Alon Marmor

Prognostic Value of Noninvasively Obtained Left Ventricular Contractile Reserve in Patients With Severe Heart Failure

OBJECTIVESnThe present study sought to evaluate the prognostic value of contractile reserve measured noninvasively during dobutamine infusion in patients with severe heart failure.nnnBACKGROUNDnIn patients with severe heart failure there is a great need for objective criteria to define candidates for heart transplantation or intensive medical treatment. Cardiac pumping performance reserve has been shown to have excellent prognostic value in patients with cardiogenic shock.nnnMETHODSnCardiac peak power, an afterload-independent contractility index, was measured noninvasively at rest and at peak dobutamine inotropic stimulation. Contractile reserve was defined as the difference between maximal cardiac power at peak dobutamine dose and baseline value. Maximal cardiac power was calculated from the maximal product of validated central arterial pressure and aortic flow.nnnRESULTSnResults were obtained from 52 subjects (42 patients, 10 control subjects). Twenty-two patients were in New York Heart Association functional classes III and IV. Of nine patients with a contractile reserve < 1.5 W/ml, eight died during the 3-year follow-up period. In contrast, all survivors had a contractile reserve > 1.5 W/ml. Using multiple logistic regression analysis, contractile reserve was shown to be the only predictor of survival.nnnCONCLUSIONSnContractile reserve measured noninvasively during dobutamine infusion is a valuable prognostic indicator in patients with severe heart failure, with added value to ejection fraction.

Effects of bilateral hystero-salpingo-oophorectomy on exercise-induced ST-segment abnormalities in young women

Abstract The high frequency of ST-segment abnormalities in response to exercise in premenopausal women is widely recognized. 1 An incidence of 14 to 67% of false-positive exercise responses has been reported. 2 It has been suggested that ST-segment shifts among women, in the absence of coronary artery disease, may be related to relatively high estrogen levels. 3,4 Although this hypothesis was not thoroughly investigated, several reports suggested that there is a relationship between high estrogen level and ST-segment response during exercise. 4,5 To clarify the role of sex hormones, estrogen and progesterone in evoking abnormal electrocardiographic responses during exercise, the present study was designed. In this study ST-segment response at peak exercise was assessed before and after unilateral versus bilateral salpingo-oophorectomy operation. This can serve as a model for drastic changes in hormonal levels, and it may clarify the issue of the effect of sex hormones on ST changes.

Endothelin release: a marker for the severity of exercise-induced ischemia

Elevated endothelin-1 levels were found in exercise-induced ischemia. To our knowledge, no attempt has been made to correlate the presence of the elevated endothelin levels with severity of ischemia. In the present study, we attempt to correlate the severity of ischemia, quantified using a bullseye visual display of scintigraphic ischemic score on SPECT technetium 99m sestamibi, with presence of endothelin at peak exercise. Twenty seven patients with documented effort angina were included in the study. All subjects underwent stress technetium 99m sestamibi and ischemic scores were evaluated on the polar map image divided into 13 segments. Endothelin levels were measured at baseline and at peak exercise. In 13 patients with elevated endothelin-1 levels, there were 88 ischemic segments, 26 of which showed severe ischemia. In the remaining 14 patients with no endothelin-1 elevation, there were 80 ischemic segments of which only four showed severe ischemia. The amount of severe ischemic segments per patient was 2+/-2.2 in the elevated endothelin positive group and 0.28+/-0.6 in the endothelin negative (P< or =0.011). When looking at ischemia as detected by sestamibi SPECT as a gold standard, we found that of 331 segments, 168 were without ischemia, 143 had mild to moderate ischemia, and 30 has severe ischemia. Endothelin levels were 1.2+/-0.6, 2.2+/-0.5, 6.2+/-0.7 pg/l (P<0.01), respectively. Thus, endothelin-1 is a marker of severity of ischemia rather than ischemia itself, and as such, may have prognostic value.

