Evaluation of pulmonary hypertension in heart transplant candidates

Assessment of the pulmonary circulation and right ventricular function is a cornerstone in the evaluation of the patient as a potential heart transplant recipient. The importance of pulmonary hypertension is linked to outcomes in the posttransplant period. Preoperative pulmonary vascular resistance is an independent risk factor for early death after heart transplantation. Pulmonary hypertension can be classified as reversible, or irreversible if not rapidly responsive to pharmacologic maneuvers. However, in most patients, the major component is likely to reverse with vasodilators, because of the central role played by the endothelium in the control of pulmonary vascular tone. To discriminate between patients with reversible and irreversible pulmonary hypertension, provocative therapies are used, and baseline and the postprovocation hemodynamic parameters are measured. To date, there is no reliable hemodynamic threshold beyond which right ventricular failure is certain to occur, nor are there values below which right ventricular failure is always avoidable. Because of this uncertainty, it becomes clear that only through careful preoperative assessment can this life-threatening condition be recognized preoperatively and, hence, managed in the posttransplant recovery period.     

Intensified medical therapy in heart transplant candidates

Background: Because of donor shortage, heart transplantation (HTx) as therapy for end-stage heart failure is limited by a mortality rate of 25% on waiting lists, and lists are steadily increasing. Aim: To analyse whether an intensive medical therapeutic regimen for heart failure (based on the results of frequent haemodynamic studies) can delay or even prevent the need for HTx. Methods: Data analysis of 517 patients who were referred to our institution for HTx from 1984 to 1996 is presented. Characteristics and management of 359 non-emergency, New York Heart Association (NYHA) III or IV heart transplant candidates, without contraindications (and with sufficient compliance) are described. All candidates receiving conventional therapy with ACE inhibitors, digitalis and diuretics at entry were evaluated. Drug therapy was intensified as follows: a further reduction of preload; a further reduction of afterload; individualised diuresis; and amiodarone therapy. Results: Under this regimen, clinical and haemodynamic parameters improved in many patients. Only 95 patients (26%) were primary non-responders to intensified medical therapy and had to be listed for HTx early (during the first year of follow-up). Actuarial survival rates of the early listed versus the early responding HTx candidates, at 1 and 5 years, were 68.3%/87% and 41%/59%, respectively (p=0.02). An additional benefit of co-therapy with amiodarone and calcium antagonists was found. The most important mode of cardiac death was sudden (32% at 5 years), whereas mortality due to pump failure was much lower (13% at 5 years). Only 38 patients (16%):had to be listed for HTx in further follow-up. Conclusions: Intensive medical therapy in heart transplant candidates may be an alternative to immediate HTx, especially in times of donor shortage or in countries without a transplantation program. Responders to therapy showed a similar or even better prognosis than HTx patients. This conservative approach may allow available donor hearts to be saved for those patients most needing a transplant.     

Dissociation between peak exercise oxygen consumption and hemodynamic dysfunction in potential heart transplant candidates

Objectives. The purpose of this study was to determine how often peak exercise oxygen consumption (Vo₂) misclassifies the severity of cardiac dysfunction in potential heart transplant candidates.Background. Cardiopulmonary exercise testing is being used to help select heart transplant candidates on the basis of the assumption that a low peak exercise Vo₂indicates severe hemodynamic dysfunction and a poor prognosis. However, noncardiac factors, such as muscle deconditioning, can also influence exercise capacity. Therefore, peak exercise Vo₂may overestimate the severity of cardiac dysfunction in some patients.Methods. Hemodynamic and respiratory responses to maximal treadmill exercise were measured in 64 sequential patientsundergoing evaluation for heart transplantation, all of whom had an ejection fraction <35% and reduced peak exercise Vo₂levels (mean [±SD] 13.3 ± 2.7 ml/min per kg).Results. Twenty-eight (44%) of 64 patients exhibited a reduced cardiac output response to exercise and pulmonary wedge pressure >20 mm Hg at peak exercise, consistent with severe hemodynamic dysfunction. Twenty-three patients (36%) exhibited a normal cardiac output response to exercise but a wedge pressure >20 mm Hg at peak exercise, suggesting moderate hemodynamic dysfunction. Thirteen patients (20%) exhibited a normal cardiac output and wedge pressure <20 mm Hg at peak exercise, suggesting mild hemodynamic dysfunction. Despite these markedly different hemodynamic responses, all three groups exhibited similar peak exercise Vo₂levels (mild dysfunction 14.2 ± 3.5 ml/min per kg, moderate dysfunction 13.9 ± 2.7 ml/min per kg, severe dysfunction 12.4 ± 2.1 ml/min per kg). A peak exercise Vo₂level <14 ml/min per kg, considered to reflect severe hemodynamic dysfunction, was observed in 18 of the patients with a normal cardiac output response to exercise, whereas 7 patients with severe hemodynamic dysfunction had a peak Vo₂level >14 ml/min per kg.Conclusions. More than 50% of potential heart transplant candidates with a reduced peak exercise Vo₂level exhibit only mild or moderate hemodynamic dysfunction during exercise. Hemodynamic responses to exercise should be directly measured in potential transplant candidates to confirm severe circulatory dysfunction.     

The alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume in heart transplant candidates

OBJECTIVES: To determine the mechanism of impairment of pulmonary transfer factor for carbon monoxide (TL(CO)) in heart transplant candidates, as this is the most common lung function abnormality. SETTING: Regional cardiopulmonary transplant centre. METHODS: TL(CO) and its components (the diffusing capacity of the alveolar-capillary membrane (D(M)) and the pulmonary capillary blood volume (V(C))) were measured using the Roughton and Forster method and the single breath technique in 38 patients with severe chronic heart failure awaiting heart transplantation (mean age 51 years, range 19 to 61; mean left ventricular ejection fraction 12.8%). Results were compared with data from 26 normal subjects (mean age 47 years, range 27 to 62). RESULTS: Mean per cent predicted TL(CO), D(M), and V(C) were significantly reduced in patients (69.9%, 81.4%, and 80.2% of predicted, respectively) compared with controls (97.7%, 100.1%, and 102.3% of predicted, respectively, p < 0.001). The relative contribution of the two components of TL(CO) in patients was similar to that of normal subjects, with each component accounting for approximately 50% of the total resistance to diffusion (1/TL(CO)). CONCLUSIONS: TL(CO) impairment in patients with severe chronic heart failure awaiting heart transplantation results from a proportionate reduction in both D(M) and V(C), suggesting a significant disturbance of the pulmonary vascular bed.     

High frequency of anti-endomysial reactivity in candidates to heart transplant

BACKGROUND: A possible link between coeliac disease and dilated cardiomyopathy has recently been suggested. AIMS:. To assess the frequency of anti-endomysial antibodies, the marker for coeliac disease, in patients with different forms of heart failure, and to establish the clinical features of those endomysial antibody positive. SUBJECTS AND METHODS:. A total of 642 consecutive patients entering the waiting list for heart transplantation from 1995 through 1997 were studied. The prevalence of endomysial IgA antibodies, determined by indirect immunofluorescence, was compared to that observed in three surveys conducted in the Italian general population. RESULTS: Of the 642 patients, 12 (1.9%; 95% confidence interval 0.97-3.2) resulted endomysial antibody positive, versus 34/9,720 healthy controls (0.35%; 95% confidence interval, 0.23-0.47), accounting for a relative risk of 5.3 (95% confidence interval, 2.8-10.3). Anti-endomysial antibodies were found in 6/275 patients with dilated cardiomyopathy and 6/367 with other forms of heart failure (2.2% versus 1.6%; 95% confidence interval 0.8-4.7 and 0.6-3.5), with no statistical difference. The 12 endomysial antibody positive patients were leaner (body mass index, 22.0 +/- 1.9 vs 24.2 +/- 3. 1, p<0. 05) than 36 seronegative patients matched for baseline demographics and aetiology of cardiomyopathy No differences were observed as regards clinical, biochemical and echocardiographic features, mortality in waiting list and 2-year post-transplant survival. CONCLUSIONS: Patients with end-stage heart failure are at increased risk for coeliac disease as compared to the general population.     

Bilateral diffuse pulmonary infiltration in a heart transplant recipient

Abstract: Pulmonary complications are not infrequent after heart transplantation. Kaposi sarcoma is a vascular tumor that can involve the skin as well as visceral organs. We describe a case of visceral and cutaneous Kaposi sarcoma that presented with diffuse bilateral pulmonary infiltration and breathlessness 6 month after heart transplantation. Following modulation of the immunosuppressive regimen and addition of chemotherapy, the patient had an excellent response and has had an uneventful 1‐year follow‐up. B. Sharif‐Kashani, Z.H. Ahmadi, B. Bikdeli, P. Tabarsi, A. Dorudinia, P. Shahabi, S. Raeissi, B. Shadafza, G. Estahbanati, A. Naji, L. Saliminejad, M. Bakhshayesh‐Karam, S. Karimi, K. Khodadad, M.‐R. Masjedi, A. Gavazzi. Bilateral diffuse pulmonary infiltration in a heart transplant recipient.
Transpl Infect Dis 2010: 12: 258–260. All rights reserved     

