Time dependence of defibrillator benefit after coronary revascularization in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: The study was designed to assess the effect of elapsed time from coronary revascularization (CR) on the benefit of the implantable cardioverter-defibrillator (ICD) and the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction. BACKGROUND: The ICD improves survival in appropriately selected high-risk cardiac patients by 30% to 54%. However, in the Coronary Artery Bypass Graft (CABG)-Patch trial no evidence of improved survival was shown among a similar population of patients in whom an ICD was implanted prophylactically at the time of elective CABG. METHODS: The outcome by time from CR was analyzed in 951 patients in whom a revascularization procedure was performed before enrollment in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. RESULTS: The adjusted hazard ratio (HR) of ICD versus conventional therapy was 0.64 (p = 0.01) among patients enrolled more than six months after CR, whereas no survival benefit with ICD therapy was shown among patients enrolled six months or earlier after CR (HR = 1.19; p = 0.76). In the conventional therapy group, the risk of cardiac death increased significantly with increasing time from CR (p for trend = 0.009), corresponding mainly to a six-fold increase in the risk of SCD among patients enrolled more than six months after CR. CONCLUSIONS: In patients with ischemic left ventricular dysfunction, the efficacy of ICD therapy after CR is time dependent, with a significant life-saving benefit in patients receiving device implantation more than six months after CR. The lack of ICD benefit when implanted early after CR may be related to a relatively low risk of SCD during this time period.     

Percutaneous revascularization of grafts versus native coronary arteries in postcoronary artery bypass graft patients

In patients with previous coronary artery bypass graft surgery, it is unknown whether better results may be obtained with percutaneous interventions of grafts versus native arteries. The clinical outcomes in 84 patients undergoing percutaneous interventions of either grafts (n = 31) or native arteries (n = 53) were compared. Procedural success rate was 95.3% (96.8% in the graft group vs 94.4% in the native group, P = .3). Mean follow-up was 19 +/- 7 months. The incidence of major adverse events was 14.2% (12.9% vs 15.1% in the graft and native groups, respectively; P = .8), mortality rate was 3.5% (6.4% vs 1.8% in the graft and native groups, respectively; P = .3), and target-lesion revascularization was performed in 4.7% (6.4% vs 3.7% in the graft and native groups, respectively, P = .6). In conclusion, both graft or native percutaneous interventions were similar for immediate and midterm clinical outcomes. The relatively low risk need for target-lesion revascularization obtained with both strategies is encouraging.     

Impact of ischemia and scar on therapeutic benefit of myocardial revascularization

The question of how to optimally manage coronary artery disease (CAD) has been a challenge for the cardiology community. The results of early, large randomized clinical trials (RCTs) comparing strategies of medical therapy alone versus revascularization plus medical therapy in patients with stable CAD suggested a survival advantage for a revascularization strategy in the setting of more advanced, higher-risk CAD (left main, three-vessel CAD), but a superiority of medical therapy in patients with more limited, relatively lower-risk CAD (one vessel, limited two-vessel CAD). The results of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials redefined the management of CAD, supporting the concept that the impact of aggressively applied modern “medical therapy” on patient survival and patient-reported outcomes is not further improved by the addition of percutaneous intervention. On the other hand, RCTs incorporating fractional flow reserve have shown that this physiologic metric can help identify which patients will benefit from a revascularization strategy. This paradigm has been extended to the use of myocardial perfusion imaging-identified ischemia to determine which patients may have enhanced survival with early revascularization versus medical therapy. Although data from a series of observational studies suggest that inducible ischemia on myocardial perfusion scintigraphy can identify revascularization candidates, several studies, including substudies from major RCTs, do not support this idea. Until RCTs comparing revascularization with medical therapy strategies are performed, many questions remain open. The correct thresholds for treatment, the metric to guide treatment, and how revascularization should be performed are as yet undefined.     

The benefit of abciximab in percutaneous coronary revascularization is not device-specific

Abciximab has been shown to decrease adverse outcomes after percutaneous coronary interventions, but it is unclear whether this beneficial effect is more or less pronounced with specific devices. This study sought to determine the relative magnitude of the benefit of abciximab among different interventional devices. Data from the 5 placebo-controlled trials of abciximab during coronary intervention were pooled. Patients were divided into groups based on whether they received balloon angioplasty alone, elective stenting, bailout stenting, or directional coronary atherectomy. In the patients undergoing balloon angioplasty, the 30-day hazard ratio for death or myocardial infarction (MI) in the group randomized to abciximab versus the placebo-treated group was 0.52 (p <0.001), for elective stenting the hazard ratio was 0.51 (p <0.001), for bailout stenting the hazard ratio was 0.38 (p <0.001), and for directional coronary atherectomy the hazard ratio was 0.38 (p = 0.007). A Cox proportional-hazards model revealed that overall, the use of abciximab decreased the composite end point of 30-day death or MI rates (hazard ratio 0.55, 95% confidence interval 0.43 to 0.69, p <0. 001). However, bailout stenting and directional coronary atherectomy were associated with increased rates of death or MI compared with balloon angioplasty, as was elective stenting in women compared with men. There was no significant increase in major bleeding episodes associated with abciximab in any of the device categories. These findings from all the controlled coronary revascularization trials using abciximab demonstrate that a decrease in death and MI is achieved with abciximab regardless of the type of device used, without an increase in significant bleeding complications.     

