Orwik

Partial mechanical long-term support with the CircuLite Synergy pump as bridge-to-transplant in congestive heart failure.

BACKGROUND: Full mechanical support with a left ventricular assist device (LVAD) is often limited to very sick patients, as the only survival option. This European multicenter study analyzes the effect of partial mechanical support as bridge-to-trans... expand abstractplant in a less sick heart failure patient group. METHODS: 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 pump itself sits in a "pacemaker" pocket subcutaneously in the right clavicular groove. It is able to pump up to 3.0 l/min and partially unload the left ventricle. RESULTS: The device was implanted in 25 patients on the cardiac transplant waiting list (20 males), aged 55.5 +/- 9.6 yrs with an ejection fraction of 21.6 +/- 6.0 %, a mean arterial pressure of 73.5 +/- 8.5 mmHg, a pulmonary capillary wedge pressure of 27.2 +/- 7.8 mmHg and cardiac index of 1.9 +/- 0.4 l/min/m (2). Duration of support ranged from 6 to 238 days. Right heart catheterization showed significant hemodynamic improvement in the short- and intermediate-term after implantation with increases in arterial pressure from 72.6 +/- 11.0 to 79.4 +/- 8.6 mmHg ( P = 0.04) and in cardiac index from 2.0 +/- 0.4 to 2.7 +/- 0.6 l/min/m (2) ( P = 0.003) with a reduction in pulmonary capillary wedge pressure from 28.5 +/- 6.0 to 19.7 +/- 6.9 mmHg ( P = 0.012). CONCLUSIONS: The CircuLite Synergy device is a partial support pump, which is easy to implant and which provides hemodynamic benefits in bridging heart failure patients to cardiac transplant. collapse abstract

Impact of cardiac contractility modulation on left ventricular global and regional function and remodeling.

OBJECTIVES: This study aimed to evaluate the impact of cardiac contractility modulation (CCM) on left ventricular (LV) size and myocardial function. BACKGROUND: CCM is a device-based therapy for patients with advanced heart failure. Previous studies ... expand abstractshowed that CCM improved symptoms and exercise capacity; however, comprehensive assessment of LV structure, function, and reverse remodeling is not available. METHODS: Thirty patients (60 + or - 11 years, 80% male) with New York Heart Association (NYHA) functional class III heart failure, ejection fraction <35%, and QRS <120 ms were assessed at baseline and 3 months. LV reverse remodeling was measured by real-time 3-dimensional echocardiography. Using tissue Doppler imaging, the peak systolic velocity (Sm) and peak early diastolic velocity (Em) were calculated for LV function, while the standard deviation of the time to peak systolic velocity (Ts-SD) and the time to peak early diastolic velocity (Te-SD) were calculated for mechanical dyssynchrony. RESULTS: LV reverse remodeling was evident, with a reduction in LV end-systolic volume by -11.5 + or - 10.5% and a gain in ejection fraction by 4.8 + or - 3.6% (both p < 0.001). Myocardial contraction was improved in all LV walls, including sites remote from CCM delivery (all p < 0.05); hence, the mean Sm of 12 (2.2 + or - 0.6 cm/s vs. 2.5 + or - 0.7 cm/s) or 6 basal LV segments (2.5 + or - 0.6 cm/s vs. 3.0 + or - 0.7 cm/s) were increased significantly (both p < 0.001). In contrast, CCM had no impact on regional or global Em (2.9 + or - 1.3 cm/s vs. 2.9 + or - 1.1 cm/s), whereas Ts-SD (28.2 + or - 11.2 ms vs. 27.9 + or - 12.7 ms) and Te-SD (30.0 + or - 18.3 ms vs. 30.1 + or - 20.7 ms) remained unchanged (all p = NS). Mitral regurgitation was reduced (22 + or - 14% vs. 17 + or - 15%, p = 0.02). Clinically, there was improvement of NYHA functional class (p < 0.001) and 6-min hall walk distance (p = 0.015). A 24-h Holter monitor showed that premature ventricular contractions were not increased during CCM. CONCLUSIONS: CCM improves both global and regional LV contractility, including regions remote from the impulse delivery, and may contribute to LV reverse remodeling and gain in systolic function. Such improvement is unrelated to diastolic function or mechanical dyssynchrony. collapse abstract

Chasing the elusive pressure-volume relationships.

