Coronary Artery Disease in Patients ≥80 Years of Age

Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients ≥80 years of age. Nonetheless, older patients have typically been under-represented in cardiovascular clinical trials. Understanding the pathophysiology, epidemiology, and optimal means of diagnosis and treatment of CAD in older adults is crucial to improving outcomes in this high-risk population. A patient-centered approach, taking into account health status, functional ability and frailty, cognitive skills, and patient preferences is essential when caring for older adults with CAD. The present systematic review focuses on the current knowledge base, gaps in understanding, and directions for future investigation pertaining to CAD in patients ≥80 years of age.     

Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women

OBJECTIVES: The objective of this study was to determine whether diastolic dysfunction is associated with increased risk of nonvalvular atrial fibrillation (NVAF) in older adults with no history of atrial arrhythmia. BACKGROUND: Few data exist regarding the relationship between diastolic function and NVAF. METHODS: The clinical and echocardiographic characteristics of patients age > or =65 years who had an echocardiogram performed between 1990 and 1998 were reviewed. Exclusion criteria were history of atrial arrhythmia, stroke, valvular or congenital heart disease, or pacemaker implantation. Patients were followed up in their medical records to the last clinical visit or death for documentation of first AF. RESULTS: Of 840 patients (39% men; mean [+/- SD] age, 75 +/- 7 years), 80 (9.5%) developed NVAF over a mean (+/- SD) follow-up of 4.1 +/- 2.7 years. Abnormal relaxation, pseudonormal, and restrictive left ventricular diastolic filling were associated with hazard ratios of 3.33 (95% confidence interval [CI], 1.5 to 7.4; p = 0.003), 4.84 (95% CI, 2.05 to 11.4; p < 0.001), and 5.26 (95% CI, 2.3 to 12.03; p < 0.001), respectively, when compared with normal diastolic function. After a number of adjustments, diastolic function profile remained incremental to history of congestive heart failure and previous myocardial infarction for prediction of NVAF. Age-adjusted Kaplan-Meier five-year risks of NVAF were 1%, 12%, 14%, and 21% for normal, abnormal relaxation, pseudonormal, and restrictive diastolic filling, respectively. CONCLUSIONS; The presence and severity of diastolic dysfunction are independently predictive of first documented NVAF in the elderly.     

Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells

Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.     

Impact of ST-segment resolution after primary angioplasty on outcomes after myocardial infarction in elderly patients: an analysis from the CADILLAC trial

Background

Age is a strong independent predictor of outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Whether lower rates of reperfusion success contribute to the poor prognosis in elderly patients is unknown.

Methods

A formal ST-segment analysis substudy was performed in 695 patients undergoing primary PCI for AMI in the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Reperfusion success (determined by the magnitude of ST-segment elevation resolution [STR] after PCI) was evaluated in 4 age groups: <50 years (n = 163), ≥50 to <60 years (n = 187), ≥60 to <70 years (n = 194), and ≥70 years (n = 151).

Results

There were no differences in the age groups for angiographic procedural success >91% in all, P = .6), postprocedural Thrombolysis in Myocardial Infarction grade 3 flow >94%, P = .8), and the proportions of patients with complete, partial, or absent STR (P >.8). However, rates of 30-day mortality (0.6%, 1.1%, 3.6%, 6.0%, respectively) and major adverse cardiac events (MACE; 2.5%, 4.8%, 6.2% 9.3%, respectively) increased with age. Rates of mortality and MACE were also inversely related to the magnitude of STR. Absent STR (hazard ratio, 3.00; 95% CI, 1.37-6.58; P = .006) and age (hazard ratio, 1.34; 95% CI, 1.01-1.77; P = .04) were independent predictors of 30-day MACE by using multivariable modeling.

Conclusions

Lack of effective myocardial reperfusion is not a contributory mechanism responsible for the high morbidity and mortality rates observed in elderly patients. Nevertheless, advanced age and absent STR are both independent predictors of adverse outcomes after primary PCI, emphasizing the importance of successful reperfusion in the elderly population.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Amiodarone and mortality among elderly patients with acute myocardial infarction with atrial fibrillation

Background Amiodarone has been shown to be safe in patients with acute myocardial infarction (AMI) who are at risk for sudden cardiac death. However, there is limited data concerning the safety of amiodarone in patients who experience AMI complicated by atrial fibrillation. Methods To determine the safety of amiodarone therapy, we conducted a retrospective analysis of elderly patients hospitalized with AMI who experienced atrial fibrillation and had survived to hospital discharge (n = 17,597). Amiodarone prescribed at discharge was evaluated for its association with short-term and long-term mortality in crude and adjusted analyses employing propensity score methods. Results Of the 17,597 patients, 550 patients (3.1%) were prescribed amiodarone, 2317 patients (13.2%) were prescribed other antiarrhythmic agents (excluded from analysis), and 14,730 (83.7%) were prescribed no antiarrhythmic medication at discharge. Thirty-day mortality rates were similar for patients prescribed amiodarone and those not prescribed amiodarone (6.8% amiodarone vs 5.4% no amiodarone, P = .21), but mortality at 1 year was higher among patients prescribed amiodarone (35.6% vs 31.6%, P = .001). However, amiodarone was not associated with mortality at 30 days (odds ratio 0.80, 95% CI 0.53-1.20) or at long-term follow-up (mean duration 612 days, hazard ratio 1.04, 95% CI 0.92-1.18) after multivariable modeling. Conclusions Amiodarone was not independently associated with short-term or long-term mortality in elderly patients discharged after a hospitalization for AMI complicated by atrial fibrillation. Although our data suggest that amiodarone may be safe to use in this population, randomized controlled trial data are needed to confirm this finding. (Am Heart J 2002;144:1095-101.)     

