Study of muscular and ventricular function in dynamic cardiomyoplasty: a ten-year follow-up

BACKGROUND: The basic physiologic principle underlying cardiomyoplasty is long-term electrostimulation of a latissimus dorsi muscle (LDM) wrapped around the heart to obtain a phasic activity that could be integrated with ventricular kinetics. The aim of cardiomyoplasty is to prolong survival and to improve the quality of life of patients with severe chronic and irreversible myocardial failure by improving systolic contraction and correcting diastolic dysfunction. METHODS: To evaluate the long-term outcome of cardiomyoplasty, we investigated 82 patients electively undergoing this procedure in-our hospital. All patients had severe chronic heart failure that did not respond to optimal medical treatment. Patients had a mean age of 50 +/- 12 years (84% males). The cause of heart failure was ischemic (55%), idiopathic cardiomyopathy (34%), ventricular tumor (6%), and other (5%). The mean follow-up was 4.3 years. RESULTS: The mean New York Heart Association functional class improved after operation from 3.2 to 1.8. Average radioisotopic left ventricular ejection fraction increased from 17% +/- 6% to 28% +/- 3% (p < 0.05). Stroke volume index increased from 35 +/- 9 to 46 +/- 8 ml/beat/m2 (p < 0.05). The heart size remained stable at long term (evaluated by echo and computed tomography scanning). After cardiomyoplasty the number of successive hospitalizations resulting from congestive heart failure was reduced to 0.4 hospitalizations/patient/year (before operation 2.5, p < 0.05). Computed tomography scans showed at long-term a preserved LDM structure in 82% of patients who underwent operation. Survival probability at 7 years was 54% for the totality of patients, and 66% for patients who underwent operation in New York Heart Association functional class 3. Five patients underwent heart transplantation after cardiomyoplasty (mean delay 29 months), principally as a result of the natural evolution of their underlying heart disease, without major technical difficulties. CONCLUSIONS: Our 10-year clinical experience demonstrates that cardiomyoplasty increases ejection fraction, improves functional class, and ameliorates quality of life. Ventricular volumes and diameters remain stable long term. LDM structure is maintained long term if electrostimulation is performed avoiding excessive myostimulation. Patient selection is the most important determinant for early and late outcome. Late death in patients undergoing cardiomyoplasty is principally due to sudden death. Our future aim is to incorporate a cardioverter-defibrillator in the cardiomyostimulator, thus improving long-term results. Cardiomyoplasty may delay or prevent end-stage heart failure and the need for heart transplantation.     

Right latissimus dorsi cardiomyoplasty augments left ventricular systolic performance

We hypothesized that the right latissimus dorsi cardiomyoplasty augments left ventricular performance. Five dogs underwent staged right latissimus dorsi cardiomyoplasty. Ventricular function was studied 1 to 3 weeks later. Left ventricular pressure was measured with a micromanometer and left ventricular dimensions with piezoelectric crystals. Inferior vena caval occlusion was used to vary preload. Pressure-volume data were collected with the muscle unstimulated and stimulated at 1:2 and 1:1 muscle/heart ratios. The end-systolic pressure-volume relation (mm Hg/mL), stroke work, preload recruitable stroke work, left ventricular end-diastolic volume, and the diastolic relaxation constant were calculated and expressed as mean +/- standard deviation. Stimulated beats at a 1:2 ratio showed an increase in stroke work of 42.1% (978 +/- 381 to 1,390 +/- 449 g.cm; p < 0.01) and preload recruitable stroke work of 28.8% (59.4 +/- 20.7 to 76.6 +/- 11.0 g.cm/cm3; p = 0.05) compared with the unstimulated beats. With the stimulator on at 1:1, smaller changes occurred: stroke work increased 9% (1,167 +/- 390 to 1,273 +/- 363 g.cm; not significant) and preload recruitable stroke work increased 27% (63.9 +/- 22.7 to 80.9 +/- 23.1 g.cm/cm3; p = 0.05). There were no significant changes in the end-systolic pressure-volume relation. The diastolic relaxation constant did not change at 1:1 (36 +/- 9.7 to 37 +/- 6.4 ms; not significant) or 1:2 (36 +/- 9.3 to 39 +/- 8.2 ms; not significant). Left ventricular end-diastolic volume was unchanged at 1:1 (34 +/- 10.7 to 32 +/- 10.3 mL) and at 1:2 (31 +/- 9.0 to 32 +/- 8.7 mL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Configuration of linear dynamic cardiomyoplasty for hypoplastic right ventricle

