APOL1 Gene Variants and Risk for Cardiovascular Disease.

INTRODUCTION: The association of APOL1 risk variants with cardiovascular risk and cardiovascular disease (CVD) in observational and clinical trials has had inconsistent results. We aim to assess the relationship between the presence of APOL1 risk variants and the CVD risk in Afro-descendant patients with end-stage renal disease (ESRD). METHODS: We performed an observational, cross-sectional study of Afro-descendant adult patients with ESRD who were on the waitlist for a kidney transplant. Associations of APOL1 genotypes (high-risk [HR] = 2 alleles; low-risk [LR] = 0 or 1 allele) with cardiovascular risk were the primary clinical endpoint. The relation was evaluated using univariate and multivariate analysis. RESULTS: We enrolled a total of 102 patients with ESRD; 37% (38 patients) had APOL1 HR status with two alleles in homozygous (G1/G1 = 21 and G2/G2 = 3) or compound heterozygote (G1/G2 = 14) form and 63% (64 patients) had APOL1 LR status. No significant association was found between HR APOL1 genotypes and high cardiovascular risk (in adjusted Colombia Framingham Risk Score). APOL1 HR versus LR variants were not independently associated with left ventricular hypertrophy or systolic dysfunction. No cardiovascular deaths occurred during the follow-up. CONCLUSION: In Afro-descendent patients with ESRD, APOL1 HR status is not associated with the increase in cardiovascular risk profile and metabolic disturbances.

Risk prediction models for survival after heart transplantation: A systematic review.

Risk prediction scores have been developed to predict survival following heart transplantation (HT). Our objective was to systematically review the model characteristics and performance for all available scores that predict survival after HT. Ovid Medline and Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Clinical Trials were searched to December 2018. Eligible articles reported a score to predict mortality following HT. Of the 5392 studies screened, 21 studies were included that derived and/or validated 16 scores. Seven (44%) scores were validated in external cohorts and 8 (50%) assessed model performance. Overall model discrimination ranged from poor to moderate (C-statistic/area under the receiver operating characteristics 0.54-0.77). The IMPACT score was the most widely validated, was well calibrated in two large registries, and was best at discriminating 3-month survival (C-statistic 0.76). Most scores did not perform particularly well in any cohort in which they were assessed. This review shows that there are insufficient data to recommend the use of one model over the others for prediction of post-HT outcomes.

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

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 VO2 ) 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 VO2 , frailty was not associated with a significant risk of all-cause death. However, when peak VO2 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 VO2 (HR 1.72, P = .006).

Early pneumopericardium after heart transplantation.

A 60-year-old woman with a history of dilated cardiomyopathy underwent heart transplantation. One month post discharge, she presented to clinic with low-grade fever and productive cough. Her chest radiograph showed air-fluid levels in the pericardial silhouette. Transthoracic echocardiogram showed a large complex pericardial collection with no evidence of cardiac tamponade. The patient was urgently taken to the operating room for exploration. A large "egg-shaped" mass in the pericardium measuring 10 × 12 cm with gaseous material was aspirated. As the posterior wall of the mass was firmly adhered to the right atrium, the capsule was incompletely excised. We present the case of a potentially life-threatening complication post transplantation that required surgical debridement and life-long antibiotic suppressive therapy. To our knowledge, this is the first report of purulent pericardial collection caused by Enterobacter cancerogenous. Further research is required to better understand the biology of this microorganism and the role it may play as a pathogen in immunocompromised patients following solid organ transplantation.

Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19.

Background: The COVID-19 pandemic has reduced access to endomyocardial biopsy (EMB) rejection surveillance in heart transplant (HT) recipients. This study is the first in Canada to assess the role for noninvasive rejection surveillance in personalizing titration of immunosuppression and patient satisfaction post-HT. Methods: In this mixed-methods prospective cohort study, adult HT recipients more than 6 months from HT had their routine EMBs replaced by noninvasive rejection surveillance with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing. Demographics, outcomes of noninvasive surveillance score, hospital admissions, patient satisfaction, and health status on the medical outcomes study 12-item short-form health survey (SF-12) were collected and analyzed, using t tests and χ2 tests. Thematic qualitative analysis was performed for open-ended responses. Results: Among 90 patients, 31 (33%) were enrolled. A total of 36 combined GEP/dd-cfDNA tests were performed; 22 (61%) had negative results for both, 10 (27%) had positive GEP/negative dd-cfDNA results, 4 (11%) had negative GEP/positive dd-cfDNA results, and 0 were positive on both. All patients with a positive dd-cfDNA result (range: 0.19%-0.81%) underwent EMB with no significant cellular or antibody-mediated rejection. A total of 15 cases (42%) had immunosuppression reduction, and this increased to 55% in patients with negative concordant testing. Overall, patients' reported satisfaction was 90%, and on thematic analysis they were more satisfied, with less anxiety, during the noninvasive testing experience. Conclusions: Noninvasive rejection surveillance was associated with the ability to lower immunosuppression, increase satisfaction, and reduce anxiety in HT recipients, minimizing exposure for patients and providers during a global pandemic.

