Steven S. Khan

Increased Mortality of Women in Coronary Artery Bypass Surgery: Evidence for Referral Bias

STUDY OBJECTIVEnTo determine whether differences in referral reasons explain the higher operative mortality of women in coronary artery bypass surgery.nnnDESIGNnCase series.nnnSETTINGnA tertiary care, private teaching hospital.nnnPATIENTSnConsecutive patients who had isolated coronary artery bypass surgery between 1982 and 1987 (total, 2297; 79% male and 21% female).nnnMEASUREMENTS AND MAIN RESULTSnThe inhospital mortality rate was significantly higher for women than for men (4.6% compared with 2.6%; P = 0.036; 95% CI for difference in mortality, 0% to 4.0%). Women were older than men (mean, 68.2 and 64.0 years, respectively; P less than 0.001), and a higher percentage of women were referred with unstable angina (P = 0.007), postmyocardial infarction angina (P = 0.029), congestive heart failure (P less than 0.001), and New York Heart Association class IV symptoms (66% compared with 45%, P less than 0.001). More men were referred with a history of an abnormal exercise test (P less than 0.001), and patients referred because of a positive exercise test had a lower mortality (P less than 0.001). Using multivariate analysis, adjustment for the higher preoperative functional class of women and for age accounted for all of the difference in mortality between men and women (odds ratio, 1.04; CI, 0.60 to 1.79; P = 0.89). After correction for functional class alone, there continued to be no significant difference in mortality between men and women (P = 0.40).nnnCONCLUSIONSnDifferences in functional class and age account for the higher operative mortality of women in coronary bypass surgery. Women are referred for coronary bypass surgery later in the course of their disease than men, and later referral may increase their changes of operative death.

Discrepancies between Doppler and catheter gradients in aortic prosthetic valves in vitro. A manifestation of localized gradients and pressure recovery.

To evaluate possible causes of discrepancy between Doppler and catheter gradients across prosthetic valves, five sizes (19-27 mm) of St. Jude and Hancock valves were studied in an aortic pulsatile flow model. Catheter gradients at multiple sites distal to the valve were compared with simultaneously obtained Doppler gradients. In the St. Jude valve, significant differences between Doppler and catheter gradients measured 30 mm downstream from the valve were found: Doppler gradients exceeded peak catheter gradients of 10 mm Hg or more by 81 +/- 35% (15 +/- 3.6 mm Hg), and mean catheter gradients by 71 +/- 11% (10.3 +/- 2.5 mm Hg). When the catheter was pulled back through the tunnel-like central orifice of the valve, high localized gradients at the valve plane and significant early pressure recovery were found. When the catheter was pulled back through the large side orifices, gradients at the same level were only 46 +/- 6% of the central orifice gradients (mean difference, 7.6 +/- 4.5 mm Hg). Doppler peak and mean gradients showed excellent agreement with the highest central orifice catheter gradients (mean difference, 1.0 +/- 3.1 and 0.9 +/- 1.5 mm Hg, respectively). A significantly better agreement between Doppler and catheter gradients at 30 mm was found for the Hancock valve, although Doppler peak and mean gradients were still slightly greater than catheter gradients. Doppler gradients exceeded catheter gradients by 18 +/- 10% (3.4 +/- 1.9 mm Hg) and 13 +/- 11% (2.1 +/- 0.9 mm Hg), respectively. When the catheter was pulled back through the valve, the highest gradients were found approximately 20 mm distal to the valve ring.(ABSTRACT TRUNCATED AT 250 WORDS)

The St. Jude valve. Thrombolysis as the first line of therapy for cardiac valve thrombosis.