BACKGROUND: The purpose of this study is to determine feasibility of linear dynamic cardiomyoplasty with a briefly preconditioned latissimus dorsi in the experimental model simulating patch enlargement of the hypoplastic right ventricle. METHODS: In 8 mongrel dogs, a diminished right ventricular chamber was reconstructed with an extended pericardial patch. A left latissimus dorsi, preconditioned for 2 weeks (2 Hz) after a previous 2-week vascular delay period, was placed on the patch, with the muscle fiber oriented in parallel to the right ventricular long axis. RESULTS: Graft pacing with trained-pulses of 25 Hz at a 1:1 ratio showed significant augmentation of pulmonary flow and pressure (158% +/- 21%, 156% +/- 14%, respectively), contributing to restoring right ventricular function comparable with preoperative control, which was also confirmed by the right ventricular function curve and pressure-volume relationship analyzes. Continuous pacing was performed in 4 animals for 7 hours without evidence of muscle fatigue, implying feasibility of "working conditioning" after minimum preconditioning for this type of right heart assist. CONCLUSIONS: Linear latissimus dorsi myoplasty can restore normal right ventricular performance at a physiologic preload, and may provide a surgical option for the hypoplastic right ventricle.     

Anti-metastatic and immunomodulating properties of the water extract from Celosia argentea seeds

Although dynamic cardiomyoplasty (DCMP) is currently being evaluated as an alternative to end-stage congestive heart failure, the overall results of DCMP are variable and inconclusive. We evaluated the effect of classic DCMP on systolic and diastolic cardiac function in normal heart using reliable indicators which minimize the influences of load conditions. Six experimental dogs were evaluated with the acute nonpreconditioning model. The slope of the linear preload recruitable stroke work relationship (Mw) showed a significant increase with latissimus dorsi muscle (LDM) stimulation (postwrap non-stimulation 59.1+/-6.3, postwrap stimulation 98.6+/-9.7 erg cm(-3) x 10(3); P < 0.01), and the x-intercept (V0) was unchanged; these were utilized as the indicators of left ventricular systolic function. The constant of pressure decay (tau) increased after LDM wrap (prewrap 45.8+/-6.0, postwrap nonstimulation 69.3+/-10.3, postwrap stimulation 72.3+/-13.9 ms; P < 0.05), and the peak filling rate was unchanged after LDM wrap, which were utilized as the indicators of diastolic function. We concluded that classic dynamic cardiomyoplasty is effective in assisting systolic cardiac function, but may to some degree have a detrimental effect on the diastolic cardiac function.     

Hemodynamic response to in situ latissimus dorsi muscle stimulation: implications in dynamic cardiomyoplasty

Dynamic cardiomyoplasty (DCM) involves the electrical stimulation of a pedicled latissimus dorsi muscle flap wrapped around the falling ventricle as a means of cardiac assist. To further elucidate a potential neurohumoral mechanism for improvement of cardiac output after myoplasty, we evaluated the hemodynamic effects of in situ stimulation of the latissimus dorsi muscle (in the absence of cardiomyoplasty). In seven mongrel dogs, a nerve cuff electrode (Medtronic 6901) was placed around the left thoracodorsal nerve (TDN). This was attached to a pulse generator (Medtronic, Itrel 7420), delivering a 4.0 volt, 0.19 second on, 0.81 second off, 33 Hz, 210 microsecond pulse width, cyclic bursts similar to that used in DCM. Stroke volume index (SVI) and other hemodynamic parameters as well as plasma norepinephrine (NE) levels were measured at five stages: baseline, stimulator on at 0, 2, and 5 minutes, and stimulator off at 30 minutes after. The animals were then subjected to 4 weeks of rapid pacing at 240 beats/min (Medtronic 8329) to induce heart failure, and as the rapid pacing was discontinued, measurements were repeated as above. After rapid pacing, cardiac function was significantly depressed, and NE was elevated (133 +/- 69 versus 500 +/- 353 pg/mL, p < 0.05). In the normal hearts, TDN stimulation increased SVI, heart rate, systemic pressure, and NE levels. In heart failure, however, no significant changes in cardiac function and NE levels were noted. In conclusion, our data indicate that in the normal hearts, afferent impulses from TDN stimulation alone may augment cardiac function by means of a neurohumoral effect that is not seen in severe heart failure. The implications of these findings in DCM are discussed.     

