PET scan predicts recovery of left ventricular function after coronary artery bypass operation

BACKGROUND: Viable but hypocontractile myocardium can show functional improvement after revascularization (hibernation). It is sometimes difficult, however, to predict viability and recovery in patients with severe left ventricular function. This study sought to identify possible predictive factors of recovery of cardiac function after revascularization in patients with three-vessel disease. METHODS: Positron emission tomography (fluoro-18-deoxyglucose uptake for metabolism; nitrogen 13-labeled ammonia for flow) and equilibrium-gated nuclear angiography (for the global ejection fraction) were performed in 59 patients with three-vessel disease before and after undergoing coronary artery bypass grafting. The positron emission tomographic data were expressed as match normal (flow and metabolism normal), mismatch (low flow, high metabolism), match viable (moderate decrease in flow and metabolism), and match necrosis (low flow and metabolism). RESULTS: Stepwise logistic regression analysis showed that only mismatch regions played a significant role in predicting postoperative improvement in function (p = 0.019). There were 1.7 +/- 1.5 mismatch regions in 31 patients who showed an improvement in their ejection fraction (0.47 +/- 0.14 versus 0.58 +/- 0.11; mean +/- standard deviation) versus 0.8 +/- 1.0 mismatch regions (p = 0.017) in patients who did not show recovery. There was more pronounced functional improvement with increasing numbers of mismatch regions, and patients with at least one mismatch region had a high likelihood of recovery (p < 0.001). In patients with a very low preoperative ejection fraction and two or more mismatch regions, there was early significant recovery (0.27 +/- 0.08 versus 0.46 +/- 0.06; p = 0.009). CONCLUSIONS: At least one mismatch region must be present for there to be a postoperative functional benefit. When a low left ventricular ejection fraction is associated with mismatch, early recovery is substantial.     

Inhaled nitric oxide reduction in systolic pulmonary artery pressure is less in patients with decreased left ventricular ejection fraction

OBJECTIVE: To assess whether inhaled nitric oxide decreases pulmonary artery pressure in patients with depressed left ventricular ejection fraction. DESIGN: Randomized, blinded, crossover clinical trial. SETTING: Tertiary care university referral hospital. PATIENTS: Thirty-three patients with pulmonary hypertension and left ventricular dysfunction or valvular heart disease were recruited by convenience. INTERVENTIONS: Systolic pulmonary artery pressure was measured by Doppler echocardiography during randomized inhalation of either 20 ppm or 40 ppm nitric oxide in 30% oxygen as well as during control periods without nitric oxide. MAIN RESULTS: Systolic pulmonary artery pressure was significantly (P < 0.05) decreased with 20 ppm nitric oxide (53.4 +/- 13.9 mmHg) and 40 ppm nitric oxide (53.1 +/- 14.4 mmHg) compared with either initial control (55.8 +/- 15.3 mmHg) or terminal control (56.3 +/- 15.2 mmHg) values. The regression equation for the change in systolic pulmonary artery pressure (y) as predicted by the left ventricular ejection fraction (x) alone for 20 ppm nitric oxide was y = 13.8x-2.9; R2adj = 0.30, P < 0.0001. For 40 ppm nitric oxide alone, the regression equation was y = 16.3x-3.3; R2adj = 0.25, P < 0.0001. Left ventricular ejection fraction was the most explanatory independent variable in the multivariate equation for nitric oxide-induced change in systolic pulmonary artery pressure (R2 = 0.61, P = 0.0000). The change in systolic pulmonary artery pressure was -5.1 +/- 5.2 versus 0.8 +/- 4.9 mmHg (P < 0.0000) in patients with left ventricular ejection fractions greater than 0.25, and 0.25 or less, respectively. CONCLUSIONS: These data imply that in patients with left ventricular ejection fraction of 0.25 or less, nitric oxide may not decrease systolic pulmonary artery pressure. Nitric oxide inhalation may result in a paradoxical increase in systolic pulmonary artery pressure in patients with severely depressed left ventricular ejection fraction. This effect would significantly limit the therapeutic role of nitric oxide in patients with severe heart failure.     

Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo

The operative mortality and morbidity in patients with severe left ventricular dysfunction who undergo coronary artery bypass grafting (CABG) remain high. The low ejection fraction is the major risk factor for operative mortality. However, ejection fraction (EF) alone may not necessarily be an accurate predictor of operative mortality. We studied the correlation between indices of left ventricular volume and operative mortality. One thousand patients undergoing isolated coronary bypass operations were divided into three groups according to their preoperative ejection fraction. Fifty patients (group I) had severe left ventricular dysfunction (EF < or = 0.3), 56 patients (group II) had moderately left ventricular dysfunction (0.3 < EF < or = 0.4) and 894 patients (group III) had good left ventricular function (EF > 0.4). We analyzed the relationship between hospital mortality and left ventricular volume in 106 patients with an EF < or = 0.4. RESULTS: Cardiac index was not significantly different among the three groups. The left ventricular end-diastolic pressure (LVEDP) and mean pulmonary artery pressure in groups I an II were higher than those in group III. The left ventricular end-diastolic volume (LVEDV) was 146 +/- 44 ml/m2 in Group I, 112 +/- 31 ml/m2 in Group II and 82 + 30 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The left ventricular end-systolic volume (LVESV) was 111 +/- 38 ml/m2 in Group I, 72 +/- 21 ml/m2 in Group II and 30 +/- 14 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The LVEDV and LVESV were higher in Group I than in Group II and both in Groups I and II were higher than in Group III. The hospital mortality of any cause before discharge was 8.0% (4/50) in Group I, 3.6% (2/56) in Group II, and 2.0% (18/894) in Group III. The mortality in Group I was higher than that in Group III, but the mortality between Groups I and II was not different. We assessed correlations between large left ventricle with left ventricular dysfunction and operative mortality in 106 patients with ejection fractions of < or = 0.4. The hospital mortality in patients with both under fraction 0.4 and an LVESV > or = 140 ml/m2 was 50% (4/8). This rate was higher than in patients with an LVESV between 80 and 140 ml/m2 (1.8%, 1/55) (p = 0.0006) and an LVESV less than 80 ml/m2 (2.3%, 1/43), (p = 0.0013). The hospital mortality in patients with an LVEDV > or = 200 ml/m2 was 67% (4/6). It was also higher than that in patients with an LVEDV between 200 and 120 ml/m2 (1.7%, 1/58), (p = 0.0001), and an LVEDV less than 120 ml/m2 (2.4%, 1/42), (p = 0.0004). We conclude that patients with a low ejection fraction and an elevated LVESV or LVEDV are at increased risk for hospital death following CABG.     

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.     

Effects of late percutaneous transluminal coronary angioplasty of an occluded infarct-related coronary artery on left ventricular function in patients with a recent (< 6 weeks) Q-wave acute myocardial infarction (Total Occlusion Post-Myocardial Infarction Intervention Study [TOMIIS]--a pilot study)

The effect of late percutaneous transluminal coronary angioplasty (PTCA) of an occluded infarct-related artery on left ventricular ejection fraction was studied in patients with a recent, first Q-wave myocardial infarction in a prospective, randomized study. Forty-four patients (31 men and 13 women, mean age 58 +/- 12 years) with an occluded infarct-related coronary artery were randomized to PTCA (n = 25) or no PTCA (n = 19). Patients received acetylsalicylic acid, a beta blocker and an angiotensin-converting enzyme inhibitor unless contraindicated. Left ventricular ejection fraction was determined at baseline and 4 months. Coronary angiography was repeated at 4 months. Baseline ejection fraction measured 20 +/- 12 days after myocardial infarction was 45 +/- 12% in both groups. PTCA was performed 21 +/- 13 days after the event. The primary PTCA success rate was 72%. One patient in each group died before angiographic follow-up, which was completed in 37 of the remaining 42 patients (88%; 21 with and 16 without PTCA). At 4 months, the infarct-related artery was patent in 43% of PTCA patients and in 19% of no PTCA patients (p = NS). Reocclusion occurred in 40% of patients after successful PTCA. Secondary analyses showed that the change in left ventricular ejection fraction was significantly greater in patients with a patent infarct-related artery (+9.4 +/- 6.2%) than in those with an occluded artery (+1.6 +/- 8.8%; p = 0.0096). Baseline ejection fraction also independently predicted improvement in left ventricular ejection fraction (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular hypercontractility and ST segment depression in patients with syndrome X

