Transient dobutamine-mediated pulsus alternans.

Pulsus alternans, alternating weak and strong beats occurring in a heart beating at a constant rate, has most often been reported in patients with severe, end-stage heart failure. This patient with New York Heart Association functional class I heart failure developed pulsus alternans during the inotropic stimulation of dobutamine that subsequently resolved in a time course consistent with dobutamine clearance. Thus, in the setting of mildly impaired myocardial contractility, the inotropic stimulus of dobutamine may precipitate the development of reversible pulsus alternans.

Diastolic dysfunction in the presence of left ventricular systolic dysfunction: implications of beta-adrenergic blocking therapy.

The contribution of left ventricular diastolic dysfunction to the impairment in overall left ventricular performance in patients with systolic dysfunction is underappreciated. This article summarizes the available data on diastolic dysfunction in patients with congestive heart failure in which the predominant abnormality was thought to be left ventricular systolic dysfunction. The prevalence and identification of diastolic abnormalities and their clinical relevance are addressed, particularly the role of beta-adrenergic blocking therapy. The potential benefits of beta-adrenergic blocking therapy to diastolic performance are discussed from both a hemodynamic and clinical standpoint, with the implication that diastolic performance and its modulation should be considered in future investigations. (c)2001 by CHF, Inc.

Relation of systemic sympathetic nervous system activation to echocardiographic left ventricular size and performance and its implications in patients with mitral regurgitation.

We have previously demonstrated that the systemic sympathetic nervous system (SNS) is activated in proportion to an increase in cineventriculographic left ventricular (LV) end-systolic volume and decrease in ejection fraction (EF) in patients with chronic mitral regurgitation (MR). However, the relation between noninvasive echocardiographic measures of LV size and performance and systemic SNS activation and their clinical implications in patients with MR is not known. We studied 17 MR patients with echocardiography, arterial norepinephrine (NE) sampling, and [3H]-NE infusions and arterial blood sampling to determine NE kinetic parameters using a 2-compartment analysis, including extravascular NE release rates (NE2, index of SNS activity) and the metabolic clearance rate from the vascular compartment. The arterial NE values correlated with LV end-systolic dimensions (r = 0.50, p = 0.04), but not with LV end-diastolic dimensions, and EF or fractional shortening measures. The NE2 values correlated with LV end-systolic dimensions (r = 0.53, p = 0.03) and inversely with LVEF (r = -0.45, p = 0.07) and fractional shortening (r = 0.43, p = 0.08) measures, but not with LV end-diastolic dimensions. The metabolic clearance rate values showed an inverse correlation with LV end-diastolic (r = -0.52, p = 0.03) and end-systolic (r = -0.49, p = 0.04) dimensions, but not with LV performance measures. The increase in NE2 values was progressive as the LV endsystolic dimensions increased and more marked at LV end-systolic dimensions > or = 40 mm. Thus, activation of the SNS is related to an increase in echocardiographic LV end-systolic dimensions and a decrease in LV performance measures in chronic MR. Medica, Inc.

Echocardiographic markers for mitral valve surgery to preserve left ventricular performance in mitral regurgitation.

