Shmuel Ravid

Congestive heart failure induced by six of the newer antiarrhythmic drugs

The incidence of drug-induced congestive heart failure with several newer antiarrhythmic agents including encainide, ethmozine, lorcainide, mexiletine, propafenone and tocainide was determined in a group of 407 patients who underwent 1,133 drug tests. The incidence rate ranged from 0.7% with lorcainide to 4.7% with propafenone. Congestive heart failure was present in 167 patients (41%) who underwent 491 drug trials. Congestive failure was induced in 15 (9%) of these 167 patients and involved 19 (3.9%) of the 491 tests. Left ventricular ejection fraction was 20 +/- 8% in patients who developed congestive failure, in contrast to 39 +/- 19% in those who did not (p less than 0.001). It is concluded that each of the six antiarrhythmic drugs examined has the potential to aggravate congestive heart failure in patients with reduced left ventricular ejection fraction or a history of congestive heart failure, but the incidence rate is low and its occurrence unpredictable.

Effect of statin dose on incidence of atrial fibrillation: Data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) and Aggrastat to Zocor (A to Z) trials

BACKGROUND Inflammation has been suggested as a factor in the initiation and maintenance of atrial fibrillation (AF). Several observational studies have suggested that statins, presumably through their anti-inflammatory properties, decrease the risk of AF. METHODS We analyzed 2 large, randomized trials, PROVE IT-TIMI 22 and phase Z of the A to Z trial, which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up. We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy. From each trial, patients experiencing the onset of AF during follow-up were identified from the adverse event reports. RESULTS Neither study showed a decreased AF risk with higher-dose statin. In PROVE IT-TIMI 22, 2.9% versus 3.3% in the high- versus standard-dose statin therapy, respectively, experienced the onset of AF over 2 years (OR 0.86, 95% CI 0.61-1.23, P = .41). In A to Z, rates were 1.6% versus 0.99%, respectively (OR 1.58, 95% CI 0.92-2.70, P = .096). In both trials, C-reactive protein levels (plasma or serum) tended to be higher among patients experiencing the onset of AF. CONCLUSION Our randomized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with standard dose statin treatment.

Exercise performance-based outcomes of medically treated patients with coronary artery disease and profound ST segment depression

OBJECTIVES We sought to determine the relationship between exercise duration and cardiovascular outcomes in patients with profound (> or =2 mm) ST segment depression during exercise treadmill testing (ETT). BACKGROUND Patients with stable symptoms but profound ST segment depression during ETT are often referred for a coronary intervention on the basis that presumed severe coronary artery disease (CAD) will lead to unfavorable cardiovascular outcomes, irrespective of symptomatic and functional status. We hypothesized that good exercise tolerance in such patients treated medically is associated with favorable long-term outcomes. METHODS We prospectively followed 203 consecutive patients (181 men; mean age 73 years) with known stable CAD and > or =2 mm ST segment depression who are performing ETT according to the Bruce protocol for an average of 41 months. The primary end point was occurrence of myocardial infarction (MI) or death. RESULTS Eight (20%) of 40 patients with an initial ETT exercise duration < or =6 min developed MI or died, as compared with five (6%) of 84 patients who exercised between 6 and 9 min and three (3.8%) of 79 patients who exercised > or =9 min (p = 0.01). Compared with patients who exercised < or =6 min, increased ETT duration was significantly associated with a reduced risk of MI/death (6 to 9 min: relative risk [RR] = 0.25, 95% confidence interval [CI] 0.08 to 0.76; >9 min: RR = 0.14, 95% CI 0.04 to 0.53). This protective effect persisted after adjustment for potentially confounding variables. We observed a 23% reduction in MI/death for each additional minute of exercise the patient was able to complete during the index ETT. CONCLUSIONS Optimal medical management in stable patients with CAD with profound exercise-induced ST segment depression but good ETT duration is an appropriate alternative to coronary revascularization and is associated with low rates of MI and death.

The prevalence of proarrhythmic events during moricizine therapy and their relationship to ventricular function

The prevalence of proarrhythmic events during moricizine therapy was studied in 144 patients who were treated for symptomatic ventricular tachycardia or ventricular fibrillation. The overall incidence of proarrhythmia was 15.3%. (Twenty-two patients exhibited 23 events.) Ventricular fibrillation occurred in six patients (which led to three deaths), incessant ventricular tachycardia occurred in seven, and new sustained ventricular tachycardia in four. Patients with proarrhythmia had significantly lower left ventricular ejection fraction (24% vs 39%; p less than 0.0001), higher prevalence of congestive heart failure (68% vs 36%; p less than 0.005), and higher incidence of previous proarrhythmia (45% vs 9%; p less than 0.0001). No significant difference between the two groups was found in respect to age, arrhythmia at presentation, underlying heart disease, moricizine dose, or concomitant drug therapy.

