Lung cancer after heart transplantation: results from a large multicenter registry.

In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan-Meier 2-year survival to 70% versus 16% among inoperable patients.

The prognosis of noncutaneous, nonlymphomatous malignancy after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

INTRODUCTION: Malignancy is a major complication in the management of solid organ transplant patients. Skin cancers show a better prognosis than other neoplasms, but not all others are equal: Ideally, patient management must take into account the natural history of each type of cancer in relation to the transplanted organs. We sought to determine the prognosis of various groups of noncutaneous nonlymphomatous (NCNL) cancers after heart transplantation (HT). METHODS: We retrospectively analyzed the records of the Spanish Post-Heart-Transplant Tumour Registry, which collects data on posttransplant tumors in all patients who have undergone HT in Spain since 1984. Data were included in the study up to December 2008. We considered only the first NCNL post-HT tumors. RESULTS: Of 4359 patients, 375 developed an NCNL cancer. The most frequent were cancers of the lung (n=97; 25.9%); gastrointestinal tract (n=52; 13.9%); prostate gland (n=47; 12.5%; 14.0% of men), bladder (n=32; 8.5%), liver (n=14; 3.7%), and pharynx (n=14; 3.7%), as well as Kaposi's sarcoma (n=11; 2.9%). The corresponding Kaplan-Meier survival curves differed significantly (P<.0001; log-rank test), with respective survival rates of 47%, 72%, 91%, 73%, 36%, 64%, and 73% at 1 year versus 26%, 62%, 89%, 56%, 21%, 64%, and 73% at 2 years; and 15%, 51%, 77%, 42%, 21%, 64%, and 52% at 5 years post-diagnosis, respectively. CONCLUSION: Mortality among HT patients with post-HT NCNL solid organ cancers was highest for cancers of the liver or lung (79%-85% at 5 years), and lowest for prostate cancer (23%).

Survival after cardiac transplantation: influence of the previous cardiopathy in the recipient.

INTRODUCTION: Data from cardiac transplantation registries have demonstrated a gradual improvement in patient survival over the last decades. Nevertheless, 5-years mortality rates may reflect the multitude of physiologic processes. Registries offer valuable information regarding predictors of mortality that may help us to improve therapeutic strategies. OBJECTIVES: To determine the influence on long term recipient survival of the type of prior cardiopathy that led to cardiac transplantation. METHODS: Analysis of a 316 patient cohort who underwent heart transplantation since 1991 at a single center. RESULTS: We analyzed the main clinical variables among a cohort with a mean follow-up of 7.2 years (standard deviation [SD], 4.8). There were 84.2% men and the overall mean age of 50.06 years (SD 12.29) at the time of transplantation. We identified 11 cardiopathies as the leading causes for transplantation: severe ischemic cardiopathy (55.3%), dilated cardiomyopathy (29.1%), terminal valvular cardiopathy (5.4%), alcoholic cardiopathy (2.5%), congenital cardiopathy (1.6%), acute myocarditis (1.6%), hypertrophic cardiomyopathy (1.6%), endomyocardial fibrosis (1.3%), anthracyclin-related dilated cardiopathy (0.9%), peripartum cardiomyopathy (0.3%), and vascular allograft disease (0.3%). The mean global survival of the cohort was 4.1 years, which showed a significant increase in the recent 8 compared with the first 11 years (P=.03). Multivariate analysis only demonstrated worse survival rate among those with chronic ischemic compared with the other cardiopathies (HR 2.17; 1.21-6.2; P=.003). Nevertheless, the signification disappeared after adjusting the analysis for the presence of ≥2 classical cardiovascular risk factors. CONCLUSION: Patients with chronic ischemic cardiopathy showed the leading cause for a lower survival after cardiac transplantation compared with other cardiopathies, which seemed to be related to the cardiovascular risk factors that produced the cardiopathy.

Cardiac allograft vasculopathy: coronary computed tomography and virtual histology assessment.