BACKGROUND: The timing of mitral valve (MV) surgery to preserve left ventricular (LV) contractility in patients with mitral regurgitation (MR) has been defined by complex cardiac catheterization techniques. Whether noninvasive methods can identify patients with MR, a normal LV ejection fraction, and early LV contractile impairment is unknown. We hypothesized that echocardiographic measures would separate patients with MR and a normal LV ejection fraction into those with and without contractile dysfunction and, thus, prospectively predict the response of LV size and performance to MV surgery. METHODS AND RESULTS: We studied 27 patients with micromanometer LV pressures and radionuclide angiography to obtain a determination of LV volumes and ejection fraction and calculate chamber elastance, a measure of LV contractility, before MV surgery. Echocardiographic studies were performed before MV surgery and repeated at 3 and 12 months after surgery. Age, New York Heart Association class, LV plus maximum pressure per unit change in time, LV systolic and end-diastolic pressures, and echocardiographic posterior wall thickness and radius to wall thickness ratio did not identify preoperative LV contractile dysfunction. However, other echocardiographic measures were related to LV contractility, including LV end-diastolic dimension (r = -0.50, P <.005), LV end-systolic dimension (r = -0.60, P <.0001), and LV fractional shortening (r = 0.50, P =.005). From analysis of receiver operator characteristic curves, an LV end-systolic dimension of >/=40 mm was identified as most predictive for separating patients with MR before surgery into those with and without LV contractile dysfunction (sensitivity of 82% and specificity of 100%). The patients with MR and impaired preoperative LV contractility showed a dramatic deterioration in LV fractional shortening at 3 months after MV surgery (P =.01), which recovered to within the normal range for fractional shortening at 12 months (P =.02) from a progressive reduction in LV end-systolic dimension. This response in LV size and performance temporally differed from that in the patients with MR and normal contractility (2-way analysis of variance P <.0001). However, at 12 months after MV surgery, LV end-diastolic dimension, end-systolic dimension, and fractional shortening were normal in both groups of patients with MR. CONCLUSION: We conclude that echocardiographic measures, particularly an end-systolic dimension of >/=40 mm, may be useful for identifying patients with MR before surgery with early, occult LV contractile dysfunction in whom MV surgery may be recommended to preserve LV systolic performance.

Evaluation of left ventricular ejection fraction as a measure of pump performance in patients with chronic mitral regurgitation.

Left ventricular (LV) ejection fraction may not adequately detect a reduction in LV systolic performance resulting from chronic mitral regurgitation (MR), due to ventricular unloading into the low-impedance left atrium. To determine whether LV ejection fraction sufficiently gauges myocardial function in MR, nine patients were studied using micromanometer-measured LV pressures and biplane cineventriculography before and 1 year after mitral valve surgery. Six control patients were also studied. LV ejection fraction was normal in MR patients, despite an increase in LV end-systolic volume index. LV end-systolic pressure-volume and stress-volume ratios in MR patients were lower than in controls (P < 0.05 and P < 0.01), suggesting that LV systolic performance fell. One year after mitral valve surgery, LV ejection fraction decreased (P < 0.05) even though LV end-systolic volume index (P < 0.05), pressure-volume (P < 0.05), and stress-volume ratios (P < 0.01) all improved. Thus, LV ejection fraction inadequately reflected LV systolic function in MR patients before and after mitral valve surgery.

Effects of beta-adrenergic blocking therapy on left ventricular diastolic relaxation properties in patients with dilated cardiomyopathy.

BACKGROUND: The hemodynamic mechanism for the improvement in left ventricle (LV) end-diastolic pressure in cardiomyopathy patients treated with beta-adrenergic blocking agents is controversial. We hypothesized that the salutary effect of this kind of therapy on LV end-diastolic pressure would be indicative of an improvement in late, passive diastolic relaxation properties. METHODS AND RESULTS: We studied 14 cardiomyopathy patients in normal sinus rhythm with no arteriographic evidence of coronary artery disease and an LV ejection fraction of

Impact of vascular adaptation to chronic aortic regurgitation on left ventricular performance.

