Nikolaos Bonaros

Long-term results of CMV hyperimmune globulin prophylaxis in 377 heart transplant recipients

BACKGROUNDnCytomegalovirus (CMV) has emerged as the most important pathogen to affect the post-operative course after heart transplantation. We performed a retrospective analysis to evaluate the efficiency of CMV hyperimmune globulin (CMVIG) prophylaxis in preventing CMV disease in aggressively immunosuppressed patients after heart transplantation.nnnMETHODSnWe studied 377 heart transplant recipients who received quadruple-immunosuppressive therapy and CMVIG as sole CMV prophylaxis. The study population was categorized into 4 groups according to donor and recipient CMV serology at the time of transplantation (D+/R+, D+/R-, D-/R+, D-/R-) and was monitored for CMV immediate early antigen in peripheral blood cells, in urine sediments, and in throat washings; for the presence of serum CMV immunoglobulin M and CMV immunoglobulin G; and for clinical evidence of CMV-related symptoms. In addition, we compared the incidence of cardiac allograft vasculopathy and infection among the groups.nnnRESULTSnDuring the first 5 years after transplantation, CMV disease developed in 79 patients (20.96%). Comparison among the groups showed significantly increased risk for CMV disease in allograft recipients of organs from seropositive donors (D+, 27.31%; D-, 11.33%; p = 0.0003). We observed 6 CMV-associated deaths, all in CMV-antibody-negative recipients. Additionally CMV-positive recipients had a greater incidence of cardiac allograft vasculopathy (p = 0.048), and a greater overall infection rate (p = 0.0034).nnnCONCLUSIONSnCytomegalovirus hyperimmune globulin administration prevents CMV disease and infection in aggressively immunosuppressed heart transplant recipients. Because fatal CMV disease in CMV-negative recipients of organs from seropositive donors could not be prevented with CMVIG alone, we recommend the additional use of prophylactic ganciclovir in this CMV-mismatched population.

Intracardiac Doppler Echocardiography for Monitoring of Pulmonary Artery Pressures in High-Risk Patients Undergoing Transcatheter Aortic Valve Replacement

BACKGROUNDnUncontrolled pulmonary hypertension may cause worse outcomes after transcatheter aortic valve replacement (TAVR), while hemodynamic monitoring is desirable for risk control. Pulmonary artery pressure (PAP) readings obtained by intracardiac Doppler echocardiography were evaluated.nnnMETHODSnIn 114 patients with symptomatic aortic stenosis and median Society of Thoracic Surgeons scores of 10.5% (interquartile range, 7.7%-15.0%), transfemoral and transapical TAVR was guided by intracardiac Doppler echocardiography. The continuous-wave Doppler beam interrogated the jet of tricuspid regurgitation from the home view position. Systolic PAP (PAPs) was estimated as the sum of the pressure gradient derived from the maximum transtricuspid regurgitation jet velocity and the central venous pressure. Mean PAP (PAPm) was calculated by the mean gradient method (1) and the Chemla formula (2). Measurements were obtained immediately before and after TAVR.nnnRESULTSnPre- and postinterventional readings showed marginal pressure underestimation in comparison with measurements derived from right-heart catheterization: PAPs, -2.7 (95% CI, -3.3 to 2.1) and -1.4 (95% CI, -1.9 to -0.9); PAPm by the mean gradient method, -1.9 (95% CI, -2.2 to -1.6) and -0.1 (95% CI, -0.4 to 0.2). Agreement (95% limits) for PAPs was -8.6 to 3.2 and -6.8 to 4.0; agreement for PAPm by the mean gradient method was -5.4 to 1.6 and -3.4 to 3.2. The repeatability coefficient (95% limits of agreement) for PAPs was excellent: 3.4 (-4.2 to 2.5) and 5.5 (-5.3 to 5.8); repeatability for PAPm was higher by the mean gradient method than by the Chemla method. In ≥ 85% of patients with pulmonary hypertension, PAPm improved after valve deployment.nnnCONCLUSIONSnIntracardiac Doppler echocardiography-derived monitoring of PAP by the mean gradient method is accurate and well applicable to high-risk TAVR candidates for intraprocedural risk control.