OBJECTIVES: This study was designed to assess the relation between rest left ventricular function and exercise capacity in patients with syndrome X. BACKGROUND: Clinical observation has suggested that some patients with syndrome X have a high rest left ventricular ejection fraction. In this study we determined the relation between left ventricular ejection fraction and exercise capacity and the electrocardiographic (ECG) changes that develop on exercise. METHODS: The pattern of left ventricular function, exercise capacity and 24-h ambulatory ECG monitoring were studied in 37 patients (9 men, 28 women; mean age 52 +/- 7 years) with syndrome X (angina with normal coronary arteries and a positive exercise test result). All patients had normal findings on echocardiogram and rest ECG. All treatment was discontinued for > or = 48 h. Left ventricular ejection fraction was determined by computerized analysis of the left ventricular angiogram. In patients with syndrome X, exercise duration and heart rate were measured at 1-mm ST segment depression and at peak exercise. RESULTS: Left ventricular hypercontractility (ejection fraction > or = 80%) was observed in 12 patients (32%) (group 1), whereas 25 patients (68%) had normal left ventricular contraction (group 2). The time to 1-mm ST depression on exercise testing was significantly earlier in group 1 than in group 2 (5.13 +/- 1.03 vs. 10.76 +/- 0.63 min, respectively, p < 0.001). The magnitude of the ST segment depression at peak exercise was significantly greater in group 1 than in group 2 (2.03 +/- 0.2 vs. 1.33 +/- 0.05 mm, respectively, p < 0.001). The mean time for ST segment depression to normalize was significantly greater in group 1 than in group 2 (4.76 +/- 0.78 vs. 3.16 +/- 0.39 min, respectively, p < 0.05). Linear regression analysis of all patients with syndrome X showed a significant correlation between exercise duration and ejection fraction (r = 0.55, p < 0.001). The mean circadian variation of heart rate and episodes of ST segment depression on 24-h ambulatory ECG monitoring were similar in the two groups of patients. CONCLUSIONS: These findings indicate that approximately one third of patients with chest pain, normal coronary angiograms and a positive exercise test have left ventricular hypercontractility, and this is associated with the development of ST segment depression at a lower heart rate and work load and a longer time to normalization of ST segment depression after exercise.     

Diminished contractile reserve in patients with left ventricular hypertrophy and increased end-systolic stress during Dobutamine stress echocardiography

Left ventricular hypertrophy (LVH) is associated with decreased contractile response to inotropic stimulation in animal models, but this has not been documented in humans. To determine whether LVH is associated with decreased myocardial contractile reserve, we measured left ventricular mass, heart rate-corrected velocity of circumferential fiber shortening (Vcfc), end-systolic stress, and LV ejection fraction (LVEF) in patients with LVH and increased end-systolic stress (n = 6) and in patients without LVH (n = 7) who had a normal response to dobutamine stress echocardiography (increased LVEF and no wall motion abnormalities). The afterload-dependent indexes of left ventricular systolic performance were normal at baseline and showed significant increases at peak dobutamine dose (LVH group: Vcfc 0.91 +/- 0.11 to 1.76 +/- 0.59, p = 0.006; LVEF 49 +/- 5 to 65 +/- 6, p = 0.001; group without LVH: Vcfc 1.16 +/- 0.24 to 1.99 +/- 0.36, p = 0.001; LVEF 61 +/- 6 to 68 +/- 6, p = 0.05). The Vcfc/ end-systolic stress relation, a load-independent index of myocardial contractility, rose in a dose-dependent fashion in both groups, but the increment was significantly less for patients with LVH (p < 0.02), suggesting a blunted myocardial contractile reserve to inotropic stimulation. The change in heart rate-corrected velocity of circumferential fiber shortening per unit of change in end-systolic stress in each patient at each dobutamine dose showed a linear and inverse relationship. The increment in heart rate-corrected velocity of circumferential fiber shortening for a given reduction in end-systolic stress was larger in patients without LVH than in patients with LVH (p = 0.01). These results suggest that in patients with LVH and increased end-systolic stress, ventricular performance is maintained at the expense of limited myocardial contractile reserve, and that inotropic stimulation unmasks this abnormality, despite a normal response in LVEF and velocity of circumferential fiber shortening. This approach may identify patients with LVH at risk of developing systolic dysfunction and heart failure.     

