Enrique V. Carbajal

Silent ischemia during daily life is an independent predictor of mortality in stable angina.

We prospectively examined the prognostic significance of silent myocardial ischemia detected by ambulatory electrocardiogram (ECG) monitoring during daily life in 107 patients with long-term stable angina who were symptomatically controlled on conventional antianginal agents. Forty-six patients (group 1) demonstrated one or more episodes (87% silent) of myocardial ischemia; the remaining 61 patients (group 2) had no ischemic ST segment changes. During the mean follow-up period of 23 +/- 8 months, 11 cardiac deaths (five sudden and six nonsudden) occurred in group 1, and five cardiac deaths (all nonsudden) occurred in group 2. Kaplan-Meier survival analysis between the groups confirmed that patients with silent ischemia (group 1) had worse prognoses during the follow-up period (p = 0.023). Although the higher incidence of hypertension, smoking, hypercholesterolemia, and diabetes in our patients might reflect a more sickly population of stable angina patients, the multivariate Coxs hazard function analysis of these and other variables including Q waves on ECG, exercise parameters, and ambulatory ECG findings revealed presence of silent ischemia during daily life as the most powerful and independent predictor of cardiac mortality (p = 0.01). These data indicate that, in such patients with stable angina, silent myocardial ischemia occurs frequently during treatment with conventional antianginal drugs and identifies a subset of patients who are at high risk of cardiac death.

Anti-ischemic effects of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia.

The anti-ischemic effects of atenolol and nifedipine were compared in a randomized double-blind crossover manner in 24 patients with stable exertional angina and transient silent ischemia during ambulatory electrocardiographic (ECG) monitoring. Both atenolol and nifedipine were effective (p less than 0.005) in reducing the average number and duration of transient ischemic events, but therapy with atenolol was associated with a significantly greater reduction in the mean number (p less than 0.05) and duration (p less than 0.01) of silent ischemic events. Analyses of the silent ischemic activity during the morning hours revealed that only therapy with atenolol produced a significant reduction in the average duration per patient (139 +/- 54 vs. 1,609 +/- 468 s, p less than 0.01) and in the average duration of silent ischemia per event between 6 AM and 12 noon (62 +/- 21 vs. 208 +/- 24 s, p less than 0.005). There were fewer adverse experiences during therapy with atenolol. These results show that although both atenolol and nifedipine are effective in reducing silent ischemic events, treatment with atenolol is associated with significantly greater efficacy, particularly on the morning surge of silent myocardial ischemia.

Prevalence and patterns of silent myocardial ischemia during daily life in stable angina patients receiving conventional antianginal drug therapy

The prevalence and patterns of silent myocardial ischemia were evaluated in 105 stable angina patients receiving conventional antianginal drug therapy. During 2,520 hours of electrocardiographic monitoring, silent ischemia was detected in 45 (43%) patients. A total of 188 ischemic episodes was observed; 163 (87%) were silent and accounted for a total ischemic duration of 5,771 minutes. There was no difference in the baseline clinical characteristics between the patients with and without ambulatory silent ischemia. However, patients with silent ischemia on ambulatory electrocardiographic monitoring had earlier onset of ischemia during exercise testing. The highest density of silent ischemic events occurred between 6 A.M. and 6 P.M. Comparison of the class or combination of antianginal agents used by the 2 groups revealed no difference. However, in patients with silent ischemia the mean duration per event was shorter for those receiving 2 (p less than 0.05) or more (p = 0.001) antianginal agents compared to those receiving monotherapy. The average duration of silent ischemia per event was significantly less (p less than 0.001) in patients receiving beta blockers. These results demonstrate that silent ischemia during ordinary daily activities occurs frequently despite conventional antianginal drugs prescribed for control of symptoms.

