Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients.

OBJECTIVES: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. DESIGN: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV. RESULTS: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases. CONCLUSION: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required.

Regulatory T Cell Biomarkers Identify Patients at Risk of Developing Acute Cellular Rejection in the First Year Following Heart Transplantation.

BACKGROUND: Acute cellular rejection (ACR), an alloimmune response involving CD4+ and CD8+ T cells, occurs in up to 20% of patients within the first year following heart transplantation. The balance between a conventional versus regulatory CD4+ T cell alloimmune response is believed to contribute to developing ACR. Therefore, tracking these cells may elucidate whether changes in these cell populations could signal ACR risk. METHODS: We used a CD4+ T cell gene signature (TGS) panel that tracks CD4+ conventional T cells (Tconv) and regulatory T cells (Treg) on longitudinal samples from 94 adult heart transplant recipients. We evaluated combined diagnostic performance of the TGS panel with a previously developed biomarker panel for ACR diagnosis, HEARTBiT, while also investigating TGS' prognostic utility. RESULTS: Compared with nonrejection samples, rejection samples showed decreased Treg- and increased Tconv-gene expression. The TGS panel was able to discriminate between ACR and nonrejection samples and, when combined with HEARTBiT, showed improved specificity compared with either model alone. Furthermore, the increased risk of ACR in the TGS model was associated with lower expression of Treg genes in patients who later developed ACR. Reduced Treg gene expression was positively associated with younger recipient age and higher intrapatient tacrolimus variability. CONCLUSIONS: We demonstrated that expression of genes associated with CD4+ Tconv and Treg could identify patients at risk of ACR. In our post hoc analysis, complementing HEARTBiT with TGS resulted in an improved classification of ACR. Our study suggests that HEARTBiT and TGS may serve as useful tools for further research and test development.

The Guyana Program to Advance Cardiac Care: A Model for Equitable Cardiovascular Care Delivery.

Guyana is one of the poorest countries in South America, with the highest rate of cardiovascular mortality on the continent. As is the case in many low- and middle-income countries, cardiovascular care is available through the private sector but is not accessible to much of the urban and rural poor. We present the 10-year experience of the Guyana Program to Advance Cardiac Care (GPACC), an academic partnership aiming to provide high-quality, equitable cardiovascular care in Georgetown's only public hospital. We discuss the implementation of a cardiac care program using the World Health Organization Framework for Action, outlining vital components for care delivery in resource-limited settings. GPACC was able to demonstrate that targeted investment, education of clinicians, and cohesive healthcare delivery strategies can contribute to sustainable service delivery for Guyana's largest burden of disease. This structured approach may provide lessons for implementation of similar programs in other resource-limited settings. Highlights: In many LMICs, specialized cardiovascular care is available in the private, but not public, sector.The WHO Framework for Action can guide development of sustainable programs in low-resource settings.GPACC can serve as a successful and innovative model for delivery of sustainable cardiovascular care.

Severity of COVID-19 among solid organ transplant recipients in Canada, 2020-2021: a prospective, multicentre cohort study.

BACKGROUND: Severe COVID-19 appears to disproportionately affect people who are immunocompromised, although Canadian data in this context are limited. We sought to determine factors associated with severe COVID-19 outcomes among recipients of organ transplants across Canada. METHODS: We performed a multicentre, prospective cohort study of all recipients of solid organ transplants from 9 transplant programs in Canada who received a diagnosis of COVID-19 from March 2020 to November 2021. Data were analyzed to determine risk factors for oxygen requirement and other metrics of disease severity. We compared outcomes by organ transplant type and examined changes in outcomes over time. We performed a multivariable analysis to determine variables associated with need for supplemental oxygen. RESULTS: A total of 509 patients with solid organ transplants had confirmed COVID-19 during the study period. Risk factors associated with needing (n = 190), compared with not needing (n = 319), supplemental oxygen included age (median 62.6 yr, interquartile range [IQR] 52.5-69.5 yr v. median 55.5 yr, IQR 47.5-66.5; p < 0.001) and number of comorbidities (median 3, IQR 2-3 v. median 2, IQR 1-3; p < 0.001), as well as parameters associated with immunosuppression. Recipients of lung transplants (n = 48) were more likely to have severe disease with a high mortality rate (n = 15, 31.3%) compared with recipients of other organ transplants, including kidney (n = 48, 14.8%), heart (n = 1, 4.4%), liver (n = 9, 11.4%) and kidney-pancreas (n = 3, 12.0%) transplants (p = 0.02). Protective factors against needing supplemental oxygen included having had a liver transplant and receiving azathioprine. Having had 2 doses of SARS-CoV-2 vaccine did not have an appreciable influence on oxygen requirement. Multivariable analysis showed that older age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07) and number of comorbidities (OR 1.63, 95% CI 1.30-2.04), among other factors, were associated with the need for supplemental oxygen. Over time, disease severity did not decline significantly. INTERPRETATION: Despite therapeutic advances and vaccination of recipients of solid organ transplants, evidence of increased severity of COVID-19, in particular among those with lung transplants, supports ongoing public health measures to protect these at-risk people, and early use of COVID-19 therapies for recipients of solid organ transplants.