Managing complex orthodontic problems: the use of implants for anchorage

In congestive heart failure captopril modifies the left ventricular filling pattern mainly by unloading the heart. We investigated whether the structural characteristics of the left ventricle may influence the acute effects of captopril on this pattern in patients with untreated hypertensive (H group, 6 patients) or idiopathic (I group, 14 patients) cardiomyopathy. We evaluated changes of pulsed Doppler mitral flow, of systemic arterial and wedge pulmonary pressures 40 min after 25 mg captopril administered sublingually, and correlated these changes with the M-mode echocardiographic relative wall thickness index (h/r). Baseline mean arterial pressure (H = 137 +/- 20 mm Hg, mean +/- SD, I = 95 +/- 19 mm Hg; p < 0.001), and h/r (H = 0.38 +/- 0.03, I = 0.28 +/- 0.09; p < 0.05) were greater in the high blood pressure group; wedge pressure, echocardiographic biplane ejection fraction, and Doppler indexes of the left ventricular filling were similar in the two populations. After captopril, ejection fraction did not change significantly, mean arterial pressure decreased significantly in hypertensive patients (H group, baseline = 137 +/- 20, captopril = 119 +/- 10, p = 0.02; I group, baseline = 95 +/- 19, captopril = 90 +/- 24, p = nonsignificant), and the wedge pressure was reduced by the same extent in both groups (H group, baseline = 27.7 +/- 3, captopril = 21 +/- 7, p < 0.05; I group, baseline = 20 +/- 12, captopril = 15 +/- 8, p < 0.05). In the H group early mitral flow increased [(E wave integral) x (mitral annulus area)] by 38 +/- 15%, and was almost steady in the I group (-1.3 +/- 30%; group H vs. I = p < 0.01); late mitral flow [(A wave integral) x (mitral annulus area)] showed a pattern exactly opposite to this (H = +0.4 +/- 40%, I = +38 +/- 19; p < 0.01). In the whole population there was a significant correlation between the early/late flow ratio variations and baseline h/r (r = 0.6, p < 0.05). In chronic congestive heart failure, changes in left ventricular filling with captopril are related to h/r: a higher index, as recorded in the H group, is associated with "true normalization' of the filling pattern after captopril; a lower index, as recorded in the I group, is associated with "pseudonormalization' despite a similar decrease of left ventricular filling pressure.     

Value of tomoscintigraphy with Fourier analysis in the diagnosis of arrhythmogenic right ventricular cardiomyopathy

ECG gated blood pool tomography has been performed in sixteen patients with right ventricular arrhythmias in whom the diagnosis of arrhythmogenic right ventricular cardiomyopathy was made based on the finding of abnormalities on contrast angiography. They were compared both to control subjects and to patients with primary dilated cardiomyopathy. Thick slices of ventricles were obtained throughout the cardiac cycle in three orthogonal planes: horizontal long axis and short axis thick slices for analysis of right and left ventricular regional wall motion abnormalities and analysis of the spread of the contraction by means of Fourier phase imaging, vertical long axis slices (one for each ventricle) for ejection fractions, because of easy and reproducible determination of valvular planes and analysis of all right ventricular segments, especially the pulmonary infundibulum. Five typical right ventricular abnormalities were seen: decreased ejection fraction (32 +/- 15% vs 55 +/- 3% in control; p < 0.001), increased diameter (ratio of right to left diameters = 1.2 +/- 0.3 vs 0.9 +/- 0.1; p < 0.01), global delayed contraction versus that of the left ventricle (22 +/- 20 degrees vs -2 +/- 6%; p < 0.01), increased dispersion of contraction (32 +/- 16 degrees vs 13 +/- 4 degrees; p < 0.01) and presence of segments with decreased and/or delayed contraction. Right ventricular disease was observed in all the patients: localized form (56%), diffused form (44%). This method provides accurate functional data for diagnosis and follow-up of patients. In future, this wall motion evaluation method may replace planar nuclear angiography as myocardial SPECT have replaced myocardial planar scintigraphy.     

