Allograft Coronary Artery Disease Research Articles

FRI093 Severe Hypertriglyceridemia Post Liver Transplant- A Multifactorial Disorder

Abstract Disclosure: A.R. Saand: None. A.R. Drinnon: None. F. Mubeen: None. J. Shakil: None. Introduction: Hypertriglyceridemia (HTG) is a known complication in solid organ transplant patients. In addition to increasing cardiovascular complications and mortality risk, these metabolic abnormalities also increase the risk of allograft atherosclerosis and vasculopathy. Although medications used in post-transplant management have a well-documented effect of worsening lipid profile, multiple factors may be contributing in the development of severe HTG. Case Description: We describe a 68-year-old male with elevated triglycerides (TG) of 3957 mg/dL on hospital admission for pneumomediastinum. He received liver transplant 2 years prior due to alcohol-related liver cirrhosis. He had normal TGs prior to the transplant. Immunosuppressant regimen included tacrolimus (TAC) and methylprednisone. Lipoprotein electrophoresis was normal. Intravenous insulin infusion was initiated with moderate improvement however, upon transition to oral medications: fenofibrate, omega-3 fatty acids, niacin and rosuvastatin, TGs continued to increase. Reinitiating insulin infusion showed no improvement. TAC was switched to cyclosporin with transient decrease in TGs. Upon discharge amylase and lipase levels remained normal despite TG elevation. When readmitted for an unrelated reason, his TGs were elevated at 2218 mg/dl. Plasmapheresis was initiated but was complicated by anaphylaxis with angioedema requiring intubation. After partial plasmapheresis, TGs significantly decreased and soon returned to normal. Post-discharge, the patient was changed back to previous TAC dosage due to cyclosporin related renal injury. His steroid dose was reduced and icosapent was added, resulting in no further recurrence of HTG. Discussion: Following liver transplant, about 15-40% recipients have increased cholesterol levels and about 40% have HTG. Although, immunosuppressant-induced dyslipidemia is seen frequently, additional risk factors have been identified. A retrospective study of 85 patients post liver transplant showed HTG developed early within the first month in about 67% patients and persisted throughout the first year. Some common factors predictive of HTG post liver transplant include pre-liver transplant hepatocellular disease and post-transplant renal dysfunction. A study in pediatric patients post liver transplant observed that changes in lipoprotein and HDL subfraction post-transplant may lead to hypertriglyceridemia. Our case suggests that HTG may be multifactorial given the persistent elevation of TGs despite the change in immunosuppressant regimen. Patient factors as well as genetic characteristics of the donor liver may be potential causes. Recognizing this variation in patient populations may be extremely important due to high risk for pancreatitis and cardiovascular events. Early identification and management may prevent complications. Presentation: Friday, June 16, 2023

87-OR: NF Kappa B Expression Is Related to Diabetes and Impaired Respiratory Capacity of Human Ventricular Myocardium

Nuclear factor kappa-B (NFkB) has been postulated to induce cardiac fibrosis and dysfunction in heart failure and triggers inflammatory pathways. NFkB can be induced by damaged mitochondria. Its association with myocardial mitochondrial respiratory function in non-ischemic diabetes-related heart failure in humans is yet unclear. We hypothesized that human ventricular myocardial NFkB expression (i) is increased by type 2 diabetes mellitus (T2DM), and (ii) relates to reduced myocardial mitochondrial respiration. Heart transplant recipients with or without T2DM (as determined by oral glucose tolerance test), about to undergo post-transplant surveillance endomyocardial biopsies, were included, if they had received hearts from donors without T2DM. Thus, time since transplantation equaled diabetes-exposure of the transplanted hearts (2.9±2.4 years). We assessed normalized NFkB p105 subunit (NFkB1) mRNA expression using real-time PCR and myocardial mitochondrial respiration using high-resolution respirometry. Study participants (T2DM: n=17, Non-DM: n=32) had no histological signs of allograft rejection, heart failure (left ventricular ejection fraction 66.2±6.5%) or coronary artery disease. Age and sex distribution were similar between Non-DM and T2DM (p=0.50; p=0.40, respectively). Myocardial NFkB1 expression was 60% higher in T2DM than in Non-DM (0.28 [0.21-0.44] vs. 0.45 [0.29-0.71] arbitrary units, p<0.05). Fasting blood glucose, but not fasting free fatty acids (p=0.55), related to myocardial NFkB1 mRNA expression (r=0.31; p<0.05). NFkB1 expression related inversely to state 3 respiration of fatty acids and glutamate (r=-0.33; p<0.05), suggesting impaired complex I-related respiration. Our findings support the concept of a key role of NFkB in diabetes-related heart failure via altered myocardial respiratory function in humans. NFkB1 might therefore serve as a future target for treating diabetes-related heart disease. Disclosure E. Zweck: None. D. Scheiber: None. T. Jelenik: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. P. Horn: None. D. Pesta: None. D. Lassner: None. H. Schultheiss: None. U. Boeken: None. P. AKhyari: None. A. Lichtenberg: None. M. Kelm: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S. R. Westenfeld: None. J. Szendroedi: None. Funding German Research Council (SFB1116); Heinrich-Heine University

