Gideon Sahar

Colchicine for the Prevention of Postpericardiotomy Syndrome

Background: Postpericardiotomy syndrome (PPS) is a troublesome complication of cardiac surgery, occurring in 10–45% of cases. Accepted modalities of treatment include nonsteroidal anti-inflammatory drugs, corticosteroids, and pericardiectomy in severe cases. The optimal method for prevention of PPS has not been established. Recent trial data have shown that colchicine is efficient in the secondary prevention of recurrent episodes of pericarditis. The iam of the present study was to evaluate the possible benefit of colchicine for the primary prevention of PPS in patients after cardiac surgery. To the best of our knowledge, this is the first study addressing this issue. Patients and Methods: A prospective, randomized, double-blind design was used. The initial study group included 163 patients who underwent cardiac surgery in two centers in Israel between October 1997 and September 1998. On the 3rd postoperative day, the patients were randomly assigned to receive colchicine (1.5 mg/day) or placebo for 1 month. All were evaluated monthly for the first 3 postoperative months for development of PPS. Results: 52 of the 163 patients were excluded because of postoperative complications, noncompliance, or gastrointestinal side effects of treatment. Of the 111 patients who completed the study, 47 (42.3%) received colchicine and 64 (57.7%) placebo. There was no statistically significant difference between the groups in clinical or surgical characteristics. PPS was diagnosed in 19 patients (17.1%), 5/47 cases (10.6%) in the colchicine group and 14/64 (21.9%) in the placebo group. The difference showed a trend toward statistical significance (p < 0.135). Conclusions: Colchicine may be efficacious for the prevention of PPS in patients after cardiac surgery. Further evaluations in larger clinical trials are warranted.Hintergrund: Das Postperikardiotomie-Syndrom (PPS) ist eine Folgeerscheinung nach Herzoperationen und tritt bei 10–45% der Patienten auf. Die Behandlung kann mit nichtsteroidalen Entzündungshemmern, Kortikosteroiden und in schweren Fällen durch eine Perikardektomie erfolgen. Ein optimales Verfahren zur Vermeidung des PPS gibt es noch nicht. Neuere klinische Studien zeigten, dass Colchicin bei der Sekundärprävention einer wiederauftretenden Perikarditis wirksam ist. Es war das Ziel der vorliegenden Untersuchung, die Wirkung von Colchicin bei der Primärprävention des PPS zu überprüfen. Eine vergleichbare Untersuchung gibt es unseres Wissens noch nicht. Patienten und Methoden: Die Untersuchung erfolgte prospektiv, randomisiert und doppelblind. In der ursprüglichen Studiengruppe wurden 163 Patienten mit geplanter Herzoperation in zwei Zentren in Israel zwischen Oktober 1997 und September 1998 eingeschlossen. Am 3. postoperativen Tag erhielten die Patienten randomisiert über 1 Monat entweder täglich 1,5 mg Colchicin oder Plazebo. Bei allen Patienten wurde das Auftreten des PPS nach 1, 2 und 3 Monaten überprüft. Ergebnisse: 52 der 163 Patienten wurden wegen postoperativer Komplikationen. Non-Compliance oder gastrointestinalen Nebenwirkungen von der Studie ausgeschlossen. Von den 111 verbliebenen Patienten erhielten 47 (42,3%) Colchicin und 64 (57,7%) Plazebo. Es gab keinen statistisch signifikanten Unterschied in klinischen oder operativen Parametern. Das PPS trat bei insgesamt 19 Patienten (17,1%) auf. In der Colchicin-Gruppe trat es bei 10.6% (5/47) und in der Plazebo-Gruppe bei 21.9% (14/64) der Patienten auf. Der Unterschied war aber nicht statistisch signifikant (p < 0,135). Schlussfolgerung: Weitere klinische Studien sind erfolgreich um die Wirksamkeit von Colchicin bei der Verhinderung des PPS bei Patienten nach Herzoperationen zu sichern.

Telomere dynamics in arteries and mononuclear cells of diabetic patients: effect of diabetes and of glycemic control.

Telomeres serve as a mitotic clock and biological marker of senescence. Diabetes mellitus (DM) is associated with damage to target organs and premature aging. We assessed the effect of glycemic control on telomere dynamics in arterial cells of 58 patients undergoing coronary artery bypass and in mononuclear blood cells of other diabetic (32 type I and 47 type II) patients comparing well controlled to uncontrolled patients. All were compared to age-dependent curve of healthy controls. Telomeres were significantly shorter in the arteries of diabetic versus non-diabetic patients (p=0.049) and in mononuclear cells of both type I and type II diabetes. In all study groups good glycemic control attenuated shortening of the telomeres. In arterial cells good glycemic control attenuated, but not abolished, the telomere shortening. In type II DM the mononuclear telomere attrition was completely prevented by adequate glycemic control. Telomere shortening in mononuclear cells of type I diabetic patients was attenuated but not prevented by good glycemic control. Results of this study suggest that diabetes is associated with premature cellular senescence which can be prevented by good glycemic control in type II DM and reduced in type I DM.