Inducible monomorphic sustained ventricular tachycardia in the conscious pig

Sustained monomorphic ventricular tachycardia (VT) is of clinical importance but has not been readily modeled in conscious animals. Eleven pigs had myocardial infarction induced by pulling snares previously placed around the left anterior descending (LAD) coronary artery. Six days after occlusion, bipolar pacing catheters were inserted in the right ventricular apex for induction of VT. Testing was repeated in conscious pigs on 6 out of 8 to 19 days after infarction. Monomorphic VT was induced in each animal during each session, using three to four extrastimuli. VT was terminated by burst pacing in 74% of trials; average VT rate was 362 +/- 26 beats/min. VT was prevented in four of eight animals by procainamide and in five of eight animals by magnesium, but was not prevented by lidocaine or metoprolol. The model may be useful in the study of potentially malignant ventricular tachyarrhythmias, important prodromes for sudden death.

Long-term statin use and psychological well-being in the elderly

Background: The effect of long-term statin use on psychometric measures was studied in a cohort of elderly patients with coronary disease. Methods The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility as measured annually with the Kellner Symptom Questionnaire. The Generalized Estimating Equation and multiple logistic regression estimated the odds ratios (ORs) and 95% confidence intervals (Cl), to represent the association between statin use and nsk of abnormal depression, anxiety. and hostility scores. Results 606 study subjects (average age 67, 80% male) mean follow-up 4 years, maximum 7 years were followed. Comparing the 140 patients with continuous statin use and 231 who did not use cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR, 0.64; 95% Cl, 0.43 0.93), anxiety scores (OR, 0.62; 95% Cl, 0.43-0.90). and hostility scores (OR, 0.65; 95% Cl, 0.45-0.93) after adjustment for confounders. NO association was found when 219 patients with intermittent statin use and non-&tin cholesterol-lowering drug use were compared with 231 patients who did not use cholesterol-lowering drugs. The risk of an abnormal psychometric score decreased over time. The beneficial psychological effects of the statins appeared to be independent of its cholesterol-lowering effect. Conclusions Long-term statin use is associated with reduced risk of anxiety. depression, and hostility in the elderly. Methods. To assess the results of TT in older patients, we analyzed the In-hospital, 6month and 24-month mortality in a cohort of 516 consecutive patients admined to a CCU for a first-time ST-segment/LBBB AMI enrrolled in the PPRIMM75 (Pron6stico del PRimer lnfalto de Miocardio en Mayores de 75 adios) Registry according to the type of treatment received: no reperlusion (n=314). TT (n=118) or primary angioplasty (PA, ll=84). Results. Patients treated with TT were admined earlier (median: 3 vs. 5 hours), nwrs frequently in Killip class I (77% vs 65%) and had a higher LVEF than non-reperfused patients (all pc.01). Compared with patients treated with PA, those who received TT had a significantly lower proportion of diabetes (27% vs 45%), anterior infarcts (42% vs 57%), LVEF < 0.31 (10% vs 24%) and Killip class I (23% vs 46%). The crude in-hospital mortality was 33.8% in non-reperiused patients, 28.8% in those treated with TT and 29.8% with PA. After excluding patients arriving in shock, the figures were: 28%, 27.4% and 17.9% respectively. The graph shows the odds ratio of in-hospital mortality and the hazard ratios for 6. and 24-month mortality for reperfused patients compared with non-reperfused patients after adjustment for baseline differences. Conclusion. Thrombolytic therapy may be associated with an early increase in morlality in elderly patients with AMI, an effect not observed with PA.

New candidates for promoting coronary revascularization: the elderly.

To the Editor: In comparing survival between medical therapy and coronary revascularization for elderly patients with coronary artery disease (CAD), Graham et al1 overstated benefits of revascularization according to their own data, as well as to the published literature. In Table 2, several characteristics of the medical therapy group are consistent with higher risk compared with the coronary bypass group, including more women, past congestive heart failure, higher serum creatinine values, and lower ejection fraction (EF). Though differences did not reach statistical significance, probably because of small numbers, their potential confounding effect cannot be discounted. The authors did not explain why patients aged 70 to 79 years were excluded from Table 2. Notably, the survival curves C in Figures 1 and 2 diverge immediately in favor of the surgical group, in contrast to typical early higher mortality of surgical patients, raising the possibility that high-risk patients in the …

LONG-TERM ALL-CAUSE MORTALITY IN SECOND OPINION CORONARY PATIENTS MANAGED WITH OPTIMAL MEDICAL THERAPY

As part of a larger cohort study of OMT for chronic CAD patients (pts), we enrolled a subcohort of 118 pts who had sought a second opinion (SO) regarding invasive evaluation and management. Management decisions were based primarily on history, physical and noninvasive data. Coronary anatomy

Antiarrhythmic drug therapy in congestive heart failure: Indications and complications

High-grade ventricular arrhythmias are common in congestive heart failure (CHF). However, antiarrhythmic drug therapy is indicated only for patients with symptomatic or hemodynamically significant sustained arrhythmias. Before such therapy is initiated, reversible causes of arrhythmias (eg, electrolyte imbalance, drug interactions and toxicity, decompensation of CHF, ongoing ischemia) should be sought out and corrected. Patients with poor ventricular function or a history of CHF should be hospitalized and monitored continuously during initiation and evaluation of antiarrhythmic therapy so that early detection of proarrhythmic response is possible. Therapy should be initiated with the smallest effective dose, which then is increased slowly to minimize the risk of side effects. Drug selection should be guided electrophysiologically or noninvasively, and empirical antiarrhythmic drug therapy must be avoided.