Bruce J. Leavitt

Altered myocardial force-frequency relation in human heart failure.

BackgroundIn congestive heart failure (idiopathic dilated cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease in end-diastolic left ventricular volume, depressed peak rates of left ventricular pressure rise and fall, and depressed heart-rate-dependent potentiation of contractility (bowditch treppe). We studied contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing hearts at physiological temperature and heart rates in order to identify and quantitate abnormalities in myocardial function that underlie abnormal ventricular function. Methods and ResultsThe isometric tension-generating ability of isolated left ventricular strips from nonfailing and failing human hearts was investigated at 37°C and contraction frequencies ranging from 12 to 240 per minute (min−1). Strips were dissected using a new method of protection against cutting injury with 2,3-butanedione monoxime (BDM) as a cardioplegic agent. In nonfailing myocardium the twitch tension-frequency relation is bell-shaped developing 25±2 mN/mm2 at a contraction frequency of 72 min−1 and peaking at 44±3.7 mN/mm2 at a contraction frequency of 174±4 min−1. In failing myocardium the peak of the curve occurs at lower frequencies between 6 and 120 min−1 averaging 81±22 min−1, and it develops 48% (p < 0.001) and 80% (p < 0.001) less tension than in nonfailing myocardium at 72 and 174 min−1, respectively. Between 60 and 150 min−1 tension increases by 107% in nonfailing myocardium, but it does not change significantly in failing myocardium. Peak rates of rise and fall of isometric twitch tension vary in parallel with twitch tension as stimulation frequency rises in nonfailing myocardium but not in failing myocardium. ConclusionsThe quantitative agreement between these results from isolated myocardium and those from catheterization laboratory measurements on intact humans suggest that alterations of myocardial origin, independent of systemic factors, may contribute to the above mentioned abnormalities in left ventricular function seen in dilated cardiomyopathy.

A regional intervention to improve the hospital mortality associated with coronary artery bypass graft surgery. The Northern New England Cardiovascular Disease Study Group.

OBJECTIVE To determine whether an organized intervention including data feedback, training in continuous quality improvement techniques, and site visits to other medical centers could improve the hospital mortality rates associated with coronary artery bypass graft (CABG) surgery. DESIGN Regional intervention study. Patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected on CABG patients in Northern New England between July 1, 1987, and July 31, 1993. SETTING This study included all 23 cardiothoracic surgeons practicing in Maine, New Hampshire, and Vermont during the study period. PATIENTS Data were collected on 15,095 consecutive patients undergoing isolated CABG procedures in Maine, New Hampshire and Vermont during the study period. INTERVENTIONS A three-component intervention aimed at reducing CABG mortality was fielded in 1990 and 1991. The interventions included feedback of outcome data, training in continuous quality improvement techniques, and site visits to other medical centers. MAIN OUTCOME MEASURE A comparison of the observed and expected hospital mortality rates during the postintervention period. RESULTS During the postintervention period, we observed the outcomes for 6488 consecutive cases of CABG surgery. There were 74 fewer deaths than would have been expected. This 24% reduction in the hospital mortality rate was statistically significant (P = .001). This reduction in mortality rate was relatively consistent across patient subgroups and was temporally associated with the interventions. CONCLUSION We conclude that a multi-institutional, regional model for the continuous improvement of surgical care is feasible and effective. This model may have applications in other settings.

Obesity and Risk of Adverse Outcomes Associated With Coronary Artery Bypass Surgery

Background—Obesity is frequently cited as a risk factor for adverse outcomes of major surgery. The results of prior studies of the relationship between obesity and risk of adverse outcomes of coronary artery bypass grafting (CABG) have been contradictory because of insufficient power to assess relatively infrequent outcomes or data to adjust for confounding factors. Methods and Results—Data on patient age, sex, height, weight, medical history, current clinical status, and treatment factors were assessed prospectively among 11 101 consecutive patients undergoing CABG. Body mass index (BMI) was used as the measure of obesity and was categorized as nonobese (1st to 74th percentiles), obese (75th to 94th percentiles), or severely obese (95th to 100th percentiles). Adverse outcomes occurring in-hospital, including mortality, intraoperative/postoperative cerebrovascular accident (CVA), postoperative bleeding, and sternal wound infection, were defined prospectively. Associations between obesity and postoperative...