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells

OBJECTIVES: To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class > or = III) with and without angina. METHODS: Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. RESULTS: A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% +/- 7% to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. CONCLUSIONS: In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization.     

Partial left ventriculectomy for idiopathic dilated cardiomyopathy: early results and six-month follow-up

BACKGROUND: Recent reports show that partial left ventriculectomy improves hemodynamic and functional status in patients with dilated cardiomyopathy. This study sought to determine the effects of partial left ventriculectomy on clinical outcome and left ventricular function during 6-month follow-up. METHODS: Twenty-two patients underwent partial left ventriculectomy. Mitral valve repair was performed whenever possible, otherwise the valve was replaced. Hemodynamic and functional data were obtained at baseline, as well as 2 weeks and 6 months postoperatively. RESULTS: Overall, 7 of 22 patients died; there were three early and four late deaths. One-year survival was 68%+/-10%. Ejection fraction increased from 23.9%+/-6.8% before the operation to 40.7%+/-12.5% at 2 weeks and to 36.8%+/-7.7% at 6 months (p<0.001, for both). The cardiac index before the operation, at 2 weeks, and at 6 months was 2.3+/-0.8, 2.9+/-0.6, and 3.4+/-1.0 L/m2 per minute, respectively (p = 0.035, and p = 0.009, compared with baseline). The increase in ejection fraction 2 weeks postoperatively was less in patients with left circumflex artery dominance (10.9%+/-3.2% compared with 19.9%+/-10.7%, respectively, p = 0.017). At 6-month follow up, all surviving patients except one improved New York Heart Association functional class when compared with preoperative status (from 3.8+/-0.4 to 1.4+/-0.6, p = 0.0002). CONCLUSIONS: Early hemodynamic improvement after partial left ventriculectomy was maintained during midterm follow-up.     

The dobutamine stress test with thallium-201 single-photon emission computed tomography and radionuclide angiography: postinfarction study

OBJECTIVES: The purpose of this study was to investigate left ventricular wall motion changes during dobutamine-induced myocardial ischemia. BACKGROUND: Dobutamine is increasingly used as a stress test. It has been assumed that high doses of the drug induce the same changes in contractility as physical exercise. However, some data suggest that ischemic myocardium can respond to dobutamine with an increase in contractility. METHODS: Sixty-three postinfarction patients twice underwent the dobutamine test (up to 40 micrograms/kg per min) within 1 to 2 days. Thallium-201 single-photon emission computed tomography (SPECT) and gated equilibrium radionuclide ventriculography were performed on each patient at rest and with dobutamine. Both global and regional ejection fractions were quantified. Sixty patients underwent coronary cineangiography within 1 week. The presence of redistribution was correlated with global and regional ejection fraction changes and with coronary lesions. RESULTS: Redistribution was present in 45 patients, and no change or a decrease in global or regional ejection fraction was detected in 22. In the entire group of patients global ejection fraction increased from 46 +/- 12% to 56 +/- 14%. The six patients with triple-vessel disease had a flat (-0.2 +/- 5%) ejection fraction response to dobutamine, whereas the remaining patients had an increase of 11 +/- 7% (p = 0.003). The regional ejection fraction of the hypokinetic area increased from 27 +/- 10% to 41 +/- 19%, showing no change or a decrease in 13 patients. The 44 patients with peri-infarct redistribution had a significantly higher increase in regional ejection fraction than those without redistribution (16.4 +/- 10% vs. 4.7 +/- 17%, p = 0.003). In the patients with peri-infarct redistribution, an inverse linear correlation was found between redistribution score and dobutamine-induced regional ejection fraction change (r = -0.44, p = 0.004). CONCLUSIONS: Mild to moderate dobutamine-induced peri-infarct ischemia is compatible with an increase in contractility, whereas severe ischemia induces worsening of wall motion.     