The natural history of aortic valve disease after mitral valve surgery

OBJECTIVES The present study evaluates the long-term course of aortic valve disease and the need for aortic valve surgery in patients with rheumatic mitral valve disease who underwent mitral valve surgery. BACKGROUND Little is known about the natural history of aortic valve disease in patients undergoing mitral valve surgery for rheumatic mitral valve disease. In addition there is no firm policy regarding the appropriate treatment of mild aortic valve disease while replacing the mitral valve. METHODS One-hundred thirty-one patients (44 male, 87 female; mean age 61+/-13 yr, range 35 to 89) were followed after mitral valve surgery for a mean period of 13+/-7 years. All patients had rheumatic heart disease. Aortic valve function was assessed preoperatively by cardiac catheterization and during follow-up by transthoracic echocardiography. RESULTS At the time of mitral valve surgery, 59 patients (45%) had mild aortic valve disease: 7 (5%) aortic stenosis (AS), 58 (44%) aortic regurgitation (AR). At the end of follow-up, 96 patients (73%) had aortic valve disease: 33 AS (mild or moderate except in two cases) and 90 AR (mild or moderate except in one case). Among patients without aortic valve disease at the time of the mitral valve surgery, only three patients developed significant aortic valve disease after 25 years of follow-up procedures. Disease progression was noted in three of the seven patients with AS (2 to severe) and in six of the fifty eight with AR (1 to severe). Fifty two (90%) with mild AR remained stable after a mean follow-up period of 16 years. In only three patients (2%) the aortic valve disease progressed significantly after 9, 17 and 22 years. In only six patients of the entire cohort (5%), aortic valve replacement was needed after a mean period of 21 years (range 15 to 33). In four of them the primary indication for the second surgery was dysfunction of the prosthetic mitral valve. CONCLUSIONS Our findings indicate that, among patients with rheumatic heart disease, a considerable number of patients have mild aortic valve disease at the time of mitral valve surgery. Yet most do not progress to severe disease, and aortic valve replacement is rarely needed after a long follow-up period. Thus, prophylactic valve replacement is not indicated in these cases.

Development of malignancy following lung transplantation

Background. A substantial excess risk of certain malignancies has been demonstrated after organ transplantation. Immunosupressive treatment to prevent allograft rejection is probably the main cause. Methods. We reviewed retrospectively all medical records of the 121 patients that underwent lung and heart-lung transplantation from 1992 until December 2004. We compared our results to the International Society for Heart and Lung Transplantation (ISHLT) registry data and previous reports concerning lung transplantation. Results. 102 of the 121 patients survived for 3 months to 12 years. Malignancies developed in 16 patients, as follows: lymphoproliferative disorder in 3, Kaposis sarcoma in 3, other nonmelanoma skin cancers in 7, urinary bladder transitional cel carcinoma in 3, and colon cancer in 1. Patients with malignancy were older at transplantation than those without (mean ± SD, 54.1±7.8 vs. 49.5±14.2 years; P=0.03). Fourteen had smoked in the past. Four died of bronchiolitis obliterans. In comparison with the ISHLT, we observed more skin cancer and transitional cell carcinoma (12.8% vs. 0.7% and 3.8% vs. 0.03%, respectively) and a similar frequency of posttransplant lymphoproliferative disease. Conclusions. We conclude that malignancy is a common complication after lung transplantation. In Israel, which is sunny most of the year, skin cancers and transitional cell carcinoma of bladder are more common. Modification of the immunosuppression late posttransplantation may reduce the risk of cancer. Patients should also be counseled to avoid sun exposure and ensure adequate hydration.

Cardiac surgery in patients on chronic hemodialysis: short and long-term survival.

OBJECTIVE Open-heart surgery carries a high risk for hemodialysis patients. This study focuses on the short and long-term outcomes of hemodialysis patients undergoing heart surgery. DESIGN The study was carried out as a retrospective analysis in the Department of Cardiothoracic Surgery in a large university-affiliated hospital. PATIENTS 115 hemodialysis patients underwent cardiac surgery in our department between 1 July 1996 and 31 July 2006. 67.5 % (77 patients) underwent isolated coronary artery bypass grafting (CABG), 13.2 % (15 patients) underwent isolated aortic valve replacement (AVR) and 20.2 % (23 patients) underwent mitral valve surgery or combined valve and coronary artery bypass grafting or multiple valve surgery. METHODS The relationship between several variables (age, sex, hypertension, diabetes, and previous myocardial infarction, type of disease, preoperative ejection fraction, and congestive heart failure) and operative (30 days) mortality and late survival was analyzed. RESULTS The overall 30-day mortality was 18.3 % (21 patients). It was 13 % (10/77 patients) for the isolated CABG group and 13.3 % (2/15) for the isolated AVR group. Patients undergoing combined valve and coronary surgery or multiple valve surgery had a higher perioperative mortality of 39.1 % (9/23) compared to the isolated CABG and isolated AVR patients. Perioperative death was also higher in patients with moderate and severe LV dysfunction, and in patients with diabetes. The duration of dialysis periods was not related to perioperative death. Mean follow-up was 26.4 +/- 29.7 months (0.1 to 104 months). Actuarial survival at 1 year and 5 years was 76 % and 55 % for isolated CABG, 59 % and 21 % for isolated AVR, and 44 % and 33 % for all other cases, respectively (log rank P = 0.001). CONCLUSION Patients on dialysis have a high risk of perioperative mortality and poor long-term survival rates. Mortality is higher and survival is worse after combined CABG and valve-related procedures or multiple valve surgery than after isolated CABG and AVR.