Evaluation of the Management of Hyperlipidemia and Hypertension in an Outpatient Cardiac Transplant Clinic

Background: Allograft coronary artery disease (ACAD) is a common cause of morbidity and mortality post-orthotopic heart transplantation (OHT). ACAD progression may be reduced by modifying cardiovascular risk factors, such as hyperlipidemia and hypertension. We sought to evaluate the management of hyperlipidemia and hypertension among OHT recipients followed in an outpatient cardiac transplant clinic. Objective: The primary objective was to assess the proportion of OHT patients achieving both the recommended LDL target of <2.0 mmol/L and BP targets of <140/90 mmHg (or <130/80 mmHg for diabetics) in an outpatient cardiac transplant clinic. Methods: A cross-sectional retrospective analysis of the medical records of all adult OHT recipients actively followed in our outpatient cardiac transplant between January-March 2009. Results: Of the 193 patients included, both the low-density lipoprotein (LDL) cholesterol and blood pressure (BP) targets were achieved in 111 (57.5%) patients. The LDL target alone was achieved by 140 (72.5%) patients and the BP target alone by 153 (79.3%) patients. Statins were prescribed in 183 (94.8%) patients with a mean LDL of 1.81 mmol/L (±0.55). Angiotensin converting enzyme-inhibitors [ACE-I] (or angiotensin receptor blockers [ARB]) were prescribed in 154 (79.8%) patients, diltiazem in 101 (52.3%) patients, and both in 85 (44.0%) patients, with a mean BP of 124.2/77.8 mmHg (±13.6/8.2). Adverse reactions related to statins, ACE-inhibitors or diltiazem were uncommon and rarely resulted in drug discontinuation. Conclusions: Guideline recommended that LDL and BP targets are achievable in a significant proportion of OHT recipients. The high utilization rates of statins for dyslipidemia and ACE-I (or ARB) and diltiazem for BP were consistent with guideline recommendations for the prevention of ACAD. Despite concerns regarding the potential for pharmacokinetic drug interactions in OHT patients, the reported rates of any drug intolerance to these medications were low in our population.

Dobutamine Stress Echocardiography in Heart Transplant Recipients' Evaluation: The Role of Reinnervation

Introduction Orthotopic heart transplantation renders the recipient denervated. This remodeling of the intrinsic cardiac nervous system should be taken in account during functional evaluation for allograft coronary artery disease. Dobutamine stress echocardiography (DSE) has been used to detect patients at greater risk. The aim of this study was to determine whether patients with various autonomic response levels, and supposed reinnervation patterns, show the same response to DSE. Methods We studied 20 patients who had survived more than 5 years after orthotopic heart transplantation. All patients underwent a Holter evaluation. We considered patients with low variability to be those with less than a 40-bpm variation from the lowest to highest heart rate, so-called “noninnenervated” (group NI). Patients who had 40-bpm or more variation were considered to show high variability and called “reinnervated” (group RI). After that, all patients performed an ergometric test and DSE. Results Groups were defined as NI ( n = 9) and RI ( n = 11). Ergometric tests confirmed this response with NI patients showing less variability when compared to RI patients ( P = .0401). During DSE, patients showed similar median heart rate responses according to the dobutamine dose. Spearmen correlation showed r = 1.0 ( P = .016). Conclusions DES was effective to reach higher heart rates, probably related to catecholamine infusion. These findings may justify a better response when evaluating cardiac allograft vasculopathy in heart transplant patients.

