Autophagy during left ventricular redilation after ventriculoplasty: Insights from a rat model of ischemic cardiomyopathy.

OBJECTIVES: Myocardial autophagy has been recognized as an important factor in heart failure. It is not known whether changes in ventricular geometry by left ventriculoplasty influence autophagy in ischemic cardiomyopathy. We hypothesized that myocardial autophagy plays an important role in left ventricular (LV) redilation after ventriculoplasty. METHODS: Four weeks after ligation of the left anterior descending artery, ventriculoplasty or sham operation was performed. The animals were euthanized at 2 days (early) or 28 days (late) after the second operation. Ventricular autophagy was evaluated by protein expression of microtubule-associated protein light chain 3 II, an autophagosome marker. Cardiomyocyte area was assessed by histologic examination. LV function was evaluated by echocardiography. To examine the implications of autophagy, an autophagy inhibitor (3-methyladenine) was injected intraperitoneally for 3 weeks before sacrifice. RESULTS: The LV was reduced in size early and redilated late after ventriculoplasty. LV systolic function was improved early and later worsened after ventriculoplasty. Light chain 3 II expression decreased early after ventriculoplasty and increased in the late period. Myocyte area increased from the early to late stage after ventriculoplasty. Autophagic inhibition exaggerated the increased myocyte hypertrophy and LV redilation. CONCLUSIONS: In a rat model of myocardial infarction, autophagy decreased early after ventriculoplasty and increased again during LV redilation. These results provide new insights into the mechanism underlying the late failure of ventriculoplasty.

[One-Stage Application of Mitral Valve Correction, Surgical Radiofrequency Ablation and Left Atrial Atrioplasty].

OBJECTIVE: Our aim was to evaluate sinus rhythm restoration and its failure predictors after one-stage application of surgical radiofrequency ablation, left atrial reduction and mitral valve correction. METHODS: This is a prospective longitudinal cohort study with historical controls. Patients were divided into 2 groups according to the performed type of operation--the main group included patients undergone one-stage mitral valve correction, surgical radiofrequency ablation and left atrial atrioplasty (n = 47); and the control group consisted of patients undergone only mitral valve correction (n = 76). Surgical radiofrequency ablation was performed under the scheme Maze-IV. Left atrial atrioplasty procedure was performed according to echocardiography data: if in women LA antero-posterior dimensions were more than 4.7 cm and in men more than 5.2 cm. RESULTS: The study included 123 patients. In the main group (age of the patients 61.0 ± 9.1 years, 55% male) sinus rhythm restoration was observed in 32 (68%) patients during the early postoperative period, but at the time of discharge it reduced to 19 (40%), but in 6 months it increased up to 37 (78%), and in 36 months sinus rhythm already was detected in 40 (85%) patients. At the same time, during the early postoperative period in the control group (patients aged 59.0 ± 11.0 years, 61% male) only 31 (40%) of patients had sinus rhythm, in 6 months it was detected in 11 (14%) cases, and in 36 months sinus rhythm--only in 28 (37%) patients. Predictors of atrial fibrillation recurrence were revealed: valve disease continuance < 4 years (p = 0.017) and atrial fibrillation history < 3 years (p =0.029). CONCLUSION: One-stage peforming of mitral valve correction, surgical radiofrequency ablation and left atrial atrioplasty restores and maintains more regular sinus rhythm, even in presence of atrial fibrillation recurrence predictors.

Cardiac bioassist: results of the French multicenter cardiomyoplasty study.

