Measures Of Left Ventricular Performance Research Articles

Non-invasive assessment of left ventricular contractility by myocardial work index in veno-arterial membrane oxygenation patients: rationale and design of the MIX-ECMO multicentre observational study.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

Comparison of different porcine models simulating myocardial cold ischemia of pediatric donor hearts.

Our team previously identified a stem cell-derived cardioprotective additive that can be added to standard cardioplegia to extend myocardial viability during prolonged myocardial cold ischemic time (CIT) in rodent models. The purpose of this study was to utilize a porcine model to compare in-vivo versus ex-vivo porcine simulation of CIT that accompanies cardiac transplantation in humans, in order to determine an optimal method for translation of our studies to larger animals. Eight 39-55kg Yorkshire X pigs were randomly assigned to either in-vivo or ex-vivo simulation. After administration of general anesthesia and endotracheal intubation, baseline measurement of left ventricular performance was obtained via transesophageal echocardiography (TEE). After midline sternotomy and heparin administration, the aorta was cross-clamped and twoliters of HTK-Custodiol were introduced via the aortic root. The in-vivo method utilized cold ischemic heart storage in the chest cavity while supporting the experimental animal with cardiopulmonary bypass (CPB). The ex-vivo method involved standard cardiac procurement, cold ischemic storage outside of the body, and subsequent cardiac reperfusion utilizing cardiac reanimation in a Langendorff heart perfusion mode. After CIT, measurements of post-ischemic left ventricular performance were obtained via echocardiography. Results are presented as: Mean ± Standard Deviation (Median, Minimum-Maximum). Weight (kilograms) was similar in the in-vivo group and the ex-vivo group: 44 ± 1.8 (44, 42-46) versus 44 ± 5.1 (43.5, 39-51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360 ± 0 (360, 360-360) versus 141 ± 26.7 (149, 102-163). Temperature (degrees Celsius) was colder in the ex-vivo group: 8 ± 0 (8, 8-8) versus 16.5 ± 4.2 (16, 12-16).In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25% ± 14.95% (48.5%, 33%-63%) and 41.25% ± 22.32% (41.5%, 20%-62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4% ± 5.9% (57%, 50%-67%) and 60.4% ± 7.7% (61.5%, 51.9%-67%), respectively. The ex-vivo technique is suitable to evaluate cardioplegia additives that may substantially extend myocardial tolerance to cold ischemia.

CARD23: Comparison of Different Porcine Models Simulating Myocardial Cold Ischemia of the Pediatric Donor Heart

Background: Our team previously identified a stem cell-derived cardioprotective additive that can extend myocardial viability during prolonged myocardial cold ischemic time (CIT) in rodent models. The purpose of this study was to utilize a porcine model to compare in-vivo versus ex-vivo simulation of CIT in porcine models in order to determine an optimized method for extension of our studies into larger animals. Methods: Eight 39-55kg Yorkshire X pigs were randomly assigned to either in-vivo or ex-vivo simulation. After administration of general anesthesia and endotracheal intubation, baseline measurement of left ventricular performance was obtained via transesophageal echocardiography (TEE). After midline sternotomy and heparin administration, the aorta was cross-clamped and 2 liters of HTK-Custodiol was introduced via the aortic root. After CIT, measurements of post-ischemic left ventricular performance were obtained. Results are presented as: Mean ± Standard Deviation (Median, Minimum–Maximum). Results: Weight (kilograms) was similar in the in-vivo and ex-vivo group: 44±1.8(44, 42–46) versus 44 ± 5.1(43.5, 39–51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360±0,(360–360) versus 141±26.7(149, 102–163). Temperature (OCelsius) was colder in the ex-vivo group: 8±0(8, 8–8) versus 16.5±4.2(16, 12–16) In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25%±14.95%(48.5%, 33%–63%) and 41.25%±22.32%(41.5%, 20%–62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4%±5.9%(57%, 50%–67%) and 60.4%±7.7%(61.5%, 51.9%–67%), respectively. Conclusion: The ex-vivo technique is suitable to evaluate cardioplegia additives that may substantially extend myocardial tolerance to cold ischemia.