Single-beat estimation of the left ventricular end-diastolic pressure-volume relationship in patients with heart failure.

Aims To test a method to predict the end-diastolic pressure-volume relationship (EDPVR) from a single beat in patients with heart failure. Methods and results Patients (New York Heart Association class III-IV) scheduled for mitral annuloplasty (n=9) ... expand abstractor ventricular restoration (n=10) and patients with normal left ventricular function undergoing coronary artery bypass grafting (n=12) were instrumented with pressure-conductance catheters to measure pressure-volume loops before and after surgery. Data obtained during vena cava occlusion provided directly measured EDPVRs. Baseline end-diastolic pressure (P(m)) and volume (V(m)) were used for single-beat prediction of EDPVRs. Root-mean-squared error (RMSE) between measured and predicted EDPVRs, was 2.79+/-0.21 mm Hg. Measured versus predicted end-diastolic volumes at pressure levels 5, 10, 15 and 20 mm Hg showed tight correlations (R(2)=0.69-0.97). Bland-Altman analyses indicated overestimation at 5 mm Hg (bias: pre-surgery 44 ml (95% CI 29 to 58 ml); post-surgery 35 ml (23 to 47 ml)) and underestimation at 20 mm Hg (bias: pre-surgery -57 ml (-80 to -34 ml); post-surgery -13 ml (-20 to -7.0 ml)). End-diastolic volumes were significantly different between groups and between conditions, but these differences were not dependent on the method (ie, measured versus predicted). RMSEs were not different between groups or conditions, nor dependent on V(m) or P(m), indicating that EDPVR prediction was equally accurate over a wide volume range. Conclusions Single-beat EDPVRs obtained from hearts spanning a wide range of sizes and conditions accurately predicted directly measured EDPVRs with low RMSE. Single-beat EDPVR indices correlated well with directly measured values, but systematic biases were present at low and high pressures. The single-beat method facilitates less invasive EDPVR estimation, particularly when coupled with emerging non-invasive techniques to measure pressures and volumes. collapse abstract

The ventilatory anaerobic threshold in heart failure: a multicenter evaluation of reliability.

BACKGROUND: 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 quantifie... expand abstractd the reliability of VT determination using data from a multicenter study in patients with heart failure. METHODS AND RESULTS: 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%. CONCLUSIONS: 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. collapse abstract

Myoblast transfer in ischemic heart failure: effects on rhythm stability.

Skeletal myoblast (SM) implantation promotes recovery of myocardial function after ischemic injury. Clinical observations suggest an association of SM implantation and ventricular arrhythmias. Support for this link has been sought in animal studies, ... expand abstractbut none employing models of congestive heart failure. In a canine model of postinfarction congestive heart failure (CHF) we compared the frequency of rhythm disturbances using ambulatory electrocardiography monitoring following skeletal myoblast or saline (SAL) implantation. In 19 mongrel dogs ischemic injury and CHF were induced by intracoronary microsphere infusions. Direct intramyocardial injection of autologous skeletal myoblasts (ASM) (2.7-8.3 x 10(8) cells) or SAL controls was administered to 11 and 8 dogs, respectively. Serial echocardiography and 24-h ambulatory electrocardiography were recorded at baseline (after CHF induction) and at 4 weeks and at 8-10 weeks after injection. Comparisons between groups of left ventricular ejection fraction (LVEF) and the frequency of ventricular arrhythmias, supraventricular arrhythmias, and measures of heart rate variability (HRV) were made at each of the three time points. LVEF increased from 41 +/- 6% to 47 +/- 2% (p < 0.03) in the ASM group, and did not change (42 +/- 6% to 40 +/- 2%, p = ns) in SAL. After injection, no differences were seen in the number of dogs demonstrating ventricular tachycardia (n = 3 vs. n = 2, p = ns) or frequent PVCs (n = 3 vs. n = 3, p = ns) in the ASM versus SAL groups, respectively. Significant changes were observed in a time-domain measure of HRV, standard deviation of normal-to-normal RR interval (in ms: 4 weeks 174 +/- 95 vs. 242 +/- 19; 8 weeks 174 +/- 78 vs. 276 +/- 78, ASM vs. SAL), but not in other time domain parameters. In this canine model of ischemic CHF, ASM implantation did not result in a significant increase in ventricular arrhythmias compared to controls animals. The potential for ASM implantation to affect time-domain parameters of HRV merits further study. collapse abstract