The French multicenter experience (6 centers) of dynamic cardiomyoplasty was analyzed for long-term survival and functional outcome, the most important endpoints in congestive heart failure therapy. Cardiomyoplasty was performed in 212 patients with symptoms of chronic heart failure despite maximal pharmacological therapy. The etiology was ischemic (48%), idiopathic (45%) or other (7%). Cardiomyoplasty was performed using the latissimus dorsi muscle which was electrostimulated after surgery. During follow-up, 88% of patients improved clinically. Hospital death occurred in 29 (14%) patients and was related to the severity of preoperative heart failure symptoms. Late mortality occurred in 99 patients due to heart failure (44%), sudden death (37%), or noncardiac causes (18%). Combined dynamic cardiomyoplasty and implantation of a cardiac rhythm management system was safely achieved in 22 patients, and 26 underwent heart transplantation for recurrent heart failure. Long-term functional improvements were observed in most patients, and the best outcome was achieved in those with isolated right ventricular failure. Dynamic cardiomyoplasty can be considered as a destination therapy or a mid- to long-term biological bridge to heart transplantation.

Heart transplantation following cardiomyoplasty: a biological bridge.

OBJECTIVE: Dynamic cardiomyoplasty (CMP) was proposed as a treatment for refractory heart failure; more than 2000 procedures have been performed worldwide. Heart transplantation was indicated afterwards in some CMP patients with recurrent heart failure symptoms. This study reviews the multicentric French experience with CMP followed by heart transplantation. METHODS: From 1985 to 2007, 212 patients (mean age 53+/-11 years) with refractory heart failure (LVEF=22+/-9%, mean NYHA 3.2) underwent CMP in France. Heart transplantation was performed in 26 patients (12.3%), mean age: 51+/-11 years, within 2.3+/-3 years after CMP. Transplantation was indicated for persistent heart failure, i.e. no immediate improvement after CMP (19%) and for recurring heart failure (81%). RESULTS: The surgical technique of heart transplantation following cardiomyoplasty presents few particularities. Routine extracorporeal bypass was instituted between the vena cavas and the ascending aorta. As in most of these patients the CMP procedure had been performed without the need of extracorporeal circulation, hearts were free of previous cannulations for cardiopulmonary bypass. The latissimus dorsi muscle flap was divided as far as possible inside the left pleural cavity and its vascular pedicle was obturated. The proximal portion of the muscle as well as the muscular pacing electrodes were kept in place in the pleural cavity. The adhesions between the flap and the heart were not released so as to achieve an en bloc resection of the heart and the muscle flap. During removal of the recipient's heart, care was taken not to injure the left phrenic nerve that was frequently in tight relation with the latissimus dorsi muscle. Heart transplantation was then performed in a routine manner, the donor heart being anastomosed to remnant atria and great vessels. Mean follow-up was 5.5 years (longest 13.5 years). Survival at 10 years was 40% for early heart transplantation (done within 4 months of CMP) and 57% for transplantation performed at 3+/-2.8 years after CMP. CONCLUSIONS: Heart transplantation after CMP is technically feasible. Hospital mortality was higher when urgent transplantation was required. Long-term survival results are similar to those for primary heart transplantation. Cardiomyoplasty, when it fails, does not preclude transplantation, and when indicated, CMP could be considered as a biological bridge to heart transplantation.

"Demand" stimulation of latissimus dorsi heart wrap: experience in humans and comparison with adynamic girdling.

