Publications by authors named "Lívia Goldraich"

49 Publications

Limited Predictive Role of the Revised Cardiac Risk Index in Kidney Transplant: Single Center Evaluation and Comparison With International Literature.

Curr Probl Cardiol 2021 May 30:100908. Epub 2021 May 30.

Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address:

Perioperative risk factors predicting major cardiovascular events (MACE) and the performance of the Revised Cardiac Risk Index (RCRI) in a retrospective cohort of 325 consecutive adult patients undergoing kidney transplant from deceased donor grafts were assessed. Primary outcome was a composite of MACE up to 30 days post-transplant. Incidence of MACE was 5.8% at 30 days. Overall proportion of patients with RCRI ≥ 4 was 5%, but was higher (28%) among those who developed MACE. Patients with RCRI ≥ 4 had lower survival free of MACE compared to those with RCRI < 4 (P <0.001); however, in multivariable analysis, RCRI was not a predictor of cardiovascular events. The RCRI demonstrated poor discrimination to predict MACE at 30 days [area under the curve 0.64 (95% CI 0.49-0.78)]. Revised Cardiac Risk Index was not associated with reduced MACE-free survival adjusted analysis and its predictive ability was poor.
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http://dx.doi.org/10.1016/j.cpcardiol.2021.100908DOI Listing
May 2021

Donor-recipient predicted heart mass ratio and right ventricular-pulmonary arterial coupling in heart transplant.

Eur J Cardiothorac Surg 2021 04;59(4):847-854

Graduate Studies Program on Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Objectives: Right ventricular-pulmonary arterial (RV-PA) coupling interactions are largely unexplored in heart transplant patients. The outcome of this study was RV-PA coupling at 7 and 30 days after heart transplant and its association with donor-recipient size matching.

Methods: Clinical, echocardiographic and haemodynamic data from a retrospective cohort of heart transplant recipients and respective donors were reviewed. Coupling between RV-PA was examined by assessing the RV fractional area change and pulmonary artery systolic pressure ratio. Donor-recipient size matching was assessed by the predicted heart mass (PHM) ratio, and groups with a PHM ratio <1 and ≥1 were compared.

Results: Forty-four heart transplant recipients were included in this study (50 years, 57% male sex). Postoperative RV-PA coupling improved from 7 to 30 days (RV fractional area change/pulmonary artery systolic pressure 0.9 ± 0.3 vs 1.2 ± 0.3; P < 0.001). A positive association was found between an adequate PHM ratio and improvement of RV fractional area change/pulmonary artery systolic pressure at 30 days, independent of graft ischaemic time and pre-existent pulmonary hypertension (B coefficient 0.54; 95% confidence interval 0.11-0.97; P = 0.016; adjusted R2 = 0.24).

Conclusions: These findings highlight the role of PHM as a metric to help donor selection and suggest its impact in RV-PA coupling interactions post-heart transplant.
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http://dx.doi.org/10.1093/ejcts/ezaa391DOI Listing
April 2021

Exercise training modalities for heart transplant recipients: a systematic review and network meta-analysis protocol.

BMJ Open 2020 12 29;10(12):e044975. Epub 2020 Dec 29.

Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Hospital das Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

Introduction: Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients.

Methods And Analysis: We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.gov and REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository.

Ethics And Dissemination: Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal.

Prospero Registration Number: CRD42020191192.
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http://dx.doi.org/10.1136/bmjopen-2020-044975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778772PMC
December 2020

Emerging Topics in Heart Failure: COVID-19 and Heart Failure.

Arq Bras Cardiol 2020 11;115(5):942-944

Hospital Pró-Cardíaco, Rio de Janeiro, RJ - Brasil.

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http://dx.doi.org/10.36660/abc.20201081DOI Listing
November 2020

Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study.

BMC Cardiovasc Disord 2020 11 24;20(1):496. Epub 2020 Nov 24.

Research Projects Office, Hospital Moinhos de Vento (HMV), Rua Ramiro Barcelos 630, 10º andar, Porto Alegre, RS, 90035-001, Brazil.