Mechanisms of cardiomyoplasty: comparative effects of adynamic versus dynamic cardiomyoplasty

BACKGROUND: The apparent paradox seen in patients who have undergone dynamic cardiomyoplasty and shown substantial clinical and functional improvements with only modest hemodynamic changes may be due to inappropriate end points chosen for study, a result of incomplete understanding of mechanisms involved. The purpose of this study was to compare the relative role of the passive "girdling effect" and the dynamic "systolic squeezing effect" of the wrapped muscle in cardiomyoplasty. METHODS: The control group of 6 dogs underwent 4 weeks of rapid pacing (250 beats/min) to induce severe heart failure followed by 8 weeks of observation without rapid pacing. The trajectory of recovery in hemodynamics and cardiac dimensions was followed with echocardiography and Swan-Ganz catheters. In the "adynamic" cardiomyoplasty group (n=4), the left latissimus dorsi muscle was wrapped around the ventricles and allowed to stabilize and mature for 4 weeks. This was followed by rapid pacing and recovery as in the control group. In the "dynamic" cardiomyoplasty group (n=3), the same protocol for the adynamic group was followed except that a synchronizable cardiomyostimulator was attached to the thoracodorsal nerve of the muscle wrap. This allowed the latter to be transformed during the rapid-pacing phase and permitted dynamic squeezing of the muscle wrap to be generated by burst stimulation synchronized with cardiac contraction in a 1:2 ratio. RESULTS: Baseline data were comparable in all groups prior to rapid pacing. After 4 weeks of rapid pacing, the left ventricular ejection fraction was higher in the adynamic (27.0%+/-3.9%; p < 0.05) and dynamic (33.3%+/-2.3%; p < 0.02) cardiomyoplasty groups compared with controls (18.8%+/-8.3%). Similarly, ventricular dilatation in both systole and diastole was less in the adynamic (51.8+/-8.7 mL, [p < 0.002] and 38.2+/-7.2 mL [p < 0.001], respectively) and dynamic (62.0+/-7.2 [p < 0.02] and 41.3+/-3.5 mL [p < 0.005], respectively) cardiomyoplasty groups compared with controls. In the dynamic group, on and off studies were carried out after cessation of rapid pacing while the heart was still in severe failure, and they demonstrated a systolic squeezing effect in stimulated beats. Only this group recovered fully to baseline after 8 weeks. CONCLUSIONS: By reducing myocardial stress, both the passive girdling effect and the dynamic systolic squeezing effect have complementary roles in the mechanisms of dynamic cardiomyoplasty.     

Effect of medication on biomechanical properties of rabbit bones: heparin induced osteoporosis

BACKGROUND: We hypothesize that the integrity of the latissimus dorsi muscle graft used to wrap the heart may affect the clinical outcome of patients undergoing dynamic cardiomyoplasty. METHODS: By correlating the pathologic findings with their clinical course in five patients who died 1 month to 6 years after dynamic cardiomyoplasty operation, we sought to discern findings that might shed light on the pathophysiology of cardiomyoplasty. RESULTS: Of the two patients who had a limited clinical response, one had an atrophic, edematous latissimus dorsi muscle with fatty infiltration resulting from cardiac cachexia, and the other had insufficient length of latissimus dorsi muscle to cover a large heart. The remaining patients responded well clinically without signs of pump failure and died at various intervals, mostly of arrhythmias. Autopsy findings included the following: (1) one patient with ischemic cardiomyopathy as the underlying disease had development of rich vascularity in the interface between the muscle wrap and the epicardium; whereas in four others with idiopathic cardiomyopathy, such evidence of collateralization was far less evident. (2) There was a variation in the skeletal muscle transformation achieved, with the fraction type I fatigue-resistant fiber in the muscle wrap ranging from 60% to 100%, in spite of the identical transformation protocol used. Such variation is believed to be genetically based. (3) In one patient, the skeletal muscle was paced to contract at 30 to 50 times/minute (2:1 ratio) for more than 5 years. Nevertheless, the pathologic specimen of the muscle wrap showed only minimal interstitial fibrosis. (4) Relatively thin muscle wrap around the heart found at autopsy could be atrophy but most likely was related to muscle transformation, which is known to reduce muscle mass and increase capillary density. (5) All skeletal muscle grafts showed geometric conformation to the shape of the epicardium and grossly looked as if they were an additional layer of the ventricular wall. Such conformation may facilitate the modulation of the ventricular remodelling process in the failing heart, as has been described both in clinical and experimental studies. CONCLUSIONS: Our findings are consistent with and support a number of mechanisms proposed for cardiomyoplasty. Thus preservation of latissimus dorsi muscle graft integrity may be important in the success of dynamic cardiomyoplasty.     