326 Long-term Outcome after Bare-Metal or Drug-Eluting Stenting for Allograft Coronary Artery Disease

Percutaneous coronary intervention (PCI) with BMS has been reported to be associated with poor outcome in heart transplant recipient. We aimed to assess the outcome of successful PCI with bare-metal stents (BMS) or drug-eluting stents (DES) in heart transplant recipients. Ninety-four consecutive heart transplant recipients with successful PCI of de novo lesions with BMS (n=53) or DES (n=60) were prospectively followed-up for 41.8±31.5 months after the PCI. The lesion-based analysis within 12 months after PCI showed a marked reduction of target lesion revascularization (TLR) and restenosis rates by the use of DES (6.9% versus 26.4%, p=0.005 and 7.1% versus 32.1%, p=0.001 respectively). The patient-based multivariable analysis identified transplantation to PCI time (HR 1.1 per month), absence of antihypertensive therapy (HR 4.53) and left ventricular ejection fraction (HR 0.95 per percent) but not stent type as independent correlates of death. BMS (HR 3.79) and tacrolimus use (HR 8.32) were independent correlates of TLR. Compared to BMS, DES are associated with a marked reduction in rates of restenosis and TLR in heart transplant recipients and may be recommended despite the absence of a relationship between the stent type and survival. Early treatment of allograft vasculopathy, extensive antihypertensive therapy and left ventricular function preservation, appear as major goals of treatment to improve long-term survival in such patients.

Long-term outcome after bare-metal or drug-eluting stenting for allograft coronary artery disease

Percutaneous coronary intervention (PCI) with bare-metal stenting (BMS) has been reported to be associated with high rates of target-lesion revascularization (TLR) in heart transplant recipients. We aimed to assess the outcome of successful PCI with BMS or drug-eluting stenting (DES) in such patients. Ninety-four consecutive heart transplant recipients with successful PCI of de novo lesions with BMS (n = 53) or DES (n = 60) were prospectively followed-up for 3.7 +/- 2.5 years after PCI. An angiographic lesion-based analysis at 12-month follow-up and a long-term, patient-based survival analysis were performed. The lesion-based analysis within 12 months after PCI showed a reduction of TLR rates with the use of DES (6.6% vs 26.4%, p < 0.01). DES were associated with better preservation of left ventricular function at this time-point. The patient-based, long-term analysis showed sustained local benefit of DES (hazard ratio 4.5 [1.4 to 14.5] for BMS vs DES), but no effect on mortality, remote-site PCI and total revascularization rates. Anti-hypertensive (hazard ratio 0.2 [0.1 to 0.5]) and aspirin (hazard ratio 0.3 [0.1 to 0.8]) therapy, and left ventricular ejection fraction (0.96 [0.94 to 0.98] per percent) were the only correlates of long-term mortality. Compared with BMS, DES are associated with a sustained reduction in rates of TLR and could safely be used in heart transplant recipients with coronary artery disease. Despite excellent local effects, DES use failed to reduce mortality. Anti-hypertensive and anti-platelet therapy, and left ventricular function preservation, may be considered as aims of treatment to improve long-term survival in such patients.

Outcome After Steroid Withdrawal in Heart Transplantation

There is a lack of consensus and insufficient data to assess the impact of late steroid withdrawal after heart transplantation (HTx). The aim of the study was to investigate the security and feasibility of corticosteroid withdrawal at 1 year after transplantation. Steroid withdrawal was attempted after at least 12 months of treatment in 86 HTx patients who fulfilled the criteria. At 1 and 3 months after drug discontinuation, patients underwent 2 endomyocardial biopsies (EMB). After a mean follow-up of 25 +/- 13 months, 63% of the patients remained steroid free. In 30 patients (35%) corticosteroids were reinitiated, in 15 cases because of acute rejection (7%), 5 (6%) because of worsening renal function, 5 (6%) because of malignancy, 3 (4%) because of adverse effects of immunosuppressive drugs, and 2 because of severe allograft coronary artery disease. Four patients (5%) died after drug discontinuation. There was a significant decrease in total cholesterol (198 +/- 35 to 181 +/- 38 mg/dL; P < .001) and low-density lipoprotain (LDL) cholesterol levels (113 +/- 30 to 105 +/- 30 mg/dL; P < .001). There were no differences in mortality between patients with and without corticosteroids. Steroid withdrawal is feasible and safe in HTx patients. In our study, it was successfully maintained in 63% of the patients. EMB is helpful to identify patients with acute rejection at 1 and 3 months after withdrawal. Short- to mid-term metabolic benefits are significant reductions in serum total and LDL cholesterol.

