-
[show abstract]
[hide abstract]
ABSTRACT: Cardiac contractility modulation (CCM) is a novel device-based therapy for heart failure that involves applying electrical signals during the absolute refractory period of the myocardial action potential. This therapy has been shown to augment the strength of left ventricular contraction independent of myocardial oxygen consumption in animal models as well as human studies of patients with heart failure and reduced ejection fractions. The mechanism underlying CCM is an alteration of myocardial calcium handling in a fashion that extends beyond the traditional pharmacological effects of inotropic agents. Analysis of myocardial tissue from both animal models and human hearts treated by CCM demonstrates a shift of abnormally expressed genes towards normal function, positively affecting pathways involving proteins that regulate calcium cycling and myocardial contraction. CCM effects are proven to be independent of QRS duration; however, clinical studies to date have primarily focused on patients with normal QRS since cardiac resynchronization therapy is a well-established option for patients with heart failure and a prolonged QRS duration. Clinical trials show that CCM improves exercise tolerance, as measured by VO2,peak and quality of life, assessed by the Minnesota Living with Heart Failure Questionnaire. The device is currently available for the treatment of heart failure in Europe. Approval in the USA is pending additional testing currently underway using a protocol approved by the US FDA.
Expert Review of Cardiovascular Therapy 05/2013; 11(5):635-45.
-
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 04/2013; 32(4):466-8. · 3.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The high mortality rate of pulmonary arterial hypertension (PAH) mainly relates to progressive right ventricular (RV) failure. With limited efficacy of medical therapies, mechanical circulatory support for the RV has been considered. However, there is lack of understanding of the hemodynamic effects of mechanical support in this setting.
We modeled the cardiovascular system, simulated cases of PAH and RV dysfunction and assessed the theoretical effects of a continuous flow micro-pump as an RV assist device (RVAD). RVAD inflow was sourced either from the RV or RA and outflow was to the pulmonary artery. RVAD support was set at various flow rates and additional simulations were carried out in the presence of atrial septostomy (ASD) and tricuspid regurgitation (TR).
RVAD support increased LV filling, thus improving cardiac output and arterial pressure, unloading the RA and RV, while raising pulmonary arterial and capillary pressures in an RVAD flow-dependent manner. These effects diminished with increasing disease severity. The presence of TR did not significantly impact the hemodynamic effects of RVAD support. ASD reduced the efficacy of RVAD support, since right-to-left shunting decreased and ultimately reversed with increasing RVAD support due to the progressive drop in RA pressure.
The results of this theoretical analysis suggest that RVAD support can effectively increase cardiac output and decreases RA pressure with the consequence of increasing pulmonary artery and capillary pressures. Especially in advanced PAH, low RVAD flow rates may mitigate these potentially detrimental effects while effectively increasing systemic hemodynamics.
Progress in cardiovascular diseases 09/2012; 55(2):234-243.e2. · 4.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report a case of a 49-year old male with a congenitally corrected transposition of the great arteries (ccTGA) implanted with a left atrial to right subclavian artery ventricular assist device (CircuLite) because of the failure of the anatomic right (systemic) ventricle. Additionally, elevated pulmonary pressures and peripheral vascular resistance (7.4 Wood units) prevented him from being put on the transplant list. The implant, performed off-pump through a right minithoracotomy, was uncomplicated and there were no adverse events. Within 1 month of the implant, there was a marked improvement in exercise tolerance and decreases in pulmonary pressures and resistance, so that the patient was able to return to work and became eligible for transplant listing. As of the time of writing, the patient has been supported for 10 months and is awaiting a heart transplant.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 06/2012; 42(4):741-3. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cardiac contractility modulation (CCM) signals are non-excitatory signals applied during the absolute refractory period that have been shown to enhance the strength of left ventricular contraction without increasing myocardial oxygen consumption in studies carried out in animals and humans with heart failure and reduced ejection fraction. Studies from myocardial tissue of animals and humans with heart failure suggest that the mechanisms of these effects is that CCM drives expression of many genes that are abnormally expressed in heart failure towards normal, including proteins involved with calcium cycling and the myocardial contractile machinery. Clinical studies have primarily focused on patients with normal QRS durations in view of the fact that cardiac resynchronization (CRT) is a viable option for patients with prolonged QRS duration. These studies show that CCM improves exercise tolerance as indexed by peak oxygen consumption (VO(2)) and quality of life indexed by the Minnesota Living with Heart Failure Questionnaire. The device is currently available for clinical use in countries recognizing the CE mark and is undergoing additional testing in the USA under a protocol approved by the Federal Drug Administration.