Contexte: La pandémie de COVID-19 a réduit l'accès à la biopsie endomyocardique pour surveiller le risque de rejet après une greffe du cœur. Cette étude est la première à être menée au Canada pour évaluer le rôle de la surveillance non invasive du risque de rejet en personnalisant le titrage de l'immunosuppression et la satisfaction du patient après la greffe cardiaque. Méthodologie: Dans le cadre de cette étude de cohorte prospective à méthodes mixtes, des adultes ayant reçu une greffe cardiaque depuis plus de six mois ont vu leurs biopsies endomyocardiques régulières remplacées par une surveillance non invasive du risque de rejet qui consiste à établir le profil de l'expression génique et à analyser l'ADN acellulaire dérivé du donneur. Les données démographiques, les résultats du score de surveillance non invasive, les admissions à l'hôpital, la satisfaction des patients et l'état de santé tirés du questionnaire SF-12 (questionnaire abrégé sur la santé comprenant 12 items) de l'étude sur les issues médicales ont été colligés et analysés au moyen des tests T et des tests χ2. Les réponses ouvertes ont fait l'objet d'une analyse qualitative thématique. Résultats: Parmi 90 patients, 31 (33 %) ont été recrutés. Au total, 36 tests combinés de profilages de l'expression génique et d'ADN acellulaire dérivé du donneur ont été réalisés; les résultats ont été négatifs pour les deux tests dans 22 cas (61 %), positifs pour le profilage de l'expression génique et négatifs pour l'ADN acellulaire dans 10 cas (27 %), négatifs pour le profilage de l'expression génique et positifs pour l'ADN acellulaire dans quatre cas (11 %) et aucun cas n'a donné de résultats positifs pour les deux types de tests. Tous les patients qui ont donné des résultats positifs à l'analyse de l'ADN acellulaire dérivé du donneur (fourchette : 0,19 % à 0,81 %) ont subi une biopsie endomyocardique n'ayant révélé aucun rejet cellulaire ou à médiation par anticorps important. Au total, 15 cas (42 %) affichaient une immunosuppression réduite, proportion qui a grimpé à 55 % chez les patients dont les tests de concordance ont donné des résultats négatifs. Dans l'ensemble, le niveau de satisfaction rapporté par les patients était de 90 % et, à l'analyse thématique, ils étaient plus satisfaits et moins anxieux pendant les tests non invasifs. Conclusions: La surveillance non invasive du risque de rejet a été associée à la capacité de diminuer l'immunosuppression, d'augmenter la satisfaction et de réduire l'anxiété chez les patients qui ont reçu une greffe cardiaque, en plus de réduire l'exposition des patients et du personnel médical dans le contexte d'une pandémie.

The Effect of Age on Outcomes After Destination-Therapy Left Ventricular Assist Device Implantation: An Analysis of the IMACS Registry.

BACKGROUND: As patients with advanced heart failure are living longer, defining the impact of left ventricular assist devices (LVADs) on outcomes in an aging population is of great importance. We describe overall survival, rates of adverse events (AEs), and post-AE survival in patients age ≥ 70 years vs age 50-69 years after destination-therapy (DT) LVAD implantation. METHODS: A retrospective analysis was conducted with the use of the International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support (IMACS) registry. All adults age ≥ 50 years with a continuous-flow DT LVAD from 2013 to 2017 were included. The primary outcome was all-cause mortality. The secondary outcomes were the incidence of and survival after gastrointestinal (GI) bleeding, infection, stroke, pump thrombosis, pump exchange, and right-side heart failure. Mortality and AEs were assessed with the use of competing risk models. RESULTS: At total of 5,572 patients were included: 3,700 aged 50-69 and 1,872 aged ≥ 70. All-cause mortality by 42 months was 55.8% in patients aged ≥ 70 and 44.8% in patients aged 50-69 (P = 0.001). Patients aged ≥ 70 had a 37.8% higher risk of death after DT LVAD implantation (hazard ratio 1.378, 95% CI 1.251-1.517). Patients aged ≥ 70 had higher risk of GI bleeding but lower risk of right-side heart failure. There was no difference between age groups for risk of infection or stroke. Experiencing any AE was associated with an increased risk of death that did not vary with age. CONCLUSIONS: Patients aged ≥ 70 years have reduced survival after DT LVAD, in part because of increased GI bleeding, while the incidence of other AEs is similar to that of patients aged 50-69 years. Careful patient selection beyond age alone may allow for optimal outcomes after DT LVAD implantation.