Background: To evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP.

Methods: Serum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality.

Results: VA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67-0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality.

Conclusions: Serum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.
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http://dx.doi.org/10.1186/s12872-020-01785-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687839PMC
November 2020

Post Heart Transplantation Coronary Artery Fistula and Coronary Artery Aneurysm Successfully Managed With the Implantation of Covered Stents.

J Invasive Cardiol 2020 Jul;32(7):E191-E192

Schulich Medicine & Dentistry Western University, London Health Sciences Centre, St. Joseph's Health Care, London, Canada.

Coronary-to-cardiac chamber fistulae and coronary aneurysms are potential complications after heart transplantation. In the setting of exercise intolerance and large fistulae at major coronary vessels, covered stents may provide an effective interventional strategy.
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July 2020

A Comprehensive and Contemporary Review on Immunosuppression Therapy for Heart Transplantation.

Curr Pharm Des 2020 ;26(28):3351-3384

Post-graduation Program in Medical Science: Cardiology and Cardiovascular Science, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. However, there are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant morbidity and survival while preventing both rejection and complications of immunosuppression. The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches are provided. Cardiac allograft rejection classification and up-to-date management are summarized. Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression in heart transplantation are highlighted.
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http://dx.doi.org/10.2174/1381612826666200603130232DOI Listing
January 2021

Cardiopulmonary exercise capacity and quality of life of patients with heart failure undergoing a functional training program: study protocol for a randomized clinical trial.

BMC Cardiovasc Disord 2020 04 25;20(1):200. Epub 2020 Apr 25.

Exercise Pathophysiology Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

Background: Exercise intolerance is a common finding in heart failure that generates a vicious cycle in which the individual starts to limit his activities even more due to progressive fatigue. Regular physical exercise can increase the cardiopulmonary exercise capacity of these individuals. A new approach to physical exercise, known as functional training, could improve the oxygen consumption and quality of life of patients with heart failure; however, there is no information about the effect of this modality of exercise in this patient population. This randomized trial will compare the effects of 36 sessions of functional training versus strength training in heart failure patients.

Methods: This randomized parallel-design examiner-blinded clinical trial includes individuals of both sexes aged ≥40 years receiving regular follow-up at a single academic hospital. Subjects will be randomly allocated to an intervention group (for 12-week functional training) or an active comparator group (for 12-week strength training). The primary outcomes will be the difference from baseline to the 3-month time point in peak oxygen consumption on cardiopulmonary exercise testing and quality of life assessed by the Minnesota Living with Heart Failure Questionnaire. Secondary outcome measures will include functionality assessed by the Duke Activity Status Index and gait speed test; peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively; endothelial function by brachial artery flow-mediated dilation; lean body mass by arm muscle circumference; and participant adherence to the exercise programs classified as a percentage of the prescribed exercise dose.

Discussion: The functional training program aims to improve the functional capacity of the individual using exercises that relate to his specific physical activity transferring gains effectively to one's daily life. In this context, we believe that that functional training can increase the cardiopulmonary exercise capacity and quality of life of patients with heart failure. The trial has been recruiting patients since October 2017.

Trial Registration: NCT03321682. Registered on October 26, 2017.
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http://dx.doi.org/10.1186/s12872-020-01481-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183632PMC
April 2020

Impaired Right Ventricular Function in Heart Transplant Rejection.

Arq Bras Cardiol 2020 04 14;114(4):638-644. Epub 2020 Feb 14.

PPG em Cardiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Background: The practice of screening for complications has provided high survival rates among heart transplantation (HTx) recipients.

Objectives: Our aim was to assess whether changes in left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) are associated with cellular rejection.