Safety and cost-effectiveness of MIDCABG in high-risk CABG patients

BACKGROUND: Myocardial revascularization without cardiopulmonary bypass has been proposed as a potential therapeutic alternative in high-risk patients undergoing coronary artery bypass grafting. To evaluate this possibility we compared 15 high-risk (HR) patients in whom minimally invasive direct coronary artery bypass grafting was used as the method of revascularization with 41 consecutive patients who underwent conventional coronary artery bypass grafting during 1 month. METHODS: Patients undergoing myocardial revascularization without cardiopulmonary bypass were significantly older than their low-risk (LR) counterparts (72.2 +/- 11.6 versus 63.3 +/- 9.7 years, p = 0.006). The demographic profile for HR versus LR patients was as follows: female patients, 60.0% versus 26.8%, p = 0.02; diabetes, 20.0% versus 24.4%, p = 0.7; prior stroke, 33.3% versus 7.4%, p = 0.03; chronic obstructive pulmonary disease, 60.0% versus 9.8%, p < 0.0001; peripheral vascular disease, 33.3% versus 12.2%, p = 0.03, congestive heart failure, 26.6% versus 9.8%, p = 0.09; impaired left ventricular (ejection fraction < 0.40), 40.0% versus 17.0%, p = 0.07; urgent operation, 86.6% versus 46.3%, p < 0.0001; and redo operation, 20.0% versus 0%, p = 0.003. RESULTS: There were no deaths in the HR group and one death in the LR group. The average intensive care unit stay was 1.1 +/- 0.5 days in HR patients versus 1.6 +/- 1.6 days in LR individuals (p = 0.2), and the average hospital stay was 6.1 +/- 1.8 versus 7.3 +/- 4.4 days, respectively (p = 0.3). We used an acuity risk score index developed by the Adult Cardiac Care Network of Ontario to predict outcome in the HR group. The expected intensive care unit stay in HR patients was 4.1 +/- 1.2 days (versus the observed stay of 1.1 +/- 0.5 days, p < 0.0001), and the expected hospital stay was 12.5 +/- 1.5 days (versus the observed stay of 6.1 +/- 1.8 days, p < 0.0001). The expected mortality in the HR group was 6.1% versus 0%, p = 0.3. A cost regression model was used to examine predicted versus actual cost (in Canadian dollars) for the HR patient cohort (based on Ontario Ministry of Health funding). The expected cost for the HR cohort would have been $11,997 per patient. In contrast, the average cost for these 15 patients was $5,997 per patient, an estimated cost saving of 50%. CONCLUSIONS: Myocardial revascularization without cardiopulmonary bypass appears to be a safe and cost-effective therapeutic modality for HR patients requiring myocardial revascularization.     

Effects of valve replacement on ventricular mechanics in mitral regurgitation and aortic stenosis

BACKGROUND: This study in humans assessed changes in left ventricular function early and late after correction of mitral regurgitation (MR) (n = 9) or aortic stenosis (AS) (n = 10). METHODS: Ventricular function was measured with radionuclide and micromanometer-derived pressure-volume loops during preload manipulation, thermodilution cardiac outputs, and echocardiograms. Late radionuclide and echocardiographic data were acquired at 24 hours and 20 months. RESULTS: Perioperative left ventricular performance (stroke work-end-diastolic volume relationship) did not change for patients with MR or AS. Significant changes in afterload occurred: ejection fraction (MR, 0.49 to 0.37; AS, 0.54 to 0.60; both, p = 0.013), mean left ventricular ejection pressure (MR, 73 to 91 mm Hg; AS, 138 to 93 mm Hg; both, p < 0.01), and end-systolic wall stress (MR, 26 to 42 x 10(3) dynes/cm2; AS, 37 to 22 x 10(3) dynes/cm2; both, p < 0.01). Ejection efficiency improved for MR patients (0.69 +/- 0.26 to 1.0 +/- 0.15; p < 0.05). The 20-month data showed improved New York Heart Association functional class, normal resting ejection fraction, and normal exercise response for both groups. CONCLUSIONS: Early after operation, a significant change in left ventricular load was seen with correction of MR and AS. Data obtained late after operation showed improvement consistent with ventricular remodeling.     