INTRODUCTION: Cardiac allograft vasculopathy remains the leading cause of late morbidity and mortality in heart transplantation. The main diagnostic methods, coronary angiography or intracoronary ultrasound (when angiography is normal), are invasive. Other study methods, such as coronary computed tomography (CT) and virtual histological analysis, have not been widely assessed in this condition. OBJECTIVE: The objective of this study was to assess the correlation between data obtained from analysis of virtual histology compared with those obtained from the performance of coronary CT in cardiac transplant recipients. MATERIALS AND METHODS: During the same admission we performed coronary angiography and intravascular ultrasound with virtual histological analysis (automatic pull-back in anterior descending artery and one additional vessel if the former was normal) as well as coronary CT. RESULTS: The study included 10 patients. Virtual histology was done in segments with intimal thickening>0.5 mm, defining 2 groups of plaque, those with an inflammatory component (necrotic core>30% and calcium) versus those without it defined as the combination of both being <30%. A calcium component of the inflammatory plaque allowed coronary CT detection. CONCLUSIONS: The detection of inflammatory plaque in graft vessel disease can be based on an initial noninvasive method, such as coronary CT, although confirmation requires further study.

Impact of overweight on survival and primary graft failure after heart transplantation.

BACKGROUND: Overweight influence on prognosis after heart transplantation remains controversial. The objective of this study was to determine the relationship between overweight and survival in this setting. METHODS: We evaluated 271 cardiac transplant recipients engrafted from 1991 to 2009 whose age was 50.3±12.1 (mean; SD) years. Their body mass index (BMI) was 25.7±3.9 kg/m2. Regarding gender, 85.2% were males. Patients were classified by pretransplantation BMI into group A (>25 kg/m2) and group B (<25 kg/m2). We analyzed the differences in mortality and related factors. RESULTS: One hundred fifty Group A patients (55.4%) showed a slightly lower median survival (7.35 vs 8.62 years; P=.152). Group A patients were at higher risk of death within 1 year of follow-up (HR, 1.71; confidence interval [CI], 0.996-2.939; P=.051). Overweight was associated with increased mortality at 1 year after adjustment for age, recipient gender, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and donor-recipient heart size mismatch. The incidence of primary graft failure was also significantly increased in group A (HR, 2.74; CI, 1.17-6.40; P=.017) after adjustment for the same variables. There were no significant differences between the groups concerning surgical ischemic time, number of acute rejection episodes, and infections during the first year. CONCLUSION: In our sample, overweight was associated with increased mortality and an increased incidence of primary graft failure within 1 year after cardiac transplantation.

Safety and effectiveness of ivabradine after cardiac transplantation.

BACKGROUND: Heart denervation is the primary cause of sinus tachycardia in transplant recipients. Drugs are usually needed to treat associated symptoms. OBJECTIVE: To evaluate the safety and effectiveness of the novel I(f) channel antagonist ivabradine to control heart rate after transplantation. METHODS: Of 316 heart transplant recipients at a single center since 1991, ivabradine was administered in 15 patients, in addition to ß-blockers in 4 patients and contraindication to use of ß-blocker therapy in the others. A prospective follow-up study was conducted to identify possible adverse effects, tolerance, and drug effects on heart rate and control of symptoms. RESULTS: Of the 15 patients, 13 were men; overall mean (SD) patient age was 46 (4.6) years. In all patients, treatment was begun after verification of basal heart rate greater than 100 bpm and after other causes of sinus tachycardia had been ruled out. During follow-up of 1.13 (0.3) years, no substantial adverse effects were observed. It was possible to reach the maximum drug dosage in all patients, achieving a reduction in basal heart rate of 33 (6.2) bpm. All patients reported substantial clinical improvement, and demonstrated an increase in functional class. CONCLUSION: Ivabradine is safe, well tolerated, and effective in heart transplant recipients.

[Evaluation of high risk syncope referred from emergency department]. / Evaluación del síncope de alto riesgo remitido desde el Servicio de Urgencias.