The value of B-type natriuretic peptide and big endothelin-1 for detection of severe pulmonary hypertension in heart transplant candidates

BACKGROUND: Severe pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) are important risk factors that predict early postoperative mortality after orthotopic heart transplantation. The aim of our study was to determine the value of B-type natriuretic peptide (BNP) and big endothelin-1 (big ET1) for prediction of severe PH in heart transplant candidates. METHODS: The study population included 43 potential heart transplant candidates (38 males, mean age 52 +/- 7 years). All underwent repeated right-heart catheterizations (2-5 studies) at an interval of 3-4 months, giving a total of 124 examinations, associated with blood sampling for BNP and big ET1 analysis. Severe PH was defined as the mean pulmonary artery pressure (MPAP) > 40 mmHg. RESULTS: Significantly high PVR (PVR > 3.0 Wood units and TPG > 15 mmHg) was noted on 12 occasions in 10 patients; always in the presence of severe PH. Low BNP levels (<67 pg/ml) ruled out the presence of severe PH with a 100% sensitivity, however, with a low specificity (34%). An increase in plasma BNP > 30 pg/ml (>40% of initial value) in subjects with a previous MPAP< or =40 mmHg detected development of severe PH with a 100% sensitivity and an 80-88% specificity. As a total of 58% of patients presented repeatedly with MPAP< or =40 mmHg, serial BNP testing could reduce the need for hemodynamic studies in this subgroup down to 12-20%. CONCLUSIONS: Serial BNP testing in hemodynamically stable heart transplant candidates with MPAP< or =40 mmHg allows reliable detection of development of severe PH, and may significantly reduce the need for repeated right-heart catheterizations in these patients.     

Prognosis of heart transplant candidates stabilized on medical therapy

INTRODUCTION AND OBJECTIVES: A significant percentage of patients selected as candidates for heart transplantation can be stabilized by medical treatment, thereby enabling indefinite postponement of inclusion on the operation list. The aim of this study was to investigate the prognosis of these patients. PATIENTS AND METHOD: We studied retrospectively 118 patients with severe left ventricular systolic dysfunction (ejection fraction < or = 35%) who were consecutively evaluated for cardiac transplantation but who did not undergo transplantation because they became clinically stable on medical treatment. The mean follow-up period was 2.14 (2.19) years. Kaplan-Meier survival analysis, and univariate and multivariate Cox proportional risk analyses of factors predicting survival were performed. RESULTS: There were 18 deaths (15.2%): 12 were sudden (66.7%), 5 were due to heart failure (27.8%), and 1, to a non-cardiac cause (5.5%). The survival rate was 88% in the first year and 82% in the following 2 years. Univariate analysis showed that the parameters associated with mortality (P< or =.05) were pulmonary artery and capillary wedge pressures, diuretic treatment, and the absence of beta-blocker therapy. In the multivariate analysis, only the absence of beta-blocker therapy remained statistically significant (P=.003; RR = 0.13; 95%CI, 0.03-0.50). CONCLUSIONS: In a population of patients with severe left ventricular systolic dysfunction who were candidates for heart transplantation but who were stabilized by medical therapy, mortality during the first year of follow-up was 12%. Beta-blocker therapy was the only variable associated with better survival.     

Alexithymia, depression and heart rate in candidates for cardiac surgery

Effects of psychological traits on heart rate (HR) and heart rate variability (HRV) were evaluated in patients awaiting cardiac surgery. Alexithymics demonstrated slowed HR, whereas high cognitive performance was associated with elevated HR in 2-3 days before surgery. Depression negatively correlated with HRV low frequency power. These data are consistent with previous findings of diverse moderate stress effects on HR regulation in cardiologic patients and healthy subjects in accordance to differences in psychological characteristics.     

Thrombolysis with resolution of pulmonary hypertension in a heart transplant candidate

We report a patient with idiopathic cardiomyopathy and high pulmonary resistance due to pulmonary emboli of unknown age. Successful thrombolytic therapy returned his pulmonary resistance to normal, allowing orthotopic cardiac transplantation. This case underscores the need to aggressively diagnose and treat pulmonary emboli in potential transplant candidates.     