European Journal of Heart Failure 06/2012; 14(7):703-12. · 4.90 Impact Factor
-
Daniel Burkhoff
European Heart Journal 09/2011; 33(14):1718-20. · 10.48 Impact Factor
-
William T Abraham,
Koonlawee Nademanee,
Kent Volosin,
Steven Krueger,
Suresh Neelagaru,
Nirav Raval,
Owen Obel,
Stanislav Weiner,
Marc Wish,
Peter Carson,
Kenneth Ellenbogen,
Robert Bourge,
Michael Parides,
Richard P Chiacchierini,
Rochelle Goldsmith,
Sidney Goldstein,
Yuval Mika, Daniel Burkhoff,
Alan Kadish
[show abstract]
[hide abstract]
ABSTRACT: Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the absolute refractory period intended to improve contraction. We previously tested the safety and efficacy of CCM in 428 NYHA functional class III/IV heart failure patients with EF ≤35% and narrow QRS randomized to optimal medical treatment (OMT) plus CCM (n = 215) versus OMT alone (n = 213) and found no significant effect on ventilatory anaerobic threshold (VAT), the study's primary end point. In the present analysis, we sought to identify if there was a subgroup of patients who showed a response to CCM.
The protocol specified that multiregression analysis would be used to determine if baseline EF, NYHA functional class, pVO(2), or etiology of heart failure influenced the impact of CCM on AT. Etiology and baseline pVO(2) did not affect efficacy. However, baseline NYHA functional class III and EF ≥25% were significant predictors of increased efficacy. In this subgroup (comprising 97 OMT and 109 CCM patients, ∼48% of the entire population) VAT increased by 0.10 ± 2.36 in CCM versus -0.54 ± 1.83 mL kg(-1) min(-1) in OMT (P = .03) and pVO(2) increased by 0.34 ± 3.11 in CCM versus -0.97 ± 2.31 (P = .001) at 24 weeks compared with baseline; 44% of CCM versus 23% of OMT subjects showed improvement of ≥1 class in NYHA functional class (P = .002), and 59% of CCM versus 42% of OMT subjects showed a ≥10-point reduction in Minnesota Living with Heart Failure Questionnaire (P = .01). All of these findings were similar to those seen at 50 weeks.
The results of this retrospective hypothesis-generating analysis indicate that CCM significantly improves objective parameters of exercise tolerance in a subgroup of patients characterized by normal QRS duration, NYHA functional class III symptoms, and EF >25%.
Journal of cardiac failure 09/2011; 17(9):710-7. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Extracardiac comorbidities are common in patients with heart failure and a preserved ejection fraction (HFPEF). We sought to evaluate the relationship between comorbidities and ventricular structure and function in patients with HFPEF through evaluation of pressure-volume analysis.
Two hundred twenty Chinese patients with a preserved ejection fraction who were either healthy (n = 75), hypertensive without heart failure (HTN; n = 89), or hypertensive with HFPEF (HFPEF; n = 56) were studied. Using echocardiographic measures, estimated end-systolic and end-diastolic pressure-volume relationships, and the area between them as a function of EDP, the isovolumic pressure-volume areas (PVA(iso)), were calculated. Ventricular capacitance, as measured by V(30), was larger in patients with HFPEF compared with normal control subjects and tended to be larger compared with hypertensive control subjects. The presence of diabetes and renal insufficiency was independently associated with greater ventricular capacitance in patients with HFPEF. The PVA(iso) was increased in patients with HFPEF compared with HTN and normal control subjects, and in particular, it was increased in HFPEF patients with multiple comorbidities.
The presence of comorbid conditions is associated with altered pressure-volume relations and enhanced pump function in subjects with HFPEF, supporting an important role for extracardiac comorbidities in the pathophysiology of patients with this condition.
Journal of cardiac failure 07/2011; 17(7):547-55. · 3.25 Impact Factor
-
Daniel Burkhoff
[show abstract]
[hide abstract]
ABSTRACT: Cardiac resynchronization therapy (CRT) is an established therapy for patients with systolic dysfunction, QRS duration greater than 120 ms, and New York Heart Association (NYHA) class III or IV symptoms. However, most patients with heart failure have QRS duration below 120 ms and 30% or more of CRT recipients are nonresponders. Cardiac contractility modulation (CCM) signals are nonexcitatory electrical impulses applied during the absolute refractory period that are intended to enhance contractile strength independent of QRS duration. Myocardial biopsy studies suggest that modulation of protein phosphorylation and gene expression underlie the mechanisms by which CCM exerts its effects. Two prospective randomized studies have investigated the impact of CCM on exercise tolerance and quality of life in patients with chronic heart failure. These studies have included predominantly patients with NYHA class III heart failure with QRS duration below 130 ms. This review summarizes results of these clinical studies and outlines additional studies underway to further clarify the role of CCM in the treatment of heart failure.