A New methodology for non-invasive clinical assessment of cardiovascular system performance and of ventricular-arterial coupling during stress

SummaryThe objective of the study was to develop a non-invasive method for the quantitative evaluation of cardiovascular performance and ventricular-arterial (VA) coupling during varying physiological states. VA-coupling was represented by the ratio between the arterial and ventricular elastances — Ea/Ees. Approximate indices of the relative change of Ees and VA-coupling during stress were developed and tested. These indices can be evaluated directly from noninvasive measurements of ejection fraction values (for VA-coupling) and measurements of stroke volumes and systolic and diastolic arterial pressures (for Ees). Additional relative indices can be evaluated from these data (e.g., stroke work, cardiac output) to yield a complete representation of the cardiovascular response to stress. The present methodology was applied to assess the exercise stress response in healthy subjects (H,n = 8) and in patients with left ventricular dysfunction (n = 24). Left ventricular volumes were determined by nuclear angiography and arterial pressures were measured non-invasively by a new, validated method. Using published data obtained invasively, we found that the relative indices of Ees and VA-coupling showed a high correlation with the invasive ones (r > 0.8,P < 0.01). The patients were subgrouped by their maximal exercise capacitance (P2 − 50W, P3 − 75W). At rest, the two patient groups had similar ejection fraction values (45 ± 15% and 48 ± 16%), which were significantly different from those of the healthy subjects (66 ± 7%,P < 0.05). During stress, a larger increase in stroke work and cardiac output was found in the healthy subjects. All three groups showed similar relative increases in Ees and heart rate, but relative Ea increased in P2 and decreased in H, while the opposite was found for the end-diastolic volume. The relative VA-coupling index in P2 was significantly larger than that in P3 and H (P < 0.05). The present non-invasively based indices can be used to quantitatively monitor the individual cardiovascular response to stress testing or drug interventions and to evaluate the importance of VAcoupling in the clinical setting.

Decrease in global ejection fraction after volume challenge in long-standing hypertension.

An easy noninvasive volume challenge method which takes advantage of the diastolic filling differences existing between patients with recent onset and long-standing hypertension is presented. By passively elevating the patients legs at 45 degrees for 5 minutes, a sudden increase in venous return was induced in 14 healthy and in 42 hypertensive subjects. The global ejection fraction measured by radionuclide ventriculography increased markedly in both 14 normal subjects and in 18 patients with recent onset hypertension (67 +/- 9% to 75 +/- 6%, p less than 0.001 and 64 +/- 10% to 71 +/- 11%, p less than 0.001, respectively). In contrast, a decrease in global ejection fraction was found in all patients with long-standing hypertension (66 +/- 4% to 58 +/- 10%, p less than 0.001). Similar results were obtained when echocardiographic measurements were made after the legs-up procedure in 24 patients. The correlation with the radionuclide measurements done in the same patients was excellent, r = 0.89. In 20 patients with long-standing hypertension in whom exercise radionuclide ventriculography was done, a marked elevation in global left (LVEF) and right ventricular ejection fraction (RVEF) was found (65 +/- 5% to 71.5 +/- 11% LVEF, and 42 +/- 5% to 45 +/- 7% RVEF, p less than 0.01), whereas the legs-up procedure induced a significant reduction in both global LVEF and RVEF (65 +/- 5% to 57 +/- 6% LVEF, and 44 +/- 7% to 37 +/- 5% RVEF, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A New Noninvasive Device for Measuring Central Ejection dP/dt Mathematical Foundation of Cardiac dP/dt Measurement Using a Model for a Collapsible Artery

We have developed a novel non-invasive device for the measurement of one of the most sensitive indices of myocardial contractility as represented by the rate of increase of intraventricular pressure (left ventricular dP/dt and arterial dP/dt performance index (dP/dtejc). Up till now, these parameters could be obtained only by invasive catheterization methods. The new technique is based on the concept of applying multiple successive occlusive pressures on the brachial artery from peak systole to diastole using a inflatable cuff and plotting the values against time intervals that leads to the reconstruction of the central aortic pressure noninvasively. The following describes the computer simulator developed for providing a mathematical foundation of the new sensor. At the core of the simulator lies a hemodynamic model of the blood flow on an artery under externally applied pressure. The purpose of the model is to reproduce the experimental results obtained in studies on patients (Gorenberg et al. in Cardiovasc Eng: 305–311, 2004; Gorenberg et al. in Emerg med J 22 (7): 486–489, 2005) and a animal model where ischemia resulted from balloon inflation during coronary catheterization (Gorenberg and Marmor in J Med Eng Technol, 2006) and to describe correlations between the dP/dtejc and other hemodynamic variables. The model has successfully reproduced the trends observed experimentally, providing a solid in-depth understanding of the hemodynamics involved in the new measurement. A high correlation between the dP/dtejc and the rate of pressure rise in the aorta during the ejection phase was observed. dP/dtejc dependence on other hemodynamic parameters was also investigated.