Proof of concept: hemodynamic response to long-term partial ventricular support with the synergy pocket micro-pump.

OBJECTIVES: The purpose of this study was to test the hemodynamic effects of partial ventricular support in patients with advanced heart failure. BACKGROUND: The use of current left ventricular assist devices (VADs) that provide full circulatory supp... expand abstractort 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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). collapse abstract

A multicenter study of noninvasive cardiac output by bioreactance during symptom-limited exercise.

BACKGROUND: 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. METHODS AND RESULTS:... expand abstract 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. CONCLUSION: 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. collapse abstract

Mechanisms underlying improvements in ejection fraction with carvedilol in heart failure.

BACKGROUND: 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 remodelin... expand abstractg to improvements in EF are unknown. METHODS AND RESULTS: 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. CONCLUSIONS: Decreased HR, improved chamber contractility and afterload reduction each contributed significantly to improved EF with carvedilol. collapse abstract

Comparison of ventricular structure and function in Chinese patients with heart failure and ejection fractions 55 versus 40 to 55 versus 40.

Subjects with heart failure (HF) and a preserved ejection fraction (EF) are heterogenous and the EF used to define this syndrome varies considerably among studies. We sought to determine if physiologic differences exist between subjects with a normal... expand abstract EF (>55%) or mildly decreased EF (40% to 55%). 357 consecutive Chinese patients who were healthy (n = 93) or had HF (n = 264) underwent comprehensive echocardiography, Doppler analysis, and measurement of neurohormones. Subjects with HF were stratified by EF into those with normal EF (>55%, n = 128), mildly decreased EF (40% to 55%, n = 38), or moderate to severely decreased EF (<40%, n = 100). Employing noninvasive pressure-volume analysis, estimated end-systolic and end-diastolic pressure-volume relations were calculated. Subjects with HF and an EF 40% to 55% more often had a previous myocardial infarction and diabetes than those with HF and an EF >55%. Physiologically, the cohort with a mildly decreased EF had eccentrically enlarged ventricles with evidence of remodeling (rightward shifted end-diastolic pressure-volume relation) and decreased chamber contractility (downward shifted end-systolic pressure-volume relation) most comparable to subjects with overt systolic HF. In conclusion, in subjects with HF and a preserved EF, there are distinct physiologic differences between those with a normal (>55%) and a mildly decreased (40% to 55%) EF. collapse abstract

Heart failure with normal ejection fraction: consideration of mechanisms other than diastolic dysfunction.

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 ventricu... expand abstractlar 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. collapse abstract

The impact of left ventricular assist device-induced left ventricular unloading on the myocardial renin-angiotensin-aldosterone system: therapeutic consequences?

AIMS: 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... expand abstract 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. METHODS AND RESULTS: 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. CONCLUSION: 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. collapse abstract

Physiologic determinants of mitral inflow pattern using a computer simulation: insights into Doppler echocardiography in diverse phenotypes.

BACKGROUND: 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 ... expand abstractare not well defined. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. collapse abstract

End-tidal CO2 pressure and cardiac performance during exercise in heart failure.