Effects of early and late-onset treatment with carvedilol in an experimental model of aortic regurgitation.

BackgroundBeta-blockade is contraindicated in severe aortic regurgitation (AR) due to the fear of prolonging diastole and thus aggravate regurgitation. However, this has never been scientifically proven and positive effects of targeting the sympathetic system in AR has been demonstrated in several studies.MethodThirty-nine Sprague–Dawley rats with AR were randomized to ten weeks of medical treatment with carvedilol or no treatment. Treatment was initiated either early or late after AR induction. The effect of carvedilol was assessed by serial echocardiography and invasive hemodynamic measurements.ResultsAR resulted in eccentric hypertrophy and left ventricular (LV) dysfunction. LV remodeling and function as measured by echocardiography was unaffected by treatment. LV dimensions were similar between treated and untreated groups and measures of LV performance (including strain and strain rate) were also unaltered. This result was confirmed by invasive measurements showing maximal and minimal pressure–time development, LV volumes, and LV pressures, to be unaltered by treatment. On the contrary, despite relative bradycardia carvedilol did not reflect any negative impact on the heart.ConclusionCarvedilol did not improve left ventricular remodeling or function in rats with surgically induced AR. Despite relative bradycardia, we did not find carvedilol to negatively impact the heart, either when treatment was initiated early or late in the course of disease.

Are measures of left ventricular systolic performance during low dose dobutamine stress echocardiograms repeatable over time?

To establish the test-retest reliability and the normal dose-response relationship of echocardiographic measures of Left Ventricular (LV) contractile function to low dose dobutamine stress in healthy individuals. Thirty healthy volunteers (23 males, 7 females) with an average age of 38 ± 13 years underwent dobutamine stress echocardiography (DSE) (at successive doses of 0, 5, 10, and 20 mcg/kg/min) on two occasions, separated by 14 days. Ejection fraction (EF) was determined from 2D echocardiographic measures of left ventricular (LV) end diastolic and end systolic volumes. Longitudinal strain (S) and strain rate (SR) were measured using 2D speckle tracking analysis from three consecutive cardiac cycles. The Intraclass Correlation Coefficient (ICC) and the Coefficient of Variation (CV) were calculated to assess reliability and variability of the study population's EF, S, and SR responses to increasing doses of dobutamine. Left ventricular S and EF gradually increased with low doses of dobutamine but reached a plateau between 10 and 20 mcg/kg/min. Strain rate, however, gradually increases with each increasing dose of dobutamine. These responses were replicated on Day 2 with a high degree of reliability as determined from the ICC and low variability as determined from the CV, which fell within acceptable limits (<10 %). Left ventricular EF, S and SR can be measured during DSE with a high degree of test-retest reliability, and may be of clinical value when serial follow up of DSE measures of LV performance is indicated over time.

Myocardial Performance Index (MPI) is not influenced by increased Left Ventricular Mass in healthy obese men

Notwithstanding its clinical use as a reliable measure of left ventricular performance, little is known about whether myocardial performing index (MPI) is influenced by increased left ventricular mass (LVM) in healthy obese individuals. The present study was targeted at investigating the impact of increased LVM on the LV MPI in healthy obese men. Sixty-six normal male subjects were involved in this study. The subjects were divided according to their body mass index (BMI), into group I (BMI=20-24.9, n=37, mean age 33.405±10.277 years) which served as the control group, and group II (BMI=≥ 30, n=29, mean age 39.208±10.214 years). The MPI was determined in all subjects using the following formula proposed by Tei: MPI=IVCT+IVRT/ET. LVM was calculated according to the following Devereux formula as: LVM=0.8[1.04(IVSd+PWTd+LVIDd)-(LVIDd)] +0.6. There were no significant differences in MPI between control subjects and obese subjects with increased LVM (p>0.05). Additionally, there was no linear correlation between MPI and LVM (R(2)=0.0003, p=0.89). MPI is a simple and accurate tool for the quantitative assessment of left ventricular function. Because of its ease of application, cost effectiveness, and reproducibility, this tool could be regarded as a principal measurement for comprehensive hemodynamic studies. MPI values (according to the Tei index) did not vary significantly between healthy obese and morbidly obese individuals, and therefore may have limited utility for predicting cardiac diseases in at-risk obese individuals.