Determinants of the pulmonary artery pressure rise in left ventricular dysfunction

Pulmonary artery hypertension in patients with left ventricular dysfunction is related to poor outcome but the role of cardiac functional abnormalities in the genesis of pulmonary hypertension remains unknown. The aim of this prospective study was to identify the determinants of pulmonary hypertension in 102 consecutive patients with primary left ventricular dysfunction (ejection fraction < 50%). Systolic pulmonary artery pressure was measured by continuous wave Doppler. Left ventricular systolic and diastolic function, severity of functional mitral regurgitation, cardiac output, and left atrial volume were assessed using Doppler echocardiography. In patients with left ventricular dysfunction, systolic pulmonary artery pressure was increased (51 +/- 14 mmHg, range 23 to 87 mmHg). Mitral deceleration time (r = -0.61; p = 0.0001) and mitral effective regurgitant orifice (r = 0.50; p = 0.0001) were the strongest parameters related to systolic pulmonary artery pressure. Multivariate analysis identified these two variables as the strongest predictors of systolic pulmonary artery pressure in association with the mitral E/A ratio (p = 0.006) and age (p = 0.005). In conclusion, pulmonary hypertension is common and variable in patients with left ventricular dysfunction. It is closely related to diastolic dysfunction and severity of functional mitral regurgitation but not independently to the degree of left ventricular systolic dysfunction. These findings underline the importance of assessing diastolic function and quantifying mitral regurgitation in patients with left ventricular dysfunction.     

Effects of dichloroacetate in patients with congestive heart failure

BACKGROUND: Conventional approaches to management of congestive heart failure (CHF) rely on drugs that increase myocardial contractility or reduce ventricular afterload. These approaches often improve cardiac symptoms and survival, but may be associated with significant deleterious effects. An alternative approach is to enhance myocardial energy production. Dichloroacetate (DCA) stimulates pyruvate dehydrogenase activity and accelerates aerobic glucose, pyruvate, and lactate metabolism in myocardial cells. These alterations would be expected to improve myocardial function. HYPOTHESIS: The purpose of the investigation was to assess the efficacy of DCA in patients with left ventricular systolic dysfunction and to examine the mechanism by which improvement occurs. METHODS: A total of 25 patients (16 men, 9 women; age range 31-72 years, mean 59) with CHF and ejection fraction < or = 40% received an intravenous infusion of 50 mg/kg DCA over 15 min. Indices of systolic and diastolic function were obtained by two-dimensional and Doppler echocardiography performed at baseline, 30 min, and 60 min following completion of DCA infusion. RESULTS: Baseline ventricular ejection fraction was 27.3 +/- 9.1%; 17 patients (68%) had nonischemic cardiomyopathy. Heart rate increased after DCA infusion from 73.9 +/- 14.5 to 79.2 +/- 14.9 beats/min at 60 min; p = 0.02. Left ventricular diastolic and systolic volumes increased at 30 min compared with baseline (248.7 +/- 98.1 vs. 259.6 +/- 99.6; p = 0.04, and 180.1 +/- 80.4 vs. 192.2 +/- 84.9; p = 0.002, respectively), but stroke volume (49.2 +/- 19.1 vs. 48.9 +/- 18.1; p = 0.9) and ejection fraction (27.3 +/- 9.1 vs. 25.7 +/- 9.8; p = 0.2) were unchanged. Indices of diastolic function were also unchanged. CONCLUSION: Dichloroacetate infusion in patients with CHF is not associated with improvement in noninvasively assessed left ventricular function.     