Outcomes of SARS-CoV-2 Infection in Unvaccinated Compared With Vaccinated Solid Organ Transplant Recipients: A Propensity Matched Cohort Study.

BACKGROUND: Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). Vaccination may mitigate this risk; however, immunogenicity appears to be significantly impaired, with reports of increased risk of breakthrough infection. It is unknown if vaccine breakthrough infections are milder or as severe as infections in unvaccinated patients. METHODS: We performed a multicenter matched cohort study between March 2020 and September 2021 to assess influence of COVID-19 vaccination on outcomes of COVID-19 infection. Treatment characteristics and disease severity outcomes were compared on the basis of vaccine status; breakthrough infections versus unvaccinated infections. Variable ratio propensity score matching based on age, sex, transplant type, and number of comorbidities, was used to develop the analytic cohort. Logistic regression was used to assess the influence of vaccination status on the selected outcomes. RESULTS: From a cohort of 511 SOT patients with COVID-19, we matched 77 partially or fully vaccinated patients with 220 unvaccinated patients. Treatment characteristics including use of dexamethasone, remdesivir, and antibiotics did not differ. Vaccinated participants were more likely to receive tocilizumab, 15 of 77 (19.5%) versus 5 of 220 (2.3%), P < 0.001. Disease severity outcomes including oxygen requirement, mechanical ventilation, and mortality were similar among medically attended vaccine breakthroughs compared with unvaccinated patients. CONCLUSIONS: SOT recipients who develop medically attended COVID-19 following 1- or 2-dose vaccination seem to have similar disease severity to unvaccinated patients who develop infection. This is consistent with the requirement that SOT recipients need 3 or more vaccine doses and emphasizes the importance of alternate strategies for this population.

Addressing Barriers to Health Care Access of Congenital Heart Disease Patients in Guyana.

In order to mitigate the late presentation and resulting poor outcomes of children with advanced cardiac disease, the Ministry of Public Health (MOPH) in Guyana has expressed interest in identifying ways to improve access to health care for these children. The goal of this study was to identify barriers faced by CHD patients and their families in accessing pediatric cardiology services in Guyana, and to identify limitations to the diagnosis and referral of CHD patients by health care professionals. Two surveys were used to gain insight into the experiences of practicing health care professionals and the parent(s) or guardian(s) of children with CHD. Patients were identified based on convenience sampling at cardiology clinics and outreach clinics in both urban and rural Guyana. Physicians were identified using convenience sampling at health posts in rural Guyana. Fifty-two (n = 52) families were identified and interviewed throughout the regions visited. The majority of families identified distance, the need to travel, and their inability, financially and practically, to attend clinic as the main barrier to accessing specialized care. Twelve (n = 12) health care providers were interviewed. They identified limited knowledge surrounding the diagnosis and management of CHD, and perceived impracticality of referring patients to specialized services, despite being aware of the referral process. This study identifies the need for improved outreach and support for health care providers and families, especially those living in rural communities. It identifies some of the challenges faced in managing patients with CHD in Guyana, while establishing specific areas for quality improvement.

Identification of cell-free DNA methylation patterns unique to the human left ventricle as a potential indicator of acute cellular rejection.