BACKGROUND: Questionable systolic assistance and latissimus dorsi (LD) muscular degeneration as a result of continuous electrical stimulation constitute important drawbacks to dynamic cardiomyoplasty. To avoid full transformation of the LD and thereby cause better systolic assistance, a new stimulation protocol was developed. Fewer impulses per day are delivered so that the LD wrap has daily periods of rest (demand), based on a heart rate cutoff. We describe our experience of demand dynamic wrapping by discriminating between patients with active systolic assistance and those with a passive girdle effect (adynamic-girdling). METHODS: Fourteen patients with primary dilated cardiomyopathy (13 men, 1 woman; mean age, 58.2 +/- 5.8 years; 12 sinus rhythm, 2 atrial fibrillation) underwent dynamic cardiomyoplasty between 1993 and 1996 as well as the demand protocol at different intervals. Clinical, echocardiographic, mechanographic, and cardiac invasive assessment records, as well as cardiovascular events (death and arrhythmias), were retrospectively reviewed. The patients were divided into two groups on the basis of the mechanographic measurement of speed of contraction of the heart wrap, as measured by tetanic fusion frequency analysis before starting demand stimulation: demand dynamic wrapping patients with fast LD (high tetanic fusion frequency, 7 patients), and adynamic-girdling patients with slow LD contraction times (low tetanic fusion frequency, 7 patients). It was assumed that in adynamic-girdling patients dynamic assistance was virtually absent, so the wrapping acted only as a passive constraint wall. RESULTS: The two groups were comparable for sex, age, dilated cardiomyopathy cause, New York Heart Association class, and left ventricular ejection fraction at the start of the demand protocol period. After a mean duration of follow-up of 41.4 +/- 21.1 months (range, 23 to 69 months), the demand dynamic wrapping group showed improved New York Heart Association class (1.14 +/- 0.34 versus 2.07 + 0.18; p = 0.0004), higher values of left ventricular ejection fraction (34.6 +/- 8.0 versus 26.5 +/- 3.1; p = 0.005) and LD wrap tetanic fusion frequency (38.3 +/- 5.88 versus 24.3 +/- 2.93; p = 0.002), and a better survival (85.7% versus 28.6%; p = 0.037) than the adynamic-girdling group. CONCLUSIONS: Demand dynamic wrapping offers good results in terms of fewer cardiovascular events and greater survival. When compared with the passive constraint effect of LD muscle, demand dynamic wrapping proved to be more effective.

Hemodynamic results of acute thoracic aortomyoplasty in a canine model: comparison of stimulation regimens.

Our previous investigations in a sheep model demonstrated that when electrical stimulation (ES) was applied to a newly mobilized latissimus dorsi muscle (LDM) in a work-rest regimen and at a rate of 15 contractions per minute, it did not damage this muscle. This regimen was used twice during a 60 minute period, once a day for 16 days, with no LDM damage. The goal of our current investigation was to apply this regimen in studies of acute thoracic aortomyoplasty. In two experimental groups, we mobilized the LDM but left it in situ. Two hours later, contractile force (CF) testing (20 g/kg preload, six impulses per burst) was performed until CF dropped to 50% of baseline. Recovery time needed to completely restore CF was calculated. In one group (six sheep), we applied continuous ES; in another (six sheep), we applied ES in a work-rest regimen (1 min work, 1 min rest). In two other groups of six dogs each, aortomyoplasty was performed; the LDM flap was subjected to ES immediately postoperatively (six impulses per burst; ventricular-LDM delay, 290 ms). Again, one group received continuous ES, and the other received work-rest ES. In the mobilized LDM under continuous ES, CF decreased to 50% of baseline values after 52 +/- 8 minutes, and returned to baseline after 84 +/- 16 minutes of rest. Under the work-rest regimen, this decrease took 105 +/- 8 minutes, and the return to baseline took 25 +/- 6 minutes (p < 0.05). In LDM subjected to work-rest ES, light microscopy revealed no additional damage to LDM tissue than was seen immediately after mobilization. However, LDM subjected to continuous ES had evidence of increased basophilic degeneration and wavy fibers. After acute thoracic aortomyoplasty, assisted hemodynamic values under the continuous ES exceeded unassisted values for only 40 minutes, compared with 100 minutes for work-rest ES (p < 0.05). When counterpulsation was completed, for continuous ES, recovery time to baseline was 96 +/- 9 minutes; for work-rest ES, it was only 43 +/- 6 minutes. In conclusion, a work-rest regimen of ES can be started safely immediately postprocedure.

Management of pacing system related complications in patients undergoing dynamic cardiomyoplasty.

Integrity of the electrical circuit is a necessary requirement for appropriate heart/wrapped skeletal muscle interaction to be achieved in cardiomyoplasty. This article describes the management of two different complications after a cardiomyoplasty procedure involving the electrical system (infection of the abdominal cardiomyostimulator pocket and intramuscular lead fracture). Minimal approaches were carried out, which ensured the successful treatment of the infective and of the mechanical insult, and represent useful strategy for solving such uncommon problems.