Current Heart Failure Reports 06/2011; 8(4):260-5.
-
Alan Kadish,
Koonlawee Nademanee,
Kent Volosin,
Steven Krueger,
Suresh Neelagaru,
Nirav Raval,
Owen Obel,
Stanislav Weiner,
Marc Wish,
Peter Carson,
Kenneth Ellenbogen,
Robert Bourge,
Michael Parides,
Richard P Chiacchierini,
Rochelle Goldsmith,
Sidney Goldstein,
Yuval Mika, Daniel Burkhoff,
William T Abraham
[show abstract]
[hide abstract]
ABSTRACT: Cardiac contractility modulation (CCM) delivers nonexcitatory electrical signals to the heart during the absolute refractory period intended to improve contraction.
We tested CCM in 428 New York Heart Association class III or IV, narrow QRS heart failure patients with ejection fraction (EF) ≤ 35% randomized to optimal medical therapy (OMT) plus CCM (n = 215) versus OMT alone (n = 213). Efficacy was assessed by ventilatory anaerobic threshold (VAT), primary end point, peak Vo₂ (pVo₂), and Minnesota Living with Heart Failure Questionnaire (MLWFQ) at 6 months. The primary safety end point was a test of noninferiority between groups at 12 months for the composite of all-cause mortality and hospitalizations (12.5% allowable delta).
The groups were comparable for age (58 ± 13 vs 59 ± 12 years), EF (26% ± 7% vs 26% ± 7%), pVo₂ (14.7 ± 2.9 vs 14.8 ± 3.2 mL kg⁻¹ min⁻¹), and other characteristics. While VAT did not improve at 6 months, CCM significantly improved pVo₂ and MLWHFQ (by 0.65 mL kg⁻¹ min⁻¹ [P = .024] and -9.7 points [P < .0001], respectively) over OMT. Forty-eight percent of OMT and 52% of CCM patients experienced a safety end point, which satisfied the noniferiority criterion (P = .03). Post hoc, hypothesis-generating analysis identified a subgroup (characterized by baseline EF ≥ 25% and New York Heart Association class III symptoms) in which all parameters were improved by CCM.
In the overall target population, CCM did not improve VAT (the primary end point) but did improve pVo₂ and MLWHFQ. Cardiac contractility modulation did not have an adverse affect on hospitalizations or mortality within the prespecified boundaries. Further study is required to clarify the role of CCM as a treatment for medically refractory heart failure.
American heart journal 02/2011; 161(2):329-337.e1-2. · 4.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To examine the association between cardiac performance during recovery and the severity of heart failure, as determined by clinical and cardiopulmonary exercise test responses.
As part of a retrospective cohort study, 46 heart failure patients and 13 normal subjects underwent cardiopulmonary exercise testing while cardiac output was measured using a noninvasive device. Cardiac output in recovery was expressed as the slope of a single exponential relationship between cardiac output and time; the recovery-time constant was assessed in relation to indices of cardiac function, along with clinical, functional, and cardiopulmonary exercise responses.
The recovery time constant was delayed in patients with heart failure compared with normal subjects (296.7 ± 238 vs. 110.1 ±27 seconds, p <0.01), and the slope of the decline of cardiac output in recovery was steeper in normal subjects compared with heart failure patients (p<0.001). The slope of the decline in cardiac output recovery was inversely related to peak VO(2) (r = -0.72, p<0.001) and directly related to the VE/VCO(2) slope (r = 0.57, p,0.001). Heart failure patients with abnormal recovery time constants had lower peak VO(2), lower VO(2) at the ventilatory threshold, lower peak cardiac output, and a heightened VE/VCO(2) slope during exercise.
Impaired cardiac output recovery kinetics can identify heart failure patients with more severe disease, lower exercise capacity, and inefficient ventilation. Estimating cardiac output in recovery from exercise may provide added insight into the cardiovascular status of patients with heart failure.