INTRODUCTION: In patients with heart failure (HF), end-tidal CO2 pressure (PetCO2) is related to ventricular function at rest and has been shown to predict prognosis. However, little is known about the association between ventricular performance and ... expand abstractPetCO2 responses to exercise. METHODS: Forty-eight patients with HF and 13 normal subjects underwent cardiopulmonary exercise testing (CPX), while cardiac output and other hemodynamic measurements at rest and during exercise were obtained using a novel, noninvasive, bioreactance device based on assessment of relative phase shifts of electric currents injected across the thorax, heart rate, and ventricular ejection time. CPX responses and indices of cardiac performance were compared between normal subjects and HF patients achieving above and below a PetCO2 of 36 mm Hg at the ventilatory threshold (PetCO2@VT). RESULTS: HF patients with an abnormal PetCO2@VT (<36 mm Hg) had a lower exercise capacity, a lower .VO2@VT, a higher .V_E/.VCO2 slope, and lower oxygen uptake efficiency slope (OUES) values compared with normal subjects and patients achieving a normal PetCO2@VT. Patients with reduced PetCO2@VT had lower peak cardiac output responses to exercise (20.0 +/- 10, 17.8 +/- 6, and 13.7 +/- 7 L x min for normal subjects and HF patients with normal and abnormal PetCO2 responses to exercise, respectively, P = 0.04). PetCO2@VT was inversely related to the .V_E/.VCO2 slope (r = -0.78, P < 0.001) and directly related to the OUES (r = 0.55, P < 0.001). CONCLUSION: Reduced PetCO2 reflects impairments in the functional, ventilatory, and cardiac performance response to exercise in patients with HF. PetCO2 can supplement other clinical and CPX indices in the functional and prognostic evaluation of patients with HF. collapse abstract

"Responder analysis" for assessing effectiveness of heart failure therapies based on measures of exercise tolerance.

BACKGROUND: 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 pati... expand abstractents 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." METHODS AND RESULTS: 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. CONCLUSIONS: Additional prospective studies will help advance understanding the optimal way to use responder analyses in heart failure trials. collapse abstract

Elective bridging to recovery after repair: the surgical approach to ventricular reverse remodeling.

We described our "surgical approach to reverse ventricular remodeling" in advanced chronic heart failure, based on the unique idea that "downstaging" class IV heart failure by supporting patients with left ventricular assist devices (LVADs) allows tr... expand abstracteatments mainly indicated for class III patients. The types of surgeries include mitral valve repair, surgical ventricular remodeling, coronary artery bypass grafting, and cardiac resynchronization. This approach has been applied to two patients with class IV chronic heart failure due to idiopathic dilated cardiomyopathy who were supported with the magnetically levitated Levacor LVAD. These were the first in-human implantations of this device. Sustained short- to medium-term recovery has been achieved in both patients. collapse abstract

Partial left ventricular support implanted through minimal access surgery as a bridge to cardiac transplant.

First human use of partial left ventricular heart support with the Circulite synergy micro-pump as a bridge to cardiac transplantation.

Cardiac contractility modulation electrical signals improve myocardial gene expression in patients with heart failure.

OBJECTIVES: The objective of this study was to test whether cardiac contractility modulation (CCM) electric signals induce reverse molecular remodeling in myocardium of patients with heart failure. BACKGROUND: Heart failure is associated with up-regu... expand abstractlation of myocardial fetal and stretch response genes and down-regulation of Ca(2+) cycling genes. Treatment with CCM signals has been associated with improved symptoms and exercise tolerance in heart failure patients. We tested the impact of CCM signals on myocardial gene expression in 11 patients. METHODS: Endomyocardial biopsies were obtained at baseline and 3 and 6 months thereafter. The CCM signals were delivered in random order of ON for 3 months and OFF for 3 months. Messenger ribonucleic acid expression was analyzed in the core lab by investigators blinded to treatment sequence. Expression of A- and B-type natriuretic peptides and alpha-myosin heavy chain (MHC), the sarcoplasmic reticulum genes SERCA-2a, phospholamban and ryanodine receptors, and the stretch response genes p38 mitogen activated protein kinase and p21 Ras were measured using reverse transcription-polymerase chain reaction and bands quantified in densitometric units. RESULTS: The 3-month therapy OFF phase was associated with increased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase, and p21 Ras and decreased expression of alpha-MHC, SERCA-2a, phospholamban, and ryanodine receptors. In contrast, the 3-month ON therapy phase resulted in decreased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase and p21 Ras and increased expression of alpha-MHC, SERCA-2a, phospholamban, and ryanodine receptors. CONCLUSIONS: The CCM signal treatment reverses the cardiac maladaptive fetal gene program and normalizes expression of key sarcoplasmic reticulum Ca(2+) cycling and stretch response genes. These changes may contribute to the clinical effects of CCM. collapse abstract