The Effect of the Intrathoracic Pressure Regulator on Hemodynamics and Cardiac Output

The intrathoracic pressure regulator (ITPR) (CirQLator; Advanced Circulatory Systems Inc, Roseville, Minn) is a novel, noninvasive device intended to increase cardiac output and blood pressure in hypovolemic or cardiogenic shock by generating a continuous low-level intrathoracic vacuum in between positive pressure ventilations. Although there are robust data supporting the benefit of the ITPR in multiple animal models of shock, the device has not been used in humans.The goals of this study were to evaluate both the safety and efficacy of the ITPR in humans. Twenty patients undergoing coronary artery bypass graft surgery were enrolled in this phase 1 study. Intraoperative use of both pulmonary artery pressure monitoring and transesophageal echocardiography (TEE) was required for study inclusion. Hemodynamic variables as well as TEE measurements of left ventricular performance were collected at baseline and after the ITPR device was activated, before surgical incision. Thermodilution cardiac output increased significantly with the application of the ITPR (4.9 vs. 5.5 L/min; P = 0.017). Similarly, cardiac output was measured by TEE (5.1 vs. 5.7 L/min; P = 0.001).There were significant increases in pulmonary artery systolic blood pressures (35 vs. 38 mmHg; P G 0.001) and mean pulmonary artery pressures (24 vs. 26 mmHg; P = 0.008). There were no significant differences in systemic blood pressures, left ventricular volumes, stroke volume, or ejection fraction as measured by TEE. Using two different measurement techniques, application of the ITPR increased cardiac output in normovolemic anesthetized patients who underwent coronary artery bypass graft before sternotomy. These data suggest that the ITPR has the potential to safely and effectively increase cardiac output in humans.

Correlation of Tei Index Obtained from Tissue Doppler Echocardiography with Invasive Measurements of Left Ventricular Performance

The aim of this study is to correlate Tei index obtained from tissue Doppler echocardiography (TDE-Tei index) defined as the ratio of the sum of isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) over the ejection time (ET) with invasive measurements of left ventricular (LV) performance. Thirty-four patients who underwent an echocardiographic examination and cardiac catheterization were studied. Invasive measurements of peak +dp/dt, peak -dp/dt, and isovolumic relaxation constant of the left ventricle (tau) were obtained from a micromanometer-tipped catheter. After a multivariate analysis, TDE-Tei index had a negative correlation with ejection fraction (EF) (beta=-0.384, P = 0.046) and positive correlation with tau (beta= 0.397, P = 0.040). ET had a negative correlation with heart rate (beta=-0.446, P = 0.005) and positive correlation with EF (beta= 0.379, P = 0.015). ICT + IRT had a positive correlation with tau (beta= 0.512, P = 0.002). ICT/ET had a negative correlation with EF (beta=-0.657, P < 0.001) and positive correlation with peak early transmitral filling wave velocity (beta= 0.385, P = 0.001). IRT/ET had a positive correlation with tau (beta= 0.402, P = 0.018). TDE-Tei index exerts a correlation both with accepted indices of LV systolic and diastolic function acquired by cardiac catheterization. Hence, TDE-Tei index is a simple and feasible indicator in assessing overall LV function.

Age dependency of the Tei index of myocardial performance

Despite its clinical use as a sensitive measure of left ventricular performance, little is known about whether the Tei index is influenced by aging. We determined the Tei index in 141 subjects without cardiovascular disease (age 16-78 years). There were statistically significant variations in ejection time, isovolumic relaxation time, and the Tei index with aging. There was a moderate linear correlation between isovolumic relaxation time and age ( r = 0.49, P < .001) and the Tei index and age ( r = 0.33, P < .001). This investigation demonstrated that when assessing myocardial performance in patients using this index, age-normalized values should be used.