Risk Factors Related to New-Onset Diabetes after Renal Transplantation in Patients of a High Complexity University Hospital in Colombia, 20 Years of Experience.

INTRODUCTION: New-onset diabetes after transplantation (NODAT) is associated with immunosuppression. Its complications can negatively influence patients' quality of life, which is why it is important to study the associated risk factors and expand the possible therapies in this particular group of patients. Materials and methods. Case-control study nested in a retrospective cohort. It included patients who received kidney transplantation at the high complexity University Hospital Fundación Valle del Lili in Cali, Colombia, between 1995 and 2014. Two controls were assigned for each case, depending on the type of donor and the date of the surgery. Information was collected from clinical records and the institutional TRENAL registry. We carried out a descriptive analysis of the selected variables and identified the risk factors with conditional logistic regression. RESULTS: 122 cases were identified to which 224 controls were assigned. The median age was 44 years (IQR: 34-55), and 54% were men. Having >50 years of age at the time of transplantation (OR: 3.18, 95% CI: 1.6-6.3, p = 0.001), body mass index >30 kg/m2 (OR: 3.6, 95% CI: 1.3-9.7, p = 0.010) and being afro-descendant (OR: 2.74, 95% CI: 1.1-6.5, p = 0.023) were identified as risk factors for the development of NODAT. Pretransplant fasting plasma glucose >100 mg/dl (OR: 2.9, 95% CI: 1.4-6.4, p = 0.005) and serum triglycerides >200 mg/dl (OR: 2.5, 95% CI: 1.4-4.4, p = 0.002) were also reported as independent risk factors. CONCLUSION: We ratify some risk factors for the development of this important disease, which include certain modifiable characteristics. Interventions aimed at changes in lifestyle could be established in a timely manner before transplant surgery.

Corrigendum to "Prevalence of APOL1 Risk Variants in Afro-Descendant Patients with Chronic Kidney Disease in a Latin American Country".

[This corrects the article DOI: 10.1155/2019/7076326.].

Physician Judgement vs Model-Predicted Prognosis in Patients With Heart Failure.

BACKGROUND: Previous evidence suggests that cardiologists and family doctors have limited accuracy in predicting patient prognosis. Predictive models with satisfactory accuracy for estimating mortality in patients with heart failure (HF) exist; physicians, however, seldom use these models. We evaluated the relative accuracy of physician vs model prediction to estimate 1-year survival in ambulatory patients with HF. METHODS: We conducted a single-centre cross-sectional study involving 150 consecutive ambulatory patients with HF >18 years of age with a left ventricular ejection fraction ≤40%. Each patient's cardiologist and family doctor provided their predicted 1-year survival, and predicted survival scores were calculated using 3 models: HF Meta-Score, Seattle Heart Failure Model (SHFM), and Meta-Analysis Global Group in Chronic HF (MAGGIC) score. We compared accuracy between physician and model predictions using intraclass correlation (ICC). RESULTS: Median predicted survival by HF cardiologists was lower (median 80%, interquartile range [IQR]: 61%-90%) than that predicted by family physicians (median 90%, IQR 70%-99%, P = 0.08). One-year median survival calculated by the HF Meta-Score (94.6%), SHFM (95.4%), and MAGGIC (88.9%,) proved as high or higher than physician estimates. Agreement among HF cardiologists (ICC 0.28-0.41) and family physicians (ICC 0.43-0.47) when compared with 1-year model-predicted survival scores proved limited, whereas the 3 models agreed well (ICC > 0.65). CONCLUSIONS: HF cardiologists underestimated survival in comparison with family physicians, whereas both physician estimates were lower than calculated model estimates. Our results provide additional evidence of potential inaccuracy of physician survival predictions in ambulatory patients with HF. These results should be validated in longitudinal studies collecting actual survival.

Prevalence of APOL1 Risk Variants in Afro-Descendant Patients with Chronic Kidney Disease in a Latin American Country.

INTRODUCTION: In Colombia, the genetic background of the populations was shaped by different levels of admixture between Natives, European, and Africans. Approximately 35.363 patients have diagnosed chronic kidney disease and according to population studies, 10.4% of these patients are Afro-descendant. We aim to assess the frequency of APOL1 variants G1 and G2 in Afro-descendant patients with ESRD treated at la Fundacion Valle del Lili University Hospital in Cali, Colombia. METHODS: This is an observational cross-sectional study. Afro-descendant patients with ESRD in waitlist or recipients of kidney transplant were evaluated. Clinical data were collected from the electronic medical records. Genotyping was carried out by amplification of the exon 7 of the APOL1 gene. For the identification of risk genotypes, the bioinformatics tool BLAST was used. RESULTS: We enrolled 102 participants. The frequency of APOL1 risk variants was 67.2%, in which 24.5% (n = 25) were G1 heterozygous and 5.8% (n = 6) were G2 heterozygous and 37% of the patients had high-risk status with two alleles in homozygous (G1/G1 = 21 and G2/G2 = 3) or compound heterozygote (G1/G2 = 14) form.

