Mary Osbakken

Mitral valve replacement for isolated mitral regurgitation: analysis of clinical course and late postoperative left ventricular ejection fraction.

One hundred five patients underwent mitral valve replacement for relief of isolated mitral regurgitation between 1974 and 1979. There were 4 in-hospital deaths (4 percent) and 12 late deaths giving an 82 percent predicted 5 year survival rate. An age of 60 years or more at the time of surgery and a preoperative left ventricular ejection fraction of less than 0.40 were the only variables that correlated with decreased survival at 3 to 5 years after operation (p less than 0.05). Postoperatively, 87 (98 percent) of 89 long-term survivors were in New York Heart Association functional class I or II (68 in class I and 19 in class II). Survival did not differ between patients with porcine versus mechanical valve replacement, but patients with a mechanical valve had a greater incidence of postoperative cerebrovascular accident (8.6/100 patient years) than did patients with a porcine valve (2.8/100 patient years) (p less than 0.002). Ejection fraction at rest was determined with multigated cardiac imaging 12 to 75 months postoperatively in 34 of 89 long-term survivors. The mean preoperative ejection fraction was 0.62 +/- 0.09 (mean +/- 1 standard deviation) and the mean postoperative ejection fraction was 0.50 +/- 0.15 (p less than 0.001). When the preoperative value was compared with the postoperative value at rest the ejection fraction increased by 0.10 or more in 1 patient (3 percent), remained within +/- 0.09 of the preoperative value in 12 patients (35 percent) and decreased by 0.10 or greater in 21 patients (62 percent). Sixteen (94 percent) of 17 patients whose postoperative ejection fraction was greater than 0.50 were in functional class I postoperatively compared with 11 (65 percent) of 17 patients whose postoperative ejection fraction was 0.50 or less (p less than 0.05). No preoperative factor, including preoperative ejection fraction or cardiothoracic ratio, predicted the postoperative ejection fraction. A postoperative exercise ejection fraction was obtained in 29 patients, and an abnormal ejection fraction change with exercise (increase less than 0.05) was observed in 20 patients (69 percent). Patient age at the time of study correlated inversely with the change in ejection fraction from rest to exercise; no other variables were predictive. It is concluded that, in addition to age, only preoperative left ventricular function as measured by ejection fraction predicts survival in patients undergoing mitral valve replacement for isolated mitral regurgitation. Clinical recovery is good even though the majority of long-term survivors have a postoperative decrease in ejection fraction.

Early changes in left ventricular size and function after correction of left ventricular volume overload

The ability to predict early postoperative left ventricular size and function in patients with isolated aortic or mitral regurgitation was determined utilizing multigated blood pool imaging before and 2 to 4 weeks after valve replacement (aortic valve, 20 patients; mitral valve, 20 patients). Early postoperatively, ejection fraction decreased significantly (p <0.001) in both patient groups (from 0.55 ± 12 to 0.40 ± 0.14 [mean ± 1 standard deviation] in patients with aortic regurgitation and from 0.66 ± 0.09 to 0.48 ± 0.11 in patients with mitral regurgitation). The decrease in ejection fraction was associated with a large decrease in stroke volume with minimal or no change in end-systolic volume; it was unrelated to the preoperative ejection fraction. Early postoperative ejection fraction correlated best with preoperative end-systolic volume and was normal in 14 (67 percent) of 21 patients with a preoperative ejection fraction above 0.60; 4 (27 percent) of 15 patients with a preoperative ejection fraction of 0.50 to 0.60; and in 0 of 4 patients with a preoperative ejection fraction below 0.50 (p <0.05). In addition, a repeated scan in 16 patients late (1 to 2 years) after operation showed a further reduction in endsystolic volume in patients with aortic regurgitation with an increase in ejection fraction toward preoperative values. There was no significant change in patients with mitral regurgitation. End-diastolic volume decreased significantly (p <0.001) early postoperatively (from 162 ± 60 to 102 ± 41 ml/m2 in patients with aortic regurgitation and from 131 ± 40 to 78 ± 30 ml/m2 in patients with mitral regurgitation). This decrease was closely related to a decrease in stroke volume and was unrelated to preoperative ejection fraction. Early postoperative end-diastolic volume correlated best with the preoperative end-systolic volume. The major part of the reduction in end-diastolic volume occurred within 2 weeks of valve replacement. Removal of chronic left ventricular volume overload due to aortic or mitral regurgitation produces a decrease in ejection fraction and end-diastolic volume. The early reduction is in part a result of altered loading conditions and may not necessarily imply alterations in myocardial contractile function. The reduction in ejection fraction appears to persist in patients with mitral regurgitation.

