Glen J. Kowalchuk

The ischemic cascade: Temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia

The development of an ischemic event, whether silent or painful, represents the cumulative impact of a sequence of pathophysiologic events. Each ischemic episode is initiated by an imbalance between myocardial oxygen supply and demand that may ultimately be manifested as angina pectoris. This sequence of events can be termed the ischemic cascade. The significance of this concept resides in the fact that it redirects the focus from the end result--angina--to the more fundamental, underlying pathophysiologic factors that precede it. Specifically, these events include diminished left ventricular compliance, decreased myocardial contractility, increased left ventricular end-diastolic pressure, ST-segment changes and, occasionally, angina pectoris.

Cardiac Outcome after Peripheral Vascular Surgery: Comparison of General and Regional Anesthesia

Background Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia, most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences. This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease. Methods Four hundred twenty‐three patients, between 1988 and 1991, were randomly assigned to receive general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral to distal artery bypass surgery. All patients were monitored with radial artery and pulmonary artery catheters. Postoperatively, patients were in a monitored setting for 48–72 h and had daily electrocardiograms for 4–5 days and creatine phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes recorded were myocardial infarction, angina, and congestive heart failure. Results Baseline clinical characteristics were not different between anesthetic groups. Overall, the patient population included 86% who were diabetic, 69% with hypertension, 36% with a history of a prior myocardial infarction, and 41% with a history of smoking. Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received. In the intention to treat analysis, incidences of cardiac event or death for general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%, respectively. The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was ‐1.6% (95% confidence interval ‐9.2%, 6.1%) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia. Conclusions The choice of anesthesia, when delivered as described, does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery.

Left ventricular filling abnormalities in asymptomatic morbid obesity

Indexes of left ventricular (LV) diastolic filling were measured by pulse Doppler echocardiography in 16 asymptomatic morbidity obese patients presenting for bariatric surgery and were compared with an age- and sex-matched lean control population. No patient had concomitant disorders known to affect diastolic function. All patients had normal systolic function. LV wall thickness and internal dimension were measured in order to calculate LV mass. Fifty percent of morbidly obese patients had LV diastolic filling abnormalities as assessed by the presence of greater than or equal to 2 abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in obese compared with control patients (1.16 +/- 0.26 vs 1.66 +/- 0.30, p less than 0.001). The peak velocity of early LV diastolic filling was significantly reduced in obese patients (75 +/- 15 vs 98 +/- 19 cm/s, p less than 0.001). The atrial contribution to stroke velocity as assessed by the time-velocity integral of late compared with total LV diastolic filling was significantly increased in obese patients (36 +/- 7 vs 27 +/- 4%, p less than 0.001). Obese patients had significantly increased LV mass (214 +/- 45 vs 138 +/- 37 g, p less than 0.001), even when corrected for body surface area (95 +/- 16 vs 76 +/- 16 g/m2, p less than 0.002). However, increased LV mass did not correlate with indexes of abnormal diastolic filling in obese patients. These data suggest that abnormalities of diastolic function occur frequently in asymptomatic morbidly obese patients and may represent a subclinical form of cardiomyopathy in the obese patient.

Silent myocardial ischemia and infarction in diabetics with peripheral vascular disease: Assessment by dipyridamole thallium-201 scintigraphy

We investigated the incidence of silent myocardial ischemia and infarction as assessed by dipyridamole thallium scintigraphy in 30 diabetic patients with peripheral vascular disease and without clinical suspicion of coronary artery disease. Seventeen patients (57%) had thallium abnormalities, with reversible thallium defects compatible with ischemia in 14 patients (47%) and evidence of prior, clinically silent myocardial infarction in 11 patients (37%). Thallium abnormalities were most frequent in patients with concomitant hypertension and cigarette smoking (p = 0.001). These results suggest that unsuspected coronary artery disease is common in this particular group of patients with diabetes mellitus.

Severity of coronary artery disease in young patients with insulin-dependent diabetes mellitus

Cardiovascular events remain a leading cause of morbidity and mortality in patients with juvenile-onset, insulin-dependent diabetes mellitus. To examine the extent and severity of the atherosclerotic lesions underlying this excess morbidity and mortality, clinical and angiographic findings were examined in 32 patients with insulin-dependent diabetes and in 31 nondiabetic patients, matched for age and symptoms, undergoing elective cardiac catheterization for evaluation of coronary artery disease. With respect to the individuals without diabetes, patients with insulin-dependent diabetes were significantly more likely to have severe narrowings, to have them in all three major coronary arteries, and to have them in distal segments. Severe narrowing of multiple vessels was significantly more common in men than in women and in individuals with hypercholesterolemia. We conclude that the high risk of cardiovascular events observed in young patients with insulin-dependent diabetes is secondary to advanced atherosclerotic lesions in coronary arteries. Involvement of distal segments of coronary arteries make these patients frequently unsuitable for bypass grafts.