Echocardiographic determinants of mortality in patients >67 years of age with chronic heart failure

This study sought to assess the prognostic significance of echocardiographic measurements of left and right ventricular dimensions and function in patients >67 years of age with chronic congestive heart failure (CHF). This is a retrospective follow-up of elderly patients who underwent an echocardiography in the tertiary cardiac center. A total of 185 patients (131 men) aged ≥68 years (mean ± SD 75 ± 5) with CHF were enrolled into the study. After undergoing a detailed echocardiographic examination, all patients were followed-up for a median of 20 months (interquartile range 9 to 36). During the follow-up period 54 patients (29%) died. Left ventricular (LV) M-mode isovolumic relaxation time (IVRT), end-diastolic and end-systolic diameters, fractional shortening and mass, transmitral E:A ratio, and left atrial dimension, as well as New York Heart Association class and the age were found by Cox proportional-hazards univariate analyses to predict the outcome in these patients (all p <0.05). In multivariate analyses including these measurements, LV IVRT (p <0.04), age (p <0.03), and New York Heart Association class (p <0.001) were found to be the independent predictors of outcome. In the Kaplan-Meier analysis, patients with LV IVRT >30 ms had a better prognosis at 3 years (cumulative survival 78% [95% confidence interval 65% to 91%]) than those with LV IVRT ≤30 ms (survival 52% [95% confidence interval 37% to 68%]). Measurements of LV performance, especially those obtained during diastole, are significantly related to prognosis in patients >67 years of age with CHF. LV M-mode IVRT is among the most important independent predictors of outcome in this population.

Two-dimensional Fourier filtration of acoustic quantification echocardiographic images: Improved reproducibility and accuracy of automated measurements of left ventricular performance

To determine the accuracy of Fourier filtration in removing the high-frequency component of noise from acoustic quantification (AQ) echocardiographic images, we processed 800 parasternal short-axis images obtained from 10 study subjects. M-mode tracings were also obtained and used as gold standard for correlating the results from raw AQ and Fourier-filtered images. Left ventricular short-axis diameters measured from the raw AQ and Fourier-filtered data were compared with the M-mode diameters ( r = 0.91, p < 0.001 for raw AQ; and r = 0.96, p < 0.001, for Fourier filtered images). Fractional shortening showed better correlation between Fourier-filtered images and M-mode ( r = 0.79, p < 0.03) versus raw AQ and M-mode ( r = 0.33, p = 0.46). Beat-to-beat reproducibility was also found to be better for fractional area change ( r = 0.82, p = 0.01 versus r = 0.66, p = 0.07), peak area filling rate ( r = 0.87, p = 0.004 versus r = 0.62, p = 0.1), and peak area emptying rate ( r = 0.99, p < 0.0001 versus r = 0.19, p < 0.7) for Fourier filtered versus raw AQ. Our results indicate that Fourier filtration of AQ data results in more accurate representation of the true endocardial borders. (J Am Soc Echocardiogr 1997;10:310-9.)

Comparative efficacy of three indexes of left ventricular performance derived from pressure-volume loops in heart failure induced by tachypacing