Increased levels of donor-derived cell-free DNA (dd-cfDNA) in recipient plasma have been associated with rejection after transplantation. DNA sequence differences have been used to distinguish between donor and recipient, but epigenetic differences could also potentially identify dd-cfDNA. This pilot study aimed to identify ventricle-specific differentially methylated regions of DNA (DMRs) that could be detected in cfDNA. We identified 24 ventricle-specific DMRs and chose two for further study, one on chromosome 9 and one on chromosome 12. The specificity of both DMRs for the left ventricle was confirmed using genomic DNA from multiple human tissues. Serial matched samples of myocardium (n = 33) and plasma (n = 24) were collected from stable adult heart transplant recipients undergoing routine endomyocardial biopsy for rejection surveillance. Plasma DMR levels increased with biopsy-proven rejection grade for individual patients. Mean cellular apoptosis in biopsy samples increased significantly with rejection severity (2.4%, 4.4% and 10.0% for ACR 0R, 1R, and 2R, respectively) but did not show a consistent relationship with DMR levels. We identified multiple DNA methylation patterns unique to the human ventricle and conclude that epigenetic differences in cfDNA populations represent a promising alternative strategy for the non-invasive detection of rejection.

Automated E-Counseling for Chronic Heart Failure: CHF-CePPORT Trial.

BACKGROUND: International task force statements advocate telehealth programs to promote health-related quality of life for patients with chronic heart failure (CHF). To that end, we evaluated the efficacy and usability of an automated e-counseling program. METHODS: This Canadian multi-site double-blind randomized trial assessed whether usual care plus either internet-based e-counseling (motivational and cognitive-behavioral tools for CHF self-care) or e-based conventional CHF self-care education (e-UC) improved 12-month Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS). Secondary outcomes included program engagement (total logon weeks, logons, and logon hours), total CHF self-care behaviors, diet (fruit and vegetable servings), 6-minute walk test, and 4-day step count. The association between program engagement and health-related quality of life was assessed using KCCQ-OS tertiles. RESULTS: We enrolled 231 patients, median age =59.5 years, 22% female, and elevated median KCCQ-OS=83.0 (interquartile range, 68-93). KCCQ-OS increase ≥5 points was not more prevalent for e-counseling, n=29 (29.6%) versus e-UC, n=32 (34.0%), P=0.51. E-Counseling versus e-UC increased total logon weeks (P=0.02), logon hours (P=0.001), and logons (P<0.001). Only e-counseling showed a positive association between 12-month KCCQ-OS tertile and logon weeks (P=0.04) and logon hours (P=0.004). E-Counseling increased CHF self-care behavior and diet but not 6-minute walk test or 4-day step count. CONCLUSIONS: The primary KCCQ-OS end point was negative for this trial. Only e-counseling showed a positive association between program engagement and 12-month KCCQ-OS tertile, and it improved CHF self-care behavior and diet. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01864369.

HEARTBiT: A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients.

BACKGROUND: Nine mRNA transcripts associated with acute cellular rejection (ACR) in previous microarray studies were ported to the clinically amenable NanoString nCounter platform. Here we report the diagnostic performance of the resulting blood test to exclude ACR in heart allograft recipients: HEARTBiT. METHODS: Blood samples for transcriptomic profiling were collected during routine post-transplantation monitoring in 8 Canadian transplant centres participating in the Biomarkers in Transplantation initiative, a large (n = 1622) prospective observational study conducted between 2009 and 2014. All adult cardiac transplant patients were invited to participate (median age = 56 [17 to 71]). The reference standard for rejection status was histopathology grading of tissue from endomyocardial biopsy (EMB). All locally graded ISHLT ≥ 2R rejection samples were selected for analysis (n = 36). ISHLT 1R (n = 38) and 0R (n = 86) samples were randomly selected to create a cohort approximately matched for site, age, sex, and days post-transplantation, with a focus on early time points (median days post-transplant = 42 [7 to 506]). RESULTS: ISHLT ≥ 2R rejection was confirmed by EMB in 18 and excluded in 92 samples in the test set. HEARTBiT achieved 47% specificity (95% confidence interval [CI], 36%-57%) given ≥ 90% sensitivity, with a corresponding area under the receiver operating characteristic curve of 0.69 (95% CI, 0.56-0.81). CONCLUSIONS: HEARTBiT's diagnostic performance compares favourably to the only currently approved minimally invasive diagnostic test to rule out ACR, AlloMap (CareDx, Brisbane, CA) and may be used to inform care decisions in the first 2 months post-transplantation, when AlloMap is not approved, and most ACR episodes occur.

Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement on Heart Transplantation: Patient Eligibility, Selection, and Post-Transplantation Care.