The association of perioperative red blood cell transfusions and decreased long-term survival after cardiac surgery.

BACKGROUND: Exposure to red blood cell (RBC) transfusions has been associated with increased mortality after cardiac surgery. We examined long-term survival for cardiac surgical patients who received one or two RBC units during index hospitalization. METHODS: Nine thousand seventy-nine consecutive patients undergoing coronary artery bypass graft, valve, or coronary artery bypass graft/valve surgery at eight centers in northern New England during 2001-2004 were examined after exclusions. A probabilistic match between the regional registry and the Social Security Administration’s Death Master File determined mortality through June 30, 2006. Cox Proportional Hazard and propensity methods were used to calculate adjusted hazard ratios. RESULTS: Thirty-six percent of patients (n = 3254) were exposed to one or two RBC units. Forty-three percent of RBCs were given intraoperatively, 56% in the postoperative period and 1% were preoperative. Patients transfused were more likely to be anemic, older, smaller, female and with more comorbid illness. Survival was significantly decreased for all patients exposed to 1 or 2 U of RBCs during hospitalization for cardiac surgery compared with those who received none (P < 0.001). After adjustment for patient and disease characteristics, patients exposed to 1 or 2 U of RBCs had a 16% higher long-term mortality risk (adjusted hazard ratios = 1.16, 95% CI: 1.01-1.34, P = 0.035). CONCLUSIONS: Exposure to 1 or 2 U of RBCs was associated with a 16% increased hazard of decreased survival after cardiac surgery.

Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy.

Myocardial failure in dilated cardiomyopathy may result from subcellular alterations in contractile protein function, excitation-contraction coupling processes, or recovery metabolism. We used isometric force and heat measurements to quantitatively investigate these subcellular systems in intact left ventricular muscle strips from nonfailing human hearts (n = 14) and from hearts with end-stage failing dilated cardiomyopathy (n = 13). In the failing myocardium, peak isometric twitch tension, maximum rate of tension rise, and maximum rate of relaxation were reduced by 46% (p = 0.013), 51% (p = 0.003), and 46% (p = 0.018), respectively (37 degrees C, 60 beats per minute). Tension-dependent heat, reflecting the number of crossbridge interactions during the isometric twitch, was reduced by 61% in the failing myocardium (p = 0.006). In terms of the individual crossbridge cycle, the average crossbridge force-time integral was increased by 33% (p = 0.04) in the failing myocardium. In the nonfailing myocardium, the crossbridge force-time integral was positively correlated with the patients age (r = 0.86, p less than 0.02), whereas there was no significant correlation with age in the failing group. The amount and rate of excitation-contraction coupling-related heat evolution (tension-independent heat) were reduced by 69% (p = 0.24) and 71% (p = 0.028), respectively, in the failing myocardium, reflecting a considerable decrease in the amount of calcium released and in the rate of calcium removal. The efficiency of the metabolic recovery process, as assessed by the ratio of initial heat to total activity-related heat, was similar in failing and nonfailing myocardium (0.54 +/- 0.03 versus 0.50 +/- 0.02, p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

Risks of Morbidity and Mortality in Dialysis Patients Undergoing Coronary Artery Bypass Surgery