Methods: Patients who underwent HTx in a single center (2015 - 2016; n = 19) were included in this retrospective analysis. A total of 170 biopsies and corresponding echocardiograms were evaluated. Comparisons were made among biopsy/echocardiogram pairs with no or mild (0R/1R) evidence of cellular rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n=15). P-values < 0.05 were considered statistically significant Results: Most patients were women (58%) with 48 ± 12.4 years of age. Compared with echocardiograms from patients with 0R/1R rejection, those of patients with 2R biopsies showed greater LV posterior wall thickness, E/e' ratio, and E/A ratio compared to the other group. LV systolic function did not differ between groups. On the other hand, RV systolic function was more reduced in the 2R group than in the other group, when evaluated by TAPSE, S wave, and RV fractional area change (all p < 0.05). Furthermore, RV GLS (-23.0 ± 4.4% in the 0R/1R group vs. -20.6 ± 4.9% in the 2R group, p = 0.038) was more reduced in the 2R group than in the 0R/1R group.

Conclusion: In HTx recipients, moderate acute cellular rejection is associated with RV systolic dysfunction as evaluated by RV strain, as well as by conventional echocardiographic parameters. Several echocardiographic parameters may be used to screen for cellular rejection.
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http://dx.doi.org/10.36660/abc.20190054DOI Listing
April 2020

Critical Care Management of the Acute Postimplant LVAD Patient.

Can J Cardiol 2020 02 20;36(2):313-316. Epub 2019 Dec 20.

Department of Surgery, Division of Cardiac Surgery, London Health Sciences Centre, Western University, London, Ontario, Canada; Critical Care Western, London Health Sciences Centre, Western University, London, Ontario, Canada. Electronic address:

Left ventricular assist devices (LVADs) improve survival and quality of life in refractory end-stage heart failure. However, the therapy itself is associated with some degree of morbidity and mortality at highest risk during the first 30 days postimplantation. Management of the patient with a freshly implanted LVAD requires an in-depth understanding of the acute postimplant period and common critical care issues including coagulopathy, hemodynamic lability, and metabolic derangements. This requires meticulous hemostatic control and a firm understanding of hemodynamic principles that focus on optimizing end-organ perfusion, right-ventricular function, and measured LVAD titration. This contemporary practical guide to management of the acute postimplant LVAD patient includes a focused approach to troubleshooting common LVAD issues that may arise from the operating room to discharge from critical care.
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http://dx.doi.org/10.1016/j.cjca.2019.11.034DOI Listing
February 2020

Expanding benefits from cardiac resynchronization therapy to exercise-induced left bundle branch block in advanced heart failure.

ESC Heart Fail 2020 02 10;7(1):329-333. Epub 2020 Jan 10.

Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rua Ramiro Barcelos, 2350, room 2060, Porto Alegre, RS, 90035-903, Brazil.

Indications of cardiac resynchronization therapy (CRT) do not include exercise-induced left bundle branch block, but functional impairment could be improved with CRT in such cases. A 57-year-old woman with idiopathic dilated cardiomyopathy (ejection fraction 23%) presented with New York Heart Association Class IV and recurrent hospitalizations. During heart transplant evaluation, a new onset of intermittent left bundle branch block was observed on the cardiopulmonary exercise test. CRT was implanted, and 97% resynchronization rate was achieved. In 12 month follow-up, both clinical and prognostic exercise parameters improved. In patients with heart failure with reduced ejection fraction and no left bundle branch block at rest, exercise test can uncover electromechanical dyssynchrony that may benefit from CRT.
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http://dx.doi.org/10.1002/ehf2.12580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083438PMC
February 2020

Continuous Intravenous Inotropes in Ward Units: Expanding Therapy Outside Intensive Care using a Safety-Oriented Protocol.

Arq Bras Cardiol 2019 06 6;112(5):573-576. Epub 2019 Jun 6.

Hospital de Clínicas de Porto Alegre, Porto Alegre, RS - Brazil.

Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.
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http://dx.doi.org/10.5935/abc.20190078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555580PMC
June 2019

Effective communication for the safe care of patients with ventricular assist device implantation.

Rev Gaucha Enferm 2019 29;40(spe):e20180344. Epub 2019 Apr 29.

Hospital de Clínicas de Porto Alegre (HCPA), Serviço de Enfermagem Cardiovascular, Nefrologia e Imagem. Porto Alegre, Rio Grande do Sul, Brasil.