Significant practice-changing developments have occurred in the care of heart transplantation candidates and recipients over the past decade. This Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement provides evidence-based, expert panel recommendations with values and preferences, and practical tips on: (1) patient selection criteria; (2) selected patient populations; and (3) post transplantation surveillance. The recommendations were developed through systematic review of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The evolving areas of importance addressed include transplant recipient age, frailty assessment, pulmonary hypertension evaluation, cannabis use, combined heart and other solid organ transplantation, adult congenital heart disease, cardiac amyloidosis, high sensitization, and post-transplantation management of antibodies to human leukocyte antigen, rejection, cardiac allograft vasculopathy, and long-term noncardiac care. Attention is also given to Canadian-specific management strategies including the prioritization of highly sensitized transplant candidates (status 4S) and heart organ allocation algorithms. The focus topics in this position statement highlight the increased complexity of patients who undergo evaluation for heart transplantation as well as improved patient selection, and advances in post-transplantation management and surveillance that have led to better long-term outcomes for heart transplant recipients.

Management and outcomes of cardiac sarcoidosis: a 20-year experience in two tertiary care centres.

AIMS: Cardiac sarcoidosis (CS) often presents with ventricular arrhythmias, heart block, and cardiomyopathy. The prognosis of CS with contemporary management is uncertain. We estimated the impact of baseline and treatment variables on left ventricular ejection fraction (LVEF), ventricular assist device placement, heart transplant, and death. METHODS AND RESULTS: We identified patients with CS seen from 1994-2014 at two large academic medical centres. All met the 2014 Heart Rhythm Society expert consensus criteria for diagnosis. From the 574 patients identified, 91 met inclusion criteria. Twenty-two (24.2%) were diagnosed by endomyocardial biopsy. Cardiomyopathy was the primary presentation in 47 patients (51.6%). Within 90 days of diagnosis, 41 patients (45.0%) received prednisone alone, 29 (31.9%) received alternative immunosuppression with or without prednisone, and 21 (23.1%) received no immunosuppression. During follow-up, 31 of 47 cardiomyopathy patients experienced improvement in LVEF, while 23 experienced decline in LVEF or clinical exacerbation, and 15 of 22 patients presenting with ventricular arrhythmia had recurrence. These results did not differ by treatment group. During a median follow-up of 44 months for our cohort, 14 patients reached the composite endpoint of ventricular assist device placement, heart transplant, or death. Survival without the composite outcome did not differ by treatment group, but was worse among patients presenting with cardiomyopathy (log-rank = 0.005). CONCLUSION: In a large series of CS subjects, rates of ventricular arrhythmia and heart failure events remain high with no treatment regimen clearly associated with better outcome. Patients with cardiomyopathy at diagnosis were more likely to reach the composite endpoint.

Implementation of a Multidisciplinary Inpatient Cardiology Service to Improve Heart Failure Outcomes in Guyana.

BACKGROUND: Guyana is a small developing country with a high burden of cardiovascular disease and extensive barriers to optimal care delivery. We investigated the effectiveness of a newly established multidisciplinary inpatient cardiology service in this setting. METHODS: We performed an interrupted time-series cohort study of heart failure (HF) patients admitted to the Georgetown Public Hospital Corporation from January to December 2015 and July 2016 to December 2017. The primary outcome was discharge on guideline-directed medical therapy (GDMT). Secondary outcomes included length of hospitalization and all-cause mortality. RESULTS: We identified 740 patients, 347 (46.9%) of whom were admitted after service implementation. The postimplementation cohort was more likely to be discharged on a beta-blocker (66.6% vs 41.7%; P < .01) and mineralocorticoid receptor antagonist (31.7% vs 15.3%; P = .01). They were also more likely to undergo echocardiography (60.8% vs 40.5%; P < .01) and chest x-rays (70.6% vs 46.6%; P < .01). Hospitalization length (10.0 ± 13.1 vs 9.8 ± 10.1 days) and readmissions within 90 days (19.0% vs 19.1%) were not significantly different. There were fewer deaths in the postimplementation cohort compared with the preimplementation cohort (12/347 vs 28/393). CONCLUSIONS: Establishment of a multidisciplinary inpatient cardiology service demonstrated increased adherence to GDMT without extending length of hospitalization.

The Canada-Guyana medical education partnership: using videoconferencing to supplement post-graduate medical education among internal medicine trainees.

