Abstract Objectives This study sought to compare techniques evaluating cardiac dysautonomia and predicting the risk of death of patients with hereditary transthyretin amyloidosis (mATTR) after liver ...transplantation (LT). Background mATTR is a multisystemic disease involving mainly the heart and the peripheral nervous system. LT is the reference treatment, and pre-operative detection of high-risk patients is critical. Cardiovascular dysautonomia is commonly encountered in ATTR and may affect patient outcome, although it is not known yet which technique should be used in the field to evaluate it. Methods In a series of 215 consecutive mATTR patients who underwent LT, cardiac dysautonomia was assessed by a dedicated clinical score, time-domain heart rate variability,123 -meta-iodobenzylguanidine heart/mediastinum (123 -MIBG H/M) ratio on scintigraphy, and heart rate response to atropine (HRRA). Results Patient median age was 43 years, 62% were male and 69% carried the Val30Met mutation. Cardiac dysautonomia was documented by at least 1 technique for all patients but 6 (97%). In univariate analysis, clinical score,123 -MIBG H/M ratio and HRRA were associated with mortality but not heart rate variability. The123 -MIBG H/M ratio and HRRA had greater area under the curve (AUC) of receiver-operating characteristic curves than clinical score and heart rate variability (AUC: 0.787, 0.748, 0.656, and 0.523, respectively). Multivariate score models were then built using the following variables: New York Heart Association functional class, interventricular septum thickness, and either123- MIBG H/M ratio ( S MIBG ) or HRRA ( S atropine ). AUC of S MIBG and S atropine were greater than AUC of univariate models, although nonsignificantly (AUC: 0.798 and 0.799, respectively). Predictive powers of S MIBG , S atropine , and a reference clinical model (AUC: 0.785) were similar. Conclusions Evaluation of cardiac dysautonomia is a valuable addition for predicting survival of mATTR patients following LT. Among the different techniques that evaluate cardiac dysautonomia,123 -MIBG scintigraphy and heart rate response to atropine had better prognostic accuracy. Multivariate models did not improve significantly prediction of outcome.
By removing the main source of the mutated TTR, liver transplantation (LT) has become the standard treatment for ATTR (1). Because the demand for liver grafts exceeds the number of available organs ...and because new treatments have recently emerged, screening patients at high risk of death after LT is critical (2). The risk score was built from variables that measured the cardiac and neurological status regardless of mutation type. ...our proposed score should be useful to gauge the risk of patients with rare variants of TTR and to take into account the phenotypic variability encountered among patients with a similar mutation.
Familial amyloid polyneuropathy (FAP) is an autosomic dominant disease with a high rate of conduction disorders and increased risk of sudden death. Prophylactic cardiac pacing may be considered in ...asymptomatic patients with FAP. However, the potential benefits are unknown.
To document conduction disorders in a large series of FAP and the incidence of high-degree atrioventricular (AV) block in patients with prophylactic pacemaker (PM).
From January 1999 to January 2010, 262 patients with FAP were retrospectively evaluated. Prophylactic PM was implanted in patients with His-ventricular interval ≥ 70 ms, His-ventricular interval >55 ms associated with a fascicular block, a first-degree AV block, or a Wenckebach anterograde point ≤ 100 beats/min. The spontaneous AV conduction was then analyzed by temporarily inhibiting the PM.
As compared with patients with prophylactic PM (n = 100) and patients implanted given a class I/IIa indication (n = 18), the patients who did not require PM (n = 144) were younger and displayed less severe cardiac involvement. Follow-up after prophylactic PM implantation was analyzed in 95 of the 100 patients over 45 ± 35 months, and a high-degree AV block was documented in 24 of the 95 patients (25%). The risk of high-degree AV block was higher in patients with first-degree AV block or Wenckebach anterograde point ≤ 100 beats/min (hazard ratio 3.5; 95% confidence interval 1.2-10) while microvoltage on surface electrocardiogram reduced the risk (hazard ratio 0.2; 95% confidence interval 0.1-0.7).
In FAP with conduction disorders, prophylactic PM implantation prevented major cardiac events in 25% of the patients over a 45-month mean follow-up. It is suggested that prophylactic PM implantation prevented symptomatic bradycardia in these patients.
Post-transplant non-Hodgkin lymphoma (NHL) is a well-recognized complication of solid-organ transplantation, and pharmacologic suppression of adaptive immunity plays a major role in its development. ...However, the role of natural killer (NK) cells in post-lung transplant de novo NHL is unknown.
Extensive phenotypic analyses of NK cells from patients diagnosed with NHL after liver or lung transplantation were conducted with multicolor flow cytometry. Polyfunctionality assays simultaneously assessed NK cell degranulation (CD107a) and intracellular cytokine production (interferon-γ and tumor necrosis factor-α) in the presence of NHL target cells.