Objective: To report the role of multiprofessional teams in the effective communication and safe care of patients with left ventricular assist device.

Methods: This is an experience report about the use of effective communication for patients with ventricular assist device in a university hospital in southern Brazil. Care based on individualized action and centered on the patients started in 2017.

Results: At the institution, the multiprofessional teams attended training sessions and care protocols were established. The patients and caregivers attended systematic educational sessions and home visits were made to arrange patient discharge and urgency plans. Also, the hospital teams located near the patients' homes received basic training.

Conclusion: Effective communication between multiprofessional teams, patients, and their families when planning care plays a pivotal role in the early identification of possible complications and their prevention, resulting in a greater survival rate and a better quality of life.
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http://dx.doi.org/10.1590/1983-1447.2019.20180344DOI Listing
January 2020

Heart Transplantation Cost Composition in Brazil: A Patient-Level Microcosting Analysis and Comparison With International Data.

J Card Fail 2018 Dec 26;24(12):860-863. Epub 2018 Oct 26.

Heart Transplant Program, Division of Cardiology, Hospital de Clínicas de Porto Alegre, Brazil; National Health Technology Assessment Institute, National Council for Scientific and Technological Development (CNPq), Brazil. Electronic address:

Background: Advanced heart failure (HF) therapies, such as heart transplantation, are resource intensive and costly. In Brazil, only one-fifth of the estimated population need is fulfilled. We examined cost expenditures of heart transplants in a public institution in Brazil.

Methods And Results: We used microcosting analysis (time-driven activity-based costing) to examine total costs and individual cost components related to the index transplant hospital admission of all consecutive heart transplant recipients at a single center from July 2015 to June 2017. Average total cost for the 27 patients included was US$ 74,341 which exceeds the reimbursement value per patient by 60%. Major cost drivers were hospital structure and personnel, similarly to what is observed in the United States (US) and other developed countries. Total costs for index transplant admission were ∼50% lower than in the US, but approximate to values reported in some European countries. Costs of heart transplantation in Brazil were lower than those reported for developed countries, and higher than national reimbursement values.

Conclusions: Advanced microcosting methodologies represent an important quality contribution to economic studies in health care and may provide insights for transplant-related health care policies in developing countries.
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http://dx.doi.org/10.1016/j.cardfail.2018.10.011DOI Listing
December 2018

Modified autotransplant with three-dimensional printing for treatment of primary cardiac sarcoma.

J Thorac Cardiovasc Surg 2019 02 25;157(2):e41-e43. Epub 2018 Sep 25.

Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2018.08.087DOI Listing
February 2019

Duration of corticosteroid use and long-term outcomes after adult heart transplantation: A contemporary analysis of the International Society for Heart and Lung Transplantation Registry.

Clin Transplant 2018 08 26;32(8):e13340. Epub 2018 Jul 26.

Cardiac Transplant Program, Peter Munk Cardiac Center, University of Toronto, Toronto, Ontario, Canada.

Background: Long-term corticosteroid (CS) maintenance remains an effective option for immunosuppression following heart transplantation. We used the International Society for Heart and Lung Transplantation Registry to examine characteristics and long-term survival among heart transplant recipients with different duration of CS therapy.

Methods: Primary adult heart recipients transplanted between 2000 and 2008 who survived at least 5 years were categorized into three groups according to CS use: early withdrawal (≤2 years) (EARLY D/C), late withdrawal (between 2 and 5 years) (LATE D/C), or long-term use (>5 years) (LONG-TERM). Recipient and donor characteristics, post-transplant morbidities, and mortality were compared among groups. Kaplan-Meier was used to estimate survival up to 10 years post-transplant.

Results: The study cohort included 8161 recipients (2043 in EARLY D/C; 2031 in LATE D/C; and 4087 in LONG-TERM). LONG-TERM use of CS decreased over time, from 60% in 2000 to 43% in 2008, while EARLY D/C increased from 19% to 33%, respectively. Survival at 10 years after transplant was lower among the LONG-TERM group (73% vs EARLY D/C 82% vs LATE D/C 80%; P < 0.0001).