BACKGROUND: A Guyana-based, internal medicine (IM) post-graduate medical education program was established in 2013. However, lack of formal teaching sessions are barriers to the program's success. OBJECTIVE: To describe the partnership between the University of Calgary and the University of Guyana's internal medicine residency programs (IMRP). This partnership was created to support the Guyana's IM academic half-day and is characterized by mutually beneficial, resident-led videoconference teaching sessions. METHODS: Calgary medical residents volunteered to create and present weekly teaching presentations to Guyanese residents via videoconference. Questionnaires were completed by Guyanese residents and provided to Calgary residents as feedback on their teaching and presentation skills. A similar survey was completed by Calgary residents. LESSONS LEARNED: Twenty-four videoconference teaching sessions were conducted over eight months with a total of 191 and 16 surveys completed by Guyana and Calgary residents, respectively. Over 92% of both Guyana and Calgary residents agreed that the sessions enhanced their learning and over 93% reported increased interest in becoming more involved in international collaborations. 88% of Calgary residents felt the sessions improved their teaching skills. CONCLUSION: The formation of a resident-led, videoconference teaching series is a mutually beneficial partnership for Canadian and Guyanese medical residents and fosters international collaboration in medical education.

Impact of a Pediatric Cardiology Clinical Program on Congenital Heart Disease Outcomes in Guyana.

Background: Children with congenital heart disease (CHD) in Guyana have not historically been managed with timely intervention, increasing the likelihood of serious, irreversible complications. In 2014, a pediatric cardiology clinical program (Guyana Paediatric Cardiology Steering Committee [GPCSC]) and partnership with International Children's Heart Foundation (BabyHeart) was developed to improve CHD care. Objectives: To describe the characteristics of CHD in Guyanese children and to determine the impact of GPCSC on CHD outcomes. Methods: Qualitative comparison between CHD patients sent for surgery prior to GPCSC (pre-GPCSC cohort) and those managed through GPCSC (post-GPCSC cohort). Findings: Eighty-eight pre-GPHC patients were identified from 2005 to 2014. A total of 319 CHD patients were referred post-GPCSC. In all, 114 patients required surgical or catheterization procedures, with 74 patients prioritized for interventions within 29 months post-GPCSC. Mean age at surgery was 77 months in both cohorts, with younger children represented in the post-GPCSC cohort. Postoperative follow-up was more frequent post-GPCSC (100% vs 35%). Vital status of 48% of pre-GPCSC patients is unknown, with more pre-GPCSC patients known to be deceased compared with post-GPCSC (9% vs 5%). Pre-GPCSC patients had more incorrect diagnosis and inoperable disease when sent for surgery. Interpretation: Patients undergoing surgery post-GPCSC had more appropriate and timely interventions, better follow-up, and increased survival. The feasibility and positive impact of this collaborative pediatric cardiology clinical program in Guyana is demonstrated, with potential applicability for other low- and middle-income countries. Obstacles to referral of children with CHD in Guyana can begin to be addressed, with the goal of more complete access to timely intervention, and improved outcomes for these children.

Barriers to Goals of Care Discussions With Patients Who Have Advanced Heart Failure: Results of a Multicenter Survey of Hospital-Based Cardiology Clinicians.

BACKGROUND: Conversations about goals of care in hospital are important to patients who have advanced heart failure (HF). METHODS: We conducted a multicenter survey of cardiology nurses, fellows, and cardiologists at 8 Canadian teaching hospitals. The primary outcome was the importance of barriers to goals-of-care discussions in hospital (1 = extremely unimportant; 7 = extremely important). We also elicited perspectives on roles of different practitioners in having these conversations. RESULTS: Questionnaires were returned by 770/1024 (75.2%) eligible clinicians. The most important perceived barriers were: family members' and patients' difficulty in accepting a poor prognosis (mean [SD] score 5.9 [1.1] and 5.7 [1.2], respectively), family members' and patients' lack of understanding about the limitations and harms of life-sustaining treatments (5.8 [1.1] and 5.7 [1.2], respectively), and lack of agreement among family members about goals of care (5.8 [1.2]). Interprofessional team members were viewed as having different but important roles in goals-of-care discussions. CONCLUSIONS: Cardiology clinicians perceive family and patient-related factors as the most important barriers to goals-of-care discussions in hospital. Many members of the interprofessional team were viewed as having important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication about goals of care in advanced HF.

Increased left ventricular extracellular volume and enhanced twist function in type 1 diabetic individuals.