BACKGROUND: This investigation was designed to test the hypothesis that vascular adaptation occurs in patients with chronic aortic regurgitation to maintain left ventricular (LV) performance. METHODS AND RESULTS: Forty-five patients with chronic aortic regurgitation (mean age 50+/-14 years) were studied using a micromanometer LV catheter to obtain LV pressures and radionuclide ventriculography to obtain LV volumes during multiple loading conditions and right atrial pacing. These 45 patients were subgrouped according to their LV contractility (Ees) and ejection fraction values. Group I consisted of 24 patients with a normal Ees. Group IIa consisted of 10 patients with impaired Ees values (Ees <1.00 mm Hg/mL) but normal LV ejection fractions; Group IIb consisted of 11 patients with impaired contractility and reduced LV ejection fractions. The left ventricular-arterial coupling ratio, Ees/Ea, where Ea was calculated by dividing the LV end-systolic pressure by LV stroke volume, averaged 1.60+/-0.91 in Group I. It decreased to 0.91+/-0.27 in Group IIa (P<0.05 versus Group I), and it decreased further in Group IIb to 0.43+/-0.24 (P<0.001 versus Groups I and IIa). The LV ejection fractions were inversely related to the Ea values in both the normal and impaired contractility groups (r=-0.48, P<0.05 and r=-0.56, P<0.01, respectively), although the slopes of these relationships differed (P<0.05). The average LV work was maximal in Group IIa when the left ventricular-arterial coupling ratio was near 1.0 because of a significant decrease in total arterial elastance (P<0.01 versus Group I). In contrast, the decrease in the left ventricular-arterial coupling ratio in Group IIb was caused by an increase in total arterial elastance, effectively double loading the LV, contributing to a decrease in LV pump efficiency (P<0.01 versus Group IIa and P<0.001 versus Group I). CONCLUSIONS: Vascular adaptation may be heterogeneous in patients with chronic aortic regurgitation. In some, total arterial elastance decreases to maximize LV work and maintain LV performance, whereas in others, it increases, thereby double loading the LV, contributing to afterload excess and a deterioration in LV performance that is most prominent in those with impaired contractility.

Frequency and severity of asymptomatic coronary disease in patients with different causes of stroke.

BACKGROUND AND PURPOSE: We sought (1) to compare the frequency and severity of asymptomatic coronary artery disease (CAD) in patients with different causes of brain ischemia and (2) to determine profiles of patients with brain ischemia who are at highest risk of asymptomatic CAD. METHODS: Sixty-nine patients with transient ischemic attack or stroke and without overt CAD underwent a cardiac stress test and a diagnostic evaluation to determine the cause of brain ischemia. The frequency of abnormal cardiac stress tests was compared in patients with large-artery cerebrovascular disease versus other causes of brain ischemia (90% of whom had penetrating artery disease or cryptogenic stroke). Additionally, the frequencies of vascular risk factors, resting electrocardiographic abnormalities, and cause of stroke (large-artery disease versus other causes) were compared in patients with abnormal stress tests versus patients with normal stress tests. RESULTS: The frequency of abnormal stress tests was 50% (15 of 30) in patients with large-artery cerebrovascular disease versus 23% (9 of 39) in patients with other causes of brain ischemia (P = .04). Moreover, 60% of abnormal stress tests (9 of 15) in patients with large-artery cerebrovascular disease suggested severe underlying CAD that was confirmed in 7 of 7 patients who underwent coronary angiography. On the other hand, less than 25% of abnormal stress tests (2 of 9) in patients with other causes of brain ischemia suggested severe underlying CAD. Features that were more common in patients with abnormal stress tests were smoking (P = .006), large-artery cerebrovascular disease (P = .02), veteran status (P = .02), and left ventricular hypertrophy (P = .07). CONCLUSIONS: Patients with penetrating artery disease or cryptogenic stroke have a significantly lower frequency of asymptomatic CAD than patients with large-artery cerebrovascular disease. Large-artery cerebrovascular disease, smoking, veteran status, and possibly left ventricular hypertrophy may be useful features for identifying patients with transient ischemic attack or stroke who are at highest risk of harboring asymptomatic CAD.

Dobutamine pharmacokinetics during dobutamine stress echocardiography.