Aortic valve replacement in a diseased bicuspid valve eleven years after transplantation

Cardiac allotransplantation is subject to a number of chronic complications that may limit graft survival. These include allograft coronary artery disease, renal dysfunction, hypertension, and malignancy, which are largely due to the immuno-modulatory and adverse effects of transplant medications. Reoperation for native allograft disease progression is a rarer phenomenon. We report a case of aortic valve replacement for bicuspid aortic valve stenosis that occurred in a patient more than ten years after cardiac transplantation.

Successful Percutaneous Intervention to Acute Myocardial Infarction Presenting With Typical Chest Pain in Transplanted Heart

Allograft coronary artery disease (CAD) is the main limiting factor of the long-term survival in cardiac transplant recipients. It is present in approximately 50% of patients at 5 years post-transplant. Allograft CAD might result in congestive heart failure, ventricular arrhythmias and sudden cardiac death. Acute coronary syndrome is a rare presentation of allograft CAD, because symptoms are usually atypical or absent as a result of cardiac denervation. However, it should be reminded that reinnervation of the transplanted heart might occur, and angina pectoris could be felt as a sign of an acute coronary syndrome. We present a 27-year-old female cardiac transplant patient with an acute myocardial infarction, who was successfully treated with percutaneous transluminal coronary angioplasty.

Risk factors for the development of coronary artery disease of a grafted heart as detected very early after orthotopic heart transplantation

Orthotopic heart transplantation (OHTx) represents a well established method of end-stage heart failure treatment. Allograft coronary artery disease (CAD) still remains to be one of the most important limiting factors for OHTx recipients' long-term survival. Unfortunately, allograft CAD can be detected very early after OHTx. Our study was designed to identify risk factors for early allograft CAD development. Eighty-three OHTx recipients (18 females, 65 males, mean age 50.55 +/- 11.04 years) with coronary intravascular ultrasound examination performed early after OHTx (29.81 +/- 12.45 days) formed the study population. The impact of a number of pre-, peri- and early post-transplant possible risk factors on early allograft CAD development was studied. By multivariate analysis, only higher donor age (P < 0.001) and higher recipient's body mass index (P = 0.003) were found to represent risk factors for the early development of allograft CAD.

Chlamydia Pneumoniae Infection Is Not Associated With Chronic Transplant Dysfunction in a Rat Aortic Allograft Model

Long-term survival of solid-organ transplants is limited as a result of chronic transplant dysfunction (CTD), which is characterized by occlusion of intragraft vascular tissue due to myointimal hyperplasia. Recent studies have shown a role for infections in vascular pathologies. For example, Chlamydia pneumoniae ( Cpn) has been shown to aggravate atherosclerosis, and Cpn immunoglobulin (Ig)G titers correlate with severity of allograft atherosclerosis after cardiac transplantation. In this study, we evaluated the effect of Cpn infection on CTD using a rat aortic allograft model. Orthotopic abdominal aorta transplantations (Tx) were performed with Brown Norway rats as donors and Lewis rats as recipients. Rats were humanely killed at 1 or 8 weeks after surgery. The graft was processed for DNA isolation and histological examination. Influx of macrophages and T cells was assessed using immunohistochemistry. At 1 week after Tx, the perivascular influx of inflammatory cells in the graft was not affected by Cpn infection. Furthermore, only limited numbers of Cpn DNA copies were found in the graft at 1 week after Tx. In addition, Cpn did not alter the severity of myointimal hyperplasia in the rat aortic allograft model at 8 weeks after surgery. Our data suggested that, in the rat aortic allograft model, Cpn infection did not influence the influx of inflammatory cells or the severity of CTD.

