A Physiological Controller for Turbodynamic Ventricular Assist Devices Based on a Measurement of the Left Ventricular Volume

The current article presents a novel physiological control algorithm for ventricular assist devices (VADs), which is inspired by the preload recruitable stroke work. This controller adapts the hydraulic power output of the VAD to the end-diastolic volume of the left ventricle. We tested this controller on a hybrid mock circulation where the left ventricular volume (LVV) is known, i.e., the problem of measuring the LVV is not addressed in the current article. Experiments were conducted to compare the response of the controller with the physiological and with the pathological circulation, with and without VAD support. A sensitivity analysis was performed to analyze the influence of the controller parameters and the influence of the quality of the LVV signal on the performance of the control algorithm. The results show that the controller induces a response similar to the physiological circulation and effectively prevents over- and underpumping, i.e., ventricular suction and backflow from the aorta to the left ventricle, respectively. The same results are obtained in the case of a disturbed LVV signal. The results presented in the current article motivate the development of a robust, long-term stable sensor to measure the LVV.

[Myocardial dysfunction in sepsis]

Myocardial dysfunction appears in 25% of patients with severe sepsis and in 50% of patients with septic shock, even in the presence of hyper dynamic states. It is characterized by a reduction in left ventricle ejection fraction, that reverts at the seventh to tenth day of evolution. Right ventricular dysfunction and diastolic left ventricular dysfunction can also appear. There is no consensus if an increase in end diastolic volume is part of the syndrome. High troponin or brain natriuretic peptide levels are associated with myocardial dysfunction and a higher mortality. The pathogenesis of myocardial dysfunction is related to micro and macro circulatory changes, inflammatory response, oxidative stress, intracellular calcium management disturbances, metabolic changes, autonomic dysfunction, activation of apoptosis, mitochondrial abnormalities and a derangement in catecholaminergic stimulation. Since there is no specific treatment for myocardial dysfunction, its management requires an adequate multi systemic support to maintain perfusion pressures and systemic flows sufficient for the regional and global demands.

Control of ventricular unloading using an electrocardiogram-synchronized Thoratec paracorporeal ventricular assist device

OBJECTIVE: Current pulsatile ventricular assist devices operate asynchronous with the left ventricle in fixed-rate or fill-to-empty modes because electrocardiogram-triggered modes have been abandoned. We hypothesize that varying the ejection delay in the synchronized mode yields more precise control of hemodynamics and left ventricular loading. This allows for a refined management that may be clinically beneficial. METHODS: Eight sheep received a Thoratec paracorporeal ventricular assist device (Thoratec Corp, Pleasanton, Calif) via ventriculo-aortic cannulation. Left ventricular pressure and volume, aortic pressure, pulmonary flow, pump chamber pressure, and pump inflow and outflow were recorded. The pump was driven by a clinical pneumatic drive unit (Medos Medizintechnik AG, Stolberg, Germany) synchronously with the native R-wave. The start of pump ejection was delayed between 0% and 100% of the cardiac period in 10% increments. For each of these delays, hemodynamic variables were compared with baseline data using paired t tests. RESULTS: The location of the minimum of stroke work was observed at a delay of 10% (soon after aortic valve opening), resulting in a median of 43% reduction in stroke work compared with baseline. Maximum stroke work occurred at a median delay of 70% with a median stroke work increase of 11% above baseline. Left ventricular volume unloading expressed by end-diastolic volume was most pronounced for copulsation (delay 0%). CONCLUSIONS: The timing of pump ejection in synchronized mode yields control over left ventricular energetics and can be a method to achieve gradual reloading of a recoverable left ventricle. The traditionally suggested counterpulsation is not optimal in ventriculo-aortic cannulation when maximum unloading is desired.

Noninvasive Doppler-derived myocardial performance index in rats with myocardial infarction: validation and correlation by conductance catheter

The rodent model of myocardial infarction (MI) is extensively used in heart failure studies. However, long-term follow-up of echocardiographic left ventricular (LV) function parameters such as the myocardial performance index (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been validated in conjunction with invasive indexes, such as those derived from the conductance catheter (CC). Sprague-Dawley rats with left anterior descending coronary artery ligation (MI group, n = 9) were compared with a sham-operated control group (n = 10) without MI. Transthoracic echocardiography (TTE) was performed every 2 wk over an 8-wk period, after which classic TTE parameters, especially MPI and LVFS/MPI, were compared with invasive indexes obtained by using a CC. Serial TTE data showed significant alterations in the majority of the noninvasive functional and structural parameters (classic and novel) studied in the presence of MI. Both MPI and LVFS/MPI significantly (P < 0.05 for all reported values) correlated with body weight (r = -0.58 and 0.76 for MPI and LVFS/MPI, respectively), preload recruitable stroke work (r = -0.61 and 0.63), LV end-diastolic pressure (LVEDP) (r = 0.82 and -0.80), end-diastolic volume (r = 0.61 and -0.58), and end-systolic volume (r = 0.46 and -0.48). Forward stepwise linear regression analysis revealed that, of all variables tested, LVEDP was the only independent determinant of MPI (r = 0.84) and LVFS/MPI (r = 0.83). We conclude that MPI and LVFS/MPI correlate strongly and better than the classic noninvasive TTE parameters with established, invasively assessed indexes of contractility, preload, and volumetry. These findings support the use of these two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.