INTRODUCTION: High-risk syncope (over aged 60, abnormal electrocardiogram, syncope without prodromes and/or background of cardiovascular disease) is associated with high mortality. More detailed attention to that which may often be considered as an emergency should be given. We have evaluated the activity of a specialized service in the care of syncope in an internal medicine service. MATERIAL AND METHODS: We have collected a series of patients diagnosed in the emergency service of "syncope." The patients were referred to the specialized unit in the care of syncope and evaluated in less than 72h. We analyzed the tests made to establish a pathophysiological diagnosis of syncope. RESULTS: A total of 107 consecutive patients were studied, 82 of whom met the criteria for being at risk of syncope. All underwent an echocardiography and outpatient Holter. A total of 23 studies were performed with tilt test, 4 electrophysiological studies were performed and 2 were implanted with an insertable Holter. A specific diagnosis could be established in 73 patients. Three patients were diagnosed with a neurological disease. The most frequent cause of the syncope was neuromediated (41 patients). After a mean follow-up of over 2 years, total mortality (9 patients) was not related with the syncope. CONCLUSIONS: A specialized service in the care of high-risk syncope increases the percentage of patients with a definitive diagnosis.

Evaluación del síncope de alto riesgo remitido desde el Servicio de Urgencias / Evaluation of high risk syncope referred from emergency department

Introducción El síncope de alto riesgo (más de 65 años, electrocardiograma anormal, síncope sin pródromos y/o antecedentes de patología cardiovascular) se asocia a una elevada mortalidad. Parece aconsejable una atención más detallada de la que puede ofrecerse en Urgencias. Hemos evaluado la actividad de una consulta monográfica de síncope en un Servicio de Cardiología. Material y métodos Hemos recogido una serie de enfermos diagnosticados en Urgencias de «sincope». Los enfermos fueron remitidos a la consulta monográfica de síncope y evaluados en menos de 72h. Hemos analizado las pruebas realizadas para establecer un diagnóstico fisiopatológico del síncope. Resultados Estudiamos 107 pacientes consecutivos, de los que 82 cumplían criterios de síncope de riesgo. A todos se les realizó una ecocardiografía y un Holter ambulatorio. Se realizaron 23 estudios con mesa basculante, 4 estudios electrofisiológicos, y se implantaron 2 Holter insertables. En 73 pacientes pudimos establecer un diagnóstico concreto. Tres pacientes fueron diagnosticados de una enfermedad neurológica. La causa más frecuente del síncope fue la neuromediada (41 pacientes). Tras un seguimiento medio superior a 2 años, la mortalidad total (9 pacientes) no se relacionó con el síncope. Conclusiones Una consulta especializada en síncope de alto riesgo aumenta el porcentaje de pacientes con diagnóstico definitivo(AU)

Introduction High-risk syncope (over aged 60, abnormal electrocardiogram, syncope without prodromes and/or background of cardiovascular disease) is associated with high mortality. More detailed attention to that which may often be considered as an emergency should be given. We have evaluated the activity of a specialized service in the care of syncope in an internal medicine service. Material and methods We have collected a series of patients diagnosed in the emergency service of “syncope.” The patients were referred to the specialized unit in the care of syncope and evaluated in less than 72h. We analyzed the tests made to establish a pathophysiological diagnosis of syncope. Results A total of 107 consecutive patients were studied, 82 of whom met the criteria for being at risk of syncope. All underwent an echocardiography and outpatient Holter. A total of 23 studies were performed with tilt test, 4 electrophysiological studies were performed and 2 were implanted with an insertable Holter. A specific diagnosis could be established in 73 patients. Three patients were diagnosed with a neurological disease. The most frequent cause of the syncope was neuromediated (41 patients). After a mean follow-up of over 2 years, total mortality (9 patients) was not related with the syncope. Conclusions A specialized service in the care of high-risk syncope increases the percentage of patients with a definitive diagnosis(AU)

Usefulness of cardio MRI on thrombosis of coronary aneurysm as an infrequent cause of ST-elevation coronary syndrome.

We present an unusual case of thrombosis of coronary aneurysm causing myocardial infarction with ST-elevation in precordial leads. Emergent coronary angiography showed thrombotic occlusion of an aneurysm in the proximal segment of the left anterior descendent coronary artery (LAD). After the administration of tenecteplase, pain and ST-elevation disappeared with no overt complications. Cardiac magnetic resonance imaging (MRI) performed two weeks after admission showed thrombi partially filling the aneurysm together with further information regarding coronary anatomy, as well as a preserved global function even though delayed enhancement of the myocardium was patent throughout the territory irrigated by LAD. This case supports cardio MR usefulness in Kawasaki disease in order not only to depict coronary abnormalities, but also to provide accurate information regarding function and viability in a non-invasive way. It also highlighted the relevance of a proper selection of the sequence technique when thrombus is suspected. All these advantages point out to cardiac MRI as the modality of choice in the follow-up of patients in this clinical scenario.

