary care teaching hospital assessed at baseline and followed up for up to 5 years. A total of 126 volunteer patients (112 men, 14 women; mean age, 59 years) with documented CAD and exercise-induced myocardial ischemia. Patients underwent baseline mental stress and exercise testing using radionuclide ventriculography and 48-hour Holter monitoring. Patients were subsequently contacted by mailed questionnaires or telephone to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. Logistic regression and Cox proportional hazards models were used to examine the prognostic value of the ischemic measures after adjusting for such potential confounding factors as age, baseline left ventricular ejection fraction (LVEF), and history of myocardial infarction. Twenty-eight patients (22%) experienced at least 1 cardiac event. Baseline mental stress-induced ischemia was associated with significantly higher rates of subsequent cardiac events (odds ratio, 2.8; 95% confidence interval [CI], 1.0-7.7; P < .05). The LVEF change during mental stress was significantly related to event-free survival (risk ratio [RR], 2.4; 95% CI, 1.12-5.14; P = .02), controlling for age, history of prior myocardial infarction, and baseline LVEF. This relationship remained significant after controlling for electrocardiogram (ECG)-defined ischemia during exercise (RR, 2.2; 95% CI, 1.01-4.81; P < .05). The RR for ECG-defined ischemia during exercise testing was 1.9 (95% CI, 0.95-3.96; P = .07) and the RR for ambulatory ECG ischemia was 0.75 (95% CI, 0.35-1.64; P = .47). The presence of mental stress-induced ischemia is associated with significantly higher rates of subsequent fatal and nonfatal cardiac events, independent of age, baseline LVEF, and previous myocardial infarction, and predicted events over and above exercise-induced ischemia. These data suggest that the relationship between psychological stress and adverse cardiac events may be mediated by the occurrence of myocardial ischemia.

Passive Smoking and Heart Disease

OBJECTIVE--Recent clinical, laboratory, and epidemiological evidence that passive smoking causes heart disease was reviewed, with particular emphasis on understanding the underlying physiological and biochemical mechanisms. DATA SOURCES--Publications in the peer-reviewed literature were located via MEDLINE, citation in other relevant articles, and appropriate reports by scientific agencies. Greatest emphasis was given to work published since 1990. CONCLUSIONS--Passive smoking reduces the blood's ability to deliver oxygen to the heart and compromises the myocardium's ability to use oxygen to create adenosine triphosphate. These effects are manifest as reduced exercise capability in people breathing secondhand smoke. Secondhand smoke increases platelet activity, accelerates atherosclerotic lesions, and increases tissue damage following ischemia or myocardial infarction. The effects of secondhand tobacco smoke on the cardiovascular system are not caused by a single component of the smoke, but rather are caused by the effects of many elements, including carbon monoxide, nicotine, polycyclic aromatic hydrocarbons, and other, not fully specified elements in the smoke. Nonsmokers exposed to secondhand smoke in everyday life exhibit an increased risk of both fatal and nonfatal cardiac events.