Objectives. The purpose of this study was to serially evaluate the response and variability of the end-systolic pressure-volume relation, the left ventricular end-diastolic volume-peak positive first derivative of left ventricular pressure (dP/dt) relation and the left ventricular end-diastolic volume-stroke work relation in the development of progressive left ventricular dysfunction.Background. Evaluation of systolic performance of the failing left ventricle may be enhanced by using relatively load-insensitive measures of left ventricular performance. The end-systolic pressure-volume, left ventricular end-diastolic volume-peak positive dP/dt and left ventricular end-diastolic volume-stroke work relations adequately define left ventricular performance under multiple leading conditions, but efficacy has not been fully assessed in the failing heart, particularly in the intact circulation.Methods. Fourteen dogs underwent instrumentation and rapid pacing to heart failure. Variably loaded pressure-volume beats were produced by inferior vena cava occlusion. The dogs were evaluated at baseline and at three progressively more severe levels of left ventricular dysfunction.Results. There was a progressive increase in left ventricular volumes at end-diastole ([mean value ± SE]60 ± 28 to 73 ± 29 ml, p < 0.001) and end-systole (39 ± 19 to 61 ± 27 ml, p < 0.001) during the 3 weeks of rapid pacing and a progressive decline in peak positive dP/dt (1,631 ± 410 to 993 ± 222 nun Hg/s, p < 0.001) and ejection fraction (37 ± 8% to 16 ± 11%, p < 0.001). There was a corresponding decline in the slope of each of the three relations: for end-systolic pressure-volume, 6.3 ± 2.2 to 2.8 ± 0.7 (p < 0.05); for left ventricular end-diastolic volume-stroke work, 61.9 ± 9,1 to 26.5 ± 2.4 (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 47.1 ± 13.6 to 20.31 ± 6.8 (p < 0.05). There was also a corresponding increase in position volumes: for end-systolic pressure-volume, 33.6 ± 3.9 to 61.2 ± 6.6 ml (p < 0.05); for left ventricular end-diastolic volume-stroke work, 46.2 ± 3.6 to 89.3 ± 7.6 ml (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 29.1 ± 19.1 to 68.6 ± 25.9 ml (p < 0.05). The relative degree of change in each of the three relations was similar as more severe heart failure developed. The coefficients of variation for position were significantly less than the variation for slopes. The response of volume intercepts was heterogeneous. For left ventricular end-diastolic volume-stroke work, the intercept increased as ventricular performance decreased. The intercept of the end-systolic pressure-volume relation was significantly more variable than the left ventricular end-diastolic volume-stroke work relation and did not change with progressive heart failure. The intercept for left ventricular end-diastolic volume-peak positive dP/dt was highly variable and showed no consistent changes as left ventricular function declined.Conclusions. All three relations consistently describe changes in left ventricular performance brought about by tachypaing. Evolution of left ventricular dysfunction causes a decline in slope and a rightward shift of these relations. The position of the relation is the most sensitive and least variable indicator of left ventricular systolic performance.

Imaging of metabolism and autonomic innervation of the heart by positron emission tomography.

Positron emission tomography (PET) allows, in combination with multiple radiopharmaceuticals, unique physiological and biochemical tissue characterization. Tracers of blood flow, metabolism and neuronal function have been employed with this technique for research application. More recently, PET has emerged in cardiology as a useful tool for the detection of coronary artery disease and the evaluation of tissue viability. Metabolic tracers such as fluorine-18 deoxyglucose (FDG) permit the specific delineation of ischaemically compromised myocardium. Clinical studies have indicated that the metabolic imaging is helpful in selecting patients for coronary artery bypass surgery or coronary angioplasty. More recent research work has concentrated on the use of carbon-11 acetate as a marker of myocardial oxygen consumption. Together with measurements of left ventricular performance, estimates of cardiac efficiency can be derived from dynamic 11C-acetate studies. The non-invasive evaluation of the autonomic nervous system of the heart was limited in the past. With the introduction of radiopharmaceuticals which specifically bind to neuronal structures, the regional integrity of the autonomic nervous system of the heart can be evaluated with PET. Numerous tracers for pre- and postsynaptic binding sites have been synthesized. 11C-hydroxyephedrine represents a new catecholamine analogue which is stored in cardiac presynaptic sympathetic nerve terminals. Initial clinical studies with it suggest a promising role for PET in the study of the sympathetic nervous system in various cardiac diseases such as cardiomyopathy, ischaemic heart disease and diabetes mellitus. The specificity of the radio-pharmaceuticals and the quantitative measurements of tissue tracer distribution provided by PET make this technology a very attractive research tool in the cardiovascular sciences with great promise in the area of cardiac metabolism and neurocardiology.