Many patients fail to achieve target heart rate during dobutamine stress echocardiography (DSE). We evaluated the pharmacokinetics of dobutamine during DSE to determine whether patients with an impaired chronotropic response have higher rates of dobutamine clearance and consequently relatively lower plasma dobutamine levels. Plasma dobutamine levels, heart rate, and left ventricular (LV) ejection fraction (EF) were measured in 13 male patients referred for DSE at baseline and at the end of stepped 3-minute dobutamine infusions of 5, 10, 20, and 30 microg/kg/min. Dobutamine levels increased with doses: 27 +/- 10, 111 +/- 17, 275 +/- 17, and 403 +/- 28 ng/ml (mean +/- SEM). There was no relation observed between the plasma dobutamine level achieved at the 30-microg infusion dose and the increase in heart rate from baseline (r = 0.066; p = 0.83). Baseline LVEF and a measure of chronotropic beta responsivity were identified as independent predictors of dobutamine clearance, together accounting for 73% of the variance in dobutamine clearance. In conclusion, (1) there is a dose-dependent increase in plasma dobutamine levels during DSE, (2) dobutamine clearance is positively related to baseline LVEF and is partially mediated by a beta-receptor mechanism, and (3) an impaired chronotropic response during DSE is not due to failure to achieve a sufficiently high dobutamine level. We conclude that in patients who lack an adequate heart rate response during the early stages of DSE (e.g., up to 20 microg/kg/min infusion), administration of atropine rather than progressively higher amounts of dobutamine may provide a more effective strategy to achieve target heart rate.

Stress testing with closed-loop arbutamine as an alternative to exercise. The International Arbutamine Study Group.

OBJECTIVES: This study compared exercise and pharmacologic stress testing using arbutamine delivered by a closed-loop device for the detection of coronary artery disease. BACKGROUND: Arbutamine, an agent designed to simulate exercise, has been developed in conjunction with a closed-loop delivery device that modulates the rate of administration on the basis of physiologic feedback. METHODS: Two hundred ten patients (180 men, 30 women) with symptoms and angiographic evidence of coronary artery disease were studied. Ischemia was categorized in three ways: 1) the presence of angina; 2) the occurrence of > or = 0.1-mV horizontal or downsloping ST segment depression or elevation at 60 ms after the J point; or 3) the presence of either condition 1 or 2. RESULTS: In the 210 patients, the mean increase in heart rate and systolic blood pressure evoked by arbutamine and exercise was 51 and 53 beats/min (p = NS) and 36 and 44 mm Hg (p < 0.0001), respectively. Arbutamine detected ischemia more often than exercise with each of the three ischemic end points. Sensitivity for detecting ischemia by either angina or ST segment change was 84% (95% confidence interval ¿ change was 84% (95% confidence interval [CI] 79% to 89%) for arbutamine and 75% (95% CI 69% to 81%) for exercise testing (p = 0.014). For angina alone, sensitivity was 73% (95% CI 67% to 79%) for arbutamine and 64% (95% CI 57% to 71%) for exercise (p = 0.026). For ST segment change alone, sensitivity was 47% (95% CI 40% to 54%) for arbutamine and 44% (95% CI 37% to 51%) for exercise (p = 0.426). Cardiac events occurred in five patients (1.8%) within 24 h of the arbutamine test. CONCLUSIONS: In detecting documented coronary artery disease, the sensitivity of arbutamine testing was equal to that of exercise for the electrocardiographic end point of ST segment change alone. Arbutamine testing was significantly superior to exercise testing for either ST change or angina or for angina alone.

Arbutamine stress thallium-201 single-photon emission computed tomography using a computerized closed-loop delivery system. Multicenter trial for evaluation of safety and diagnostic accuracy. The International Arbutamine Study Group.