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.

Conservative treatment of a paracardial abscess following post-infarct patch grafting.

A patient with previous patch grafts at the site of a ventricular aneurysm and over an ischaemic septal defect presented with an oval hypodense mediastinal mass consistent with a mediastinal abscess with blood cultures positive for Staphylococcus aureus. Surgical re-operation in this region was considered to be too risky and conservative treatment was pursued. Antibiotics were continued for a total of nearly 5 months of treatment. A computed tomographic scan prior to discharge indicated that the abscess was completely resolved.

Acute muscle damage in latissimus dorsi grafts mobilized for cardiac assist: is vasospasm an important factor?

BACKGROUND: Muscle damage in latissimus dorsi grafts is known to occur following surgical mobilization for cardiomyoplasty. It is believed that ischemia may be a contributory factor. We tested the hypothesis that surgical manipulation of the muscle graft resulted in vasospasm of the intramuscular arteries that compromised muscle viability by examining the effects of vasodilators in the early ischemic period. METHODS: Rat latissimus dorsi muscles were mobilized from all truncal attachments with preservation of the thoracodorsal neurovascular pedicle. Undisturbed contralateral muscles served as controls. After 24 hours, regional analysis of muscle viability was performed by enzyme macrohistochemistry and histologic assessment. The experimental interventions in four randomized groups (n = 5 each) included: group A, control; group B, topical papaverine (1%); group C, intravenous hydralazine (0.5 mg/kg); and group D, intravenous verapamil (75 microg/kg). RESULTS: All mobilized muscles showed loss of viability, as compared to controls, with damage most apparent in the distal part (mobilized vs control: viable area = 56.76% [51.26-62.26] vs 98.54% [97.87-99.21]; p < 0.001). All three vasodilators failed to prevent muscle necrosis whereas papaverine appeared to aggravate the damage (papaverine vs control: viable area = 53.60% [30.73-76.47] vs 76.60% [75.02-78.18] in the middle region; p < 0.05 and 44.27% [29.53-59.01] vs 56.76% [51.26-62.26] in the distal region; p < 0.05). CONCLUSIONS: The rodent model appears to be useful for studying latissimus dorsi muscle injury. The use of vasodilators at the time of surgical mobilization of the latissimus dorsi muscle does not appear to influence the degree of early muscle damage. Topical papaverine may be detrimental to the muscle in this regard.

[Dynamic cardiomyoplasty: models of action and indications]. / Cardiomyoplastie dynamique: modes d'action et indications.

Cardiomyoplasty, proposed as an alternative to cardiac transplantation for the first time in 1985, has been carried out in over 500 patients over the world. The functional improvement after the procedure may be spectacular. The haemodynamic improvement at rest is generally small in terms of pre and postoperative ejection fractions. A dynamic effect of systolic assistance due to stimulation of the latissimus dorsi may be demonstrated in some cases by analysis of ventricular pressure-volume curves. However, it is probable that cardiomyoplasty prevents ventricular remodelling (girdling effect) and that chronic stimulation of latissimus dorsi, necessary to prevent atrophy and fibrosis, reduces wall stress. Therefore, many mechanisms, probably associated, may explain the clinical efficacy of cardiomyoplasty. Though the contraindications of this technique are now better known, its role with respect to cardiac transplantation in cases of severe congestive cardiac failure resistant to medical therapy still remain undefined.

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.