Conclusions: In this large multinational cohort, the practice of long-term CS maintenance was associated with lower long-term survival compared with shorter CS use.
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http://dx.doi.org/10.1111/ctr.13340DOI Listing
August 2018

Chronic painful oral ulcers in a heart transplant recipient.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 06 21;127(6):468-476. Epub 2018 Feb 21.

Department of Oral Medicine, Porto Alegre Clinics Hospital (HCPA/UFRGS), Porto Alegre, RS, Brazil; Department of Oral Pathology, Dental School, Federal University of Rio do Sul, Porto Alegre, RS, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.oooo.2018.01.026DOI Listing
June 2019

The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure.

Clin Transplant 2018 01 8;32(1). Epub 2018 Jan 8.

Ted Rogers Centre of Excellence in Heart Function, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.

Frailty assessment has become an integral part of the evaluation of potential candidates for heart transplantation and ventricular assist device (HTx/VAD). The impact of frailty, as a heart failure risk factor or to identify those who will derive the greatest benefit with HTx/VAD remains unclear. The aim of this study was to evaluate the independent prognostic relevance of frailty assessment from peak oxygen consumption (peak VO ) or B-type natriuretic peptide (BNP) on mortality in patients referred for advanced heart failure therapies. Frailty was measured using modified Fried frailty criteria. In 201 consecutive patients, during a median follow-up of 17.5 months (IQR 11-29.2), there were 25 (12.4%) deaths. One-year survival was 100%, 94%, and 78% in nonfrail, prefrail, and frail patients, respectively (log rank P = .0001). Frailty was associated with a twofold increase risk of death (HR 2.01, P < .0001, 95% CI 1.42-2.84). When adjusted for BNP or peak VO , frailty was not associated with a significant risk of all-cause death. However, when peak VO is stratified into two categories (≥12 mL/kg/min vs <12 mL/kg/min), frailty was associated with increased mortality in patients with a lower peak VO (HR 1.72, P = .006).
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http://dx.doi.org/10.1111/ctr.13158DOI Listing
January 2018

Outbreak of invasive aspergillosis in heart transplant recipients: The role of screening computed tomography scans in asymptomatic patients and universal antifungal prophylaxis.

Transpl Infect Dis 2018 Feb 26;20(1). Epub 2017 Dec 26.

Division of Infectious Diseases, University of Toronto, University Health Network, Toronto General Hospital, Toronto, ON, Canada.

Background: Delays in diagnosing pulmonary invasive aspergillosis (IA), a significant cause of morbidity and mortality among heart transplant recipients (HTRs), may impact on successful treatment. The appropriate screening strategy for IA in these patients remains undefined, particularly in the setting of nosocomial outbreaks. We describe our experience employing chest computed tomography (CT) scans as a screening method for IA. In addition, we comment on antimicrobial prophylaxis in HTRs in the setting of an outbreak.

Methods: Screening CT scans of the chest and serum galactomannan (GM) were performed in HTRs during an outbreak that followed the index case of IA. Abnormal CT findings prompted a diagnostic workup. Antimicrobial prophylaxis for new transplants recipients included intravenous micafungin while hospitalized, followed by outpatient inhaled amphotericin B for up to 3 months.

Results: During a 10-month period, five cases of IA were identified among HTRs. Two additional asymptomatic patients were diagnosed with IA among 15 asymptomatic HTRs who underwent screening chest CT scans. Among the five cases of IA in HTRs, two of five (40%) had a partial response and the other three failed voriconazole therapy. Complete response to voriconazole therapy assessed at 12 weeks was achieved in these two asymptomatic HTRs diagnosed via screening CTs. Serum GM was positive only in one of the symptomatic cases. The negative predictive value of CT scans was 100% (95% confidence interval, 71.5%-100%).