The Arterial Response to an Exercise Stress Test in Healthy Subjects, Hypertensives, and Patients with Left-Ventricular Dysfunction

Quantitative assessment of the arterial load response to an exercise stress test may add valuable insight to the assessment of cardiovascular performance in cardiac patients. Noninvasive pressure-volume measurements were taken during an exercise test in 42 subjects: 24 with left-ventricular dysfunction (LVD), 10 hypertensives, and 8 healthy subjects. Systemic vascular resistance (SVR), arterial elastance (Ea), and total and pulsatile power were calculated from the measured data. The LVD patients were subgrouped to patients with good exercise performance (3 stages; n = 16) and low exercise performance (2 stages; n = 8). Significantly different arterial response was found in patients with lower exercise capacity (Ea increased from 1.5 ± 0.3 to 2.6 ± 1.6 mmHg/ml at P < .05, contrasting with nonsignificant (NS) decrease in the other three groups). These changes were associated with inadequate increase of global cardiovascular performance in patients with low exercise performance (e.g., cardiac output increased from 6 ± 1 (rest) to 8 ± 4 (stress stage 2), P= NS, compared with 8 ± 4 increased to 15 ± 4 in healthy). The ratio between pulsatile and total power was similar in healthy and LVD patients, while the hypertensive patients had a higher pulsatile component. In conclusion, LVD patients with reduced exercise capacity demonstrated inadequate decrease of arterial load during exercise, suggesting a relationship between load reduction and impaired exercise capacity. Similar power ratios in healthy and in LVD patients suggested that energy transmission efficiency is not affected by heart failure. In hypertensives, however, a higher pulsatile component during rest and exercise implies higher energy waste for the same amount of work.

1016-51 From Myocardial O2 Consumption to Mean Arterial Power — Analysis of Optimal Cardiovascular Performance

Mathematical model and numerical simulation are used to analyze optimal conditions of cardiovascular performance, with an emphasis on the effect of ventricular-arterial (VA) coupling. The following research questions were posed: Does the VA-coupling affect the cardiovascular system (CVS) performance in addition to the direct effects of the left ventricle and of the vascular load? Is there an optimal coupling state? Does the CVS in human subjects, either healthy or diseased, operate with optimal VA-coupling? and finally, is it possible to improve the CVS performance by controlling the VA-coupling? To answer these questions, a clinically oriented integral model of the CVS is introduced, based on the ventricular and arterial elastances. The main advantages of the model are its simplicity and the fact that all its variables can be measured non-invasively in the clinical practice. Traditionally, the optimal state of CVS operation was evaluated by two criteria — the energetic efficiencyof the left ventricle and the efficiency of energy transfer through the vascular system. In the present study a combined criterion of the total energetic efficiency is utilized — from the input metabolic energy consumed by the ventricle to the net energy available to the peripheral tissues. It is found that optimal coupling for maximal global efficiency depends in a complex, non-linear way on all the classical determinants of CVS performance — the preload, the myocardial contractility, the afterload and the heart rate. Response surfaces of the analyzed variables as function of two independent variables were generated by numerical simulation. Based on the analysis of the global efficiency as the optimization criterion, answers to the research questions were found: The VA-coupling affects the CVS performance in addition to the direct effects of its determinants; there is an optimal state of coupling which results in maximal efficiency; the CVS in healthy subject operates in the region of optimal coupling; during stress, changes in the state of coupling result in additional contribution to CVS performance; in patients with left ventricular dysfunction the efficiency is reduced and it further decreases during exercise. The model shows that there is, however, an optimal coupling which improves performance even in cases of severe heart failure. This optimal state can theoretically be approached by titrating the vascular resistance and the end-diastolic volume (the preload) to optimal levels. These results suggest, and lay the theoretical foundation for the notion, that vasodilator drugs can be used to optimize VA-coupling and CVS performance in heart failure patients.