Cardiomyoplasty: hemodynamic benefit to normal and depressed canine left ventricular function

This study examined the effects of cardiomyoplasty with vascular delay on canine normal and depressed left ventricular (LV) function. To improve viability of the latissimus dorsi muscle (LDM), vascular delay was performed 2 weeks before cardiomyoplasty in 10 mongrel dogs. Two weeks after cardiomyoplasty, LV function was evaluated by simultaneously measuring LV and aortic pressure, and aortic flow. The LDM was stimulated at a ratio of 1:4-1:7 synchronously with ventricular systole. Microspheres (90 mu) were sequentially injected into the left coronary artery to depress LV function. Data were acquired and analyzed on a beat to beat basis. Results were as follows: LDM stimulation significantly augmented LV systolic pressure (LVSP) from 138 +/- 2 to 161 +/- 2* mmHg, the peak rate of change of LV pressure (+dP/dt) from 1888 +/- 46 to 2584 +/- 43* mmHg/sec, aortic systolic pressure (AoSP) from 140 +/- 2 to 159 +/- 2* mmHg, stroke volume (SV) from 11.2 +/- 0.3 to 13.3 +/- 0.3* ml, stroke work (SW) from 19 +/- 1 to 26 +/- 1* gm.m, peak aortic flow (P Qa) from 5542 +/- 142 to 7190 +/- 161* ml/min, and decreased -dP/dt from -1683 +/- 31 to -1689 +/- 49* mmHg/sec (* = p < 0.05). Microsphere injections depressed LV function, but did not affect the magnitude of the net changes between stimulated and nonstimulated beats. However, the percent changes significantly increased. Preconditioning of LDM with vascular delay augments cardiac function in LDM assisted beats. This improved performance was present in both normal as well as depressed LV function groups. Thus, investigations of cardiomyoplasty may not necessarily require a model of severe myocardial dysfunction. Vascular delay offers an important preconditioning method of LDM to augment cardiac function in cardiomyoplasty.     

Delayed stimulation of the latissimus dorsi may result in disuse atrophy

BACKGROUND: The latissimus dorsi is usually left unstimulated for 2 weeks after cardiomyoplasty to allow the muscle to recover from the loss of the collateral circulation. To determine whether the 2-week delay may cause muscle atrophy, we randomized 15 mongrel dogs to a control group or a disuse atrophy group. METHODS: The collateral circulation to the latissimus dorsi was ligated in all animals before cardiomyoplasty to reduce the risk of ischemic injury to the muscle during mobilization. Two weeks after collateral ligation, the atrophy group had the tendinous attachment of the latissimus dorsi severed and then 2 weeks later underwent cardiomyoplasty. The control group had a 2-week delay after collateral ligation followed by cardiomyoplasty. Biopsies were performed before collateral ligation and before cardiomyoplasty. After heart failure was induced, hemodynamic function was assessed during synchronized contraction of the latissimus dorsi by measuring the maximum systolic elastance, stroke volume, preload recruitable stroke work index, and diastolic compliance. RESULTS: Comparison of muscle morphology between the two groups demonstrated the presence of muscle atrophy in those animals that had been randomized to the atrophy protocol. During synchronized contraction of the latissimus dorsi, there was no significant increase in maximum systolic elastance in either group. However, both stroke volume and pulmonary recruitable stroke work index were significantly higher in the control animals during assisted beats. The left ventricle was less compliant in the atrophy group, suggesting that muscle atrophy had adversely affected diastolic function. CONCLUSIONS: Delayed electrical stimulation of the latissimus dorsi may result in atrophy and loss of function.     