Restrictive hemodynamics are present at the time of diagnosis of allograft coronary artery disease in children

Clinical recognition of allograft coronary artery disease (ACAD) is challenging. We examined whether right heart hemodynamics can aid its diagnosis in pediatric recipients. We retrospective analyzed hemodynamic data of recipients with ACAD versus age and date-of-transplant matched controls. From 1982-2001, 18 cases fulfilled study entry criteria. Median age at transplant was 12 years for subjects and 8 years for controls. Median time to diagnosis of ACAD was 65 months (14.5-124 months) and 67 months (16-140 months) to arteriography for controls. The median right ventricular end-diastolic pressure (RVEDP) at diagnosis was 11.0 vs. 6.0 mmHg for controls (p = 0.003). Pulmonary capillary wedge pressure (PCWP) at diagnosis was 14.0 vs. 8.0 mmHg for controls (p = 0.001). When subdivided by severity of ACAD, the difference was greater in the moderate/severe group. Compared to the previous catheterization (median interval 10 months for subjects, 12.0 for controls ), there was an increase of 4.0 mmHg in RVEDP in ACAD subjects (n = 13, p = .003) versus 0 mmHg in controls (p = 0.042), and an increase in PCWP of 5.5 in subjects (p = .002) versus 0 mmHg in controls (p = 0.066). The presence of elevated filling pressures plus an interim increase should alert to the presence of ACAD and help guide further investigation.

Are Heart-Lung Transplant Recipients Protected From Developing Bronchiolitis Obliterans Syndrome?

Heart-lung transplant recipients, when compared with heart transplant recipients, are relatively spared from allograft coronary artery disease. This study was undertaken to investigate whether heart-lung transplant recipients are also spared from experiencing bronchiolitis obliterans syndrome (BOS) when compared with double-lung transplant recipients. In addition, the risk factors for developing BOS after lung transplantation were analyzed. Heart-lung and bilateral sequential double-lung transplant recipients were reviewed retrospectively from 1990 to 2000 using the Stanford Transplant Database. The heart-lung transplant group consisted of 77 heart-lung transplant recipients and the double-lung transplant group consisted of 51 double-lung transplant recipients. The rates of BOS, survival, acute rejection, and cytomegalovirus infection at 1, 3, and 5 years were measured. There were no significant differences in patient demographics between the two groups. Rates of survival and acute rejection were similar in the two transplant groups. The incidence of cytomegalovirus infection was significantly higher in heart-lung transplant recipients. Freedom from BOS was similar in the two transplant groups. Risk factors for the development of BOS in the heart-lung and double-lung transplant recipients included male donor, younger recipient age, a diagnosis other than cystic fibrosis, nonuse of cardiopulmonary bypass, and the use of OKT3 induction therapy. Heart-lung transplant recipients exhibit BOS at a rate similar to double-lung transplant recipients. The immunoprotective effect the lung allograft presumably provides the heart is not reciprocated by the heart in preventing the development of BOS.

Angiographic, Pathologic, and Clinical Relationships in Coronary Artery Disease in Cardiac Allografts

To date, the etiologic factors involved in the development of allograft coronary disease remain speculative and the treatment uncertain. The purpose of this study was to review the relationship of clinical, angiographic, and pathologic features of cardiac allograft vascular disease in a large population of heart transplant recipients followed for up to 15 years. From 1981 to 1996, 789 angiograms from 255 cardiac allografts were reviewed to determine the prevalence and severity of coronary artery disease. Demographic, clinical, and laboratory variables were analyzed to identify factors associated with the presence of angiographic coronary artery disease. In addition, pathologic examination was performed on many of the lost grafts. Unsuspected severe donor coronary artery disease may be responsible for up to 10% of early graft failures. Angiographic coronary artery disease prevalence increased by approximately 10% with every 2-year interval after transplantation. Angiographic coronary artery disease consisted most often of minor luminal irregularities. Severe disease occurred in 12% of patients. At 1 year, the most significant factors associated with the presence of coronary artery disease were older donor age and the number of rejection episodes. Immunologic factors as well as traditional coronary risk factors such as hypercholesterolemia and hyperglycemia may play an important role in the genesis and progression of later-developing abnormalities. Cardiac allograft coronary artery disease is a major limiting factor to the long-term success of cardiac transplantation. Immune processes, as well as traditional coronary artery disease risk factors, appear to play a role in the development of this disease.

Is biopsy-proven cellular rejection an important clinical consideration in heart transplantation?