OBJECTIVES: This study sought to evaluate the efficacy and safety of arbutamine when used in conjunction with thallium-201 single-photon emission computed tomography (SPECT) in a multicenter trial and to compare arbutamine stress and treadmill exercise thallium-201 SPECT for diagnostic sensitivity and myocardial perfusion pattern. BACKGROUND: Arbutamine is a potent beta-agonist developed specifically for pharmacologic stress testing. METHODS: Arbutamine was administered by a novel computerized closed-loop device that measures heart rate and adjusts arbutamine infusion to achieve a selected rate of heart rate increase toward a predetermined limit. The cohort included 184 patients who underwent arbutamine stress testing, of whom 122 (catheterization group) had angiographically defined coronary artery disease ( > or = 50% diameter stenosis of a major coronary artery), and 62 had a low pretest likelihood of coronary artery disease (low likelihood group). A subset of 69 patients from the catheterization group underwent both arbutamine and exercise stress testing. RESULTS: Hemodynamic responses during arbutamine and exercise stress testing demonstrated no significant difference in percent increase in heart rate (81% vs. 76%) or systolic blood pressure (26% vs. 30%). The sensitivity for detecting coronary artery disease ( > or = 50% stenosis) using arbutamine thallium-201 SPECT was 87% (95% for detecting > or = 70% stenoses), and the normalcy rate in the low likelihood group was 90%. In patients completing both arbutamine and exercise stress testing, thallium-201 SPECT sensitivity for detecting coronary artery disease ( > or = 50% stenosis) was 94% and 97% (p = NS), respectively Furthermore, SPECT segmental visual score agreement (defect vs. no defect) showed a concordance of 92% between arbutamine and exercise results (kappa 0.80, p < 0.001). The stress thallium-201 SPECT segmental scores showed 83% exact agreement (kappa 0.69, p < 0.001), and analysis of the reversibility of segments with stress perfusion defects demonstrated 86% exact agreement (kappa 0.68, p < 0.001). In general, side effects associated with arbutamine were well tolerated and resolved with discontinuation of infusion. CONCLUSIONS: Arbutamine, administered by a closed-loop feed-back system was shown to be a safe and effective pharmacologic stress agent. Arbutamine stress thallium-201 SPECT appears to be accurate for the diagnosis of coronary artery disease with a diagnostic efficacy similar to that of treadmill exercise thallium-201 studies.

Arbutamine echocardiography: efficacy and safety of a new pharmacologic stress agent to induce myocardial ischemia and detect coronary artery disease. The International Arbutamine Study Group.

OBJECTIVES: This study sought to determine the efficacy and safety of arbutamine echocardiography in inducing myocardial ischemia and detecting coronary artery disease. BACKGROUND: Exercise and pharmacologic stress echocardiography are clinically accepted techniques for detecting coronary artery disease. Arbutamine is a new synthetic beta-adrenoceptor agonist developed specifically as a stress agent. Arbutamine is delivered by a new computerized drug delivery device that adjusts the rate of drug infusion according to the patient's heart rate response during stress testing. METHODS: The sensitivity of arbutamine echocardiography was determined in 143 patients who had coronary artery disease documented by coronary angiography. A subset of these patients (n = 114) also underwent exercise echocardiography. The specificity, or normalcy, of arbutamine echocardiography was determined in 54 patients considered to have a low likelihood of coronary artery disease. RESULTS: Among those patients who had both stress test results, the incidence of inducing myocardial ischemia (new or worsening wall motion abnormalities) was 79% (95% confidence interval [CI] 69% to 86%, n = 98) for arbutamine and 77% (95% CI 67% to 85%, n = 98) for exercise echocardiography. The sensitivity of detecting coronary artery disease (ischemia or rest wall motion abnormality) was 87% (95% CI 79% to 93%, n = 101) for arbutamine and 83% (95% CI 74% to 90%, n = 101) for exercise echocardiography. The specificity (normalcy) of arbutamine echocardiogrpahy was 96% (95% CI 87% to 100%, n = 52). Arbutamine was well tolerated, and there were no serious adverse events. CONCLUSIONS: Arbutamine echocardiography is an effective and safe pharmacologic stress test technique for diagnosing or excluding the presence of coronary artery disease. The ability of arbutamine stress to induce myocardial ischemia, detectable by echocardiography, was comparable to that for exercise.

Effects of valve surgery on left ventricular contractile function in patients with long-term mitral regurgitation.