Taquicardia de QRS ancho en mujer joven con síndrome coronario agudo secundario a disección coronaria espontánea / Wide QRS tachycardia in a young woman with acute coronary syndrome secondary to spontaneous coronary dissection

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Comparison between two drugs on the hemodynamic evaluation of pulmonary hypertension prior to heart transplantation.

INTRODUCTION: Invasive estimation of pulmonary pressure is part of the usual protocol prior to heart transplantation. The aim of this study was to compare the results of 2 different vasodilators, nitric oxide (NO) and prostacyclin, in an acute vasodilator test (AVT) for patients with pulmonary venous hypertension. MATERIALS AND METHODS: From January 2000 to December 2006, 94 right-sided heart catheterizations were performed in our center within pretransplantation evaluations. AVT was performed if the mean pulmonary artery pressure (mPAP) >35 mm Hg or if the pulmonary vascular resistance (PVR) was >4 Wood units (WU). Epoprostenol was administered to 40 patients, NO to 6 patients, and both agents to 8 patients. RESULTS: A significant decrease in both mPAP and PVR was shown with maximum doses of epoprostenol, with an average variation of 8.96 mm Hg in mPAP (P < .001) and 3.26 WU in PVR (P < .001). An increased cardiac output (CO) was observed with epoprostenol, with a mean difference of 1.9 L/min (P < .001) at maximum compared with baseline doses. A tendency for the mPAP and PVR to decrease was also observed with maximum NO doses, with mean decreases of mPAP and PVR of 5.62 mm Hg and 1.14 WU, respectively. A tendency for CO to decrease was observed with NO (0.75 L/min; P = .039). CONCLUSIONS: In our experience, NO is the best drug for AVT due to its pulmonary tree selectivity. A study with epoprostenol was complementary; both drugs can be used in these patients prior to heart transplantation.

Correlation of echocardiographic and hemodynamic parameters in pulmonary hypertension assessment prior to heart transplantation.

INTRODUCTION: Invasive assessment of pulmonary artery pressure (PAP), via right heart catheterization, is part of the usual protocol prior to heart transplantation. Echocardiography is considered a valuable technique to evaluate PAP. We sought to determine the reliability of measurements of PAP via a noninvasive technique, echocardiography, in relation to the estimated PAP via right catheterization. We also determined its safety when invasive procedures are restricted to just patients with pulmonary hypertension (PHT) according to echocardiographic parameters. MATERIALS AND METHODS: We performed a retrospective study of 67 right catheterizations performed in our hospital, within the heart transplant study protocol, from January 2000 to December 2006. PAP parameters were estimated by echocardiography and right catheterization. RESULTS: Hemodynamically, 57.1% of the patients had severe PHT (more than 45 mm Hg mean PAP); 13.2% moderate PHT (between 35 and 45 mm Hg mean PAP); 12.1% had mild PHT (between 25 and 35 mm Hg mean PAP); and 17.6% of patients showed no PHT. Pearson correlation index with systolic PAP (estimated via echocardiography) and mean PAP (calculated via invasive method) was 0.69 (P < .001). PHT was considered significant when systolic PAP estimated via echocardiography reached more than 40 mm Hg and mean PAP estimated via right catheterization reached more than 35 mm Hg, the value from which the vasodilator test was carried out. According to these parameters, echocardiography showed a sensitivity of 89% to diagnose significant PHT and 46% specificity, with positive and negative predictive values of 70% and 76%, respectively.

Prognosis after heart transplant in patients with pulmonary hypertension secondary to cardiopathy.