Clinics (São Paulo, Brazil) 01/2011; 66(4):649-56. · 1.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Full mechanical support with a left-ventricular assist device (LVAD) is generally limited to end-stage heart-failure patients. We have been studying the safety and efficacy of the partial support Synergy® Pocket Micro-pump as bridge-to-transplant in a less-sick group of patients as a prelude to a study of its use for destination therapy.
The CircuLite® Synergy device is implanted via a small right-sided thoracotomy with an inflow cannula in the left atrium and an outflow graft connected to the right subclavian artery without the use of extracorporeal circulation. The micro-pump is the size of an AA battery, sits in the 'pacemaker' pocket subcutaneously in the right clavicular groove and pumps up to 3.0 l min⁻¹ from the left atrium to the right subclavian artery.
The device has been implanted in 27 patients awaiting cardiac transplant (22 males), age 54.8 ± 10.0 years with ejection fraction (EF) 21 ± 6%, mean arterial pressure 73.5 ± 8.8 mm Hg, pulmonary capillary wedge pressure (PCWP) 27.5 ± 7.8 mm Hg and cardiac index (CI) 2.0 ± 0.4 l min⁻¹ m⁻². Duration of support has ranged from 6 to 281 days. Right-heart catheterization showed significant hemodynamic improvement in the short- and intermediate term after implant, with increases in CI from 2.0 ± 0.4 to 2.8 ± 0.6 l min⁻¹ m⁻² (p < 0.001) and reductions in PCWP from 28 ± 6 to 18 ± 7 mm Hg (p = 0.002) at an average of 9.5 ± 5.5 weeks.
The Synergy device provides partial hemodynamic support and its use is associated with significantly improved hemodynamics, thus appearing to interrupt and partially reverse the progressive hemodynamic deterioration typical of end-stage heart failure. Ongoing efforts are aimed at demonstrating additional clinical benefits and continuing to further improve the risk/benefit ratio.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 10/2010; 39(5):693-8. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The ventilatory threshold (VT) is usually determined by visual assessment of the point where the rate of elimination of carbon dioxide (VCO(2)) increases nonlinearly with respect to oxygen uptake (VO(2)) (the V-Slope method). We quantified the reliability of VT determination using data from a multicenter study in patients with heart failure.
The Fix-Heart Failure-5 study of cardiac contractility modulation enrolled 428 patients from 50 centers in the United States. Cardiopulmonary exercise tests were performed at baseline and 12, 24, and 50 weeks after randomization, which provided 1679 tests. The VT was determined from each test in a core laboratory by 2 independent readers. VT could not be determined for 276 tests (16.4% indeterminate). Inter-observer variability (quantified by the 95% limits of agreement, LoA, expressed as a percent of the mean value) was 20.2% between the 2 readers, with a coefficient of variation (CV) of 7.3%. Intra-observer variability was assessed by resubmitting (blinded) 179 tests to the same readers; the LoA was 24.7% for reader 1 and 16.9% for reader 2, with CVs of 6.1 and 8.9%, respectively. Ninety-one tests were submitted to 2 additional readers at a second core lab. Inter-observer variability in the second lab was 26.7% with a CV of 9.6%. Inter-laboratory variability was 21.4%, with a CV of 7.7%.
Inter-observer, intra-observer, and inter-site variation in determining the VT should be considered when using the VT as an end point in clinical trials of heart failure.
Journal of cardiac failure 01/2010; 16(1):76-83. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hemodynamic responses to exercise were assessed in patients with varying degrees of chronic heart failure (CHF) to determine the feasibility of using bioreactance during exercise testing in multicenter studies of CHF.
A total of 210 symptomatic CHF patients and 22 subjects without heart failure were subjected to symptom-limited exercise testing on a bicycle (105) or treadmill (127) while measuring gas exchange for VO(2), cardiac output (CO) noninvasively by a bioreactance technique, heart rate, and blood pressure. Peak CO (pCO) and VO(2) (pVO(2)) during exercise were lower in patients with higher New York Heart Association (NYHA) class, in females and in older patients. Multiple linear regression analysis showed that pCO (L/min)=19.6+4.M -2.1.NYHA+1.9.G -0.09.Age, where M=1 for treadmill and 0 for bicycle and G=1 for males and 0 for females. Similarly, pVO(2) (mL/kg/min)=24+2.1.M -2.9.NYHA+1.26.G -0.08.Age. VO(2) and CO were also highly correlated to each other: pCO (mL/kg/min)=0.059+0.007.pVO(2)+0.036.M -0.025.G. Similar correlations were determined for other parameters of exercise, including left ventricular power, and the ratio of peak/resting VO(2) (cardiovascular reserve), the ratio of peak/resting CO (cardiac reserve), and total peripheral vascular resistance.