Optimization of synchronization delay in latissimus dorsi dynamic cardiomyoplasty

BACKGROUND: Optimal synchronization delay (SD) for triggering the implanted cardiomyostimulators in patients undergoing latissimus dorsi dynamic cardiomyoplasty has not been clearly defined. Generally a synchronization delay time of 45 to 60 ms is used in the current practice, in which the implanted cardiomyostimulator stimulates the latissimus dorsi muscle 45 to 60 ms after mitral valve closure acquired with M-mode echocardiography. We investigated the effect of shortening or prolonging the delay time on cardiac functions. METHODS: We studied 10 patients who were in their first 2 years postoperatively. Three values for SD (SD = 0 ms, 45 to 60 ms, and 150 to 160 ms) were echocardiographically evaluated for their influence on both systolic and diastolic left ventricular parameters. RESULTS: Ejection fractions were 0.27 +/- 0.07, 0.28 +/- 0.07, and 0.32 +/- 0.06; peak aortic velocities were 0.85 +/- 0.8, 0.86 +/- 0.11, and 0.92 +/- 0.8 m/s; and velocity-time integrals were 0.16 +/- 0.03, 0.16 +/- 0.03, and 0.19 +/- 0.03 m for the SD values of 0, 45 to 60 ms, and 150 to 160 ms, respectively. Diastolic parameters were also measured. Isovolumetric diastolic relaxation time was 97.5 +/- 49, 97.20 +/- 44, and 111.8 +/- 49 ms; deceleration time was 83.67 +/- 32, 88.48 +/- 35, and 92.68 +/- 34 ms; and ratio or velocity-time integral of e wave to velocity-time integral of a wave was 3.09 +/- 0.98, 2.48 +/- 0.69, and 2.38 +/- 0.65 for the SD values of 0, 45 to 60 ms, and 150 to 160 ms, respectively. Systolic functions were better when SD was set at 150 to 160 ms, but there was a diastolic compromise. On the other hand, diastolic parameters were more favorable when SD = 0 (i.e., cardiomyostimulator triggered without delay) but the systolic assist was suboptimal. Systolic and diastolic parameters seemed relatively well-balanced with the current practice of setting the synchronization delay at 45 to 60 ms. CONCLUSIONS: The most favorable systolic effects were obtained with a prolonged delay of synchronization (150 to 160 ms), at some expense of diastolic functions. On the other hand, with a short or absent delay, diastolic parameters were improved but systolic parameters became suboptimal. Therefore, the current practice of setting the SD between 45 and 60 ms after echocardiographic mitral valve closure is suggested for the optimal timing for cardiomyostimulator stimulation in patients who have undergone latissimus dorsi dynamic cardiomyoplasty. Yet a great deal of individualization is necessary, and fixed preset values cannot definitely be determined because one setting does not fit all patients.     

Cardiomyoplasty - improvement of muscle fibre type transformation by an anabolic steroid (metenolone)

Dynamic cardiomyoplasty, a method to support ventricular function by the chronically stimulated latissimus dorsi muscle wrapped around the heart is accompanied by a loss of mass and force of the transplanted muscle. These effects and the fast-to-slow transformation of the muscle could be possibly influenced by the additional administration of anabolic steroids. In this study, the left latissimus dorsi muscles of 12 sheep were electrically conditioned (group A). In 12 other animals (group B), stimulation was combined with the administration of metenolone (100 mg/week). Biopsies were taken from the right and left muscles at the beginning and after 6 and 12 weeks of treatment, frozen and cross-sectioned. The muscle fibre type composition was studied enzymhistochemically (SDH-staining and Myosin-ATPase-reaction) and immunocytochemically (using antibodies against different myosin heavy chains, MHC). Furthermore, the expression of different MHC isoforms was investigated electrophoretically. The untreated latissimus dorsi muscle contains 20% type I fibres expressing slow MHC and 80% type II fibres expressing fast MHC. After 6 weeks, the respective fibre type composition was 42 and 58% (group A) and 80 and 20% (group B). After 12 weeks, the percentage of the type I fibres rose in group A to 59% and in group B to 98%. In accordance with these morphological results, the MHC pattern determined electrophoretically showed a corresponding shift from the fast to the slow isoform. Therefore, the administration of metenolone avoids severe muscle atrophy, and improves and accelerates fast to slow fibre type conversion necessary for successful cardiomyoplasty.     