Usefulness of ambulatory silent myocardial ischemia added to the prognostic value of exercise test parameters in predicting risk of cardiac death in patients with stable angina pectoris and exercise-induced myocardial ischemia

The prognostic significance of ambulatory silent ischemia detected by Holter monitoring during daily life was prospectively evaluated and compared with several exercise test parameters in 86 patients with stable angina and positive exercise tests. Forty-seven patients (group 1) had no evidence of ischemia and 39 (group 2) had 1 or more episodes of silent ischemia during the monitoring period. During mean follow-up of 24 +/- 8 months there were only 2 cardiac deaths (nonsudden) in group 1 (4% mortality) compared with 9 (3 sudden and 6 nonsudden) in group 2 (23% mortality). Kaplan-Meier actuarial analysis revealed worse survival (p less than 0.008) for patients in group 2. The Cox regression analysis of clinical variables, electrocardiographic and exercise parameters, angiographic data and Holter monitoring results revealed silent ischemia during daily life as the most powerful predictor of cardiac mortality (p = 0.003). These results demonstrate that in patients with chronic stable angina and abnormal exercise tests, ambulatory ischemia detected by Holter monitoring provides significant additional prognostic information to that derived from evaluation of exercise test parameters alone.

Exercise test predictors of ambulatory silent ischemia during daily life in stable angina pectoris

The predictive value of several exercise test parameters in identifying stable angina patients at risk of silent myocardial ischemia during daily life were examined. A total of 97 patients with coronary artery disease, stable angina and ambulatory electrocardiographic data were evaluated. Of the 86 patients with a positive exercise test, 39 (group 1) had greater than or equal to 1 episodes of ST-segment depression and 47 (group 2) did not develop ST changes during ambulatory electrocardiographic monitoring. Comparison of the exercise test parameters between the 2 groups revealed early onset of ischemia during exercise tests as the single most significant (p less than 0.0005) predictor of ambulatory silent ischemia. The other exercise test parameters showing significant differences between the 2 groups were the peak exercise heart rate (117 +/- 23 vs 126 +/- 20 beats/min, p less than 0.05) and peak systolic blood pressure (160 +/- 27 vs 176 +/- 27 mm Hg, p less than 0.01), both of which were significantly lower in the group 1 patients. These data were used to derive simple mathematical formulas for calculating the risk of ambulatory silent ischemia. These results demonstrate that stable angina patients at risk of silent ischemia during daily life can be accurately identified by evaluation of selected exercise test parameters.

Role of Beta Blockade in the Treatment of Myocardial Ischemia

A number of antianginal drugs and therapeutic strategies are now available for the treatment of patients with coronary artery disease (CAD) and myocardial ischemia. Of the available antianginal drugs, beta blockers appear to be most effective in suppressing myocardial ischemia. The superior anti-ischemic efficacy of beta blockers can be explained by their beneficial actions on hemodynamic parameters, vasomotion, and platelet function. Compared with other anti-ischemic drugs, beta blockers appear to be more efficacious in reducing the magnitude of myocardial ischemia during routine daily activities. In addition, the results of recent studies indicate that treatment with beta blockers not only suppresses myocardial ischemia, but also improves the clinical outcome in patients with CAD. These beneficial effects, along with the well-demonstrated cardioprotective effects of beta blockade in the postinfarction period, clearly suggest that this class of anti-ischemic drugs is an ideal therapeutic choice in most patients with CAD.

Evidence-Based Therapy for Heart Failure

Heart failure (HF) is a major public health problem associated with increased morbidity and mortality. As the US life expectancy increases and the population ages, the overall prevalence of HF will continue to escalate. The increasing use of effective selective therapies such as neurohormonal blockade in the treatment of patients with HF has led to considerable improvement in their prognosis. During the past several decades, some studies have demonstrated the benefits of treatment; based on the evidence available from these studies, various national and international guidelines have specific recommendations for the evidence-based therapy with these drugs in patients with HF.