Bioreactance-based noninvasive measurements of CO at rest and during exertion identified abnormalities of cardiovascular function consistent with those identified by pVO(2) and in prior studies using invasive CO measurements. This technique might therefore be useful for indexing disease severity, prognostication, and for tracking responses to treatment in clinical practice and in clinical trials.
Journal of cardiac failure 10/2009; 15(8):689-99. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to test the hemodynamic effects of partial ventricular support in patients with advanced heart failure.
The use of current left ventricular assist devices (VADs) that provide full circulatory support is restricted to critically ill patients because of associated risks. Smaller, less-invasive devices could expand VAD use to a larger pool of less-sick patients but would pump less blood, providing only partial support.
The Synergy Pocket Micro-pump device (CircuLite, Inc., Saddle Brook, New Jersey) pumps approximately 3.0 l/min, is implanted (off pump) via a mini-thoracotomy, and is positioned in a right subclavicular subcutaneous pocket (like a pacemaker). The inflow cannula inserts into the left atrium; the outflow graft connects to the right subclavian artery.
A total of 17 patients (14 men), age 53 +/- 9 years with ejection fraction 21 +/- 6%, mean arterial pressure 73 +/- 7 mm Hg, pulmonary capillary wedge pressure 29 +/- 6 mm Hg, and cardiac index 1.9 +/- 0.4 l/min/m(2) received an implant. Duration of support ranged from 6 to 213 (median 81) days. In addition to demonstration of significant acute hemodynamic improvements in the first day of support, 9 patients underwent follow-up right heart catheterization at 10.6 +/- 6 weeks. These patients showed significant increases in arterial pressure (67 +/- 8 mm Hg vs. 80 +/- 9 mm Hg, p = 0.01) and cardiac index (2.0 +/- 0.4 l/min/m(2) vs. 2.8 +/- 0.6 l/min/m(2), p = 0.01) with large reductions in pulmonary capillary wedge pressure (30 +/- 5 mm Hg vs. 18 +/- 5 mm Hg, p = 0.001).
Partial support appears to interrupt the progressive hemodynamic deterioration typical of late-stage heart failure. If proven safe and durable, this device could be used in a relatively large population of patients with severe heart failure who are not sick enough to justify use of currently available full support VADs. (Safety and Performance Evaluation of CircuLite Synergy; NCT00878527).
Journal of the American College of Cardiology 07/2009; 54(1):79-86. · 14.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Reductions in heart rate (HR) with beta-blocker therapy have been associated with improvements in ejection fraction (EF). However, the relative contributions of HR reduction, positive inotropism, afterload reduction, and reverse remodeling to improvements in EF are unknown.
Twenty-nine patients (63+/-12 years old) with New York Heart Association class II-III heart failure underwent serial measurements of left ventricular volumes using 3-dimensional echocardiography and blood pressures by sphygmomanometry at baseline, 2 weeks, 2, 6, and 12 months after initiation of carvedilol. From these parameters, left ventricular contractility (indexed by the end-systolic pressure-volume ratio), total peripheral resistance, and effective arterial elastance (E(a)) were derived. Overall, EF increased by 7-percentage points after 6 months of therapy (from 25+/-9 to 32+/-9, P<0.0001). This change was due to an increase in stroke volume (P<0.001) with no significant change in end-diastolic volume (P=0.15). The EF change correlated with increased contractility, decreased HR and decreased total peripheral resistance (P<0.003 in each case). In those patients whose EF increased at least 5 points, approximately 60% of the increase was due to HR reduction, approximately 30% was due to increased contractility, and <20% was due to the decrease in total peripheral resistance.
Decreased HR, improved chamber contractility and afterload reduction each contributed significantly to improved EF with carvedilol.
Circulation Heart Failure 05/2009; 2(3):189-96. · 6.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: More than half of patients with heart failure (HF) have a normal ejection fraction (EF). These patients are typically elderly, are predominantly female, and have a high incidence of multiple comorbid conditions associated with development of ventricular hypertrophy and/or interstitial fibrosis. Thus, the cause of HF has been attributed to diastolic dysfunction. However, the same comorbidities may also impact myocardial systolic, ventricular, vascular, renal, and extracardiovascular properties in ways that can also contribute to symptoms of HF by way of mechanisms not related to diastolic dysfunction. Accordingly, the descriptive term HF with normal EF has been suggested as an alternative to the mechanistic term diastolic HF. In this article, we review the current understanding of nondiastolic mechanisms that may contribute to the HF with normal EF syndrome to highlight potential pathways for research that may lead to new targets for therapy.
