Interim analysis of the Reitan Catheter Pump (RCP) heart failure efficacy study: RCP improves cardiovascular and renal function in acute decompensated heart failure (ADHF)

Background: The RCP is a 14 French collapsable percutaneous cardiovascular support device positioned in the descending part of the thoracic aorta via the femoral artery. A 10 patient first in man study demonstrated device safety and significant improvement in renal function among high risk PCI patients. We now report haemodynamic and renal efficacy in patients with ADHF.Methods: Prospective non randomised study seeking to recruit 20 patients with ADHF with a need for inotropic or mechanical circulatory support with: i) EF < 30% ii)Cardiac index(CI) < 2.2 L / min / m2 Outcome measures included: 1) Cardiac index (CI) 2) Pulmonary Capillary Wedge Pressure (PCWP) 3) Urine output / serum creatinine 4) Vascular / device complications 5) 30 day mortalityResults: INTERIM ANALYSIS (n=12) The mean age of the study group was 64 years, with a mean baseline creatinine of 193 umol/L, eGFR 38 ml/min. The intended RCP treatment period was 24 hours. During RCP treatment there was a significant mean reduction of PCWP at 4 hours of 17% (25 to 21 mmHg p=0.04). Mean CI increased at 12 hours by 11%, though not reaching significance (1.78 to 1.96 L/min/m2 p=0.08). RCP insertion prompted substantial diuresis. Urine output tripled over the first 12 hours compared to baseline (55 ml/hr vs 213 ml/hr p=0.03). This was associated with significantly improved renal function, a 28% reduction in serum creatinine at 12 hours (193 to 151 umol/L p=0.003), and a increase in eGFR from 38 ml/min to 50 ml/min (p=0.0007). 2 patients previously refused cardiac transplantation were reassessed and successfully transplanted within 9 months of RCP treatment on the basis of demonstrable renal reversibility. There were no vascular or device complications. There were 2 deaths at 30 days, one from multi-organ failure and sepsis, and one from intractable heart failure - neither were device related.Conclusion: RCP support in ADHF patients was associated with improved haemodynamics, and an improvement in renal function. The Reitan Catheter Pump may have a role in providing percutaneous cardiovascular and renal support in the acutely decompensated cardiac patient, and may have a role in suggesting renal reversibility in potential cardiac transplant patients. Further data will be reported at recruitment completion.

Colecistectomia videolaparoscópica em paciente submetido a transplante cardíaco

Cardiac transplant has been performed with an increased frequency as the treatment for end-stage cardiac disease. Although cholelithiasis is more frequent in both pretransplant and posttransplant patients, no standard management approach exists. Pretransplant patients are well recognized for cardiac events, and posttransplant immunossupressed patients are at a considerable risk for septic complications. Because the first presentation of gallstones in this population is often acute cholecystitis, asymptomatic calculi cannot be considered benign and it seems reasonable to recommend pretransplant screening and posttransplant surveillance for gallstones. Prophylatic laparoscopic cholecistectomy should be undertaken in the stable patient to avoid the substantial mortality associated with postoperative acute cholecystitis and urgent cholecystectomy. In this case report we present a 44 year-old male with acute cholecystitis after cardiac transplantation who was submitted to a safe laparoscopic cholecystectomy one year and seven months later.

Facteurs de risque d’insuffisance rénale chronique chez les greffés cardiaques : du phénotype aux tests pharmacogénomiques