Conclusions: In an outbreak setting, screening CT scans of the chest may aid in early detection of asymptomatic HTRs with IA and improve outcome.
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http://dx.doi.org/10.1111/tid.12808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169681PMC
February 2018

ISHLT Transplant Registry: Youthful Investment-The Path to Progress.

J Heart Lung Transplant 2017 10 25;36(10):1027-1036. Epub 2017 Jul 25.

Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. Electronic address:

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http://dx.doi.org/10.1016/j.healun.2017.07.024DOI Listing
October 2017

Reevaluating Modality of Cardiopulmonary Exercise Testing in Patients with Heart Failure and Resynchronization Therapy: Relevance of Heart Rate-Adaptive Pacing.

J Card Fail 2017 May 20;23(5):422-426. Epub 2017 Jan 20.

Heart Failure and Cardiac Transplant Programs, Peter Munk Cardiac Center, University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: Chronotropic incompetence (CI) in heart failure (HF) patients with cardiac resynchronization therapy (CRT) and activity sensors may vary according to exercise modality. We hypothesized that chronotropic response and exercise capacity differ when HF patients with CRT and heart rate (HR) adaptive pacing are exercised on cycloergometer versus treadmill.

Methods And Results: This is a crossover study in which stable HF patients with CRT and HR-adaptive pacing triggered by activity sensors underwent maximal symptom-limited cardiopulmonary exercise testing on both a cycloergometer and treadmill. Adjusted percent of HR reserve (%HRR) was calculated as HRR/age-predicted HRR. CI was defined as ≤62% of age-predicted HRR. Among 16 patients (59 ± 10 years, ejection fraction 27 ± 12%, 87% on beta-blockers), prevalence of CI was high irrespective of exercise modality (87.5% on cycloergometer vs 62.5% on treadmill; P = .12). Chronotropic responses were better on the treadmill; %HRR was higher on a treadmill vs cycloergometer (61 ± 26% vs 22 ± 31%; P = .003). Peak oxygen consumption was increased by 24% on a treadmill vs cycloergometer (15.8 vs 12.7 mL/kg/min; P < .0001).

Conclusions: In HF patients with CRT and HR-adaptive pacing, treadmill cardiopulmonary exercise testing enhances chronotropic response, HRR, and peak oxygen consumption compared with a cycloergometer. These findings may have implications in exercise prescription and thresholds for advanced therapies such as heart transplantation and ventricular assist devices.
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http://dx.doi.org/10.1016/j.cardfail.2017.01.006DOI Listing
May 2017

Care Setting Intensity and Outcomes After Emergency Department Presentation Among Patients With Acute Heart Failure.

J Am Heart Assoc 2016 07 22;5(7). Epub 2016 Jul 22.

Division of Cardiology, Peter Munk Cardiac Center, University Health Network, Toronto, Ontario, Canada The Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada The Institute for Health Policy, Management, and Evaluation, Toronto, Ontario, Canada The University of Toronto, Ontario, Canada

Background: Patients with heart failure (HF) presenting to the emergency department (ED) can be admitted to care settings of different intensity, where the intensive care unit (ICU) is the highest intensity, ward admission is intermediate intensity, and those discharged home are of lowest intensity. Despite the costs associated with higher-intensity care, little is known about disposition decisions and outcomes of HF patients treated in different care settings.

Methods And Results: We identified predictors of ICU or ward admission and determined whether survival differs in patients admitted to higher-intensity versus lower-intensity care settings (ie, ICU vs ward, or ward vs ED-discharged). Among 9054 patients (median, 78 years; 51% men) presenting to an ED in Ontario, Canada, 1163 were ICU-admitted, 5240 ward-admitted, and 2651 were ED-discharged. Predictors of ICU (vs ward) admission included: use of noninvasive positive pressure ventilation (adjusted odds ratio [OR], 2.01; 95% CI, 1.36-2.98), higher respiratory rate (OR, 1.10 per 5 breaths/min; 95% CI, 1.05-1.15), and lower oxygen saturation (OR, 0.90 per 5%; 95% CI, 0.86-0.94; all P<0.001). Predictors of ward-admitted versus ED-discharged were similar. Propensity-matched analysis comparing lower-risk ICU to ward-admitted patients demonstrated a nonsignificant trend at 100 days (relative risk [RR], 0.69; 95% CI, 0.43-1.10; P=0.148). At 1 year, however, survival was higher among those initially admitted to ICU (RR, 0.68; 95% CI, 0.49-0.94; P=0.022). There was no survival difference among low-risk ward-admitted versus ED-discharged patients.