Continuous measurement of left ventricular performance during and after maximal isometric deadlift exercise.

Isometric exercise produces a reflex increase in arterial blood pressure that is proportional to the intensity and mass of muscle used during contraction. Little is known about the transient effects of heavy weight lifting on left ventricular performance. In this study, we measured continuous changes in left ventricular performance during maximal large-muscle isometric exercise using the standing deadlift position. Ten healthy young men performed serial deadlifts at 50% of maximal voluntary effort for 90 seconds and 100% of maximal effort for 30 seconds. Echocardiographic imaging (apical four-chamber view), arterial blood pressure (brachial artery catheter), and electrocardiographic monitoring were recorded throughout the deadlift and for 30 seconds of recovery. Aortic flow velocity was also monitored during a separate series of deadlifts. During 100% maximal deadlift, mean arterial pressure increased from 108 +/- 4 to 164 +/- 6 mm Hg. Left ventricular ejection fraction declined initially (from 57 +/- 2% to 49 +/- 3%) at 15 seconds into the lift and recovered (56 +/- 1%) due to significant increases in end-diastolic volume (104 +/- 11 ml to 132 +/- 16 ml) by the end of the lift. The peak systolic pressure/end-systolic volume ratio did not change during the deadlift. After cessation of the deadlift, mean arterial pressure declined precipitously (to 88 +/- 4 mm Hg) within 5 seconds and gradually returned to baseline after 30 seconds. Left ventricular performance indexes all increased significantly during the recovery phase (ejection fraction to 68 +/- 3%, peak systolic pressure/end-systolic volume ratio to 5.9 +/- 0.9). Findings were qualitatively similar for the 50% deadlift. During an intense isometric deadlift, left ventricular performance declines initially but is restored by the Frank-Starling mechanism. Upon release of the deadlift, increased left ventricular performance develops in conjunction with a rapid decrease in arterial pressure. The combined effects of increased wall stress during the lift phase and enhanced contractility during the release phase probably contribute to left ventricular hypertrophy associated with repetitive weight training.

Seismocardiography for measurement of left ventricular performance at rest and immediately post exercise

Seismocardiography for measurement of left ventricular performance at rest and immediately post exercise

Acute effects of mildly intoxicating levels of alcohol on left ventricular function in conscious dogs.

We assessed the effect of alcohol, before and after autonomic blockade, on left ventricular (LV) performance in conscious dogs. 10 animals were instrumented to determine LV volume from ultrasonic LV internal dimensions and measure LV pressure with a micromanometer. The animals were studied in the conscious state after full recovery from the operation. Blood alcohol was undetectable before and 67 +/- 14 mg/dl (mean +/- SD) at 20 min after alcohol administration. In response to alcohol, the LV systolic pressure was reduced slightly, the left ventricular end-diastolic pressure increased slightly. The maximum time derivative of LV pressure (dP/dtmax) and stroke volume were decreased. The end-systolic volume (VES), as well as effective arterial elastance, were significantly increased. There was no significant change in heart rate. Variably loaded pressure-volume loops were generated by acute caval occlusion before, immediately, and 20 min after the intravenous infusion of alcohol (0.2 g/kg). Three measures of LV performance were derived from these variably loaded pressure-volume loops: the end-systolic pressure-volume relation; the stroke work-end-diastolic volume relation; and maximum dP/dt-VED relation. The slopes of all three relations were significantly decreased in response to alcohol, and all three relations were shifted toward the right, indicating a depression of LV contractile performance. Similar, but greater depressions of LV performance with alcohol were observed following autonomic blockade. LV performance was restored by infusing dobutamine. We conclude that mildly intoxicating levels of alcohol (blood concentration less than 100 mg/dl) are capable of producing LV contractile depression in conscious animals, which is more marked after autonomic blockade. This suggests that patients with impaired LV function should avoid even small amounts of alcohol.