The use of latissimus dorsi muscle flap in reconstructive heart surgery

Dynamic cardiomyoplasty is a technique for ventricular assistance indicated for the correction of left ventricle aneurysm and for cardiomyopathies in which heart transplantation is contraindicated. In this article, our first four patients to undergo cardiomyoplasty (from February 1991 until April 1992) with a left latissimus dorsi island flap, rotated into the thorax after a 3-week training period, are reviewed. Therapeutic indications were cardiomyopathy with contraindication for heart transplant in patients 1 and 4 and associated to surgery for left ventricle aneurysm for patients 2 and 3. Patient 1 died 4 months after surgery because of a cerebral embolism when he was at functional class II. The other three patients remain at functional class I, carrying out normal activities. All the data were evaluated with the paired t test. Ejection fraction values (obtained through echocardiography and scintigraphy studies) and maximum minute flow rate of blood (measured with an echo-Doppler) have increased significantly (p < 0.001, p < 0.05, and p < 0.01, respectively) after heart surgery. Clinical improvement has been found after cardiomyoplasty, which correlates with an increase in ejection fraction and maximum minute flow rate of blood.     

Evaluation of a pulsatile pediatric ventricular assist device in an acute right heart failure model

BACKGROUND: The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume = 9 mL) in a neonatal lamb model of acute right ventricular failure. METHODS: Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n = 5) had no mechanical support whereas experimental group 2 (n = 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery. RESULTS: All results are expressed as mean +/- standard deviation and analyzed by Student's t test. A p value less than 0.05 was considered statistically significant. Base-line measurements were not significantly different between groups and included systemic arterial pressure, 80.6 +/- 12.7 mm Hg; right atrial pressure, 4.6 +/- 1.6 mm Hg; mean pulmonary arterial pressure, 15.6 +/- 4.2 mm Hg; left atrial pressure, 4.8 +/- 0.8 mm Hg; and cardiac output, 1.4 +/- 0.2 L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, 38.8 +/- 10.4 mm Hg; right atrial pressure, 16.8 +/- 2.3 mm Hg; left atrial pressure, 1.4 +/- 0.5 mm Hg; and cardiac output, 0.6 +/- 0.1 L/min. All group 1 animals died at a mean of 71.4 +/- 9.4 minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, 68.0 +/- 13.0 mm Hg; right atrial pressure, 8.2 +/- 2.3 mm Hg; left atrial pressure, 6.4 +/- 2.1 mm Hg; and cardiac output, 1.0 +/- 0.2 L/min. CONCLUSIONS: The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates.     

A comparison of the early and midterm results after dynamic cardiomyoplasty in patients with ischemic or idiopathic cardiomyopathy

OBJECTIVE: The main goal of this study is to determine the efficiency of the cardiomyoplasty procedure on patients with cardiomyopathy of different origins (ischemic and idiopathic origins). METHOD: Between June 1993 and August 1995, 24 patients underwent dynamic cardiomyoplasty with the left latissimus dorsi muscle in our institution. Early and midterm results, as well as the changes in hemodynamics and functional status during follow-up, were compared. RESULTS: Early mortality rate was 20.8% (five patients). Concomitant coronary revascularization, a preoperative left ventricular ejection fraction below 20%, and a functional capacity of class IV (intermittently) were associated with early mortality. The mean follow-up time was 17.3 months. Survival analysis (including early mortality) extending to the twenty-fourth month revealed no difference between the ischemic and idiopathic groups (55% vs 85%, respectively, p = 0.09). Functional status improved in the both groups. Ejection fractions were improved after cardiomyoplasty in all patients, regardless of their cause. Cardiac indices were higher 6 months after the operation. Changes in pulmonary capillary wedge pressure, peak pulmonary artery pressure, and left ventricular end-diastolic volume were not significant. CONCLUSION: Although cardiomyoplasty improves functional capacity and hemodynamics in patients with both idiopathic and ischemic cardiomyopathy, the idiopathic group is thought to achieve optimal benefit with regard to lower complication rates and lower early mortality expectancy owing to the absence of concomitant coronary revascularization.     