Multicenter evaluation of noninvasive cardiac output measurement by bioreactance technique.

OBJECTIVES: Bioreactance, the analysis of intrabeat variations in phase of a transthoracic voltage in response to an applied high frequency transthoracic current, was recently introduced for noninvasive cardiac output measurement (NICOM). We evaluate... expand abstractd NICOM compared to thermo- dilution (TD) in several clinical settings. METHODS: 111 patients with a clinical indication for TD cardiac output (CO) measurement were recruited at five centers, including patients in cardiac catheterization laboratories, cardiac care units and intensive care units. CO measurements were made simulta- neously with TD and the bioreactance method and compared by regression analysis. RESULTS: For studies in the intensive care units, TD-based CO and NICOM were highly correlated (r = 0.78, P < 0.0001) and did not differ significantly from each other (P = 0.55). Results in the cardiac catheterization laboratory were similar (r = 0.71, P < 0.001; P = 0.28 NICOM versus TD). In subsets of patients, NICOM was shown to be better corre- lated with TD-CO than CO obtained with the Fick method or with standard bioimpedance-based measurements of CO. CONCLUSIONS: On average, compared to TD, bioreactance- based NICOM has acceptable accuracy in challenging clinical environments. Availability of such a tool may allow clinicians to have information about CO in patients where this information is not currently available to help diagnosis and guide therapy. collapse abstract

Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure.

AIMS: We performed a randomized, double blind, crossover study of cardiac contractility modulation (CCM) signals in heart failure patients. METHODS AND RESULTS: One hundred and sixty-four subjects with ejection fraction (EF) < 35% and NYHA Class II (... expand abstract24%) or III (76%) symptoms received a CCM pulse generator. Patients were randomly assigned to Group 1 (n = 80, CCM treatment 3 months, sham treatment second 3 months) or Group 2 (n = 84, sham treatment 3 months, CCM treatment second 3 months). The co-primary endpoints were changes in peak oxygen consumption (VO2,peak) and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Baseline EF (29.3 +/- 6.7% vs. 29.8 +/- 7.8%), VO2,peak (14.1 +/- 3.0 vs. 13.6 +/- 2.7 mL/kg/min), and MLWHFQ (38.9 +/- 27.4 vs. 36.5 +/- 27.1) were similar between the groups. VO2,peak increased similarly in both groups during the first 3 months (0.40 +/- 3.0 vs. 0.37 +/- 3.3 mL/kg/min, placebo effect). During the next 3 months, VO2,peak decreased in the group switched to sham (-0.86 +/- 3.06 mL/kg/min) and increased in patients switched to active treatment (0.16 +/- 2.50 mL/kg/min). MLWHFQ trended better with treatment (-12.06 +/- 15.33 vs. -9.70 +/- 16.71) during the first 3 months, increased during the second 3 months in the group switched to sham (+4.70 +/- 16.57), and decreased further in patients switched to active treatment (-0.70 +/- 15.13). A comparison of values at the end of active treatment periods vs. end of sham treatment periods indicates statistically significantly improved VO2,peak and MLWHFQ (P = 0.03 for each parameter). CONCLUSION: In patients with heart failure and left ventricular dysfunction, CCM signals appear safe; exercise tolerance and quality of life (MLWHFQ) were significantly better while patients were receiving active treatment with CCM for a 3-month period. collapse abstract

Impact of left ventricular assist device (LVAD) support on the cardiac reverse remodeling process.