BACKGROUND: Patients with long-term mitral regurgitation were studied both before and 1 year after successful valve surgery to test the hypothesis that impaired left ventricular contractile function improves after surgery for long-term mitral regurgitation in humans. METHODS AND RESULTS: Fifteen patients with long-term mitral regurgitation were studied. Micromanometer left ventricular pressures and radionuclide angiograms for left ventricular volumes were acquired over a range of loading conditions both before and 1 year after successful valve surgery for long-term mitral regurgitation. To assess both left ventriculoarterial coupling to evaluate the interaction of the left ventricle with the arterial system with the use of the left ventricular contractile index, Ees, and effective arterial elastance, Ea. Left ventricular pump efficiency was expressed as the ratio of forward left ventricular stroke work to the corresponding pressure-volume area. All patients had successful mitral valve surgery as manifest by no or only trivial residual mitral regurgitation on physical examination and Doppler echocardiography. The average radionuclide regurgitant index of 1.28 +/- 0.56 was also less than the preoperative value of 2.70 +/- 0.80 (P < .0001). The mean left ventricular end-diastolic volume index decreased from 137 +/- 37 to 90 +/- 31 mL/m2 (P < .001), and the average left ventricular end-systolic volume index also decreased (59 +/- 29 to 45 +/- 27 mL/m2, P < .01), although individual variation was observed. The average left ventricular ejection fraction fell from 0.58 +/- 0.12 to 0.53 +/- 0.16, which was not significant. In contrast, Ees increased from a mean value of 0.95 +/- 0.66 mm Hg/mL during the preoperative study to 2.62 +/- 2.16 mm Hg/mL at the 1-year postsurgical study (P < .01). This improvement in left ventricular contractility was observed in patients with long-term mitral regurgitation, who before surgery had preserved left ventricular ejection fraction (P < .001), less left ventricular dilation at end diastole (P < .01) and end systole (P < .001), and less impaired left ventricular contractility. Because effective arterial elastance was unchanged, left ventriculoarterial coupling also improved from an average of 0.47 +/- 0.39 to 1.81 +/- 1.63 (P < .01). Consequently, left ventricular pump efficiency improved from a mean preoperative value of 0.23 +/- 0.10 to 0.55 +/- 0.22 at the 1-year postsurgical study (P < .0001). CONCLUSIONS: The results indicate that left ventricular contractile impairment is reversible in many patients with long-term mitral regurgitation. In fact, these data indicate that mitral valve surgery can be recommended to preserve left ventricular contractility in patients with long-term mitral regurgitation, particularly in those patients who before surgery have normal left ventricular ejection fractions and less left ventricular dilation and contractile impairment.

Effects of low-dose flosequinan on left ventricular systolic and diastolic chamber performance.

Flosequinan (manoplax) is a new vasodilating agent for the treatment of congestive heart failure. Although it may have several mechanisms of action, whether it has effects on left ventricular inotropic or luisotropic events in hemodynamically relevant low doses when added to standard therapy for congestive heart failure is unknown. Ten patients with dilated congestive cardiomyopathy who were receiving standard therapy for heart failure were studied. A bipolar right atrial pacing catheter was used to maintain a constant heart rate. A 7F thermodilution catheter was used to measure right heart pressures and obtain cardiac outputs. An 8F micromanometer catheter was used to measure left ventricular and ascending aortic pressures. Gated equilibrium radionuclide angiography was performed both before and during a steady-state infusion of flosequinan. The average flosequinan infusion rate was 2.03 +/- 0.85 mg/min, and the total administered dose averaged 84 +/- 35 mg. The hemodynamic data documented substantial systemic vasodilation manifest by a reduction in right atrial pressure (p = 0.01), mean pulmonary artery pressure (p < 0.0001), pulmonary capillary wedge pressure (p < 0.0001), and left ventricular end-diastolic pressure (p < 0.0001). These hemodynamic changes were associated with increases in cardiac index (p = 0.01) and left ventricular ejection fraction (p = 0.02) and reductions in mean aortic pressure (p = 0.02), systemic vascular resistance (p = 0.01), and left ventricular volumes (p < 0.05). There was, however, no significant effect on left ventricular contractile function measured by end-systolic pressure-volume relationship (Emax), Emax corrected for the change in left ventricular volume, or preload recruitable stroke work (Msw). In contrast, there was an improvement in isovolumic relaxation manifest by an increase in maximum rate of fall of left ventricular pressure standardized for left ventricular end-systolic pressure [(-)dP/dtmin/Pes]; p = 0.02), an acceleration in the rate of isovolumic relaxation (p = 0.01), and an improvement in left ventricular chamber stiffness (p = 0.02). These data indicate that when flosequinan, a new therapeutic agent for the treatment of congestive heart failure, is administered in hemodynamically relevant low doses to patients with dilated congestive cardiomyopathy who were receiving standard therapy for heart failure, left ventricular pump function and diastolic function is further improved. There was, however, no significant effect on left ventricular contractility. This study emphasizes that new therapeutic agents like flosequinan, when administered in lower doses to avoid the potential deleterious effects of enhanced inotropy, may be useful additions to standard therapy in patients with congestive heart failure.