Evolving Knowledge About Age and Hypothermic Circulatory Arrest in Aortic Surgery

In ascending aortic surgery, progress in surgical and perfusion technology is continuous and quiet and does not produce frequent reports of short-term success. Changes in strategy show their effects years after their implementation, and may then be recommended to the broad community to adapt therapeutic strategy and thus to improve overall outcome. An example is the report by the Berne group1 in the current issue of Circulation on the effect of age on mortality and neurological injury in patients after surgical repair with hypothermic circulatory arrest in acute and chronic proximal thoracic pathology. Traditionally, age has been associated with a higher risk for both mortality and neurological injury, as has been shown by large databases such as the International Registry of Acute Aortic Dissection (IRAD).2 As a consequence, some centers refuse surgery in elderly patients because of dismal results, especially loss of quality of life, which has emerged as one of the most important surrogates for treatment success.3nnArticle see p 1407nnHowever, the aforementioned reports stem from a time when deep hypothermic circulatory arrest was used as the only adjunctive technique for brain protection. Improvements in modern surgical therapy of aortic aneurysms include several important changes: subclavian artery perfusion, heparin-coated circuits for cardiopulmonary bypass, and most important, antegrade cerebral perfusion via the subclavian artery or selective perfusion catheters of supraaortic branches. Antegrade cerebral perfusion allows operating on the aortic arch in moderate hypothermia, thus reducing the side effects of deep hypothermia (eg, coagulopathy, inflammatory reactions). Additionally, concomitant treatment of the descending thoracic aorta with an open placement of a stent graft enables even more extensive repair of pathologies of the entire thoracic aorta. Commercially available trifurcated prostheses facilitate surgical aortic arch repair …

Aortic Valve Surgery and Reduced Ventricular Function

Aortic valve disease is a fatal disease with but a single cure. Removal of the mechanical obstruction in aortic stenosis (surgery or TAVI) and replacement of an incompetent valve (so far only surgery) are the only treatment options. While aortic valve replacement in patients with isolated valve disease and normal pumpfunction of the heart has become a routine procedure and is performed with excellent results all over the world, it can be a rather challenging procedure in severely ill patients with heart failure and comorbidities. Patients with low ejection fraction are one of the most challenging patient groups in cardiac surgery. According to the guidelines for the management of patients with valvular heart disease as recommended by all major heart associations including the European Society of Cardiology, American College of Cardiology, American Heart a ventricular function reduced to below 50% ejection fraction is considered a class I, level of evidence B and C indication respectively for aortic valve surgery. (ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease, Bonow et al., 2006) Despite this fact there is a high number of patients presenting with severely reduced ventricular function for aortic valve surgery. In aortic insufficiency 70% have a function reduced to below 50% and around 10% present with a significantly reduced function of less than 30% EF. In case of aortic stenosis the numbers are a less dramatic but still more than 40 % of patients referred for valve surgery have an ejection fraction below 50%. This is due to the fact that aortic valve disease can go unnoticed for a very long time resulting in heart failure at time of presentation. Another fact is that at least some patients are treated conservatively for a too long period of time until their EF deteriorates. Apart from that, due to the demographic development there is an increasing number of patients with aortic valve disease and advanced age resulting in a high number of elderly patients with more comorbidities and reduced ejection fraction.

Enhanced immune response in CMV D+/R- heart transplant patients receiving combined CMV prophylaxis

were similar. No measurable antibody was found for 61% of controls and 17% of HR recipients (P 0.001). Antibody was reactive to only HLA class I, only HLA class II, or both class I and II for 7%, 22% and 10% of controls respectively, compared to 7%, 17% and 60% of HR recipients. The incidence of transplant coronary artery disease or death (TCAD) was 21% for controls and 41% for those diagnosed with HR (P 0.06). The positive predictive value for HR and TCAD was 42%. TCAD was not observed in 4 of 5 HR patients negative for post-transplant antibody. Requiring post-transplant antibody for HR diagnosis increased the positive predictive value to 56% (P 0.04). Post-transplant antibody testing increased the clinical significance of HR diagnosis.