Conclusions: Respiratory factors were associated with admission to higher-intensity settings. There was no difference in early survival between some lower-risk patients admitted to higher-intensity units compared to those treated in lower-intensity settings.
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http://dx.doi.org/10.1161/JAHA.116.003232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015368PMC
July 2016

Human leukocyte antigen G single-nucleotide polymorphism -201 (CC-CC) donor-recipient genotype matching as a predictor of severe cardiac allograft vasculopathy.

J Heart Lung Transplant 2016 09 6;35(9):1101-7. Epub 2016 May 6.

Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital-University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: In heart transplant recipients, human leukocyte antigen G (HLA-G) has been shown to inhibit endothelial and smooth muscle cells injury in vitro, suggesting protection against cardiac allograft vasculopathy (CAV). Although the expression of HLA-G is regulated by single-nucleotide polymorphisms (SNPs), their association with CAV remains unknown. Therefore, the objective of this study was to determine the association between recipient and donor HLA-G SNPs with CAV.

Methods: We retrospectively analyzed DNA for HLA-G SNPs of 251 adult heart recipients, 196 of whom had their corresponding donors included. Severe CAV was defined as ISHLT Category 2 or 3. The association between donor-recipient genotypes and diagnosis of severe CAV over time was evaluated with parametric hazard regression models.

Results: Recipient age was 48 ± 12 years, whereas donor age was 35 ± 14 years. Median follow-up was 5.0 years (range 1 day to 13.2 years). At 10 years after transplantation, freedom from severe CAV, retransplantation or death was 64%. In multivariable analysis adjusted for donor age, recipient weight and pre-transplant Class II antibodies, the presence of donor-recipient SNP -201 (CC-CC) matching was associated with an increased risk of severe CAV (hazard ratio 11.9; 95% confidence interval 4.3 to 32.9; p < 0.001).

Conclusions: Matching of donor-recipient SNP -201 (CC-CC) was an independent risk factor for the diagnosis of severe CAV. HLA-G SNP genotypes may reveal a pathogenic pathway to be explored for diagnostic and therapeutic strategies for CAV.
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http://dx.doi.org/10.1016/j.healun.2016.04.014DOI Listing
September 2016

Association between Spirituality and Adherence to Management in Outpatients with Heart Failure.

Arq Bras Cardiol 2016 Jun 17;106(6):491-501. Epub 2016 May 17.

Division of Cardiology, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Background: Spirituality may influence how patients cope with their illness.

Objectives: We assessed whether spirituality may influence adherence to management of outpatients with heart failure.

Methods: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence.

Results: One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments.

Conclusion: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient's care may lead to an improvement in adherence patterns in the complex heart failure management.
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http://dx.doi.org/10.5935/abc.20160076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940148PMC
June 2016

Human Leukocyte Antigen-G Polymorphisms Association With Cancer Post-Heart Transplantation.

Hum Immunol 2016 Sep 8;77(9):805-11. Epub 2016 Jan 8.

Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital-University Health Network, Toronto, Ontario, Canada.

Background: Post transplantation, a major complication is the development of malignancies. Human Leukocyte Antigen (HLA)-G is a molecule that inhibits the immune system and it is utilized by malignant cells to hide from the immune system. Expression of HLA-G from the donor and recipient cells in transplant patients is regulated by gene variations however, the association between genotype and cancer remains unknown. Our objective was to determine the association between genotype and outcome.

Methods: Heart transplant recipients (251) and available corresponding donors (196) samples were genotyped for polymorphisms and the association of polymorphisms to outcome was evaluated with parametric hazard regression models.