Combined endurance/resistance training early on, after a first myocardial infarction, does not induce negative left ventricular remodelling

BACKGROUND: Resistance training (RT) is safe and practicable in low-risk populations with coronary artery disease. In patients with left ventricular (LV) dysfunction after an acute ischaemic event, few data exist about the impact of RT on LV remodelling. METHODS: In this prospective, randomized, controlled study, 38 patients, after a first myocardial infarction and a maximum ejection fraction (EF) of 45%, were assigned either to combined endurance training (ET)/RT (n=17; 15 men; 54.7+/-9.4 years and EF: 40.3+/-4.5%) or to ET alone (n=21; 17 men; 57.0+/-9.6 years and EF: 41.9+/-4.9%) for 12 weeks. ET was effectuated at an intensity of 70-85% of peak heart rate; RT, between 40 and 60% of the one-repetition maximum. LV remodelling was assessed by MRI. RESULTS: No statistically significant differences between the groups in the changes of end-diastolic volume (P=0.914), LV mass (P=0.885) and EF (P=0.763) were observed. Over 1 year, the end-diastolic volume increased from 206+/-41 to 210+/-48 ml (P=0.379) vs. 183+/-44 to 186+/-52 ml (P=0.586); LV mass from 149+/-28 to 155+/-31 g (P=0.408) vs. 144+/-36 to 149+/-42 g (P=0.227) and EF from 49.1+/-12.3 to 49.3+/-12.0% (P=0.959) vs. 51.5+/-13.1 to 54.1% (P=0.463), in the ET/RT and ET groups, respectively. Peak VO2 and muscle strength increased significantly in both groups, but no difference between the groups was noticed. CONCLUSION: RT with an intensity of up to 60% of the one-repetition maximum, after an acute myocardial infarction, does not lead to a more pronounced LV dilatation than ET alone. A combined ET/RT, or ET alone, for 3 months can both increase the peak VO2 and muscle strength significantly.

Reply to the editor

We appreciate the comments and concerns expressed by Arakawa and colleagues regarding our article, titled “Pulsatile control of rotary blood pumps: Does the modulation waveform matter?”1 Unfortunately, we have to disagree with Arakawa and colleagues. As is obvious from the title of our article, it investigates the effect of different waveforms on the heart–device interaction. In contrast to the authors' claim, this is the first article in the literature that uses basic waveforms (sine, triangle, saw tooth, and rectangular) with different phase shifts to examines their impact on left ventricular unloading. The previous publications2, 3 and 4 just varied the pump speed during systole and diastole, which was first reported by Bearnson and associates5 in 1996, and studied its effect on aortic pressure, coronary flow, and end-diastolic volume. We should mention that dp/dtmax is a load-sensitive parameter of contractility and not representative for the degree of unloading. Moreover, none of the aforementioned reports has studied mechanical unloading and in particular the stroke work of the left ventricle. Our method is unique because we do not just alternate between high and low speed but have accurate control of the waveform because of the direct drive system of Levitronix Technologies LLC (Waltham, Mass) and a custom-developed pump controller. Without referring, Arakawa and associates state “several previous studies have already reported the coronary flow diminishes as the left ventricular assist device support increases.” It should be noted that all the waveforms used in our study have 2000 rpm average value with 1000 rpm amplitude, which is not an excessive speed for the CentriMag rotary pump (Levitronix) to collapse the ventricle and diminish the coronary flow. We agree with Arakawa and coworkers that there is a need for a heart failure model to come to more relevant results with respect to clinical expectations. However, we have explored many existing models, including species and breeds that have a native proneness to cardiomyopathy, but all of them differ from the genetic presentation in humans. We certainly do not believe that the use of microembolization, in which the coronary circulation is impaired by the injection of microspheres, would form a good model from which to draw conclusions about coronary flow change under different loading conditions. A model would be needed in which either an infarct is created to mimic ischemic heart failure or the coronary circulation remains untouched to simulate, for instance, dilated cardiomyopathy. Furthermore, in discussion we clearly mention that “lack of heart failure is a major limitation of our study.” We also believe that unloading is not the only factor of the cardiac functional recovery, and an excessive unloading of the left ventricle might lead to cardiac tissue atrophy. Therefore, in our article we mention that control of the level of cardiac unloading by assist devices has been suggested as a mechanical tool to promote recovery, and more studies are required to find better strategies for the speed modulation of rotary pumps and to achieve an optimal heart load control to enhance myocardial recovery. Finally, there are many publications about pulsing rotary blood pumps and it was impossible to include them all. We preferred to reference some of the earlier basic works such as an original research by Bearnson and coworkers5 and another article published by our group,6 which is more relevant.

Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

BACKGROUND The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. METHODS This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20-29, 30-49, 50-69, and ≥70 years) and cardiac measurements were compared using Pearson's rank correlation over the four different groups. RESULTS With advanced age a slight but significant decrease in ESV (r=-0.41 for both ventricles, P<0.001) and EDV (r=-0.39 for left ventricle, r=-0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). CONCLUSIONS The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies.

A cardiovascular mathematical model of graded head-up tilt

A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.

CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis

OBJECTIVES This study aimed to demonstrate that the presence of late gadolinium enhancement (LGE) is a predictor of death and other adverse events in patients with suspected cardiac sarcoidosis. BACKGROUND Cardiac sarcoidosis is the most important cause of patient mortality in systemic sarcoidosis, yielding a 5-year mortality rate between 25% and 66% despite immunosuppressive treatment. Other groups have shown that LGE may hold promise in predicting future adverse events in this patient group. METHODS We included 155 consecutive patients with systemic sarcoidosis who underwent cardiac magnetic resonance (CMR) for workup of suspected cardiac sarcoid involvement. The median follow-up time was 2.6 years. Primary endpoints were death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator (ICD) discharge. Secondary endpoints were ventricular tachycardia (VT) and nonsustained VT. RESULTS LGE was present in 39 patients (25.5%). The presence of LGE yields a Cox hazard ratio (HR) of 31.6 for death, aborted sudden cardiac death, or appropriate ICD discharge, and of 33.9 for any event. This is superior to functional or clinical parameters such as left ventricular (LV) ejection fraction (EF), LV end-diastolic volume, or presentation as heart failure, yielding HRs between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure), and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively. Except for 1 patient dying from pulmonary infection, no patient without LGE died or experienced any event during follow-up, even if the LV was enlarged and the LVEF severely impaired. CONCLUSIONS Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.

Early repolarization, left ventricular diastolic function, and left atrial size in professional soccer players

Recent data have suggested a relation among long-term endurance sport practice, left atrial remodeling, and atrial fibrillation. We investigated the influence of an increased vagal tone, represented by the early repolarization (ER) pattern, on diastolic function and left atrial size in professional soccer players. Fifty-four consecutive athletes underwent electrocardiography, echocardiography, and exercise testing as part of their preparticipation screening. Athletes were divided into 2 groups according to presence or absence of an ER pattern, defined as a ST-segment elevation at the J-point (STE) > or =0.1 mm in 2 leads. For linear comparisons average STE was calculated. Mean age was 24 +/- 4 years. Twenty-five athletes (46%) showed an ER pattern. Athletes with an ER pattern had a significant lower heart rate (54 +/- 9 vs 62 +/- 11 beats/min, p = 0.024), an increased E/e' ratio (6.1 +/- 1.2 vs 5.1 +/- 1.0, p = 0.002), and larger volumes of the left atrium (25.6 +/- 7.3 vs 21.8 +/- 5.0 ml/m(2), p = 0.031) compared to athletes without an ER pattern. There were no significant differences concerning maximum workload, left ventricular dimensions, and systolic function. Univariate regression analysis revealed significant correlations among age, STE, and left atrial volume. In a stepwise multivariate regression analysis age, STE and e' contributed independently to left atrial size (r = 0.659, p <0.001). In conclusion, athletes with an ER pattern had an increased E/e' ratio, reflecting a higher left atrial filling pressure, contributing to left atrial remodeling over time.

Left ventricular torsion abnormalities in septic shock and corrective effect of volume loading: a pilot study

BACKGROUND Ventricular torsion is an important component of cardiac function. The effect of septic shock on left ventricular torsion is not known. Because torsion is influenced by changes in preload, we compared the effect of fluid loading on left ventricular torsion in septic shock with the response in matched healthy control subjects. METHODS We assessed left ventricular torsion parameters using transthoracic echocardiography in 11 patients during early septic shock and in 11 age- and sex-matched healthy volunteers before and after rapid volume loading with 250 mL of a Ringer's lactate solution. RESULTS Peak torsion and peak apical rotation were reduced in septic shock (10.2 ± 5.2° and 5.6 ± 5.4°) compared with healthy volunteers (16.3 ± 4.5° and 9.6 ± 1.5°; P = 0.009 and P = 0.006 respectively). Basal rotation was delayed and diastolic untwisting velocity reached its maximum later during diastole in septic shock patients than in healthy volunteers (104 ± 16% vs 111 ± 14% and 13 ± 5% vs 21 ± 10%; P = 0.03 and P = 0.034, respectively). Fluid challenge increased peak torsion in both groups (septic shock, 10.2 ± 5.3° vs 12.6 ± 3.9°; healthy volunteers, 16.3 ± 4.5° vs 18.1 ± 6°; P = 0.01). Fluid challenge increased left ventricular stroke volume in septic shock patients (P = 0.003). CONCLUSIONS Compared with healthy volunteers, left ventricular torsion is impaired in septic shock patients. Fluid loading attenuates torsion abnormalities in parallel with increasing stroke volume. Reduced torsional motion might constitute a relevant component of septic cardiomyopathy, a notion that merits further testing in larger populations.