Comparison of the Subacute Hemodynamic Effects of Atenolol, Propranolol, Pindolol, and Nebivolol

In an observer-blind four-way crossover study, 7 healthy volunteers received in random sequence, one month apart, atenolol 100 mg od, propranolol (slow release) 160 mg od, pindolol 5 mg tid, and nebivolol 5 mg od for a period of seven days, followed by a single-blind placebo washout period of seven days. The decrease of peak exercise heart rate and systolic blood pressure was significant (p = 0.02) and comparable for the four drugs studied and varied between 15% and 23% for heart rate and between 15% and 20% for systolic blood pressure. Although no statistically significant difference was observed among the four drug regimens, the decrease of peak exercise heart rate was less pronounced with nebivolol than with the three reference beta-blocking agents. The ratio of the preejection period (PEPc) to the left ventricular ejection time (LVETc), an indirect measure of left ventricular performance, tended to increase with atenolol and propranolol and remained unchanged with pindolol. PEPc/LVETc progressively and significantly improved with nebivolol from a control value of 0.37 +/- 0.012 to 0.31 +/- 0.009 (p = 0.03) after seven days of treatment, owing to a decrease in PEPc and an increase in LVETc, suggestive of a combined effect both on preload and afterload. Postexercise LVETc, an index of the intrinsic positive inotropy of exercise, was significantly suppressed by atenolol, propranolol, and pindolol, but not during treating with nebivolol. These data suggest that nebivolol is a beta 1-selective adrenergic antagonist with an unusual hemodynamic profile, probably improving left ventricular compliance.

Part II: Radionuclide evaluation of aortic regurgitation

The timing for valve replacement in patients with aortic regurgitation remains a complex clinical problem. Rest radionuclide angiography measurement of ejection fraction is a simple informative study to help evaluate the appropriate timing for valve replacement in the asymptomatic patients or those with mild symptoms. In patients with normal ejection fractions the disease probably has not yet evolved to the phase in which valve replacement is essential. If the ejection fraction is mildly depressed (0.40 to 0.49) the time is right for intervention. By the time the ejection fraction falls to < 0.40 the left ventricle is likely damaged and unlikely to regain normal function. If the patient has severe symptoms with maximal medical therapy, surgery is indicated no matter what the ejection fraction. The latter situation can arise especially when aortic regurgitation evolves over a short period, as might be the case in patients with bacterial endocarditis. A single ejection fraction measurement is not as reliable as serial studies. If, for example, the ejection fraction (under similar circumstances) falls from the ≥0.50 range to the 0.40 to 0.49 range, the physician should be alerted to the possibility that the left ventricle is deteriorating, and surgery should be considered. It should be understood that multiple hemodynamic factors in aortic regurgitation can alter the ejection fraction and could limit its use as the sole measure of left ventricular performance. Other systolic or diastolic parameters cannot be relied on in isolation as an indication or contraindication for aortic valve replacement. The exercise ejection fraction response reflects the total stroke volume and does not distinguish between regurgitant flow and forward flow. It is therefore possible to observe a decrease in ejection fraction in association with an increase in forward stroke volume during exercise as a result of an increase in heart rate and a decrease in peripheral resistance. Accordingly, it is not appropriate to compare the ejection fraction during exercise in aortic insufficiency with the expected response of the normal ventricle. Exercise position (sitting vs. supine) affects loading conditions and ejection fraction response. 44Because of the complexity of the exercise ejection fraction response, it is not clear that there is a role for exercise ejection fraction measurements in determining the appropriate time for aortic valve replacement. Criteria based on supine exercise may not be applicable to studies in the upright position. Other markers of left ventricular performance, including end-systolic volumes and pressure-volume relationships, also have been examined. These parameters are preload independent and incorporate the effects of afterload. End-ejection pressure-volume ratios appear to be reasonable predictors of left ventricular contractile performance in chronic aortic regurgitation. 45 The continued problem of the timing of aortic valve replacement inspires the hope that serial measurement left ventricular function with exercise may have some predictive power. Parameters other than ejection fraction, such as regurgitant fraction and end-systolic and end-diastolic volume response, also may be useful. Careful consideration of aortic valve replacement should be given to patients with deterioration of these other radionuclide angiographic parameters, particularly when associated with a decrease in functional performance and worsening of symptoms. Nevertheless, only the resting LVEF has been shown to correlate with survival after valve replacement. Radionuclide studies provide a means to assess the change in left ventricular function after valve replacement. It has been observed that soon after valve replacement LVEF decreases, likely due to acute reduction in preload and increase in heart rate. This reduction should not be misconstrued as reduction in left ventricular performance, and under these circumstances end-systolic volume-endsystolic pressure may be a more useful test of left ventricular function. However, over the ensuing weeks to months ejection fraction tends to normalize in those patients in whom surgery was appropriately timed. The frequent occurrence of late postoperative deaths due to chronic congestive heart failure (78% in the National Institutes of Health study 46) underscores the importance of continued serial radionuclide evaluation of left ventricular performance in the improved methods to better time when aortic valve replacement should be performed. Operated and unoperated patients receiving chronic vasodilator therapy also benefit from serial evaluation of ventricular function to assess the response to therapy and define prognosis.