Background—Although dialysis patients are undergoing CABG with increasing frequency, large studies specifically comparing patient characteristics and procedure-related risks in this population have not been performed. Methods and Results—We conducted a regional prospective cohort study of 15 500 consecutive patients undergoing CABG in northern New England from 1992 to 1997. We used multiple logistic regression analysis to examine associations between preoperative dialysis-dependent renal failure and postoperative events and to adjust for potentially confounding variables. The 279 dialysis-dependent renal failure patients (1.8%) were 4.4 times more likely to experience in-hospital mortality than were other CABG patients (12.2% versus 3.0%, respectively;P <0.001). Dialysis-dependent renal failure patients were older and had more comorbidities and more severe cardiac disease than did other CABG patients. After adjusting for these factors in multivariate analysis, however, dialysis-dependent renal failure patients remained 3.1 times more likely to die after CABG (adjusted odds ratio [OR] 3.1, 95% CI 2.1 to 4.7;P <0.001). Dialysis-dependent renal failure patients compared with other CABG patients also had a substantially increased risk of postoperative mediastinitis (3.6% versus 1.2%, respectively; adjusted OR 2.4, 95% CI 1.2 to 4.7;P =0.011) and postoperative stroke (4.3% versus 1.7%, respectively; adjusted OR 2.1, 95% CI 1.1 to 3.9;P =0.016), even after controlling for potentially confounding variables. Risks of reexploration for bleeding were similar for patients with and without dialysis-dependent renal failure. Conclusions—Preoperative dialysis-dependent renal failure is a strong independent risk factor for in-hospital mortality and mediastinitis after CABG.

Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients

BACKGROUND Discontinuing aspirin use in patients before coronary artery bypass grafting (CABG) has focused on bleeding risks. The effect of aspirin use on overall mortality with this procedure has not been studied. METHODS We performed a case patient-control patient study of the 8,641 consecutive isolated CABG procedures performed between July 1987 and May 1991 in Maine, New Hampshire, and Vermont. Patients included all 368 deaths. Each case patient was paired with approximately two matched survivors (control patients). Aspirin use was defined by identification of ingestion within 7 days before the operation. RESULTS CABG patients using preoperative aspirin were less likely to experience in-hospital mortality in univariate (odds ratio [OR] = 0.73, 95% confidence interval [0.54, 0.97]) and multivariate [OR = 0.55, (0.31, 0.98)] analysis compared to nonusers. No significant difference was seen in the amount of chest tube drainage, transfusion of blood products, or need for reexploration for hemorrhage between patients who did and did not receive aspirin. CONCLUSIONS Preoperative aspirin use appears to be associated with a decreased risk of mortality in CABG patients without significant increase in hemorrhage, blood product requirements, or related morbidities.

Comparing long-term survival of patients with multivessel coronary disease after CABG or PCI: Analysis of BARI-like patients in Northern New England

Background—Randomized trials comparing coronary artery bypass graft surgery (CABG) with percutaneous coronary interventions (PCIs) for patients with multivessel coronary disease (MVD) report similar long-term survival for CABG and PCI. These studies used a highly selected population of patients and providers, and their results may not be generalizable to actual care. Our goal in this study was to compare long-term survival of MVD patients treated with CABG vs PCI in contemporary practice. Methods and Results—From our northern New England registries of consecutive coronary revascularizations, we identified 10 198 CABG and 4295 PCI patients with MVD who may have been eligible for either procedure between 1994 and 2001. Vital status was obtained by linkage to the National Death Index. Proportional-hazards regression was used to calculate hazard ratios (HRs) for survival in CABG vs PCI patients after adjustment for comorbidities and disease characteristics. CABG patients were older; had more comorbidities, more 3-vessel disease, and lower ejection fractions; and were more completely revascularized. Adjusted long-term survival for patients with 3-vessel disease was better after CABG than PCI (HR, 0.60; P<0.01) but not for patients with 2-vessel disease (HR, 0.98; P=0.77). The survival advantage of CABG for 3-vessel disease patients was present in all patient populations, including women, diabetics, and the elderly and in the era of high stent utilization. Conclusions—In contemporary practice, survival for patients with 3-vessel coronary disease is better after CABG than PCI, an observation that patients and physicians should carefully consider when deciding on a revascularization strategy.