Individuals with type 1 diabetes (T1D) characteristically have high glycemic levels that over time can result in reactive fibrosis and abnormalities in myocardial function. T1 mapping with magnetic resonance imaging (MRI) can estimate the extent of reactive fibrosis by measurement of the extracellular volume fraction (ECV). The extent of alterations in the ECV and associated changes in left ventricular (LV) function and morphology in individuals with T1D is unknown. Fourteen individuals with long-term T1D and 14 sex-, age-, and body mass index-matched controls without diabetes underwent MRI measurement of myocardial T1 and ECV values as well as LV function and morphology. Ventricular mass, volumes, and global function (LVEF and circumferential/longitudinal/radial strain) were similar in those with T1D and controls. However, those with T1D had larger myocardial ECV (22.1 ± 1.8 vs. 20.1 ± 2.1, P = 0.008) and increased native (noncontrast) myocardial T1 values (1,211 ± 44 vs. 1,172 ± 43 ms, P < 0.001) as compared with controls. Both the ECV and native T1 values significantly correlated with several components of torsion and circumferential-longitudinal shear strain (Ecl, the shear strain component associated with twist). Individuals with T1D had increased systolic torsion (P = 0.035), systolic torsion rate (P = 0.032), peak Ecl (P = 0.001), and rates of change of systolic (P = 0.007) and diastolic (P = 0.007) Ecl Individuals with T1D, with normal structure, LVEF, and strain, have increased extracellular volume and increased native T1 values with associated augmented torsion and Ecl These measures may be useful in detecting the early stages of diabetic cardiomyopathy and warrant larger prospective studies.NEW & NOTEWORTHY Individuals with type 1 diabetes, with normal left ventricular structure and function (ejection fraction and strain), have signs of interstitial fibrosis, measured with MRI as increased extracellular volume fraction and increased native myocardial T1, which significantly correlated with a number of measures of augmented left ventricular twist function. These measures may be useful in detecting the early stages of diabetic cardiomyopathy.

Multicenter evaluation of a national organ sharing policy for highly sensitized patients listed for heart transplantation in Canada.

BACKGROUND: Transplantation of sensitized recipients has been associated with increased risk of post-transplant complications. In 2010, the Canadian Cardiac Transplant Network (CCTN) created a unique status listing for highly sensitized heart transplant candidates. Status 4S listing requires calculated panel-reactive antibody (cPRA) level >80% as the sole listing criteria and enables geographic expansion of the donor pool by providing national access. In this study, we describe patient characteristics and outcomes of those transplanted as Status 4S in Canada. METHODS: Patients' characteristics and clinical outcomes were retrospectively collected from all 11 adult heart transplant centers in Canada. RESULTS: Ninety-six patients were listed Status 4S from January 2010 to September 2015. Fifty-two were transplanted as Status 4S. Of these 52 transplants, mean cPRA level was 93.4%, mean age was 47 years, 46% were male, 44% had dilated cardiomyopathy and 17% were re-transplanted for cardiac allograft vasculopathy (CAV). Blood group O comprised 42% and 53% had a left ventricular assist device as a bridge to transplant. Desensitization therapy occurred in 9 patients (17%). Over a mean follow-up period of 28 months (1 week to 5.3 years), 9 patients died (17%). Kaplan-Meier 1-year year survival is 86%. Two patients were treated for antibody-mediated rejection (AMR) in the first year post-transplant and 33% of patients had at least 1 ISHLT Grade ≥2R cellular rejection in the first year. Twenty-nine percent of patients developed de novo door-specific antibodies and demonstrated no correlation with AMR. Freedom from CAV at 1 year is 88.5% and at 5 years is 81.0%. Fifty-two percent of donor hearts originated from outside the recipients' geographic and organ donation organization. CONCLUSIONS: A national strategy of prioritizing highly sensitized heart transplant recipients has demonstrated effective expansion of the donor pool, acceptable short-term survival, freedom from CAV and low rates of clinically relevant AMR. However, we observed significantly higher rates of cellular rejection and de novo donor-specific antibody development in this population. It is currently unknown whether this will translate into poorer long-term outcome.

Orthostatic Hypotension After Continuous-Flow Left Ventricular Assist Device Implantation in a Patient With Longstanding Diabetes Mellitus.

A continuous-flow left ventricular assist device (CF-LVAD) benefits patients with advanced heart failure as a bridge to cardiac transplantation. However, unanticipated complications may occur. We report a patient with end-stage heart failure and longstanding diabetes who experienced functionally debilitating orthostatic hypotension from autonomic insufficiency after CF-LVAD implantation. This case demonstrates a role for comprehensive autonomic function testing in the workup of orthostatic hypotension after LVAD implantation.