Frequent Atrial Premature Complexes and Their Association With Risk of Atrial Fibrillation

Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. This study aimed to examine the association between frequent atrial premature complexes (APCs) and incidence of AF. For this retrospective cohort study, we analyzed Holter recordings obtained from 2000 to 2010 of 1,357 veterans free of AF at baseline. All pertinent data in electronic medical records were reviewed to ascertain baseline characteristics. Holter groups with frequent (≥100/day) and infrequent (<100/day) APCs were compared for development of new AF over a median follow-up of 7.5 years. Multivariate Cox regression analyses were performed before and after propensity score matching. Mean age was 64 years with 93% men. Mean body mass index, hemoglobin A1C, low-density lipoprotein, left atrial size, and heart rate were 31.24 kg/m(2), 6.42%, 107.92 mg/dl, 4.26 cm, and 73 beats/min, respectively. AF was noted in 21.8% of patients with frequent APCs compared to 5.6% of those with infrequent APCs. After adjusting for demographics, medication use, co-morbidities, and laboratory and echocardiographic findings, multivariate Cox regression analyses confirmed frequent APCs to be independently associated with higher incidence of AF (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.85 to 4.80; p <0.001). In propensity-matched groups, this association remained significant (HR 2.87, 95% CI 1.65 to 4.98; p <0.001). Additionally, atrial couplets (≥50/day), atrial bigeminy (≥50/day), frequent runs of ≥3 APCs (≥20 runs/day), and longer runs (≥10 beats/run) were significantly associated with AF (HR 3.11, 3.67, 2.94, and 1.73, respectively, all p <0.05). In conclusion, frequent APCs (≥100/day) are associated with greater risk of AF.

Medical Therapy Versus Myocardial Revascularization in Chronic Coronary Syndrome and Stable Angina

Coronary artery disease is a leading cause of death in the United States. Angina is encountered frequently in clinical practice. Effective management of patients with coronary artery disease and stable angina should consist of therapy aimed at symptom control and reduction of adverse clinical outcomes. Therapeutic options for angina include antianginal drugs: nitrates, beta-blockers, calcium channel blockers, ranolazine, and myocardial revascularization. Recent trials have shown that although revascularization is slightly better in controlling symptoms, optimal medical therapy that includes aggressive risk factor modification is equally effective in reducing the risk of future coronary events and death. On the basis of the available data, it seems appropriate to prescribe optimal medical therapy in most patients with coronary artery disease and stable angina, and reserve myocardial revascularization for selected patients with disabling symptoms despite optimal medical therapy.

Role of myocardial oxygen demand in the pathogenesis of silent ischemia during daily life

The role of myocardial oxygen demand in the pathogenesis of silent ambulatory myocardial ischemia was evaluated by reviewing and assessing the methods and results of recent studies. The performance of simultaneous ambulatory electrocardiographic and blood pressure monitoring in 25 men with proven coronary artery disease (CAD) revealed significant increases in heart rate and blood pressure (p < 0.001) preceding most silent ischemic events. By plotting the mean heart rate obtained at 5-minute intervals during the 30 minutes before an ischemic event, the ischemic heart rate was shown to be significantly higher (95 +/- 15 vs 74 +/- 11 beats per minute [bpm]; p < 0.01) than the nonischemic heart rate. The evaluation of heart rate changes during ambulatory ischemia (in patients with CAD and ischemia induced by an exercise test using gradual work load increments) showed a significant heart rate increase (> 10 bpm) at 1-5 minutes preceding the onset of ST-segment depression. Heart rate increases during exercise testing according to the gradual work load increments of the National Institutes of Health protocol were compared with the heart rate preceding ischemic events during daily life monitored by ambulatory electrocardiography and were found to be closely related. In contrast, heart rate increases that occurred during exercise testing using the standard Bruce protocol were higher and correlated less with those preceding ischemia in daily life. Heart rate and blood pressure increased significantly in most silent ischemic episodes, indicating that increased myocardial oxygen demand plays a significant role in the pathogenesis of myocardial ischemia during daily life.