Improvement of myocardial mitochondrial function after hemodynamic support with left ventricular assist devices in patients with heart failure

OBJECTIVES Mitochondrial abnormalities have been described in cardiac tissue of patients with heart failure. These changes may result from chronic hypoxia. Our goal was to determine whether mitochondrial functional capacity can be improved in patients with heart failure by means of long-term left ventricular assist device therapy, which improves myocardial oxygen supply by decreasing myocardial work. METHODS Mitochondria were isolated from myocardial tissue obtained from 13 patients with heart failure without a left ventricular assist device (HF group) and seven patients with heart failure treated with a left ventricular assist device (LVAD-HF group). Mitochondrial respiratory rates (State 2, State 3, and State 4) were measured by means of polarographic techniques with reduced nicotinamide adenine dinucleotide-dependent (pyruvate/malate, alpha-ketoglutarate, glutamate) and -independent (succinate) substrates. The respiratory control index of Chance (State 3/State 4) and Lardy (State 3/State 2) and phosphorus to oxygen ratios were determined. RESULTS The respiratory control index of Chance was higher in LVAD-HF than in HF when using NADH-dependent substrates pyruvate/malate and alpha-ketoglutarate (pyruvate/malate HF: 4.9 +/- 1.0; LVAD-HF: 6.5 +/- 1.5; alpha-ketoglutarate HF: 8.5 +/- 2.4; LVAD-HF: 11.8 +/- 2.9; both p = 0.04). Similarly, the respiratory control index of Lardy was greater in the LVAD-HF than the HF group when alpha-ketoglutarate and glutamate were used as substrates (alpha-ketoglutarate HF: 7.8 +/- 1.7; LVAD-HF: 9.9 +/- 1.5; glutamate HF: 7.6 +/- 2.2; LVAD-HF: 10.7 +/- 2.1; both p = 0.04). The phosphorus to oxygen ratio was comparable for both groups using all substrates. No change in mitochondrial respiration was observed after left ventricular assist device therapy with the NADH-independent substrate, succinate. CONCLUSION Cardiomyocyte mitochondrial function is improved by long-term therapy with a left ventricular assist device. This improvement suggests that cardiomyocyte metabolic dysfunction in heart failure may be reversed with left ventricular assist device support.

Spectrum of global left ventricular responses to supine exercise. Limitation in the use of ejection fraction in identifying patients with coronary artery disease.

Left ventricular function was evaluated with rest and supine bicycle exercise-multigated blood pool scans in 53 patients who had previously undergone coronary angiography for evaluation of a chest pain syndrome. There were 21 normal patients (less than 25% stenosis in any coronary artery, left ventricular end-diastolic pressure less than or equal to 12 mm Hg, and normal left ventriculography) and 32 patients with coronary artery disease (CAD) (greater than 50% narrowing in 1 or more major coronary arteries). Thirty-two (60%) were receiving propranolol at the time of the study. The normal patient group had a significant increase in mean ejection fraction (EF) during exercise (+0.08 +/- 0.09), while the CAD group had no increase (0 +/- 0.11; p less than 0.05). Mean end-systolic volume decreased significantly in the normal group (-5 +/- 8 ml/m2) but demonstrated no significant change in the CAD group (1 +/- 12 ml/m2; p less than 0.05 compared with normal patients). There was no significant change in mean end-diastolic volume in either group. Mean ejection rate, mean peak systolic pressure/end-systolic volume ratio, and mean pulmonary blood volume ratio also differed in the normal versus CAD patients. Despite mean differences, there was considerable overlap in both groups of individual EF responses: 8 of 21 (38%) of the normal group did not have an increase in EF of 0.05 with exercise, while 15 of 32 (47%) of the CAD group did have an increase in EF of 0.05 with exercise. However, the addition of peak systolic pressure/end-systolic volume ratio and pulmonary blood volume (exercise/rest) ratio improved the sensitivity for detecting CAD from 53 to 84% without adversely affecting specificity. Thus, there is a wide spectrum of left ventricular EF responses to supine exercise. In our patient population, EF alone was an insensitive and nonspecific marker of CAD. The addition of other parameters of global left ventricular function, which may be generated using radionuclide angiography, helps distinguish patients with CAD from normal subjects.

Comparison of exercise perfusion and ventricular function imaging: an analysis of factors affecting the diagnostic accuracy of each technique.

Exercise thallium-201 perfusion scans and gated equilibrium blood pool scans were performed in 120 catheterized patients with a chest pain syndrome. Eighty-six patients had coronary artery disease and 34 patients did not. The effects of gender, propranolol, exercise level, exercise ischemia, history of typical angina, history of previous myocardial infarction, electrocardiographic Q waves, number of diseases vessels and extent of coronary artery obstruction on diagnostic accuracy were evaluated. The overall sensitivity and specificity of thallium scans were 76 and 68%, respectively, and those of gated blood pool scans 80 and 62% (p = not significant). Propranolol decreased the specificity of thallium scans (propranolol = 42%; no propranolol = 87%, p less than 0.05). Thallium scans and anginal history were less sensitive for detecting coronary disease in women (men: thallium = 79%; angina = 77%; women: 54 and 46%, respectively; p less than 0.05). Exercise level did not significantly affect the diagnostic accuracy of either scan. Thallium and gated scans were both highly sensitive (95%) in detecting disease in 20 patients with a prior myocardial infarction, angina and a positive electrocardiogram. The sensitivity of the thallium scan significantly decreased as the number of diseased vessels decreased. Both thallium and gated scans were less frequently positive in patients with atypical angina or no Q waves, but were not significantly influenced by electrocardiographic ischemia. The sensitivity and specificity of both scans were low in 57 patients with the combination of atypical angina, no history of infarction and equivocal stress electrocardiogram thallium = 61 and 63%, respectively; gated = 61 and 67%). When stress thallium scan evaluation included the electrocardiogram and thallium scan interpretation, the diagnostic accuracy was 81%. When all the information from gated scans (wall motion, ejection fraction, pulmonary blood volume) was combined for final gated scan evaluation, the diagnostic accuracy was 83%. When electrocardiographic data were added to all three gated scan variables, diagnostic accuracy was 77%. In conclusion, thallium perfusion and gated blood pool scans have reasonable diagnostic accuracy for coronary artery disease in a group of patients with a moderately high prevalence of disease. However, combined variables from each test are needed to provide reliable diagnostic accuracy.

Positive exercise thallium-201 test responses in patients with less than 50% maximal coronary stenosis: Angiographic and clinical predictors

The incidence and causes of abnormal thallium-201 (TI-201) myocardial perfusion studies in the absence of significant coronary artery disease were examined. The study group consisted of 100 consecutive patients undergoing exercise TI-201 testing and coronary angiography who were found to have maximal coronary artery diameter narrowing of less than 50%. Maximal coronary stenosis ranged from 0 to 40%. The independent and relative influences of patient clinical, exercise and angiographic data were assessed by logistic regression analysis. Significant predictors of a positive stress TI-201 test result were: (1) percent maximal coronary stenosis (p less than 0.0005), (2) propranolol use (p less than 0.01), (3) interaction of propranolol use and percent maximal stenosis (p less than 0.005), and (4) stress-induced chest pain (p = 0.05). No other patient variable had a significant influence. Positive TI-201 test results were more common in patients with 21 to 40% maximal stenosis (59%) than in patients with 0 to 20% maximal stenosis (27%) (p less than 0.01). Among patients with 21 to 40% stenosis, a positive test response was more common when 85% of maximal predicted heart rate was achieved (75%) than when it was not (40%) (p less than 0.05). Of 16 nonapical perfusion defects seen in patients with 21 to 40% maximal stenosis, 14 were in the territory that corresponded with such a coronary stenosis. Patients taking propranolol were more likely to have a positive TI-201 test result (45%) than patients not taking propranolol (22%) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine and Cyclocreatine Effects on Ischemic Myocardium: 31P Nuclear Magnetic Resonance Evaluation of Intact Heart