Risk evaluation using gene expression screening to monitor for acute cellular rejection in heart transplant recipients.

BACKGROUND: Gene expression profiling (GEP) was developed for non-invasive surveillance of acute cellular rejection. Despite its widespread use, there has been a paucity in outcome data for patients managed with GEP outside of clinical trials. METHODS: The Outcomes AlloMap Registry (OAR) is an observational, prospective, multicenter study including patients aged ≥ 15 years and ≥ 55 days post-cardiac transplant. Primary outcome was death and a composite outcome of hemodynamically significant rejection, graft dysfunction, retransplantation, or death. Secondary outcomes included readmission rates and development of coronary allograft vasculopathy and malignancies. RESULTS: The study included 1,504 patients, who were predominantly Caucasian (69%), male (74%), and aged 54.1 ± 12.9 years. The prevalence of moderate to severe acute cellular rejection (≥2R) was 2.0% from 2 to 6 months and 2.2% after 6 months. In the OAR there was no association between higher GEP scores and coronary allograft vasculopathy (p = 0.25), cancer (p = 0.16), or non-cytomegalovirus infection (p = 0.10). Survival at 1, 2, and 5 years post-transplant was 99%, 98%, and 94%, respectively. The composite outcome occurred in 103 patients during the follow-up period. GEP scores in dual-organ recipients (heart-kidney and heart-liver) were comparable to heart-alone recipients. CONCLUSIONS: This registry comprises the largest contemporary cohort of patients undergoing GEP for surveillance. Among patients selected for GEP surveillance, survival is excellent, and rates of acute rejection, graft dysfunction, readmission, and death are low.

Gene expression profiling and racial disparities in outcomes after heart transplantation.

BACKGROUND: African Americans (AAs) have lower survival rates after heart transplantation (HTx) than Caucasians. The aim of this analysis was to evaluate racial differences in gene expression and their associations with survival and the composite outcome of death, retransplant, rejection with hemodynamic compromise, and graft dysfunction in the Outcomes AlloMap Registry. METHODS: Registry participants included low-risk Caucasian and AA heart transplant recipients with a baseline and at least 1 follow-up gene expression test (AlloMap(C)) within the first year after HTx. The Kaplan-Meier method with delayed entry was used to describe differences in outcomes. Multivariable Cox hazard regression was used to evaluate the associations of overall gene expression profiling score, MARCH8 and FLT3 expression, and tacrolimus levels with each outcome, and stratified Cox models were developed to quantify race-specific associations. RESULTS: Among 933 eligible recipients, 737 (79%) were Caucasian and 196 (21%) were AA. Compared with Caucasians, AAs were significantly younger (55 vs 59 years, p < 0.001), with higher rates of non-ischemic cardiomyopathy (68% vs 50%, p < 0.001), sensitization (>10% panel reactive antibody, 16% vs 9.1%, p = 0.009), and human leukocyte antigen mismatches (7 vs 7, p = 0.01), but less frequent primary cytomegalovirus serostatus mismatch (14.31% vs 27.3%, p < 0.001). Overall, AAs had an increased adjusted mortality risk (hazard ratio [HR] 4.13, p = 0.007). Higher tacrolimus levels were associated with decreased mortality in AAs (HR 0.62, p = 0.009). Overall gene expression profiling score was associated with increased mortality among Caucasians (HR 1.21, p = 0.048). In Caucasians, but not AAs, overexpression of MARCH8 was associated with increased mortality (HR 2.90, p = 0.001). FLT3 upregulation was associated with increased mortality (HR 2.42, p = 0.033) in AAs. There was an inverse relationship between FLT3 expression and tacrolimus levels (-0.029 and -0.176, respectively) in Caucasians and AAs. CONCLUSIONS: AAs have a significantly higher mortality risk after HTx than Caucasians, even in the low-risk Outcomes AlloMap Registry population. AAs and Caucasians had differential outcomes based upon the varying expression of MARCH8 and FLT3 genes following HTx.

Avoiding Clinical Errors With Bedside Echocardiography: A Randomized Clinical Study.

Clinicians have strong opinions about whether they should be provided the clinical history before or after bedside testing. We hypothesized that diagnostic accuracy is improved when a concordant clinical history is provided before a diagnostic test. To investigate whether the timing (before or after) and the consistency (concordant vs discordant) of the clinical history in the setting of focused bedside echocardiography affects clinician diagnostic accuracy and management decisions. Thirty-two cardiology residents were asked to perform a bedside echocardiogram on a Vimedix 3D mannequin. Half of the histories were provided before echocardiography and half after echocardiography. