Novel non-synonymous polymorphisms in the COX-1 gene in Turkish pediatric patients with cardiovascular anomalies.

Variation in the gene encoding cyclooxygenase-1 (COX-1) is involved in the process of aspirin resistance. This study investigated the genetic variations in the COX-1 gene. The 4 coding regions of the human COX-1 gene in 90 pediatric patients (median age of 6.5 months, 55% males) with cardiovascular anomalies were screened using DNA sequencing. Twenty coding-region variants causing amino acid substitutions as well as 2 new non-synonymous polymorphisms were identified. All variants were compared with an independent Caucasian population (N = 24 unrelated individuals). Most of the discovered polymorphisms were rare, although some variants resulted in amino acid changes occurring at a frequency >5% (W8R, P17L, Q41Q, Q240Q, D189E, and P188P). In addition, 2 new non-synonymous polymorphisms (F200L and D189E) were identified. These findings demonstrated novel genetic variants of the human COX- 1 gene. Future studies characterizing the functional impact of these variants are warranted.

Left ventricular assist device implantation in heart failure patients with a left ventricular thrombus.

BACKGROUND: In this report, we share our experience with left ventricular assist device (LVAD) implantation in cases with a left ventricular (LV) thrombus. METHOD: Over the 3 years, more than 100 end-stage heart failure cases have been treated with LVAD implantation in our center, including 6 patients with a LV thrombus. Three were detected using preoperative transthoracic echocardiography. Fifty percent of the patients had dilated cardiomyopathy and the remaining cases had an ischemic etiology. Double inotropic support with dopamine and dobutamine was used in all, with 3 drugs with the addition of adrenaline in 2 patients. In 4 cases we implanted the HeartWare Ventricular Assist System (HeartWare, Inc., Miramar, Fla, United States) and in the remaining 2 patients, the Berlin Heart EXCOR ventricular assist device (Berlin Heart AG, Berlin, Germany) for biventricular support. In 1 patient the apical ventriculotomy was extended to remove an intertrabecular thrombosis and ventricular septal surface covered with a dacron patch to minimize the thrombogenic potential. RESULTS: Two patients died due to sepsis and multiorgan failure. None of the patients experienced a neurological event, pump thrombosis, or pump malfunction. Two subjects underwent re-explorations due to hemorrhage. Two candidates underwent successfull transplantation without any evidence of thrombosis in the explanted heart or device. CONCLUSION: We believe that patients with a LV thrombus and preserved right ventricular function are good candidates for implantation of a LVAD after removing the intracavitary thrombus.

Valvular procedures during ventricular assist device implantation.

BACKGROUND: Increased experience and success with ventricular assist devices (VAD) has permitted more aggressive use in patients formerly believed to be inappropriate for mechanical circulatory support (MCS). There is no clearly proven policy to manage end-stage heart failure patients with valvular pathologies. The aim of this report was to analysis our experience with combined approach of VAD implantation and valvular procedures among patients with valvular heart disease and end-stage heart failure. METHODS: We evaluated the clinical records of 67 patients who underwent MCS from April 2007 to September 2011. We identified 12 patients (17.9%) who received concomitant valvular procedures, four of whom had significant aortic insufficiency and received a simple coaptation stitch at the center to approximate the fibrous nodules of Arantius. The mechanical aortic valve was replaced with a stentless bioprosthesis in three patients. Mitral valve commissurotomy was performed in one patient with mitral stenosis and seven patients underwent tricuspit valve repair using an annuloplasty ring. RESULTS: All 12 patients were males, of mean age 50.3 ± 11.5 years (range = 25-66). Eleven of them (91.6%) survived the early and late postoperative periods. Ten subjects (83.3%) continue to be supported with VAD; 1 (8.3%) was successfully bridged to transplantation. Each study participant regression of the valvular pathologies by early echocardiography demonstrated. CONCLUSION: Concomitant valve surgery during VAD implantation appeared to be a reasonable option in end-stage heart failure patients with valvular heart disease.

Evaluation of changes in quality of life among Turkish patients undergoing ventricular assist device implantation.

BACKGROUND: Ventricular assist device (VAD) application has become an increasingly common method to treatment end-stage heart failure. In this study we evaluated the effect of VAD implantation upon the quality of life among Turkish patients with end-stage heart failure. METHODS: Twenty-eight VAD implantation patients included 3 (10.7%) with biventricular support using the Berlin Heart Excor; 15 (53.6%), left ventricular support with the Berlin Heart Excor; and 10 (35.7%), Heartware implantation for left ventricular support. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Short Form 36 (SF-36) Health Questionnaire were used to assess changes in the quality of life (QOL). RESULTS: Of the 28 patients, 2 were females (7.1%) and 26 were males (92.9%) of overall mean age of 44.6 ± 15.3 years (range, 8-66). Preoperative mean score of MLHFQ was significantly improved at 200.4 ± 147.4 days follow-up (72.8 ± 11.5 vs 13.7 ± 10.5; P < .05). SF-36 physical scores and mental scores were improved postoperatively (physical scores, 20.0 ± 24.4 vs 70.2 ± 19.9; mental scores, 38.4 ± 18.8 vs 73.9 ± 15.7; P < .05). No significant relation was observed between the postoperative scores of questionnaires and type of surgery. More improvement in postoperative MLHFQ scores was seen in patients younger than 45 years of age (P = .027). The severity of chronic heart failure (CHF) regressed from New York Heart Association (NYHA) class IV to NYHA class II in 26 and to NYHA class III in 2 patients (P = .000). CONCLUSION: The QOL among patients with end-stage heart failure improved dramatically soon after VAD implantation.

New circulatory support system: heartware.

INTRODUCTION: Through the new developments in medicine, heart failure therapy has advanced to mechanical circulatory support systems. The HeartWare Ventricular Assist System HVAD; HeartWare, Inc.; Miramar, Fla, USA) is a new device that is a centrifugal, intracorporeal, miniaturized and continuous flow pump that serves simple patient use and enhanced life quality. This article reports the midterm results of patients who underwent the heartware support system. MATERIALS AND METHODS: We retrospectively compiled our data from December 2010, including 10 patients of mean age 51.8 years with 90% males, 70% of the overall patient cohort had dilated cardiomyopathy and remaining ones, ischemic disease. Mean left ventricular ejection fraction was 20.1% and mean systolic pulmonary artery pressure was 49.2 mm Hg. A single patient was grade 1; seven were grade 2; and remaining ones, grade 3 according to the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) scale. All patients were operated with cardiopulmonary bypass (CPB) with moderate hypothermia. Tricuspid ring annuloplasty was performed in 3 (30%) patients. In one patient we removed a left ventricular thrombus. In a case with severe aortic regurgitation, we placed a simple coaptation stitch at the central portion of the three aortic cusps under the aortic cross clamp. The mean CPB duration was 95.5 minutes. RESULTS: There was no operative or in-hospital mortality. Mean support time was 250.67 days. During the early postoperative period, one patient experienced a minor hemorrhagic neurological event also requiring a tracheostomy due to pneumonia. This patient has completely healed and on follow-up continues a normal life. All patients were asymptomatic regarding heart failure. One patient unfortunately died because of possible pancreatic cancer and sepsis. Two patients underwent transplantations on days 159 and 172 of support. CONCLUSION: The HVAD system provided effective circulatory support for patients with end-stage heart failure with low adverse event rates. Long-term results are needed particularly for destination therapy candidates.

Ventricular assist system applications in end-stage heart failure.

BACKGROUND: Mechanical circulatory support has an important role in the surgical therapy for heart failure. Patients deteriorating on transplantation waiting lists or those unsuitable for transplantation have been treated with ventricular assist devices. In this report, we have presented application of ventricular assist systems for patients with end-stage heart failure. METHODS: Between April 2007 and September 2010, we treated 37 patients with end-stage heart failure with mechanical circulatory support, including 5 children younger than 16 years of age. Three patients were females, and the overall mean age was 40 ± 18 years (range, 1.5-67). In 29 patients we implanted paracorporeal pneumatic ventricular assist devices. Axial flow pumps were chosen to support the left ventricle in 8 patients. Biventricular support was applied in 9 patients because of their poor preoperative clinical conditions and advanced evidence of right ventricular failure. RESULTS: Heart transplantation was performed in 16 patients (43%). One subject, who was managed with a left ventricular assist device implantation and coronary bypass grafting, was weaned from the system because of recovery of ventricular functions. Eleven patients (30%) are still on pump support. Nine patients (24%) died during mechanical circulatory support. The most prevalent cause of mortality was multiorgan failure (n = 5; 13.5%). Cerebrovascular hemorrhage was the cause of death in 2 patients. One patient died due to acute lung injury, and an other due to malignant melanoma. CONCLUSION: Use of a ventricular assist device as a bridge-to-transplantation or as destination therapy can be performed with acceptable mortality. It may be the most promising option for patients with end-stage heart failure. Development of device technology, advanced monitoring of anticoagulation and anti-aggregation therapy, and greater clinical experience may yield better results.

Ventricular assist device as a bridge to heart transplantation in adults.

BACKGROUND: Because of the shortage of donor hearts, various ventricular asist devices (VAD) have been used in decompensated patients to prolong patient survival until a suitable heart becomes available. In this paper, we present our single-center report of adult patients in whom bridging was used with VAD. METHODS: We performed a retrospective review of 14 adult patients who underwent heart transplantation after insertion of a long-term VAD. The study spans from February 2006 until September 2010. The mean patient age was 44.28 ± 11.06 years. We used the Berlin Heart EXCOR VADs (n = 11; Berlin Heart AG Berlin, Germany), or the Berlin Heart Incor (n = 2), or the Abiomed AB500 (n = 1). Preimplantation status of the subjects were critical cardiogenic shock (n = 6), deterioration on inotropes (n = 3), or stable but inotrope-dependent (n = 5). RESULTS: Mean VAD support time was 153.71 days (range, 25-517). Major adverse events during VAD support included reexploration for bleeding (n = 3; 21.4%), neurologic events (n = 2; 14.3%), left VAD-related infection (n = 2; 14.3%), pneumonia (n = 1; 14.3%), or primary device failure (n = 1; 7.1%). One (7.1%) patient showed evidence of human leukocyte antigen sensitization. There were 2 deaths (14.3%) over a mean of 324 days follow-up after heart transplantation: One due to biventricular failure in the early postoperative period and the other, at 69 days from pneumonia. Rejection was observed in 2 patients who had International Society for Heart and Lung Transplantation grade 2R without hemodynamic deterioration. In our series, the 1-year mortality was 14.4% among heart transplantations without VAD implantation and 14.2% among the bridge-to-transplantation group. CONCLUSION: We conclude that VAD implantation improved end-organ function before heart transplantation in critically ill patients.

Long-term results of autologous stem cell transplantation in the treatment of patients with congestive heart failure.

BACKGROUND: The aim of this study was to assess the long-term efficacy of stem cell transplantation with revascularization for patients with ischemic cardiomyopathy. METHODS: We enrolled 17 patients with ischemic cardiomyopathy who had undergone autologous stem cell treatment. To assess myocardial ischemia and viability they underwent coronary angiography, stress tests with dobutamine, echocardiography, and positron emission tomography. Peripheral stem cells mobilized using granulocyte colony-stimulating factor (G-CSF) were collected by aphseresis for transplantation transmyocardially into the areas of injury during coronary artery bypass surgery to increase blood flow to the engrafted areas. RESULTS: Three patients died in the early follow-up period and 4 patients with cardiac failure died during mid-term follow-up; they all underwent stem cell transplantation at 6 months after acute myocardial infarction. The mean follow-up period of the remaining 10 patients was 85.8 ± 9.2 months (range, 70-100). Mean left ventricular ejection fraction improved to 30.0 ± 6.7, whereas the preoperative mean left ventricular ejection fraction of the surviving patients was 25.6 ± 4.5 (P = .035). Mean New York Heart Association (NYHA) functional class decreased from 3.2 to 1.5 (P = .006). When the study population was divided into 2 subgroups according to the interval between acute myocardial infraction and surgery, the patients who underwent autologous stem cell transplantation within the first 6 months after myocardial infraction (Group 1) showed significantly lower NYHA scores at the last follow-up (P = .024 in Group 1 and P = .102 in Group 2). No side effects were observed to be due to the stem cell or G-CSF injections. CONCLUSION: Treatment of ischemic cardiomyopathy with autologous stem cell transplantation is easy and safe, opening a new window in the treatment of "no hope" patients.

Surgical therapy of end-stage heart failure in pediatric patients.

OBJECTIVE: We herein review our experience with ventricular assist device (VAD) implantation and heart transplantation in children with end-stage heart failure. METHODS: We performed a retrospective nonrandomized review of all patients who underwent insertion of a Berlin Heart Excor VAD or heart transplantation in our clinic. The study spans from July 2005 to July 2010. We transplanted 11 patients of mean age 11.8 ± 4.49 years, 3 of whom with critical hemodynamic situations were bridged to heart transplantation by VAD implantation. Despite the poor right ventricular systolic functions, they did not require right rVAD. In addition, 2 patients who underwent VAD implantation are still awaiting a donor heart. The mean follow-up was 825.27 ± 630.23 days (range, 21-1,888 days). RESULTS: There was no serious complication during VAD support. The overall heart transplantation mortality rate was 9.1% (1/11). In all patients, impaired end-organ functions were improved by VAD implantation before the heart transplantation. Cardiac biopsies revealed 4 grade 2R rejection episodes, which were successfully controlled in 3 patients. CONCLUSION: Heart transplantation is highly effective therapy for pediatric patients with end-stage heart failure. Pediatric VAD implantation provided satisfactory safe circulatory support for small children in poor condition on the waiting list. This option should be considered for all pediatric candidates who show a poor hemodynamic status.

Ege University experience in cardiac transplantation.

BACKGROUND: End-stage heart failure can result from many cardiac and noncardiac entities that produce a poor prognosis. Medical and interventional modalities are widely used to treat this condition, although the ultimate therapy remains heart transplantation. Herein we present our clinical experience with 140 patients who underwent orthotopic heart transplantation. METHODS: Between February 1998 and September 2010, we transplanted 140 patients with a mean age of 40 ± 13 years, including 109 men (77.8%) and 31 women (22%). There were 101 patients (73%) with dilated cardiomyopathy and 39 (27%) with ischemic cardiomyopathy. Two patients were retransplanted owing to graft failure. Sixteen patients on assist device support were successfully bridged to transplantation. RESULTS: Eighteen patients (12.8%) died within 30 days with the most common causes being right ventricular failure (8/18, 44%) and infection (4/18, 22%). Overall mortality of 39% (55/140) was most commonly caused by infection (29%, 16/55) or right ventricular failure (20%, 11/55). Nine patients (16%) died suddenly outside of the hospital. Three patients died of rejection; 4 of graft failure, and 4 of malignant disease. CONCLUSIONS: Heart transplantation remains the standard treatment modality for end-stage cardiac failure. But significant waiting list mortality rates are due to the worldwide shortage of donors. Heart transplantation in Turkey is feasible for a small and strictly selected number of patients with nonreversible congestive heart failure. In recent years, ventricular assist device applications have successful bridged subjects to transplantation, saving many patients on active waiting lists.

The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.

BACKGROUND: Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. MATERIALS AND METHODS: Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. RESULTS: The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. CONCLUSIONS: In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the descending aorta.