Left ventricular pump efficiency in long-term mitral regurgitation assessed by means of left ventricular-arterial coupling relations.

The left ventricular-arterial coupling relationship was used in patients with long-term mitral regurgitation to test the hypothesis that the low impedance left atrial contribution to left ventricular ejection obscures an impairment in left ventricular-arterial coupling and forward left ventricular pump efficiency. Twenty-two control patients and 26 patients with long-term mitral regurgitation were studied. Micromanometer left ventricular pressures and radionuclide angiograms for left ventricular volumes were acquired over a range of loading conditions. Left ventricular-arterial coupling was assessed by the ratio of left ventricular chamber elastance, E(es), to total arterial elastance, E(a). Forward left ventricular pump efficiency was calculated as the ratio of forward left ventricular stroke work to the corresponding pressure-volume area. There was a progressive decrease in E(es) in the patients with long-term mitral regurgitation (p < 0.001), but there was no significant difference in E(a) in comparison to the control patients. Consequently, E(es)/E(a) demonstrated a progressive decrease (p < 0.001). Although the efficiency of performing total left ventricular stroke work was only reduced when left ventricular contractile function was severely impaired (p < 0.001), there was a progressive reduction in left ventricular pump efficiency for performing forward left ventricular stroke work in the patients with long-term mitral regurgitation (p < 0.001). Further, normalized left ventricular stroke work was reduced for any left ventricular-arterial coupling ratio in the patients with long-term mitral regurgitation compared with the control patients. These data indicate that despite the outward evidence for normal left ventricular ejection in patients with long-term mitral regurgitation, a progressive deterioration in left ventricular contractile state leads to impaired left ventricular-arterial coupling and to an impairment in the efficiency of performing forward left ventricular stroke work. Once the left ventricle begins to dilate in patients with long-term mitral regurgitation, the progressive deterioration in left ventricular-arterial coupling and pump efficiency suggests that an earlier consideration of mitral valve surgery may be warranted to preserve left ventricular contractile function.

An approach to ventricular efficiency by use of carbon 11-labeled acetate and positron emission tomography.

BACKGROUND: Positron emission tomography-derived 11C-labeled acetate kinetics have been shown to reflect myocardial oxidative metabolism. The objective of the study was to use this metabolic imaging technique in combination with an evaluation of left ventricular work as an index of ventricular mechanical efficiency. METHODS AND RESULTS: The effects of ventricular ejection fraction and loading on this index were studied quantitatively in a canine experimental model. There was a curvilinear relationship between efficiency and the end-diastolic volume per unit mass (r = 0.84), which appeared to integrate the main determinants of left ventricular mechanical performance successfully and allowed the detection of a decreased ventricular efficiency in acute experimental heart failure. CONCLUSIONS: This approach appears to have the potential to assess the energetic working point of the ventricle in clinical heart disease and follow the effects of therapy. The data demonstrate the feasibility of an estimate of ventricular efficiency that relies on noninvasive data-acquisition techniques.

Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167.

BACKGROUND AND PURPOSE: Patients with carotid stenosis have a high frequency of asymptomatic coronary artery disease (CAD). The purpose of this study of patients with asymptomatic carotid stenosis was to test the hypothesis that patients without a history of CAD have the same cardiac prognosis as patients with a history of CAD. METHODS: Men enrolled in the Department of Veterans Affairs study on the efficacy of carotid endarterectomy for asymptomatic carotid stenosis underwent a baseline cardiac evaluation (history, physical examination, and electrocardiogram) to document previous angina or myocardial infarction. Patients were randomized to medical therapy alone or medical therapy and carotid endarterectomy. Medical therapy consisted of aspirin 650 mg twice daily and treatment of risk factors. All episodes of angina, myocardial infarction, or sudden death during follow-up (average of 47.9 months) were recorded. RESULTS: Of 444 men enrolled in the study, 200 (45%) had a history of CAD. During the study 86 (43%) of 200 patients with CAD and 81 (33%) of 244 patients without a history of CAD had cardiac ischemic events (P = .03). In patients without a history of CAD, the first cardiac event was myocardial infarction or sudden death in 45 patients (56%). Factors that were independently associated with cardiac events in patients without a history of CAD were diabetes (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.15 to 3.97), intracranial occlusive disease (OR, 2.13; 95% CI, 1.13 to 4.02), and peripheral vascular disease (OR, 2.04; 95% CI, 1.14 to 3.66). Forty-two percent of patients with two of these factors and 69% of patients with all three factors had cardiac events. CONCLUSIONS: Men with carotid stenosis and no history of CAD have a lower rate of cardiac events than men with carotid stenosis who have a history of CAD. However, a subgroup of patients with carotid stenosis and no history of CAD who have coexistent intracranial occlusive disease, diabetes, or peripheral vascular disease have a risk of cardiac events similar to that of patients with a history of CAD.

Impaired left ventricular contractile function in patients with long-term mitral regurgitation and normal ejection fraction.

OBJECTIVES: We tested the hypotheses that left ventricular chamber elastance would detect impaired contractile function in patients with long-term mitral regurgitation and a normal ejection fraction and that these patients would have unique temporal left ventricular size and ejection fraction responses to mitral valve surgery. BACKGROUND: Although it has been suggested that left ventricular contractile function may begin deteriorating in patients with long-term mitral regurgitation whereas ejection fraction remains normal, no data exist in humans. METHODS: We studied 11 control patients and 28 patients with long-term mitral regurgitation using micromanometer-measured pressures, biplane contrast cineventriculography and radionuclide angiography under control conditions and with alterations in load during right atrial pacing to calculate left ventricular chamber elastance and myocardial stiffness. RESULTS: The patients with mitral regurgitation were classified into subgroups: Group I, normal contractile function; Group II, impaired contractile function (reduced Emax) but normal ejection fraction, and Group III, impaired contractile function (reduced Emax) with reduced systolic myocardial stiffness. Twenty-two of the patients with mitral regurgitation underwent mitral valve surgery. In Group I, comparable decreases in left ventricular volume indexes (p < 0.01 and p = 0.05, respectively) were associated with no change in ejection fraction at 3 months and 1 year. In contrast, in Group II, reductions in volume indexes (p < 0.0001 and p < 0.001) were associated with a short-term decrease in ejection fraction (p < 0.001) that recovered at 1 year (p < 0.01 vs. short-term). Finally, in Group III, variable responses in volume indexes were associated with a consistent decrease in ejection fraction at 3 months and 1 year. CONCLUSIONS: An analysis of left ventricular chamber elastance provides data to support the concepts that 1) contractile function is impaired in some patients with long-term mitral regurgitation and a normal ejection fraction, 2) impaired contractile function may not be irreversible in all of these patients, and 3) an earlier consideration of mitral valve surgery may be warranted to preserve contractile function in these patients.