Immunosuppression strategies to prevent allograft rejection represent the cornerstone of long-term survival after heart transplantation. Endomyocardial biopsy has defined rejection in clinical cardiac transplantation and established a threshold for therapy. With the development of more effective immunosuppression modalities and the asymptomatic nature of most histologic rejection episodes, controversy exists regarding the need to augment immunosuppression based purely on histologic findings. The frequency of histologic rejection has declined with current immunosuppression. Resolution of lower grades of histologic rejection without treatment is the norm in both pediatric and adult heart transplant studies. Recurrent rejection episodes have been linked to the subsequent development of allograft coronary artery disease, and late rejection (even if asymptomatic) is associated with decreased survival in pediatric heart transplant recipients. Black race is a risk factor for recurrent rejection and reduced survival after late cellular rejection. Apoptosis of inflammatory cells is more evident during and after histologic rejection treated with corticosteroids. Despite numerous noninvasive modalities evaluated for the detection of rejection, to date noninvasive methods cannot reliably predict histologic rejection. Histologic rejection appears less common with current immunosuppressive strategies, and controversy exists about the need to treat asymptomatic rejection. It remains unproven whether non-treatment of moderate or greater rejection (>/=3A) increases the likelihood of recurrent rejection, which if present, may increase the risk of allograft coronary disease and/or reduced long-term survival.

Transplant coronary artery disease: Incidence, progression and interventional revascularization

Background Allograft coronary artery disease (CAD) remains the main factor responsible for late graft loss. This analysis describes data on incidence and progression of allograft CAD at our institute, as well as our experience with coronary interventions in heart transplant recipients. Methods Angiographic results of cardiac transplant patients undergoing coronary angiography were prospectively selected and analyzed. Angiographic outcome at follow-up were assessed for all coronary revascularizations in denovo lesions. Results Four hundred thirty-two coronary angiographies were performed in a total of 246 patients. Seventy-six patients (30.9%) showed angiographic evidence of CAD with %DS>50%, of which 48 patients revealed significant stenosis with %DS>70% (19.5%). Within the first 5 years after the transplantation, 10.1% show angiographic signs of a CAD; at the time of 10.1 years, 50% of all heart transplant patients have developed a CAD. Once a CAD with %DS between 50% and 60% has evolved, the disease shows fast progression. Coronary intervention was performed in 28 vessels at an average time of 9.5 years after heart transplantation. Follow-up angiography was available for 27 vessels (1 death before re-angiography) within a mean follow-up period of 19.3 months. Binary restenosis was found in 7 out of 27 vessels (25.9%). Comparison of the occurrence of total occlusion in vessels with %DS>70% which were not revascularized to the occurrence of MACE after successful revascularization revealed better long term results in the group of patients with coronary intervention ( p=0.04). Conclusion Whereas coronary artery disease is found in rare cases within the first 5 years after heart transplantation, the incidence grows in exponential manner after this period. Mid-term follow-up after coronary intervention exhibit restenosis-rates which are similar to the ones of other high risk patients. Comparison of coronary intervention versus conservative treatment in vessels with %DS>70% show significant better mid-term outcome in the interventional group.

Noninfectious constrictive pericarditis in a heart transplant recipient

Acute rejection, infection, and allograft coronary artery disease have been recognized as the major causes of postoperative morbidity and mortality in cardiac transplant patients. More recently, pericardial and mediastinal complications have been recognized as a more common complication than previously believed. We describe a case of a heart transplant recipient admitted for apparent congestive heart failure exacerbation who was unresponsive to standard medical management of congestive heart failure and rejection. After further invasive evaluation, it was discovered the patient’s condition was attributable to posttransplantation constrictive pericarditis. It is appropriate to consider this diagnosis in any postcardiac surgery (especially heart transplant recipients) in patients presenting with congestive heart failure exacerbations refractory to usual medical management.

New therapeutic option for cardiac ischemia in transplant vasculopathy: spinal cord stimulation