BackgroundThrombolytic therapy is a promising alternative to valve replacement in the management of prosthetic valve thrombosis. We sought to determine the short- and long-term results of treating thrombosed St. Jude heart valves with thrombolytic therapy as the primary treatment modality. Methods and ResultsBetween March 1978 and December 1991, 988 patients underwent implantation of St. Jude prosthetic valves at our medical center, and all patients with thrombosed valves were identified prospectively. During this period, 17 patients (13 women; mean age, 66.8±19.0 years) developed prosthetic valve thrombosis (11 aortic, six mitral). In six patients, Coumadin was stopped in preparation for elective surgery. The clinical presentation was congestive heart failure in 13, syncope and fatigue in two, and a cerebrovascular accident in one; one patient was asymptomatic. The average duration of symptoms was 11.7±12.0 days (range, 1–45 days). Anticoagulation was subtherapeutic in all but one patient at the time of presentation. Cinefluoroscopy was the primary method used for diagnosis and was also used to follow the response to therapy. Twelve patients were treated medically (10 with thrombolytic therapy and two with heparin), three were treated surgically, and two were diagnosed at autopsy. Of the 12 medically treated patients, 10 had marked improvement in leaflet movement and symptoms within 12 hours. Thus, 10 of 12 patients (83%) had a satisfactory response to medical therapy alone. No medically treated patient died or had a major complication resulting in permanent damage. However, four of the 12 medically treated patients had minor complications, including a transient episode of facial weakness in one patient, hematomas in two, and epistaxis in one. Late rethrombosis recurred in two patients in the medically treated group and was successfuly retreated with thrombolytic therapy. At 3 months, all patients were alive and well. ConclusionsThrombolytic therapy can be used as the first line of therapy for thrombosed St. Jude valves with a low risk of permanent side effects and excellent chances of success. In most cases, surgery can be reserved for patients who do not respond to thrombolytic therapy.

Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up ☆

OBJECTIVESnThis study explored the association between the initiation of hormone replacement therapy (HRT) and early cardiac events (<1 year) in women with a recent myocardial infarction (MI).nnnBACKGROUNDnObservational studies have linked postmenopausal hormone use with a reduced risk of death from heart disease. However, a recent randomized trial of HRT found no long-term benefit, primarily due to an increase in cardiac events in the first year.nnnMETHODSnThe Coumadin Aspirin Reinfarction Study (CARS) database contains information on HRT use and menopausal status for women with a recent MI. We classified the 1,857 postmenopausal women in CARS as prior/current HRT users if they took HRT before enrollment, new users if they began HRT during the study period or never users. We assessed the incidence of cardiac events (death, MI, unstable angina [UA]) during follow-up.nnnRESULTSnIn our cohort, 28% (n = 524) used HRT at some point. Of these, 21% (n = 111) began HRT after their MI. New users had a higher incidence of death/MI/UA (41% vs. 28%, p = 0.001) during follow-up than never users, largely due to a higher incidence of UA (39% vs. 20%, p = 0.001). After adjustment, new users still had a significantly higher risk of death/MI/UA than never users during follow-up (relative risk [RR] = 1.44 [1.05-1.99]). Prior/current users had no excess risk of the composite end point after adjustment. Users of estrogen/progestin had a lower incidence of death/MI/UA during follow-up than users of estrogen only (RR = 0.56 [0.37-0.85]).nnnCONCLUSIONSnPostmenopausal women who initiated HRT after a recent MI had an increased risk of cardiac events largely due to excess UA during follow-up.

Ten-year experience of cardiac surgery in patients aged 80 years and over.

Five hundred twenty-eight consecutive patients aged 80 years and over (mean age, 83.1 +/- 2.7 years) underwent cardiac operations with hypothermia (mean, 21.9 degrees +/- 2.2 degrees C), hyperkalemic cardioplegia, and cardiopulmonary bypass in a 10-year period. Fifty-six percent of the patients were male. Preoperatively, 68% of the patients were in New York Heart Association functional class IV, and 31% were in class III. Among them, 303 patients had isolated coronary artery bypass grafting (CABG) (group I), 132 had aortic valve replacement only or combined with CABG (group II), 42 had mitral valve replacement only or combined with CABG (group III), 31 had mitral valve repair and CABG (group IV), and 20 had double-valve procedure only or combined with CABG (group V). The 30-day or in-hospital mortality was 8.3% in group I, 4.5% in group II, 29% in group III, 23% in group IV, and 30% in group V. Total 30-day or in-hospital mortality was 10.6%. One-year and 5-year actuarial survival rates were as follows: group I, 82% and 62%; group II, 85% and 58%; group III, 61% and 37%; group IV, 56% and 19%; and group V, 63% and 15%. Total 1-year and 5-year actuarial survival were 79% and 54%. At follow-up (mean, 2 years), 70% of overall survivors reported that their general health had improved. Our experience demonstrates that for select patients aged 80 years and over with unmanageable cardiac symptoms, CABG and aortic valve replacement groups had better results in improving quality of life as compared with patients having mitral or combined procedures.

Morbidity and mortality after coronary artery bypass in octogenarians.