Cardiomioplastia dinámica: resultados / Dynamic cardiomyoplasty: results

El objetivo del presente trabajo fue evaluar los resultados inmediatos y a los 17 (5-40) meses promedio, de la Cardiomioplastia en pacientes con miocardiopatía dilatada en insuficiencia cardíaca con capacidad funcional III - IV (New York Heart Association), a pesar del tratamiento médico. Fueron intervenidos 10 pacientes con una edad promedio de 60,7 ñ 5,5 años. En 5 de ellos el origen de su afección fue idiopático y en los otros 5 isquémico necrótico; con valores promedio de fracción de eyección del ventrículo izquierdo: 22,2 ñ 5,3 por ciento, diámetro diastólico del ventrículo izquierdo: 74 ñ 6 mm, aurícula izquierda: 59 ñ 7 mm, y fracción de acortamiento: 13,9 ñ 3,4 por ciento. Para tener una mejor prueba de la capacidad funcional se les hizo una prueba de caminata de 6 minutos desarrollando un promedio de 332 ñ 134 m. Se produjo 1 muerte en el postoperatorio temprano y 2 durante el seguimiento alejado. En 6 pacientes que completaron los 6 meses del postoperatorio se han encontrado los siguientes resultados promedio: clase funcional: 1,7 ñ 0,5, fracción de eyección del ventrículo izquierdo: 32 ñ 0,3 por ciento, diámetro diastólico del ventrículo izquierdo: 72 ñ 9 mm, fracción de acortamiento: 19 ñ 7 por ciento, caminata a los 6 minutos: 391 ñ 28 m. La cardiomioplastia ha revelado a los 6 meses de seguimiento mejoría en la capacidad funcional y en la función sistólica del ventrículo izquierdo

Cardiomioplastia dinámica: resultados / Dynamic cardiomyoplasty: results

El objetivo del presente trabajo fue evaluar los resultados inmediatos y a los 17 (5-40) meses promedio, de la Cardiomioplastia en pacientes con miocardiopatía dilatada en insuficiencia cardíaca con capacidad funcional III - IV (New York Heart Association), a pesar del tratamiento médico. Fueron intervenidos 10 pacientes con una edad promedio de 60,7 ñ 5,5 años. En 5 de ellos el origen de su afección fue idiopático y en los otros 5 isquémico necrótico; con valores promedio de fracción de eyección del ventrículo izquierdo: 22,2 ñ 5,3 por ciento, diámetro diastólico del ventrículo izquierdo: 74 ñ 6 mm, aurícula izquierda: 59 ñ 7 mm, y fracción de acortamiento: 13,9 ñ 3,4 por ciento. Para tener una mejor prueba de la capacidad funcional se les hizo una prueba de caminata de 6 minutos desarrollando un promedio de 332 ñ 134 m. Se produjo 1 muerte en el postoperatorio temprano y 2 durante el seguimiento alejado. En 6 pacientes que completaron los 6 meses del postoperatorio se han encontrado los siguientes resultados promedio: clase funcional: 1,7 ñ 0,5, fracción de eyección del ventrículo izquierdo: 32 ñ 0,3 por ciento, diámetro diastólico del ventrículo izquierdo: 72 ñ 9 mm, fracción de acortamiento: 19 ñ 7 por ciento, caminata a los 6 minutos: 391 ñ 28 m. La cardiomioplastia ha revelado a los 6 meses de seguimiento mejoría en la capacidad funcional y en la función sistólica del ventrículo izquierdo (AU)

Effects of dynamic cardiomyoplasty on right ventricular function.

This study was planned to document the right ventricular function immediately after cardiomyoplasty. Right ventricular volumes were calculated with the use of fast response thermistor. Right ventricular end-diastolic volume was reduced from 91 +/- 8 mL/M2 to 75 +/- 7 mL/M2 (p < 0.05) and right ventricular end-systolic volumes increased from 51 +/- 5 mL/M2 to 59 +/- 4 mL/M2 24 hours after the operation. Central venous pressure was raised from 2 +/- 1 to 9 +/- 3 mm H2O. These changes were interpreted as impairment of the right ventricular diastolic function. Cardiac index raised from 1.8 +/- 0.5 L/M2 per minute to 2.7 +/- 0.3 L/m2 per minute within a period of 7 days (p < 0.05). As a result of this study, we concluded that preoperatively normal right ventricular function deteriorates after the cardiomyoplasty. In the intensive care unit volume balance must be carefully monitored to avoid creating right ventricular dysfunction.