L’insuffisance rénale chronique (IRC) est un problème majeur fréquemment rencontré chez les greffés cardiaques. Les inhibiteurs de la calcineurine, pierre angulaire de l’immunosuppression en transplantation d’organes solides, sont considérés comme une des principales causes de dysfonction rénale postgreffe. Plusieurs autres éléments tels que les caractéristiques démographiques, cliniques et génétiques du receveur contribuent également au phénomène, mais il demeure plutôt difficile de déterminer quels sont les patients les plus à risque de développer une IRC après la transplantation. Ainsi, la découverte de nouveaux marqueurs génétiques de dysfonction rénale pourrait un jour mener à l’individualisation de la thérapie immunosuppressive selon le profil génétique de chaque patient. Or, on ne connaît pas les opinions des greffés à l’égard des tests pharmacogénomiques et l’on ne sait pas si celles-ci diffèrent des opinions exprimées par les individus en bonne santé. Cette thèse de doctorat a donc pour objectifs : 1- De décrire l’évolution de la fonction rénale à très long terme après la transplantation et d’identifier les marqueurs démographiques et phénotypiques associés à l’IRC postgreffe cardiaque; 2- D’identifier les marqueurs génétiques associés à la néphrotoxicité induite par les inhibiteurs de la calcineurine; 3- D’évaluer et de comparer les attitudes des patients et des individus en bonne santé par rapport à l’intégration clinique potentielle des marqueurs pharmacogénomiques. Trois projets ont été réalisés pour répondre à ces questions. Le premier repose sur une analyse rétrospective de l’évolution de la fonction rénale chez les patients greffés au sein de notre établissement entre 1983 et 2008. Nous y avons découvert que le déclin de la fonction rénale se poursuit jusqu’à 20 ans après la transplantation cardiaque et que les facteurs de risque d’IRC incluent entre autres l’âge avancé, le sexe féminin, la dysfonction rénale prégreffe, l’hypertension, l’hyperglycémie et l’utilisation de la prednisone. Le deuxième projet est une étude pharmacogénomique s’intéressant aux déterminants génétiques de la néphrotoxicité induite par les inhibiteurs de la calcineurine. Elle nous a permis d’illustrer pour la première fois qu’un polymorphisme génétique lié à PRKCB (gène codant pour la protéine kinase C-β) est associé avec la fonction rénale des patients greffés cardiaques, alors que cela n’est probablement pas le cas pour les polymorphismes de TGFB1 (gène codant pour le transforming growth factor-β1). La troisième section de cette thèse rapporte les résultats d’un questionnaire dont le but était de comparer les attitudes envers les tests pharmacogénomiques parmi un groupe de personnes en bonne santé, de patients greffés cardiaques et de patients souffrant d’insuffisance cardiaque. Cette étude a démontré que, bien que l’enthousiasme pour la pharmacogénomique soit partagé par tous ces individus, les craintes liées à la confidentialité et aux répercussions potentielles sur l’emploi et les assurances sont plus prononcées chez les personnes en bonne santé. En résumé, les travaux issus de cette thèse ont révélé que l’identification précoce des patients greffés cardiaques les plus susceptibles de présenter une détérioration de la fonction rénale ainsi que l’adoption d’une approche thérapeutique individualisée reposant notamment sur les applications cliniques de la pharmacogénomique pourraient éventuellement permettre de freiner cette complication postgreffe.

Concordancia de presión sistólica pulmonar estimada por ultrasonografía y cateterismo cardíaco derecho en pacientes candidatos a trasplante cardíaco

Introducción: A los pacientes con Insuficiencia Cardíaca (IC) estadio D candidatos a trasplante cardiaco se les realiza la determinación de las presiones de la arteria pulmonar por CCD considerada como prueba de oro. Se decidió conocer si la medición de las presión de la arteria pulmonar obtenidas por ECO TT tenían concordancia con las obtenidas por el CCDen estos paciente que fueron evaluados para trasplante cardiaco. Metodología: Se realizó una recolección retrospectiva de los datos consignados en las historias clínicas de todos los pacientes que fueron receptores de un trasplante cardiaco en la FCI-IC desde septiembre del 2005 hasta Mayo del 2013 y se determinó la concordancia entre la presión sistólica pulmonar evaluado por ECO TT y CCD. Resultados: Se incluyeron 46 pacientes. El 76,1% son hombres y con edad promedio de 46,4 ± 13,1. La PSAP estimada por CCD fue 48,3 ± 13,1 mmHg Vs 45,1 ± 12,1 mmHg por ECO TT. La fracción de eyección fue 15,1 ± 4,06% (IC: 13,95-16,36). El 75,9% de los pacientes tenían HTP moderada y severa. La concordancia entre la PSAP determinada por ambos métodos fue 0,475 (I,C: 0.256 - 0.694), y el coeficiente de correlación intraclase fue de 0,090, indicando una baja concordancia entre los dos métodos. Discusión: La determinación de las presiones pulmonares determinada por ECO TT tiene mala concordancia con las obtenidas por CCD. No se debe usar este estudio para excluir los pacientes candidatos a trasplante cardiaco ni para evaluar las variaciones de las misma en la evolución de la enfermedad.