One hundred fifty seven consecutive octogenarians (mean age +/- standard deviation, 82.4 +/- 1.9 years) underwent coronary artery bypass grafting with hypothermia (mean temperature, 21.8 degrees +/- 1.8 degrees C), hyperkalemic cardioplegia, and cardiopulmonary bypass in a 9-year period. Sixty-six percent were male. Preoperatively, 115 patients (73%) were in New York Heart Association functional class IV, with the remainder being in either class III (23%) or class II (4%). Twenty percent of the patients had major complications including postoperative hemorrhage (15), sepsis (9), cerebrovascular accident (6), third-degree heart block (5), renal failure requiring dialysis (1), and pulmonary embolism (1). The 30-day or in-hospital mortality rate was 7.0%. Mean total hospital stay was 26.1 +/- 17.9 days. One-year and 5-year actuarial survival rates were 85% and 62%, respectively. Higher mortality was seen to be associated with New York Heart Association class IV, left ventricular ejection fraction less than 0.40, and lesser values for cardiac output and cardiac index. At the 6-month postoperative follow-up, 73% of the survivors reported that their general health had improved as compared with before operation. This experience demonstrates that for select octogenarians with unmanageable angina pectoris, coronary artery bypass grafting is an effective therapeutic option.

Doppler assessment of prosthetic valve orifice area. An in vitro study.

BackgroundAlthough Doppler echocardiography has been shown to be accurate in assessing stenotic orifice areas in native valves, its accuracy in evaluating the prosthetic valve orifice area remains undetermined. Methods and ResultsDoppler-estimated valve areas were studied for their agreement with catheterderived Gorlin effective orifice areas and their flow dependence in five sizes (19/20–27 mm) of St. Jude, Medtronic-Hall, and Hancock aortic valves using a pulsatile flow model. Doppler areas were calculated three ways: using the standard continuity equation; using its simplified modification (peak flow/peak velocity); and using the Gorlin equation with Doppler pressure gradients. The results were compared with Gorlin effective orifice areas derived from direct flow and catheter pressure measurements. Excellent correlation between Gorlin effective orifice areas and the three Doppler approaches was found in all three valve types (r=0.93-0.99, SEE=0.07-0.11 cm2). In Medtronic-Hall and Hancock valves, there was only slight underestimation by Doppler (mean difference, 0.003-0.25 cm2). In St. Jude valves, however, all three Doppler methods significantly underestimated effective orifice areas derived from direct flow and pressure measurements (mean difference, 0.40-0.57 cm2) with differences as great as 1.6 cm2. In general, the modified continuity equation calculated the largest Doppler areas. When orifice areas were calculated from the valve geometry using the area determined from the inner valve diameter reduced by the projected area of the opened leaflets, Gorlin effective orifice areas were much closer to the geometric orifice areas than Doppler areas (mean difference, 0.40±0.31 versus 1.04±0.20 cm2). In St. Jude and Medtronic-Hall valves, areas calculated by either technique did not show a consistent or clinically significant flow dependence. In Hancock valves, however, areas calculated by both the continuity equation and the Gorlin equation decreased significantly (p<0.001) with low flow rates. ConclusionsDoppler echocardiography using either the continuity equation or Gorlin formula allows in vitro calculation of Medtronic-Hall and Hancock effective valve orifice areas but underestimates valve areas in St. Jude valves. This phenomenon is due to localized high velocities in St. Jude valves, which do not reflect the mean velocity distribution across the orifice. Valve areas are flow independent in St. Jude and Medtronic-Hall prostheses but decrease significantly with low flow in Hancock valves, suggesting that bioprosthetic leaflets may not open fully at low flow rates.

Action potential alternans and irregular dynamics in quinidine-intoxicated ventricular muscle cells. Implications for ventricular proarrhythmia.