The main limitation to long-term survival for allogeneic heart transplant recipients is the onset of “accelerated allograft coronary artery disease” (ACAD). Over the years, different treatment options for the management of ACAD-induced critical ischemia have been taken into consideration. The use of percutaneous transluminal coronary angioplasty (PTCA) is still controversial, performed mostly for Type B/C and Type A lesions measuring 2.5 mm. According to Musci et al, there is no difference between PTCA-treated and non–PTCAtreated patients with ACAD. Myocardial re-vascularization surgery is burdened with high peri-operative mortality and poor long-term results. Transmyocardial laser re-vascularization initially provided encouraging short-term results, but these were not borne out by long-term outcome. In consideration of the increasing number of potential heart transplant recipients and the limited donors pool, which is not increasing proportionally, re-transplantation does not appear to be an ethically sufficient option, because a second transplantation entails a far higher short-term mortality than a first transplantation and is accompanied by a high probability of coronary artery disease (CAD) recurrence. The good outcome reported in the literature and our own experience since 1986 in the management of refractory angina with spinal cord stimulation (SCS) has led us to use this technique in posttransplantation CAD as well. To our knowledge SCS treatment for cardiac transplant recipients has not been reported to date. The Brussels Consensus Statement on SCS in 1998 stated that “to be accepted for SCS treatment, angina pectoris must be refractory both to drug therapy (beta-blockers, calcium channel antagonists, long action nitrates, aspirin) and revascularization methods.” We report a 32-year-old man (weight 58 kg, height 168 cm) who underwent orthotopic cardiac transplantation in February 1992 because of dilated cardiomyopathy, which was diagnosed 2 years earlier and probably had a viral etiology. Post-transplantation follow-up revealed hyperlipoproteinemia, hyperuricemia with sporadic episodes of gout, and obesity. During the 4 years after surgery the patient’s tolerance to the allograft was good. Following the onset of diastolic hypertension and atypical chest pain, left cardiac catheterization with coronary angiography was performed in July 1996. Hemodynamic study showed lesion-free coronary arteries. In January 2000 the patient’s weight increased to 97 kg. Also, he complained of chest pain, typical of exercise-induced angina. The pain was “band-like,” retrosternal, with short duration, and decreased at rest (CCS Functional Class II to III). One month From the Divisions of Pain Therapy and Palliative Care, and Cardiac Surgery, University of Turin, Turin, Italy. Submitted June 11, 2002; revised February 13, 2003; accepted February 13, 2003. Reprint requests: Paolo Centofanti, MD, Divisione di Cardiochirurgia, Ospedale Molinette, C.so A.M. Dogliotti 14, 10126 Turin, Italy. E-mail: paolocentofanti@tiscalinet.it Copyright © 2004 by the International Society for Heart and Lung Transplantation. 1053-2498/04/$–see front matter doi:10.1016/S1053-2498(03)00151-7

Vascular endothelial growth factor gene polymorphism are associated with allograft coronary artery disease after clinical heart transplantation

Statement of purpose: Cardiac allograft arteriosclerosis is a complex process of alloimmune response, chronic inflammation and smooth muscle cell proliferation. It is a major cause of morbidity and mortality after orthotopic heart transplantation (HTx). Vascular Endothelial Growth Factor (VEGF) is a mitogen for endothelial cells and is expressed by myocardial tissue and T-cells. VEGF induces migration and proliferation of endothelial cells and stimulates production of thrombogenic protein tissue factor in endothelial cell and monocytes. This study investigates whether genetically determined variation in VEGF expression influences the development of allograft coronary artery disease (CAD) after clinical HTx.

Long-term results of heart transplantation in patients older than 60 years

Background Advanced age has been traditionally considered a relative contraindication for heart transplantation. Older patients are now considered as potential candidates for heart transplantation. The objective of this study was to evaluate the long-term results of heart transplantation in patients older than 60 years. Methods Between 1986 and 2001, 81 patients aged between 60 and 70 years (mean, 63 ± 2 years) underwent heart transplantation. These patients were compared with 403 adult recipients younger than 60 years (mean, 47 ± 11 years) who underwent transplantation during the same period. Results Thirty-day mortality was 6% (5/81) and 6% (25/403) in the older and younger patients, respectively ( P = NS). Actuarial survival at 1, 5, and 10 years was 88% ± 4% versus 83% ± 2%, 75% ± 5% versus 69% ± 2%, and 50% ± 9% versus 51% ± 3% in the older and younger patients, respectively ( P = NS). Older patients had significantly fewer rejection episodes ( P = .003). Freedom from allograft coronary artery disease at 1, 5, and 10 years was 98% ± 2% versus 92% ± 2%, 85% ± 6% versus 76% ± 3%, and 81% ± 7% versus 68% ± 3% ( P = .1). The incidences of infectious complication, cytomegalovirus infection, and posttransplant lymphoproliferative disorder were similar between the 2 groups, but older recipients were more likely to have a nonposttransplant lymphoproliferative disorder cancer ( P = .002). Age at transplantation was not identified as an independent risk factor for early and late death. Conclusion Heart transplantation in selected patients aged 60 years and older results in survival comparable with that of younger patients. Older patients have a lower risk of rejection but an increased risk of development of a nonposttransplant lymphoproliferative disorder cancer. Advanced age per se should not be considered as an exclusion criterion for transplantation.