Results: Risk of cancer was 22% at 10years post-transplantation. The mean follow-up was of 4.9±3.6years. In a multivariable analysis, donor-recipient SNP 3187 matching was identified as a protective factor for cancer (hazard ratio 0.43; 95% confidence interval 0.19-0.93; p=0.03). While coding region allele (haplotype 6) was identified as an independent risk factor (hazard ratio 3.7; 95% confidence interval 1.36-10.06; p=0.01).

Conclusion: In this investigation, we identified an association between cancer post-transplantation and HLA-G polymorphisms, which may reveal a pathway for potential diagnostic and therapeutic strategies for cancer post-transplantation.
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http://dx.doi.org/10.1016/j.humimm.2016.01.005DOI Listing
September 2016

Tricuspid Valve Annular Dilation as a Predictor of Right Ventricular Failure After Implantation of a Left Ventricular Assist Device.

J Card Surg 2016 Feb 8;31(2):110-6. Epub 2016 Jan 8.

Mechanical Circulatory Support Program, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada.

Background: Tricuspid annular (TA) dilation has been suggested as a more reliable marker of concomitant advanced right ventricular failure (RVF) than severity of tricuspid regurgitation (TR). Our objective was to examine the impact of TA dilation on occurrence of RVF and in-hospital mortality following left ventricular assist device (LVAD) implant.

Methods: Consecutive patients undergoing implantation of a continuous-flow LVAD implant were grouped according to the presence or absence of preoperative dilated TA. Clinical characteristics, hemodynamics, and short-term postoperative outcomes were compared between groups. RVF was defined as unplanned right ventricular assist device (RVAD) or postoperative use of inotropes for >14 days. Linear and logistic regressions were used to explore associations of TA with occurrence of RVF and duration of inotrope use.

Results: We included 69 patients who had continuous-flow LVAD implanted between 2006 and 2013 (50 ± 13 years old; 69% males; 37% ischemic etiology; 69% bridge-to-transplant LVAD; 18% INTERMACS 1-2; 48% with significant TR). RVF occurred in nine cases, and overall in-hospital mortality rate was 14%. Tricuspid valve repair was performed in ten cases. Dilated TA (OR 4.86; 95% CI 1.05-22.33; p = 0.04) was associated with RVF. In an adjusted multivariable analysis, indexed TA was an independent predictor of increased days of inotrope use (0.8-day increase in inotrope use for every 1 mm/m2 increase; p = 0.04).

Conclusion: In this cohort, TA dilation was a predictor of RVF after LVAD implant. The potential benefit of concomitant TVR in selected patients with a dilated TA undergoing LVAD implantation remains to be determined.
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http://dx.doi.org/10.1111/jocs.12685DOI Listing
February 2016

Transcoronary gradient of plasma microRNA 423-5p in heart failure: evidence of altered myocardial expression.

Biomarkers 2014 Mar 10;19(2):135-41. Epub 2014 Feb 10.

Heart Failure and Cardiac Transplant Group, Cardiovascular Experimental and Molecular Laboratory, Division of Cardiology, Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil and.

Context: Elevated plasmatic microRNAs (miRs) are observed in heart failure (HF). However, the cardiac origin of these miRs remains unclear.

Objective: We calculated transcoronary gradients of miR-29b, miR-133a and miR-423-5p in 17 outpatients with stable systolic HF and in controls without structural cardiac disease.

Materials And Methods: MicroRNAs were measured by quantitative real-time polymerase chain reaction.

Results: Positive transcoronary miR gradients were observed in patients with HF but not in controls (p = 0.03). B-type natriuretic peptide (BNP) moderately correlated with the transcoronary gradients of miR-133a and miR-423-5p.

Discussion And Conclusions: The difference in transcoronary gradients between HF outpatients and controls suggests that miR-423-5p has a cardiac origin. The positive correlation between miR-423-5p and BNP transcoronary gradients supports this hypothesis.
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http://dx.doi.org/10.3109/1354750X.2013.870605DOI Listing
March 2014