La experiencia de los receptores en el trasplante de órganos y tejidos

El trasplante de órganos y/o tejidos es considerado como una opción terapéutica viable para el tratamiento tanto de enfermedades crónicas o en estadios terminales, como de afectaciones no vitales, pero que generen una disminución en la calidad de vida percibida por el paciente. Este procedimiento, de carácter multidimensional, está compuesto por 3 actores principales: el donante, el órgano/tejido, y el receptor. Si bien un porcentaje significativo de investigaciones y planes de intervención han girado en torno a la dimensión biológica del trasplante, y a la promoción de la donación; el interés por la experiencia psicosocial y la calidad de vida de los receptores en este proceso ha aumentado durante la última década. En relación con esto, la presente monografía se plantea como objetivo general la exploración de la experiencia y los significados construidos por los pacientes trasplantados, a través de una revisión sistemática de la literatura sobre esta temática. Para ello, se plantearon unos objetivos específicos derivados del general, se seleccionaron términos o palabras claves por cada uno de estos, y se realizó una búsqueda en 5 bases de datos para revistas indexadas: Ebsco Host (Academic Search; y Psychology and Behavioral Sciences Collection); Proquest; Pubmed; y Science Direct. A partir de los resultados, se establece que si bien la vivencia de los receptores ha comenzado a ser investigada, aún es necesaria una mayor exploración sobre la experiencia de estos pacientes; exploración que carecería de objetivo si no se hiciera a través de las narrativas o testimonios de los mismos receptores

Sildenafil vs. Nitroprussiato de Sódio durante Teste de Reatividade Pulmonar pré-transplante cardíaco

FUNDAMENTO: A hipertensão pulmonar é associada ao pior prognóstico no pós-transplante cardíaco. O teste de reatividade pulmonar com Nitroprussiato de Sódio (NPS) está associado a elevados índices de hipotensão arterial sistêmica, disfunção ventricular do enxerto transplantado e elevadas taxas de desqualificação para o transplante. OBJETIVO: Neste estudo, objetivou-se comparar os efeitos do Sildenafil (SIL) e NPS sobre variáveis hemodinâmicas, neuro-hormonais e ecocardiográficas durante teste de reatividade pulmonar. MÉTODOS: Os pacientes foram submetidos, simultaneamente, ao cateterismo cardíaco direito, ao ecocardiograma e à dosagem de BNP e gasometria venosa, antes e após administração de NPS (1 - 2 µg/Kg/min) ou SIL (100 mg, dose única). RESULTADOS: Ambos reduziram a hipertensão pulmonar, porém o nitrato promoveu hipotensão sistêmica significativa (Pressão Arterial Média - PAM: 85,2 vs. 69,8 mmHg, p < 0,001). Ambos reduziram as dimensões cardíacas e melhoraram a função cardíaca esquerda (NPS: 23,5 vs. 24,8 %, p = 0,02; SIL: 23,8 vs. 26 %, p < 0,001) e direita (SIL: 6,57 ± 2,08 vs. 8,11 ± 1,81 cm/s, p = 0,002; NPS: 6,64 ± 1,51 vs. 7,72 ± 1,44 cm/s, p = 0,003), medidas pela fração de ejeção ventricular esquerda e Doppler tecidual, respectivamente. O SIL, ao contrário do NPS, apresentou melhora no índice de saturação venosa de oxigênio, medido pela gasometria venosa. CONCLUSÃO: Sildenafil e NPS são vasodilatadores que reduzem, de forma significativa, a hipertensão pulmonar e a geometria cardíaca, além de melhorar a função biventricular. O NPS, ao contrário do SIL, esteve associado a hipotensão arterial sistêmica e piora da saturação venosa de oxigênio.