The purpose of this study was to investigate the effects of prior dietary supplementation with creatine (Cr) or cyclocreatine (Cy, a synthetic analogue of Cr) on high energy phosphate metabolism of the ischemic myocardium. To this end, 48 rats were fed the following powdered rat chow diet for 21 days: 16 were fed chow without additives (CON); 16 were fed a diet containing 1% Cr by weight (CR); 16 were fed a diet containing 1% Cy by weight (CY). At the end of the feeding period, rats were anesthetized, hearts harvested and perfused in the Langendorff mode using Krebs-Henseleit buffer (maintained at 37 degrees C, equilibrated with 95% O2/5% CO2) to which 11 mM glucose was added. 31P nuclear magnetic resonance (NMR) studies of myocardial bioenergetics were done using a Bruker AM 500 spectrometer. After acquisition of preischemic spectra, global ischemia was produced by clamping aortic inflow. Ischemia was maintained until adenosine triphosphate (ATP) became NMR invisible (CON = 34 +/- 11 min; CR = 32 +/- 13 min; CY = 56 +/- 13 min; p less than 0.05 CY vs. CR and CON). Half-lives of ATP were 19 min for CON and CR and 37.5 min for CY; half-lives of phosphagen were 4 min for CON and CR and 11 min for CY. Time for return of mechanical function (heart rate x systolic pressure) after ischemia was similar for all three groups (CON = 28 +/- 28, CR = 34 +/- 22, and CY = 22 +/- 15 min), even though the CY group was subjected to longer periods of ischemia). These data indicate that CY, but not CR, pretreatment provides myocardial protection either during and/or after ischemia and allows return of mechanical function after much longer episodes of ischemia than in CON and CR. One factor in the mechanism of protection may be the prolonged maintenance of phosphagen due to the higher equilibrium concentration of phosphocyclocreatine which in turn provides substrate for continued synthesis of ATP during and after ischemia, thus defining Cy as a bioenergetic protective agent. Other mechanisms of protection remain to be defined.

In vivo Mechanisms of Myocardial Functional Stability during Physiological Interventions

Metabolic regulatory mechanisms are designed to maintain stable myocardial function during extremes in physiological insult; they can now be studied in vivo and may provide insight into mechanisms of altered myocardial functional decompensation during disease processes. To determine mechanisms of myocardial stability during hypoxia and acute pressure loading, creatine kinase (CK) kinetics (forward rate constant, Kf, and flux of phosphocreatine, PCr, to adenosine triphosphate, ATP), and nicotinamide adenine dinucleotide (NADH) redox state were determined with 31P nuclear magnetic resonance (NMR) and NADH fluorometry, respectively, and correlated with heart work (heart rate x systolic blood pressure, HR x SBP), cardiac output (CO) and O2 consumption (MVO2) in 15 anesthetized open chest dogs. Hypoxia (PaO2 of 30-35 mm Hg) was produced in 6 dogs with an inspired O2/N2 of 200/3,000. Cardiac loading was produced in 9 dogs by administration of norepinephrine (NE, 1 micrograms/kg/min). Each dog acted as its own control. Baseline NADH fluorometry, 31P-NMR saturation transfer and cardiac function measurements were performed simultaneously in each dog, after which the experimental interventions were made. Similar increases in HR x SBP, CO, and MVO2 which occurred during both interventions were associated with different bioenergetic responses. During NE infusion, the Kf of CK increased from control; during hypoxia, the Kf decreased from control (p less than 0.05). Flux of PCr----ATP was significantly lower during hypoxia than during NE infusion (p less than 0.05). PCr was decreased significantly during NE infusion (p less than 0.05). In addition, NADH redox state increased (from baseline of 100%) during hypoxia (140 +/- 10%) and decreased during NE infusion (78 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

The detection of abnormal pulmonary capillary wedge pressure from the distribution of regional pulmonary blood volume on the gated blood pool scan

THE DETECTION OF ABNORMAL PULMONARY CAPILLARY HEDGE PRESSURE FROM THE DISTRIBUTION OF REGIONAL PUIMONARY BLOOD VOLUME ON THE GATED BLOOD POOL SCAN Adalberto Urbina, MD; Robert D. Okada, MD, FACC; Mary D. Osbakken. MD: Charles A. Boucher. MD. FACC: Gerald M. Pohost, MD, FACC; H. William Strauss, MD, FACC; Igor Palacios, MD, Massachusetts General Hospital, Boston, MA To determine if the apex-to-base relative distribution of pulmonary blood volume obtained from gated blood pool scans could be used as a noninvasive method to estimate pulmonary capillary wedge pressure (PCWP), 77 patients had PCWP determination at cardiac catheterization and gated blood pool scans within 15 days of catheterization (47% within 24 hours, including 10 simultaneous measurements). The relative distribution of pulmonary blood volume at the apex and base of the lung was determined from the end-systolic left anterior oblique view frame by placing equal-sized regions-of-interest over the right lung. Apex counts divided by base counts (A/B ratio) was considered abnormal if >l. Ejection fraction (EF) was also calculated from the gated blood pool scan and considered abnormal if ~45%. The PCWP was considered normal if 512 mm Hg and abnormal if >12 mm Hg.