Intraoperative Red Blood Cell Transfusion During Coronary Artery Bypass Graft Surgery Increases the Risk of Postoperative Low-Output Heart Failure

Background— Hemodilutional anemia during cardiopulmonary bypass (CPB) is associated with increased mortality during coronary artery bypass graft (CABG) surgery. The impact of intraoperative red blood cell (RBC) transfusion to treat anemia during surgery is less understood. We examined the relationship between anemia during CPB, RBC transfusion, and risk of low-output heart failure (LOF). Methods and Results— Data were collected on 8004 isolated CABG patients in northern New England between 1996 and 2004. Patients were excluded if they experienced postoperative bleeding or received ≥3 units of transfused RBCs. LOF was defined as need for intraoperative or postoperative intra-aortic balloon pump, return to CPB, or ≥2 inotropes at 48 hours. Having a lower nadir HCT was also associated with an increased risk of developing LOF (adjusted odds ratio, 0.90; 95% CI, 0.82 to 0.92; P=0.016), and that risk was further increased when patients received RBC transfusion. When adjusted for nadir hematocrit, exposure to RBC transfusion was a significant, independent predictor of LOF (adjusted odds ratio, 1.27; 95% CI, 1.00 to 1.61; P=0.047). Conclusions— In this study, we observed that exposure to both hemodilutional anemia and RBC transfusion during surgery are associated with increased risk of LOF, defined as placement of an intraoperative or postoperative intra-aortic balloon pump, return to CPB after initial separation, or treatment with ≥2 inotropes at 48 hours postoperatively, after CABG. The risk of LOF is greater among patients exposed to intraoperative RBCs versus anemia alone.

Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species.

Alteration in crossbridge behavior and myocardial performance have been associated with myosin isoenzyme composition in animal models of myocardial hypertrophy or atrophy. In the hypertrophied human heart, myocardial performance is altered without significant changes in myosin isoenzymes. To better understand this discrepancy, isometric heat and force measurements were carried out in 1) control and volume-overload human myocardium, 2) control, pressure-overload, and hyperthyroid rabbit myocardium, and 3) control and hypothyroid rat myocardium. In control human myocardium, peak isometric twitch tension was 44.0 +/- 11.7 mN/mm2, and maximum rate of tension rise was 69.2 +/- 21.0 mN/sec.mm2. In volume-overload human myocardium, peak twitch tension and maximum rate of tension rise were reduced by 55% (p less than 0.05) and 65% (p less than 0.05), respectively. The average force-time integral of the individual crossbridge cycle, calculated by myothermal techniques, was increased by 85% (p less than 0.005) in volume-overload human myocardium. In control and hormonally altered myocardium, both across and within species (control human, control rat, control rabbit, hypothyroid rat, and hyperthyroid rabbit), there was a close relation between the crossbridge force-time integral and the percentage of V3-type myosin isoenzyme in the myocardium. However, hemodynamically altered (volume-overload human and pressure-overload rabbit) myocardium did not follow this relation. Across and within species, there were significant correlations between maximum rate of tension rise and average tension-dependent heat rate (r = 0.97, p less than 0.001) and between maximum rate of tension fall and average tension-independent heat rate (r = 0.82; p less than 0.025). Furthermore, there were close inverse relations between these heat rates and the crossbridge force-time integral. In addition, there was an inverse relation between tension-independent heat and the crossbridge force-time integral. Across and within species total myocardial energy turnover was significantly correlated with the crossbridge force-time integral (relative total heat, r = -0.84, p less than 0.02; relative total-activity related heat, r = -0.88, p less than 0.01). The present findings indicate that 1) factors separate from myosin isoenzymes account for the altered crossbridge cycle in volume-overload human and pressure-overload rabbit myocardium, 2) changes in excitation-contraction coupling processes accompany changes in the crossbridge cycle within and across species, and 3) the force-time integral of the crossbridge cycle is a major determinant of total myocardial energy turnover.