With improved technology and expanding indications for use, left ventricular assist devices (LVADs) are assuming a greater role in the care of patients with end-stage heart failure. Following LVAD implantation with the intention of bridge to transpla... expand abstractnt, it became evident that some patients exhibit substantial recovery of ventricular function. This prompted explantation of some devices in lieu of transplantation, the so-called bridge-to-recovery (BTR) therapy. However, clinical outcomes following these experiences are not always successful. Patients treated in this fashion have often progressed rapidly back to heart failure. Special knowledge has emerged from studies of hearts supported by LVADs that provides insights into the basic mechanisms of ventricular remodeling and possible limits of ventricular recovery. In general, it was these studies that spawned the concept of reverse remodeling now recognized as an important goal of many heart failure treatments. Important examples of myocardial and/or ventricular properties that do not regress towards normal during LVAD support include abnormal extracellular matrix metabolism, increased tissue angiotensin levels, myocardial stiffening and partial recovery of gene expression involved with metabolism. Nevertheless, studies of LVAD-heart interactions have led to the understanding that although we once considered the end-stage failing heart of patients near death to be irreversibly diseased, an unprecedented degree of myocardial recovery is possible, when given sufficient mechanical unloading and restoration of more normal neurohormonal milieu. Evidence supporting and unsupporting the notion of reverse remodeling and clinical implications of this process will be reviewed. collapse abstract

The conundrum of functional mitral regurgitation in chronic heart failure.

A computational method of prediction of the end-diastolic pressure-volume relationship by single beat.

The end-diastolic pressure-volume relation (EDPVR) is an important descriptor of passive cardiac pump properties. However, clinical utility has been limited by the need for measurement of pressures and volumes over relatively large ranges. In this pr... expand abstractotocol, we describe an algorithm to estimate the entire EDPVR in humans from a single measured pressure-volume (P-V) point. This algorithm was developed from observations made from accurately measured EDPVRs of human hearts, which indicated that when normalized by appropriate left ventricular volume scaling (to arrive at volume-normalized EDPVRs, EDPVR(n)) EDPVR(n)s were nearly identical in all patients. In this protocol, we demonstrate how to use EDPVR(n)s to predict a second P-V point on the EDPVR, in which case the entire EDPVR can then be predicted. With recent advances for accurate noninvasive measurement of end-diastolic pressure and volumes, this protocol permits the assessment of passive properties in a broader range of research and clinical settings. collapse abstract

Feasibility study of a temporary percutaneous left ventricular assist device in cardiac surgery.

BACKGROUND: The aim of this study is to evaluate a percutaneous left ventricular assist device (Tandem Heart pVAD; Cardiac Assist, Pittsburgh, Pennsylvania) in the postcardiotomy setting. METHODS: Between August 2001 and August 2004, 11 high-risk mal... expand abstracte patients who had undergone heart failure surgery or surgical revascularization were supported by the TandemHeart postcardiotomy. The major indication for pVAD insertion was failure to wean from cardiopulmonary bypass. Three different techniques were employed for cannulation: the closed percutaneous technique, the "open transeptal" technique with percutaneous cannulas insertion, and direct central cannulation. RESULTS: The mean duration of support was 88 hours. The mean pump flow was 3.09 L/min. The weaning rate was 72.72%. Survival to discharge and at 1 and 4 years was 54.54%, 45.45%, and 36.36%, respectively. The main complication was pericardial bleeding, noted mainly in patients receiving antiplatelet treatment preoperatively. CONCLUSIONS: The TandemHeart appears to be safe for temporary support after cardiotomy. It is a versatile device allowing different techniques of insertion. Device application yielded high weaning rate and satisfactory early and long-term survival. collapse abstract