Altered myocardial phenotype after mechanical support in human beings with advanced cardiomyopathy

BACKGROUND: Left ventricular assist devices (LVAD) provide lifesaving circulatory support to patients awaiting heart transplantation. To date, the extent to which sustained mechanical unloading alters the phenotype of pathologic myocardial hypertrophy in dilated cardiomyopathy is unknown. METHODS: We examined left ventricular size, myocyte and myocardial immunoreactivity for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in eight patients with advanced dilated cardiomyopathy before and after LVAD support. The mean duration of congestive heart failure was 18 +/- 5 months, and LVAD support averaged 42 +/- 4 days before heart transplantation. RESULTS: Echocardiographically determined left ventricular mass decreased from 505 +/- 83 to 297 +/- 52 gm (p < 0.05) during LVAD support, whereas minimum myocyte diameter decreased from 28.1 +/- 0.9 to 21.7 +/- 0.6 microns (p < 0.01) in transmural myocardial tissue specimens. Overall left ventricular ANP immunopositivity decreased from 48% at LVAD placement to 12% at transplantation (p < 0.05), whereas BNP immunopositivity decreased from 28% to 4% after LVAD support. Moreover, a gradient of ANP and BNP immunostaining from subendocardium to epicardium observed before mechanical unloading diminished after LVAD support. Analysis of the relationship between left ventricular mass and ANP immunopositivity revealed a close and highly significant correlation between these variables. CONCLUSIONS: These studies demonstrate remarkable left ventricular plasticity even in the presence of advanced cardiomyopathy. Parallel reductions in myocardial mass and myocyte size with reductions in ventricular ANP and BNP immunostaining indicate a novel regression of the phenotype of pathologic hypertrophy within the human myocardium after LVAD support.     

Influence of longer term left ventricular assist device support on valvular regurgitation

The authors previously published data that describe acute alterations in ventricular dimensions and in the severity of mitral and tricuspid regurgitation (MR/TR) after initiation of left ventricular assist device (LVAD) pumping. In the current study, measurements of ventricular size and regurgitant jet area acquired after LVAD implantation are presented. Eight patients had LVAD implanted pending cardiac transplantation (duration of assist 70-279 days; mean, 162 +/- 29 days). Echocardiograms were obtained at the time of LVAD implant and later during LVAD support (mean time for late echo, 95 +/- 32 days post-implant). Comparisons of pre-implant with late post-implant data showed: increased TR jet area (4.8 +/- 1.0 cm2 vs. 8.0 +/- 1.7 cm2 P < 0.05); increased right ventricular (RV) end-systolic dimension (31 +/- 4 vs 40 +/- 5 mm, P < 0.05); and increased RV end-diastolic dimension (35 +/- 4 vs. 45 +/- 5 mm, P < 0.065). Decreased MR jet area and decreased LV dimensions (P < 0.05) also were noted on comparison of pre-implant and late post-implant data. There were no significant differences between any immediate post-implant and late post-implant echocardiographic measurements. No patient had clinical evidence of RV failure. LV mechanical assist causes an acute increase in TR, presumably by volume loading the RV. TR and RV enlargement persisted but did not discernibly worsen on subsequent post-implant echocardiograms. LV dimensions and MR remained less than the pre-implant values on later post-implant determinations.     

Clinical features of relative focal hyperfusion in patients with intracerebral hemorrhage detected by contrast-enhanced xenon CT

Optimization of the skeletal muscle contraction during cardiac assist is important to achieve maximal cardiac assist and yet avoid overstimulation that may injure skeletal muscle. Dynamic cardiomyoplasty suffers from lack of an objective, reproducible, and accurate technique to measure skeletal muscle shortening fraction after wrap and training of the muscle. A recruitment curve is considered the best way to select the proper stimulation level to achieve supramaximal contraction without overstimulating the muscle. A fluoroscopic technique of determining latissimus dorsi recruitment curve was evaluated in five goats undergoing dynamic cardiomyoplasty with an anterior cardio-subcutaneous wrap. Two pairs of stainless steel targets (0.5 and 1 cm of diameter) were implanted on each side of the muscle wrap. One pair of sonomicrometer crystals was also implanted. Displacement of the targets was measured under fluoroscopy at five different stimulation levels. Correlation coefficients between targets on the inside surface of the wrap and the sonomicrometer crystals, and targets on the outside surface of the wrap and the sonomicrometer crystals were 0.71 (P < 0.05) and 0.60 (P < 0.05), respectively. Targets on the inside surface of the wrap were more accurate than targets on the outside surface of the wrap for measurement of skeletal muscle shortening fraction and establishment of a recruitment curve. Adverse effects from the targets were not observed.     