Physical coronary arteriogenesis: a human "model" of collateral growth promotion

In patients with coronary artery disease, the size of myocardial infarction mainly determines the subsequent clinical outcome. Accordingly, it is the primary strategy to decrease cardiovascular mortality by minimizing infarct size. Promotion of collateral artery growth (arteriogenesis) is an appealing option of reducing infarct size. It has been demonstrated in experimental models that tangential fluid shear stress is the major trigger of arterial remodeling and, thus, of collateral growth. Lower-leg, high-pressure external counterpulsation triggered to occur during diastole induces a flow velocity signal and thus tangential endothelial shear stress in addition to the flow signal caused by cardiac stroke volume. We here present two cases of cardiac transplant recipients as human "models" of physical coronary arteriogenesis, providing an example of progressing and regressing clinical arteriogenesis, and review available evidence from clinical studies on other feasible forms of physical arteriogenesis.

Electric therapy for heart failure

The different means for treating congestive heart failure have not yet achieved the improvement in quality of life and the prognosis of people with terminal stage cardiac disease. Some treatment resources, such as cardiac transplant, are only accessible for a selected group of patients. In the last decade, the interest on the role of electromechanic disturbances has grown and has motivated special interest for the use of the pacemaker as a tool for the treatment of congestive heart failure. During this period we have seen an important progress of this kind of treatment and, nowadays, multicenter studies have shown the hemodynamic improvement of the patients treated with this method. Selection of patients for this kind of treatment should be careful; although today it can be known which patients can benefit from this device in the treatment of congestive heart failure.

Total Thyroidectomy for Amiodarone-induced Thyrotoxicosis in the Hyperthyroid State.

Amiodarone is a potent antiarrhythmic agent, indicated for the treatment of refractory arrhythmias, which may lead to thyrotoxicosis. In these patients, thyroidectomy is a valid therapeutic option. Antithyroid therapy in the immediate preoperative setting and the subsequently accepted minimal delay until thyroidectomy have not been clearly defined yet. The aim of the present study was to show, that total thyroidectomy under general anaesthesia in patients with amiodarone-induced thyrotoxicosis (AIT) is safe without necessarily obtaining an euthyroid state preoperatively.We conducted a retrospective cohort study of prospectively gathered data on 11 patients undergoing total thyroidectomy under general anaesthesia between January 2008 and December 2013 for AIT at our University Hospital.All patients were preoperatively treated with carbimazole, steroids and β-receptor antagonists. Additionally, 3 patients received potassium perchlorate and in one patient carbimazole was changed to propylthiouracil. Plasmapheresis was performed in 3 patients. Only one patient was euthyroid at the time of operation. There were no significant intra- and postoperative complications, especially no signs of thyroid storm. One patient could postoperatively be removed from the cardiac transplant waiting list due to improved cardiac function.Improvements in the interdisciplinary surgical management for AIT between cardiologists, endocrinologists, anaesthetists and endocrine surgeons provide the basis of safe total thyroidectomy under general anaesthesia in hyperthyroid state. Early surgery without long delay for medical antithyroid treatment (with its potential negative side effects) is recommended.

Validation of a strategy to diagnose coronary artery disease and predict cardiac events in high-risk renal transplant candidates

Background We validated a strategy for diagnosis of coronary artery disease ( CAD) and prediction of cardiac events in high-risk renal transplant candidates ( at least one of the following: age >= 50 years, diabetes, cardiovascular disease). Methods A diagnosis and risk assessment strategy was used in 228 renal transplant candidates to validate an algorithm. Patients underwent dipyridamole myocardial stress testing and coronary angiography and were followed up until death, renal transplantation, or cardiac events. Results The prevalence of CAD was 47%. Stress testing did not detect significant CAD in 1/3 of patients. The sensitivity, specificity, and positive and negative predictive values of the stress test for detecting CAD were 70, 74, 69, and 71%, respectively. CAD, defined by angiography, was associated with increased probability of cardiac events [log-rank: 0.001; hazard ratio: 1.90, 95% confidence interval (CI): 1.29-2.92]. Diabetes (P=0.03; hazard ratio: 1.58, 95% CI: 1.06-2.45) and angiographically defined CAD (P=0.03; hazard ratio: 1.69, 95% CI: 1.08-2.78) were the independent predictors of events. Conclusion The results validate our observations in a smaller number of high-risk transplant candidates and indicate that stress testing is not appropriate for the diagnosis of CAD or prediction of cardiac events in this group of patients. Coronary angiography was correlated with events but, because less than 50% of patients had significant disease, it seems premature to recommend the test to all high-risk renal transplant candidates. The results suggest that angiography is necessary in many high-risk renal transplant candidates and that better noninvasive methods are still lacking to identify with precision patients who will benefit from invasive procedures. Coron Artery Dis 21: 164-167 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients

Background: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. Methods: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. Results: Asymptomatic patients with normal myocardial scans (n = 57) had significantly fewer cardiac events (log-rank = 0.0002) and deaths (log-rank = 0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n = 76) and individuals with CAD (n = 34) documented angiographically. CAD increased the probability of events (HR = 2.27, % CI 1.007-5.11; p = 0.04). The incidence of cardiac events (log-rank = 0.349) and deaths (log-rank = 0.588) was similar among patients treated medically (n = 23) or by intervention (n = 11). Conclusion: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support pre-emptive myocardial revascularization for renal transplant candidates.

Regression of cardiac growth in kidney transplant recipients using anti-m-TOR drugs plus RAS blockers: a controlled longitudinal study.

BACKGROUND Left ventricular hypertrophy (LVH) is common in kidney transplant (KT) recipients. LVH is associated with a worse outcome, though m-TOR therapy may help to revert this complication. We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up. METHODS We undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor (CNI) to m-TOR therapy. A control group received immunosuppressive therapy based on CNIs. Two echocardiograms were done during the follow-up. RESULTS Nineteen patients were switched to SRL and 11 to EVL. The m-TOR group showed a significant reduction in LVMi after 1 year (from 62 ± 22 to 55 ± 20 g/m2.7; P=0.003, paired t-test). A higher proportion of patients showing LVMi reduction was observed in the m-TOR group (53.3 versus 29.3%, P=0.048) at the study end. In addition, only 56% of the m-TOR patients had LVH at the study end compared to 77% of the control group (P=0.047). A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group (P=0.019). CONCLUSIONS Switching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH, independently of blood pressure changes and follow-up time. This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass.

Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients.

BACKGROUND Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. METHODS A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. RESULTS Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. CONCLUSIONS CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

Transfer of Cholesterol and Other Lipids From a Lipid Nanoemulsion to High-density Lipoprotein in Heart Transplant Patients

Background: Beyond the first year after a heart transplant (HT) procedure, patients often develop dyslipidemias, which may be implicated in the genesis of transplant coronary heart disease. High-density lipoprotein (HDL) has a several anti-atherogenic properties, but the status of HDL in HT patients is still controversial. Nonetheless, determination of HDL cholesterol concentration is not sufficient for evaluation of the overall HDL protective role. In this study, a fundamental functional property of HDL, the ability to simultaneously receive the major lipid classes, was tested in HT patients. Methods: Twenty HT patients and 20 healthy normolipidemic subjects paired for gender, age and body mass index were studied. Blood samples were collected after 12-hour fasting for determination of plasma lipids, glucose, paraxonase I (PON 1) activity, HDL diameter and transfer of labeled lipids from an artificial nanoemulsion to HDL. Results: Plasma triglycerides (159 +/- 63 vs 94 +/- 35 mg/dl) and glucose (104 +/- 20 vs 86 +/- 10 mg/dl) were greater in HT patients than in control subjects. HDL cholesterol was lower and HDL diameter was smaller in the HT group (HDL cholesterol: 44 +/- 11 vs 55 +/- 15 mg/dl; HDL diameter: 8.8 +/- 0.6 vs 9.0 +/- 1.2 nm). PON 1 activity did not differ (87 +/- 47 vs 75 +/- 37 nmol/min/ml). The transfer rates of free cholesterol and cholesteryl esters were diminished in HT patients (HT: 8.4 +/- 1.2% and 3.8 +/- 0.6%; controls: 9.7 +/- 1.9% and 4.7 +/- 1.2%, respectively). Conclusions: The transfer of free cholesterol and cholesteryl esters to HDL is diminished in HT patients; disturbance in the ability of HDL to receive lipids may affect the anti-atherogenic properties of the lipoprotein. J Heart Lung Transplant 2009;28:1075-80. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.