Advantages of the ultrasonic harmonic scalpel for radial artery harvesting.

The aim of the study was to examine the safety and effectiveness of the Harmonic Scalpel® for reducing spasm caused by thermal injury during radial artery harvesting. The study sample included 100 candidates undergoing coronary artery bypass grafting. In half the patients, radial artery harvesting was performed using the ultrasonic Harmonic Scalpel equipped with coagulating curved shears and a 14 cm scissor-grip handle and in the other half, hemostatic clips, scissors, and minimal electrocautery were employed. Comparison of outcome between the groups showed that radial artery harvesting with the Harmonic Scalpel was associated with a shorter harvesting time, lower frequency of spasm, larger internal diameter of the radial artery graft, and a significantly reduced need for clips to control bleeding than the standard method. In addition, there were no cases of hematoma or superficial wound infection in the arm, and no postoperative reduction in soft touch sensation or objective pin-prick sensation. In conclusion, the Harmonic Scalpel provides excellent control of bleeding without the need for potentially damaging electrocautery, and with a markedly decreased use of hemostatic clips. Harvesting time is also shorter. The minimized thermal injury decreases the rate of radial artery spasm. Further studies using additional objective measures are currently underway to confirm these findings.

The physiologic and histologic properties of the distal internal thoracic artery and its subdivisions

OBJECTIVE We compared the flow rates, reactivity, and morphology of the distal internal thoracic artery and its branches, the superior epigastric and musculophrenic arteries, to test their applicability as possible conduits in coronary artery bypass grafting surgeries. METHODS Skeletonized internal thoracic artery and subdivisions of patients undergoing coronary artery bypass grafting were studied intraoperatively (n = 100) for flow and length measurements and in vitro in organ baths (n = 58) for active response to norepinephrine. Quantitative microscopic analysis of the muscle density and degree of intimal hyperplasia was performed. Results were analyzed according to age, gender, risk factors, and medications. RESULTS Internal thoracic artery subdivisions contributed an average extra length of 2 cm. Free flow rates were 129 ± 45 mL/min, 114 ± 41 mL/min, and 93 ± 36 mL/min in the internal thoracic artery, superior epigastric artery, and musculophrenic artery, respectively. Sternum and internal thoracic artery length and free flow rates were significantly lower in women. The subdivisions were significantly more reactive to norepinephrine than the distal internal thoracic artery (P ∼ .005), although sensitivity to norepinephrine was similar. Patients treated with beta-blockers had significantly decreased reactivity (P = .009). Microscopic analysis suggests similar muscle content in the internal thoracic artery and subdivisions. Eccentric (28%) and concentric (62%) intimal hyperplasia were observed in 90% of specimens, with no evidence for atherosclerotic plaques. There was no significant difference in the degree of intimal hyperplasia between the distal internal thoracic artery and its subdivisions, and there was no correlation to risk factors. CONCLUSIONS Our results confirm the previous studies on the higher contractility in internal thoracic artery subdivisions, suggesting caution in the use of the bifurcation for revascularization. However, the extra length, sufficient flow, and favorable histologic properties suggest that the bifurcation may be appropriate for coronary revascularization in selected cases.

Lipid metabolism and immunosuppressive therapy in heart transplant recipients

This study included 30 heart transplant patients with follow up to 6 years. The subjects were retrospectively divided in two groups based on the immunosuppressive therapy—cyclosporine or FK506. Total cholesterol blood levels were measured regularly together with the immunosuppressant drug levels and anti-lipidic treatmentrecorded. Concomitant therapy with low-dose steroids and azathioprine was similar in both groups. T-tests were performed to compare the mean values of the two groups.

Atrial fibrillation after adult lung transplantation

ATRIAL fibrillation (AF) is the most common dysrhythmia seen early after major thoracic surgery. Atrial dysrhythmia has been observed in children undergoing lung transplantation, but AF after adult lung transplantation in the early postoperative period has not previously been reported. A Heart and Lung Transplantation Unit in the Department of Cardiothoracic Surgery in a university hospital is the setting for this retrospective analysis.

Outcome of Marginal Donors in Heart Transplantation

THE NUMBER of patients awaiting organ transplantation has progressively increased over the last decade. The progression of the discrepancy between suitable donors and potential recipients on waiting lists will have the consequence of an increasing use of organs from marginal donors. Organs that would have been thought unsuitable for transplantation not so long ago are currently used for transplantation. Advanced age, prolonged CPR, heavy inotropic support, or coronary lesions define marginal donors. Marginal recipients are advanced in age, have other diseases as limiting factors, or have been hospitalized in critical condition. From a total number of 100 transplantations (heart and/or lung) performed in our center, we present three cases in which ethical difficulties arose.