The development of de novo NHL is linked to NK-cell maturation defects, including overexpression of NKG2A and CD62L and down-modulation of inhibitory killer immunoglobulin-like receptors and CD57 receptors. More importantly, in patients who developed NHL after lung transplantation, we observed a specific down-modulation of the activating receptors (NKp30, NKp46, and NKG2D) and a sharp decrease in perforin expression and degranulation against NHL target cells.
Our results suggest that accumulation of abnormal NK cells could play a role in the outgrowth of NHL after lung transplantation, independently of the immunosuppressive regimen.
Abstract Background For patients at high risk for bleeding, a polymer-free metallic stent coated with biolimus-A9 followed by one-month dual antiplatelet therapy was safer and more effective than a ...bare metal stent at one year. Objectives Longer-term follow-up is needed to determine whether these benefits are maintained. Methods In a prospective, multi-center, double blind trial, we randomly assigned 2466 high bleeding risk patients to receive a drug coated stent (DCS) or a bare metal stent (BMS) followed by one month dual antiplatelet therapy and 98.1% completed a two-year follow-up. The primary safety end point was a composite of cardiac death, myocardial infarction (MI), or stent thrombosis (ST). The primary efficacy end point was clinically driven target-lesion revascularization. Results At 2 years, the primary safety endpoint had occurred in 147 DCS (12.6%) and 180 BMS patients (15.3%) (hazard ratio 0.80; 95% CI, 0.64 to 0.99; p=0.039). Clinically driven target-lesion revascularization occurred for 77 DCS (6.8%) and 136 BMS patients (12.0%) (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P<0.0001). Major bleeding occurred in 8.9% DCS and 9.2% BMS patients (p=0.95), and a coronary thrombotic event (MI and/or ST) in 8.2% DCS and 10.6% BMS patients (p=0.045). Mortality was 27.1% one year after a major bleed, and 26.3% one year after a thrombotic event. At two years, multivariate correlates of major bleeding were age > 75, anemia, raised plasma creatinine and planned long-term anticoagulation. Correlates of the primary safety endpoint were age anemia, congestive heart failure, multivessel disease, number of stents implanted and use of a BMS rather than a DCS. Conclusions The safety and efficacy benefits of DCS over BMS were maintained up to two years in high bleeding risk patients. During that period, overall rates of major bleeding and coronary thrombotic events were no different and associated with a substantial and comparable mortality risk.
Clinician-investigators have an important role in the development and implantation of new therapies and treatment modalities; however, there have been several reports highlighting a pending shortage ...in the clinician-investigators' workforce. In Canada, the Royal College has promoted the development of clinician-investigators programs (CIP) to facilitate the training of these individuals. There is currently a paucity of data regarding the outcomes of such programs. This study aims to identify the strengths and areas of improvement of the Montreal University CIP. Methods: An internet-based 51-question survey was distributed to all the alumni from the University of Montreal CIP. Participation was voluntary and no incentives were provided. The response rate was 64%. Results: Among respondents, 50% (n=16) had completed their clinical residency and all CIP requirements. The majority of these individuals (63%) had become independent investigators and had secured provincial and national funding. Satisfaction of the respondents was high regarding the overall program (85%), the research skills developed during the CIP (84%) and the financial support obtained during the program (72%). The satisfaction rate regarding career planning was lower (63%). Conclusion: This survey demonstrates that, while indicators are favorable, some areas still require improvement. Several steps to improve the CIP have been identified; notably, the transition from the CIP to early independent career has been identified as critical in the development of clinician-investigators and steps have been taken to improve this progression.
Abstract Introduction Ascites may contribute to the loss of lung volume and alter the gas exchange in cirrhotic patients with acute lung injury (ALI). Aim The aim of the study was to evaluate the ...effects of paracentesis on respiratory parameters in ventilated cirrhotic patients with ALI. Study Design This was a prospective trial in an intensive care unit of a university hospital. Patients and Methods Thirty-one cirrhotic patients on mechanical ventilation (with ALI) requiring paracentesis were included in this study. Arterial blood gases, intraabdominal pressures, ventilator parameters, and lung volumes were measured before and after the ascitic drainage. Results Following paracentesis, the intraabdominal pressure decreased (24.1 ± 7.0 vs 12.3 ± 8.9 mm Hg, P < .0001) and the Pa o2 /Fi o2 improved significantly (190.0 ± 65.2 vs 284.9 ± 76.1 mm Hg, P < .0001), without hemodynamic disturbances. End-expiratory lung volume, markedly reduced before drainage, increased significantly following paracentesis (Δ end-expiratory lung volume: +463 ± 249 mL, P = .0009). No adverse effects related to the paracentesis were encountered. Conclusion In contrast to ventilatory recruitment maneuvers, paracentesis is a simple and well-tolerated technique able to improve oxygenation and alveolar recruitment without the risk of the lung overdistension in severely hypoxemic cirrhotic patients.
Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or ...decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.
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