Use of ultrasonography to evaluate muscle thickness and blood flow in free flaps

The purpose of this study was to investigate the common belief that a microvascular transfer of a non-innervated free muscle flap loses muscle bulk over time. Sixteen patients (latissimus dorsi = 8, rectus abdominis = 7, and gracilis muscle = 1) were evaluated an average of 41 months after free flap transfer. Latissimus dorsi and lower extremity flaps displayed significantly more swelling than the other flaps. Flap bulk was measured by ultrasound. The mean thickness of upper extremity flaps was 10.3 +/- 1.8 mm (control muscles 11.8 +/- 2.8), lower-extremity 14.5 +/- 3.7 mm (control muscles 10.9 +/- 0.7), latissimus dorsi 14.3 +/- 2.2 mm (control muscles 10.3 +/- 0.8, P = 0.018), and rectus abdominis 11.2 +/- 1.2 mm (control muscles 12.4 +/- 1.9). Color Doppler ultrasonography was used to detect the pedicles of the free flaps and also to measure the peak velocity of blood flow intramuscularly and in the pedicles. In the upper extremities (n = 5) the pedicles could be found in only 20% of cases whereas in the lower extremities (n = 11) 91% of pedicles were located. (P = 0.013). Peak flow within the free flaps was significantly higher in the lower extremity (50% of the peak flow of the common femoral artery) than in the upper extremity (5% of the peak flow of the common femoral artery, P = 0.013). This study demonstrated that non-innervated free muscle flaps in the extremities maintain the original muscle thickness, although lower extremity and latissimus dorsi flaps have a trend to be thicker. Most pedicles of free muscle flaps in the upper extremities could not be located by ultrasound. However, flaps in the lower extremities most often have patent pedicles and also more vigorous intramuscular blood flow.     

Biologic glue increases capillary ingrowth after cardiomyoplasty in an ischemic cardiomyopathy model

The authors investigated the multi-step mechanism of healing after cardiomyoplasty, focusing on the process of angiogenesis. The authors contend that enhancement of angiogenesis and prevention of ischemia-reperfusion injuries immediately after muscle mobilization will be effective in improving cardiomyoplasty results. After cardiomyoplasty, autologous biologic glue (ABG) was administered between the latissimus dorsi muscle (LDM) and myocardium. By 2 months, a new pseudo interlayer was present that bridged the gap between the LDM and myocardium. Neovascularization was visible in the form of numerous small capillaries. Marked degeneration of the LDM was noted, possibly caused by muscle ischemia-reperfusion damage after mobilization. Pockets were created of ischemic and nonischemic LDM to test for angiogenesis. One was left free of ABG (control); one received ABG only; one received ABG and pyrrolostatin. Some of the capillaries were large and had erythrocytes inside. biopsy samples showed 9.4 +/- 1.9% of the sample was occupied by blood vessels (compared with 3.6 +/- 0.7% in control muscle). These preliminary studies prove the feasibility of the authors' concept and provide evidence that angiogenesis can accelerate the healing process and provide an organic bridge between the LDM and myocardium after cardiomyoplasty.     

Quantification of early damage in latissimus dorsi muscle grafts

Acute damage in the latissimus dorsi muscle may account for variable clinical results following dynamic cardiomyoplasty and an ischemic cause has been suggested. Using established techniques, we set out to demonstrate and to quantify the acute muscle damage in a rodent model. The left latissimus dorsi muscle of 5 Sprague-Dawley rats was mobilized on its thoracodorsal vascular pedicle, thus interrupting the regional blood supply to its distal part. The undisturbed contralateral muscle served as a matched control. After 24 hours, the muscle was excised and divided into proximal, middle, and distal thirds. Damage was graded histologically and quantified by nitroblue tetrazolium macrohistochemistry. Both methods of assessment correlated well (r=-0.936; P < 0.001) and demonstrated significant damage, principally in the middle and the distal regions of the ischemic muscles. Therefore, the rodent model appears to be useful for investigating the pathogenesis and prevention of acute ischemic damage in the latissimus dorsi graft under conditions resembling the clinical scenario.