Comparison of continuous left ventricular volumes by transthoracic two-dimensional digital echo quantification with simultaneous conductance catheter measurements in patients with cardiac diseases

Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 +/- 15 years, range 22 to 70; ejection fraction 63 +/- 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter = slope. DEQ + intercept, slope = 0.94 +/- 0.09, intercept = 5 +/- 8 ml, r2 = 0.86 +/- 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 +/- 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. End-diastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 +/- 0.31, mean intercept 14 +/- 37 ml, average r2 = 0.89 +/- 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 +/- 0.43, intercept = -20 +/- 26 ml, r2 = 0.67 +/- 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans.     

Prey selection in the leopard frog: choosing in biased and unbiased situations

We evaluated left ventricular function by echocardiography in a prospective study that included 98 consecutive human immunodeficiency virus (HIV)-infected patients and 40 HIV-seronegative normal controls. When compared with controls, HIV patients showed increased isovolumic relaxation time (101+/-18 ms versus 71+/-10 ms; p<0.0001) and left ventricular diastolic diameters (51+/-6 mm versus 47+/-3 mm; p<0.0005), and decreased fractional shortening (31+/-6% versus 37+/-2%; p<0.0001). Diastolic dysfunction was the most frequent finding (63% of the patients). We found depressed ejection fraction in 31 (32%) patients. Only 8 (8%) patients had symptomatic congestive heart failure. Left ventricular dysfunction was not attributable to intravenous drug abuse or to therapy. It was less severe in earlier stages of the infection (fractional shortening: acquired immunodeficiency syndrome=30%+/-6%, asymptomatic HIV-seropositives 34%+/-5%; p<0.005) and in HIV-2-infected patients. Patients with opportunistic infections (all aetiologies mixed) had more frequent congestive heart failure than those without infections (16% of the patients with versus 4% of the patients without infections; p<0.05). The fact that even asymptomatic HIV-seropositives had signs of left ventricular dysfunction (fractional shortening: asymptomatic HIV-seropositives=34%+/-5%; controls=37%+/-2%; p<0.05) favours the hypothesis of the HIV being one of the causes of these abnormalities.     

Impairment of exercise capacity and peak oxygen consumption in patients with mild left ventricular dysfunction and coronary artery disease

AIMS: Most studies in chronic heart failure have only included patients with marked left ventricular systolic dysfunction (i.e. ejection fraction < or =0.35), and patients with mild left ventricular dysfunction are usually excluded. Further, exercise capacity strongly depends on age, but age-adjustment is usually not applied in these studies. Therefore, this study sought to establish whether (age-adjusted) peak VO2 was impaired in patients with mild left ventricular dysfunction. METHODS: Peak VO2 and ventilatory anaerobic threshold were measured in 56 male patients with mild left ventricular dysfunction (ejection fraction 0.35-0.55; study population) and in 17 male patients with a normal left ventricular function (ejection fraction >0.55; control population). All patients had an old (>4 weeks) myocardial infarction. By using age-adjusted peak VO2 values, a 'decreased' exercise capacity was defined as < or = predicted peak VO2 - 1 x SD (0.81 of predicted peak VO2), and a severely decreased exercise capacity as < or = predicted peak VO2 - 2 x SD (0.62 of predicted peak VO2). RESULTS: Patients in the study population (age 52+/-9 years; ejection fraction 0.46+/-0.06) were mostly asymptomatic (NYHA class I: n=40, 76%), while 16 patients (24%) had mild symptoms, i.e. NYHA class II. All 17 controls (age 57+/-8 years) were asymptomatic. Mean peak VO2 was lower in patients with mild left ventricular dysfunction (23.6+/-5.7 vs 27.1+/-4.6 ml x min(-1) x kg(-1) in controls, P<0.05). In 75% of the study population patients (n=42) age-adjusted peak VO2 was decreased (NYHA I/II: n=29/13) and in 18% of them severely decreased (n=10; NYHA I/II: n=6/4). In contrast, only three patients (18%) in the control population had a decreased and none a severely decreased age-adjusted peak VO2. CONCLUSION: In patients with mild left ventricular dysfunction, who have either no or only mild symptoms of chronic heart failure, a substantial proportion has an impaired exercise capacity. By using age-adjustment, impairment of exercise capacity becomes more evident in younger patients. Patients with mild left ventricular dysfunction are probably under-diagnosed, and this finding has clinical and therapeutic implications.