Possible role of cardioaortic reflexes in postcoronary bypass hypertension.

A study of hemodynamic and humoral characteristics of postcoronary bypass hypertension has been pursued in 85 patients in the immediate postoperative period. Paroxysmal hypertension developed in 69 of these patients. None of the 85 patients had a history of hypertension before operation. Hemodynamic evaluation demonstrated that the increase in blood pressure was associated with an elevation in systemic vascular resistance and a rapid heart rate. The increase in mean arterial pressure correlated significantly with the change in plasma catecholamine levels (r = 0.50, P < 0.05). There was no significant change in cardiac output. Changes in plasma renin activity showed no correlation with the increase in blood pressure. Average values of plasma renin activity on sequential determinations were not significantly different either in those who remained normotensive or in those who became hypertensive. Similarly, blood volume did not seem to play an important role. Baroreceptor sensitivity appeared blunted in both normotensive and hypertensive patients. The increase in systemic catecholamines associated with the increase in blood pressure suggested a sympathetic overdrive. This was further supported by the control of hypertension in 81 percent of patients by unilateral stellate block. The reduction in pressure consequent to the block was associated with a reduction in systemic vascular resistance (P < 0.025). Heart rate slowed slightly but significantly (P < 0.01) after stellate block irrespective of the effect on blood pressure whereas cardiac output did not change significantly. The results suggest that postcoronary bypass hypertension could be due to an afferent sympathetic reflex originating from the heart, great vessels or coronary arteries.     

Time dependence of radioprotective effects of A. flavus conidia.

No essential difference in radioprotection results when conidia of A. flavus are applied to mice within a time lapse of a few minutes up to 48 hours prior to irradiation. When applied 72 hr before irradiation, they fail to affect mouse resistance. Application of conidia provide no protection to mice irradiated for 18-20 hr at the dose rate of 1 R/min; similarly ineffective are the chemoprotectors cistafos and mexamine. A combined administration of conidia and the two protective substances increases survival in mice and prolongs the mean survival period.     

Off-pump coronary revascularization: A potential benefit for female patients?

Coronary artery disease is one of the leading causes of illness for both men and women. However, women are 3 times more likely to die for coronary artery disease as they are of breast cancer. There are an increasing prevalence of coronary artery disease in women and thus facing the need for surgical revascularization. It has long being accepted that women carry a high risk of coronary surgery than men. Many investigators have suggested that female itself is predictive of poor outcome after on pump coronary surgery. We thought to search the litlature to investigate whether women who undergo off-pump surgery receive any benefits compared with women undergoing on-pump surgery.     

T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation

In a trial of prophylactic implantation of a defibrillator, a mortality benefit was seen among patients with previous myocardial infarction and a left-ventricular ejection fraction of 0.30 or less. We identified 129 similar patients from two previously published clinical trials in which microvolt T-wave alternans testing was prospectively assessed. At 24 months of follow-up, no sudden cardiac death or cardiac arrest was seen among patients who tested T-wave alternans negative, compared with an event rate of 15.6% among the remaining patients. Testing of T-wave alternans seems to identify patients who are at low risk of ventricular tachyarrhythmic event and who may not benefit from defibrillator therapy.     

Perceptions of benefit and risk of patients undergoing first-time elective percutaneous coronary revascularization

OBJECTIVE: To assess reasons why patients undergo elective percutaneous coronary revascularization (PCR), patient expectations of the benefits of PCR, and their understanding of the risks associated with PCR. We hypothesized that patients overestimate the benefits and underestimate the risks associated with PCR. DESIGN: A prospective, semistructured questionnaire. PARTICIPANTS: Patients undergoing their first elective PCR. MAIN RESULTS: Fifty-two consecutive patients with a mean age of 64.3 years (range 39–87) completed the interview. Although 30 (57%) patients cited relief of symptoms as at least 1 reason to have PCR, 32 (62%) patients cited either an abnormal diagnostic test result (i.e., exercise stress test or catheterization) or “pathophysiologic” problem (i.e., “I have a blockage”), with 17 patients (33%) citing these reasons alone as indications for PCR. Thirty-nine (75%) patients believed PCR would prevent a future myocardial infarction, and 37 (71%) patients felt PCR would prolong their life. Regarding the potential complications, only 24 patients (46%) could recall at least 1 possible complication. However, on a Deber questionnaire, the majority of patients (67%) stated that they should determine either mostly alone or equally with a physician how acceptable the risks of the procedure are for themselves. CONCLUSIONS: The majority of patients had unrealistic expectatations about the long-term benefits of elective PCR and was not aware of the potential risks, even though they expressed a strong interest in participating in the decision to have PCR. More work is needed to define the optimal strategy to educate patients about the benefits and risks of elective PCR, and whether such education will affect patient decision making. The views represented by this paper are solely those of the authors and do not represent the views of opinions of the United States Navy or Department of Defense. Dr. Holmboe and Dr. Fiellin were Robert Wood Johnson Clinical Scholars during completion of this work. Dr. Harlan M. Krumholz is a Paul Beeson Faculty Scholar. Dr. Fiellin is supported in part by grant K12DA00167 from the National Institute on Drug Abuse.