Comparison of Peak and Modal Aortic Blood Flow Velocities With Invasive Measures of Left Ventricular Performance

The purpose of this study was to determine the accuracy of Doppler-derived modal and maximum velocity and peak and mean acceleration of ascending aortic blood for the assessment of left ventricular systolic function. Studies were performed in six anesthetized open-chest dogs. Doppler-derived modal velocity, maximum velocity, and peak and mean acceleration were compared with left ventricular dP/dt, maximum aortic blood flow, and rate of blood flow measured with an electromagnetic flow probe under varying inotropic states. Maximum Doppler velocity showed better correlation (r = 0.94, y = 0.34 + 3.95) with maximum aortic blood flow than the modal velocity (r = 0.85, y = 1.49 + 3.85x). Peak acceleration also correlated better with the rate of blood flow (r = 0.92, y = 12.3 + 4.92x) than the mean acceleration (r = 0.83, y = 12.2 + 4.27x). Modal and maximum velocity and mean and peak acceleration correlated well with left ventricular dP/dt. We conclude that peak modal and peak maximum velocity and peak and mean acceleration are accurate measurements of left ventricular function. Maximum velocity and peak acceleration are more accurate than modal velocity and mean acceleration.

Subacute hemodynamic effects of nebivolol in man at rest and during exercise.

In a subacute experiment 7 apparently healthy volunteers received a daily oral dose of 5 mg nebivolol for seven days, followed by a seven-day washout period with placebo. From the first day during treatment with nebivolol, peak exercise heart rate and systolic blood pressure, as measured during a standardized submaximal treadmill exercise, significantly decreased by 15% and 19% respectively. A prolonged treatment for one week did not further increase the response of exercise heart rate and systolic blood pressure to nebivolol. However, the ratio of preejection period (PEPc) to left ventricular ejection time (LVETc), an indirect and valuable measure of left ventricular performance, progressively and significantly decreased during the seven-day treatment period with nebivolol from a mean value of 0.37 +/- 0.012 to 0.31 +/- 0.009. The improvement of systolic time intervals resulted from a shortening of the PEPc and a lengthening of the LVETc. At rest, heart rate did not change significantly with nebivolol, whereas both systolic and diastolic blood pressure gradually and significantly lowered. The postexercise LVETc significantly shortened during treatment with nebivolol, and this shortening was more pronounced after seven days of treatment. After discontinuation of treatment with nebivolol, all these effects persisted for more than thirty hours after the last intake and gradually returned to pretreatment values thereafter. From these data it appears that nebivolol effectively reduces blood pressure at rest and during exercise in healthy volunteers, beneficially influencing preload and afterload, as measured by systolic time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)