Low prevalence of prior streptococcus pneumoniae vaccination among potential lung transplant candidates

INTRODUCTION: Appropriate vaccination status in the pre-solid organ transplant period is critically important. METHODS: To determine if lung transplant candidates are adequately vaccinated for Streptococcus pneumoniae, a cross-sectional study was performed. Electronic records of patients referred to our institution for transplantation evaluation between July 2002 and January 2004 were reviewed. RESULTS: Only 98 of 157 patients (62.4%; 95% confidence interval [CI], 54.8 to 70.1%) evaluated for lung transplantation reported prior receipt of S pneumoniae vaccine. COPD was the only factor significantly associated with vaccination. Patients with COPD were more likely to have received vaccination compared to patients with other diagnoses (odds ratio, 4.66; 95% CI, 2.26 to 9.60). CONCLUSIONS: S pneumoniae vaccination rates among potential lung transplant candidates fall substantially short of current recommendations for universal immunization. Transplant programs should thoroughly review vaccination status and develop strategies to ensure that candidates receive all appropriate vaccines before transplantation.     

Ischemic heart disease in renal transplant candidates: towards non-invasive approaches for preoperative risk stratification.

This editorial refers to the paper of R. Sharma et al. entitled "Dobutamine stress echocardiography and cardiac troponin T for the detection of significant coronary artery disease and predicting outcome in renal transplant candidates". The editorial discusses different strategies for cardiac risk assessment in patients with end-stage renal disease undergoing renal transplantation.     

The relationship between cardiac function and neuropsychological status among heart transplant candidates

Background: Cognitive deficits among heart transplant candidates have been well documented. This study was designed to examine the hypothesis that impaired cognitive test performance among heart transplant candidates may be attributed, in part, to decreased cerebral perfusion secondary to poor cardiac function.Methods and Results: Sixty-two patients participated in the study who underwent heart catheterization within 1 day of completing a battery of cognitive tests. Multiple demographic and patient characteristics were examined for their potential moderating role in the relationship between measures of cardiac function and cognitive performance including age, education, race, gender, psychiatric history, medication usage, cardiac surgical history, and self-reported symptoms of depression and anxiety. Only age and education were significantly related to cognitive performance (P < .01). Thus, partial correlation analyses controlling for age and education were used to examine the relationship between cardiac function and cognitive performance. In general, increasing hemodynamic pressure variables (ie, pulmonary artery pressure and right atrial pressure), and to a lesser extent cardiac output and cardiac index, were related (r = − .32 to − .43; P < .01) to decreased performance on cognitive tasks that assessed simple attention, speed of mental processing, and mental flexibility (Digit Span-Forward, Trail Making Test-Part B, Symbol Digits Modalities Test, and Stroop Neuropsychological Screening Test). Left ventricular ejection fraction, systemic and pulmonary vascular resistance, and mean arterial pressure were largely unrelated to cognitive performance in this sample of patients with end stage cardiac disease.Conclusions: Hemodynamic pressure variables seem to be most consistently related (ie, inversely) to cognitive functioning among heart transplant candidates.     

Portopulmonary hypertension in liver transplant candidates

Pulmonary vascular disorders including portopulmonary hypertension(PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure(PAP) and liver transplant surgery, survival of patients with Po PHT and advanced liver disease is significantly improved. Because of the prognostic significance of Po PHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild Po PHT can safely undergo liver transplant surgery. In cases of moderate to severe Po PHT, right heart catheterization(RHC) should be performed. In patients with moderate to severe Po PHT on RHC(mean PAP 35-45 mm Hg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed.     

Ventilatory and diffusion abnormalities in potential heart transplant recipients

Few data are available concerning pulmonary function in patients with severe chronic congestive heart failure. Of 315 patients evaluated for potential cardiac transplantation at UCLA, 132 underwent pulmonary function tests. The latter patients had severe heart failure with a mean left ventricular ejection fraction of 19 percent and mean cardiac index of 2.1 L/min/m2. Diffusion impairment either alone or combined with restrictive and/or obstructive ventilatory defects occurred in 67 percent of the patients evaluated. Diffusion impairment occurred as the sole abnormality in 31 percent of the patients and in combination with a restrictive ventilatory defect in 21 percent. A reduction in diffusing capacity has not been previously described as a frequent finding in patients with chronic congestive heart failure. In contrast to other studies involving patients with acute heart failure, obstructive ventilatory defects were uncommon. None of the lung function abnormalities was associated with smoking status, prior drug use, chest roentgenographic changes, hemodynamic findings, or clinical features, including duration of congestive heart failure. The mechanism for the diffusion impairment is unclear but could be due to chronic passive congestion with pulmonary fibrosis and/or recurrent pulmonary emboli. Recognition of diffusion impairment as a common finding in patients with severe chronic congestive heart failure who are candidates for heart transplantation is important for proper interpretation of possible post-transplant changes in diffusing capacity due to other causes.