BackgroundCardiac cells display rate-dependent beat-to-beat variations in action-atential duration (APD), action potential amplitude (APA), and excitability during periodic stimulation. We hypothesized that quinidine causes a marked increase in the variability of APD, APA, and excitability of ventricular cells isolated from quinidine-toxic, arrhythmic ventricles. Methods and ResultsAction potentials were recorded from right ventricular endocardial tissues (2× 1 cm, <2 mm thick) isolated from dogs in which ventricular tachycardia and ventricular fibrillation (VT/VF) were induced with intravenous quinidine (80-100 mg/kg) over a 5-hour period in vivo (n=7). As the basic cycle length (BCL) of stimulation was progressively shortened, rate-dependent variations in APD and APA occurred. The initial dynamic change was alternans of APD and APA that could be either in or out of phase between two cells. The magnitude of alternans was a function of the BCL and the strength of the stimulation current. At critically short BCLs, irregular APD and APA behavior emerged in the quinidine-intoxicated cells. In control cells (n=16) isolated from three nontreated dogs, APD and APA remained constant at all BCLs tested (2,000-300 msec). Quinidine increased the slope of the APD restitution curve compared with control. The observed quinidine APD restitution curve was fitted with a biexponential equation, and computer simulation using the fitted restitution curve reproduced the aperiodic APD seen in the quinidine toxic cells during periodic stimulation. Thus, the observed irregular APD behavior was predictable from the restitution curve. ConclusionsQuinidine toxicity increases the temporal and spatial variability of APD and APA in the ventricle that may promote the initiation of reentrant VT/VF in vivo. The slope of the APD restitution curve provides a method to quantitate inhomogeneities in repolarization time and could be a useful marker for proarrhythmia.

The St. Jude Medical valve: Experience with 1000 cases

We analyzed the long-term results of valve replacement with the St. Jude Medical bileaflet valve (St. Jude Medical, Inc., St. Paul, Minn.) in our first 1000 implantations between 1978 and 1992. A total of 399 patients had mitral valve replacement, 471 aortic valve, and 130 double (mitral and aortic) valve replacement. The average patient age was 64 +/- 15 years and the majority of patients (52%) had concomitant coronary disease. With 4328 patient-years of follow-up, 83% of the mitral group, 76% of the aortic group, and 77% of the double valve group were free of thromboembolism at 10 years after operation, and 87% of the mitral group, 82% of the aortic group, and 85% of the double valve group were free of valve-related hemorrhage. At 10 years, 91% of the mitral group, 84% of the aortic group, and 84% of the double valve group were free of valve-related death. However, overall survival at 10 years was only 42% +/- 4% for the mitral group, 43% +/- 4% for the aortic group, and 43% +/- 6% for the double valve group. For all three groups, age was a highly significant factor stratifying survival (p < 0.001), as was the presence of coronary disease (all p < 0.001). The excellent freedom from valve-related death at 10 years of 84% to 91% is in striking contrast to the overall survivals of 42% to 43% at 10 years. This difference suggests that the primary factors limiting long-term survival after valve replacement with the St. Jude Medical valve are not valve-related factors, but other patient factors such as age and concomitant coronary disease.

Cellular mechanisms of differential action potential duration restitution in canine ventricular muscle cells during single versus double premature stimuli.

BackgroundWe tested the hypothesis that action potential duration (APD) restitution of normal ventricular muscle cells is different during double premature stimuli (S3) compared with a single premature stimulus (S2). We propose a possible ionic mechanism for such a difference. Methods and ResultsAction potentials and isometric tension were recorded simultaneously from isolated canine right ventricular trabeculae (2×2×10 mm) (n=35). APD and tension restitution curves (APD and peak tension versus diastolic interval [DI]) of S2 and S3 were constructed by the extrastimulus method during pacing at 1,500 msec. The following results were obtained. 1) The APD restitution curve of S2 was different from that of S3. During the restitution of S2, an early biphasic upward hump was present at short DIs. In contrast, a smooth exponential rise was consistently seen during S3 restitution. 2) Peak tension remained significantly (p<0.001) lower during the restitution of S2 than during S3 restitution at all DIs tested. 3) The variation of APD during the initial 100 msec of DI was significantly longer during S3 than S2 (22±5 msec versus 41±5 msec, p<0.001). 4) Caffeine (2 mM, n=5) and ryanodine (10 μM n=5) blocked cyclic variations of tension, presumably by blocking cyclic variations of intracellular calcium ion concentrations ([Ca2+]1), and eliminated the differences in APD restitution between S2 and S3. 5) Nisoldipine at high (5 μM) but not at lower (2 μM n=5) concentration eliminated the differences in restitution of both APD and tension between S2 and S3. 6) BAY K 8644 (100 nM, n=5) had no effect on this difference. ConclusionsGreater variations of APD occur during the restitution of S3 than during S2 at short DIs. These differences appear to be caused by cyclic variations in tension and thus in [Ca2+]1. Calciumsensitive outward currents could explain these differences in APD restitution.