CORONARY ARTERY DISEASE IN THE OCTOGENARIAN : ANGIOGRAPHIC SPECTRUM AND SUITABILITY FOR REVASCULARIZATION

The angiographic findings of 84 consecutive octogenarians presenting with symptoms of coronary artery disease (CAD) were examined to determine the extent of CAD as well as suitability for both coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). The frequency of 0-, 1-, 2-, and 3-vessel and left main CAD was 7, 14, 21, 57 and 13%, respectively. Based on angiographic criteria, 69 of 78 patients (88%) with significant CAD had suitable coronary anatomy for CABG. Only 24 patients (31%) had coronary anatomy amenable to PTCA. CABG was performed in 19 patients with an operative mortality of 16% and major complication rate of 37%. PTCA was performed in 12 patients with a clinical success rate of 83%, mortality of 8% and major complication rate of 8%. It is concluded that in octogenarians with CAD, cardiac catheterization will often reveal coronary anatomy that is suitable for CABG but less suitable for PTCA. The morbidity and mortality associated with these interventions are high.

Sequential combination thrombolytic therapy for acute myocardial infarction: results of the pro-urokinase and t-PA enhancement of thrombolysis (PATENT) trial

OBJECTIVES The present study was designed to test the efficacy and safety of a sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction. BACKGROUND Efforts continue to identify a thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-PA and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As a result, certain combinations of these activators have been found to be synergistic in vitro and in vivo. METHODS In a multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and given a low dose bolus of rt-PA (5 to 10 mg) followed by a 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min. RESULTS Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect a possible reocclusion. All 28 patients with a patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death. CONCLUSIONS A sequential combination of low dose rt-PA and reduced-dose pro-urokinase produced a high TIMI 3 patency rate, was well tolerated and was associated with a low reocclusion rate.

Calcium antagonists and myocardial protection

Painful and asymptomatic ischemia has been associated with left ventricular dysfunction, an important variable related to survival in patients with coronary artery disease. The treatment of patients with coronary artery disease with agents such as calcium channel blockers has been directed at reducing ischemia by restoring the balance between myocardial oxygen supply and demand, which ultimately serves to protect against myocardial dysfunction. Once ischemia has occurred, calcium channel blockers may protect myocardial cellular integrity and function. By reducing intracellular calcium overload during ischemia, mitochondrial function is preserved and adenosine triphosphate stores are maintained. Numerous in vitro and isolated heart preparations have shown that ischemia in the presence of calcium blockade is associated with less cellular dysfunction than in the situation of ischemia in the absence of calcium channel blockade.

Age and History of Cardiac Disease as Risk Factors for Cardiac Complications After Peripheral Vascular Surgery in Diabetic Patients

OBJECTIVE To examine the relationship of age and clinical factors to postoperative cardiovascular events in a cohort of diabetic patients undergoing peripheral vascular surgery. PATIENTS AND METHODS In this cohort study, 316 diabetic patients were followed up prospectively after femoral-to-distal artery bypass surgery. The major end points of the study were all-cause mortality and cardiac morbidity (cardiac events defined as nonfatal myocardial infarction, unstable angina, and congestive heart failure). RESULTS The overall postoperative cardiac event rate was 17.1% (54/316), with a 7.6% (24/316) rate of postoperative death or nonfatal myocardial infarction. Older diabetic patients (> or = 65 years) had a complication rate of 19.9% (43/216) compared with an 11.0% (11/100) complication rate in younger diabetic patients (< 65 years) (P = .02). Younger diabetic patients with a clinical history of coronary artery disease had an event rate of 18.2% (39/216) compared with an event rate of 2.4% (1/42) in younger diabetic patients without known cardiac disease (P = .02). In contrast, event rates were similar (20.7% [150/208] vs 18.2% [66/108]) in older diabetic patients with or without prior evidence of cardiac disease. CONCLUSION Advanced age and clinical evidence of coronary artery disease are important determinants of postoperative outcome in diabetic patients undergoing peripheral vascular surgery.