INTRODUCTION: Pulmonary hypertension (PHT) is associated with greater posttransplant mortality. In the last few years, many vasodilator drugs have been developed and some patients have therefore been transplanted. However, conflicting data exist regarding the impact of reversible PHT on posttransplant outcomes. The aim of this study was to determine the evolution of our transplanted patients with reactive PHT and the causes of right cardiac insufficiency and perioperative mortality. MATERIAL AND METHODS: We performed a retrospective analysis of 39 consecutive heart transplant recipients from January 2005 to December 2006. We analyzed significant pretransplant PHT, the percentage of emergency transplants, surgical technique, as well as ischemia and extracorporeal circulation times. RESULTS: Before transplantation, significant PHT was present in 12 patients (30.8%), all of whom had a positive acute vasoreactivity test or response to oral treatment with pulmonary vasodilators. A nonsignificant tendency to increased posttransplant mortality was observed among patients with pretransplant PHT. We observed a significant increase in mortality in patients with prolonged operative times, over the third percentile, odds ratio (OR) for ECC of 21% (P = .001) and OR for prolonged ischemia time of 9.5% (P = .022). However, mortality did not increase significantly in cases of emergent transplantation (P = .08) or in the use of the Shumway bicaval surgical technique (P = .9). CONCLUSIONS: There seemed to be a slight tendency to increased mortality among patients with reversible HTP, suggesting that high-risk patients need closer monitoring but are not absolutely contraindicated for transplantation.

Preliminary experience with conversion from calcineurin inhibitors to everolimus in cardiac transplantation maintenance therapy.

INTRODUCTION: Everolimus has been prescribed both for initial and maintenance therapy after cardiac transplantation. Herein, we present our initial experience with everolimus as maintenance therapy after cardiac transplantation. METHODS: We retrospectively included all of our patients in whom therapy was changed from calcineurin inhibitors to everolimus between September 2006 and October 2007. We analyzed their baseline clinical characteristics, indications for conversion to everolimus therapy, and beneficial vs adverse effects of the maneuver. RESULTS: In 16 heart transplant recipients, therapy was changed to everolimus because of allograft vasculopathy (n = 8), renal failure (n = 4), or sirolimus toxicity (n = 4). Treatment with everolimus was initiated at a mean (SD) of 79.8 (52.7) months (range, 10-163 mo) after transplantation. The initial dose was 1.4 (0.2) mg (range, 1.0-1.5 mg), and the maintenance dose was 1 (0.31) mg (range, 0.5-1.5 mg). Follow-up was 7.28 (3.22) months (range, 0.5-13 mo). Observed side effects included hypertriglyceridemia, hypertension, and edema. Only 1 of 4 patients included because of sirolimus intolerance did not tolerate everolimus; renal dysfunction did not worsen in any of these 4 patients. No allograft vasculopathy was observed. CONCLUSIONS: Renal function seem to stabilize after conversion to everolimus therapy in patients with previous progressive dysfunction. The safety profile was proved in all patients, although conclusions cannot be established about the evolution of allograft vasculopathy.

Incidence and importance of de novo diabetes mellitus after heart transplantation.

INTRODUCTION: Diabetes mellitus is one of the main metabolic complications after heart transplantation. The aims of our study were to determine the incidence and factors that determine the appearance of posttransplantation diabetes mellitus (PTDM) and its prognostic value. MATERIALS AND METHODS: We performed a retrospective study of all heart transplant recipients in our hospital from January 1993 to December 2005, including 116 patients with prolonged monitoring with 59-month median follow-up. We divided the patients into two groups, according to whether they had de novo diabetes (group 1) or no diabetes (group 2). RESULTS: Patients with PTDM were significantly older, with a median difference (MD) of 5.4 years (95% confidence interval [CI], 1.53-9.28) and a greater body mass index (MD, 3.37 kg/m(2); 95% CI, 1.68-5.06). Moreover, a greater percentage of patients in group 1 had ischemia compared to other etiologies. However, no significant differences were observed regarding other cardiovascular risk factors. PTDM was associated with a greater incidence of posttransplant hypertension (51.6% in group 1 vs 48.4% in group 2, P = .08) and posttransplant renal failure (59.5% in group 1 vs 40.5% in group 2, P = .001). However, no differences were observed in overall survival. CONCLUSIONS: Age, overweight, and ischemic origin of cardiopathy were the main risk factors for the development of PTDM in our population. Although no differences were observed in survival rates, PTDM was associated with a greater incidence of hypertension and renal insufficiency, which may have long-term influences on patient survival.

Hipertensión arterial secundaria a estenosis arterial renal de origen arterioesclerótico en mujer joven que precisó angioplastia y colocación de stent / HBP secondary to renal arterial stenosis of arteriosclerotic origin in young woman who required angioplasty and stent placement

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