Current Heart Failure Reports 04/2009; 6(1):57-64.
-
[show abstract]
[hide abstract]
ABSTRACT: Although many studies of heart failure therapies test improvements of patient condition in terms of mean changes of quality of life (QoL) or exercise tolerance (ET) measures, it is of increasing interest to quantify the proportion of patients that "respond" to therapy and understand factors predicting response. These questions can be address through the use of a "responder analysis," in which the proportion of patients in whom a measure of QoL or ET improves by a minimum amount is determined. Here, we review the principles of a "responder analysis."
We used data from published studies of cardiac resynchronization therapy to model the results of a responder analysis and original data from a recent study of cardiac contractility modulation to illustrate the many facets of such an analysis that need to be understood and investigated further. Some of these areas include: understanding how to choose criteria for response; how to deal with differing results obtained with different measures of response; and how to deal with potentially conflicting information provided by a responder analysis and the more standard comparison of mean changes.
Additional prospective studies will help advance understanding the optimal way to use responder analyses in heart failure trials.
Journal of cardiac failure 04/2009; 15(2):108-15. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although echo Doppler recordings of mitral inflow patterns are often employed clinically to identify "diastolic dysfunction," abnormal flow profiles may be seen in a diverse set of disorders in which the specific physiologic determinants are not well defined.
We used a validated cardiovascular simulation model to assess the effects of four hemodynamic parameters on Doppler measures of LV filling: (1) total blood volume, (2) diastolic stiffness (LV Beta), (3) systemic vascular resistance (SVR), and (4) pulmonary vascular resistance (PVR). In each simulation, we calculated instantaneous flow through the mitral valve as a function of time.
Increases in blood volume led to an increase in the E:A ratio and a decrease in deceleration time (DT), such that for every 100 mL of volume, DT decreased by approximately 3 ms. Increases in LV Beta increased the E:A ratio and decreased DT such that for every 0.005 mmHg/mL increase in LV Beta, DT decreased by approximately 8 ms. While changes in SVR did not significantly alter the Doppler pattern, increases in PVR effected a prolongation of DT and an impaired relaxation E:A pattern. Increasing blood volume and LV Beta simultaneously was additive, while increasing PVR attenuated the effect of increasing volume on the E:A ratio.
Computer simulations demonstrate that both blood volume and LV stiffness significantly impact the mitral inflow profile indicating that both filling pressure and intrinsic properties of the ventricle are contributors. These data confirm that there are multiple determinants of the Doppler mitral inflow pattern and suggest a new approach toward understanding complex physiologic interactions.
Echocardiography 03/2009; 26(2):155-62. · 1.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiotensin-converting enzyme inhibitors (ACE-Is) prevent the rise in myocardial angiotensin II that occurs after left ventricular assist device (LVAD) implantation, but do not fully normalize cardiac function. Here, we determined the effect of LVAD implantation, with or without ACE-Is, on cardiac renin, aldosterone, and norepinephrine, since these hormones, like angiotensin II, are likely determinants of myocardial recovery during LVAD support.
Biochemical measurements were made in paired LV myocardial samples obtained from 20 patients before and after LVAD support in patients with and without ACE-I therapy. Pre-LVAD renin levels were 100x normal and resulted in almost complete cardiac angiotensinogen depletion. In non-ACE-I users, LVAD support, by normalizing blood pressure, reversed this situation. Cardiac aldosterone decreased in parallel with cardiac renin, in agreement with the concept that cardiac aldosterone is blood-derived. Cardiac norepinephrine increased seven-fold, possibly due to the rise in angiotensin II. Angiotensin-converting enzyme inhibitor therapy prevented these changes: renin and aldosterone remained high, and no increase in norepinephrine occurred.
Although LV unloading lowers renin and aldosterone, it allows cardiac angiotensin generation to increase and thus to activate the sympathetic nervous system. Angiotensin-converting enzyme inhibitors prevent the latter, but do not affect aldosterone. Thus, mineralocorticoid receptor antagonist therapy during LVAD support may play a role in further promoting recovery.
European Heart Journal 03/2009; 30(7):805-12. · 10.48 Impact Factor