Familial atrial fibrillation is a genetically heterogeneous disorder

OBJECTIVES: The aims of this study were to identify and characterize familial cases of atrial fibrillation (AF) in our clinical practice and to determine whether AF is genetically heterogeneous. BACKGROUND: Atrial fibrillation is not generally regarded as a heritable disorder, yet a genetic locus for familial AF was previously mapped to chromosome 10. METHODS: Of 2,610 patients seen in our arrhythmia clinic during an 18-month study period, 914 (35%) were diagnosed with AF. Familial cases were identified by history and medical records review. Four multi-generation families with autosomal dominant AF (FAF 1 to 4) were tested for linkage to the chromosome 10 AF locus. RESULTS: Fifty probands (5% of all AF patients; 15% of lone AF patients) were identified with lone AF (age 41 +/- 9 years) and a positive family history (1 to 9 additional relatives affected). In FAF 1 to 3, AF was associated with rapid ventricular response. In contrast, AF in FAF-4 was associated with a slow ventricular response and, with progression of the disease, junctional rhythm and cardiomyopathy. Genotyping of FAF 1 to 4 with deoxyribonucleic acid markers spanning the chromosome 10q22-q24 region excluded linkage of AF to this locus. In FAF-4, linkage was also excluded to the chromosome 3p22-p25 and lamin A/C loci associated with familial AF, conduction system disease, and dilated cardiomyopathy. CONCLUSIONS: Familial AF is more common than previously recognized, highlighting the importance of genetics in disease pathogenesis. In four families with AF, we have excluded linkage to chromosome 10q22-q24, establishing that at least two disease genes are responsible for this disorder.     

Sex differences in coronary artery size assessed by intravascular ultrasound

BACKGROUND: Women have worse outcomes after myocardial infarction and coronary revascularization. The explanations are likely multifactorial but may include smaller coronary artery size. Smaller luminal diameter has been confirmed angiographically; however, because of possible confounding effects of coronary remodeling, angiographically silent atherosclerosis, and body size, it is unclear if there is a true sex influence on arterial size. METHODS: We performed intravascular ultrasound on left main (LM) and proximal left anterior descending (LAD) coronary artery segments that were free of significant atherosclerosis in 50 men and 25 women. Arterial and luminal areas were measured by planimetry and corrected for body surface area. We evaluated associations between sex and coronary dimensions with univariate and then multiple linear regression analyses. RESULTS: Mean uncorrected LM and LAD arterial areas were smaller in women than in men (21.53 vs 26.95 mm(2), P <.001, and 14. 68 vs 19.94 mm(2), P =.002, respectively), as were mean LM and LAD luminal areas (15.94 vs 18.79 mm(2), P =.020, and 10.13 vs 12.71 mm(2), P =.036, respectively). In multivariate models accounting for body surface area and controlling for other factors, sex independently predicted corrected LM and LAD arterial area. In analyses that additionally controlled for plaque area, sex independently predicted corrected LAD luminal area. CONCLUSIONS: LM and LAD arteries are smaller in women, independent of body size. This suggests an intrinsic sex effect on coronary dimensions. Future studies should investigate underlying mechanisms because they may lead to novel therapeutic strategies and improved outcomes for women with coronary artery disease.     

Inhospital outcome of acute myocardial infarction in patients with prior coronary artery bypass surgery

Objectives Our goals were to compare the characteristics of patients with and without prior coronary artery bypass graft (CABG) presenting with acute myocardial infarction (MI) with or without ST elevation/left bundle branch block (LBBB), and to evaluate the effect of ST shift on inhospital mortality. Methods and Results Using the National Registry of Myocardial Infarction-3 Registry, we identified 112,697 patients with acute MI without exclusion criteria. Of these, 15,936 (14.1%) had prior CABG. Patients with prior CABG had more adverse characteristics and were less likely to have ST elevation/LBBB than patients without prior CABG. The unadjusted mortality for ST elevation/LBBB patients was higher in patients with prior CABG versus without (16.2% vs 14.1%, P = .0001), whereas in patients without ST elevation/LBBB, prior CABG conferred a lower unadjusted mortality versus without (10.1% vs 12.4%, P = .0001). Adjusting for baseline differences, prior CABG was weakly associated with inhospital mortality in ST elevation/LBBB patients (odds ratio [OR], 1.11, 95% CI 1.00-1.23), but not in patients without ST elevation/LBBB (OR 0.99, 95% CI 0.92-1.07). Conclusion Acute MI patients with prior CABG are more likely to present without ST elevation/LBBB than patients without prior CABG. Prior CABG was weakly associated with inhospital mortality in patients with ST elevation/LBBB, but not in patients without these electrocardiographic findings. This suggests the differences in absolute mortality rates between patients presenting with MI with and without a history of prior CABG are largely caused by differences in baseline characteristics and presentation. (Am Heart J 2002;144:463-9.)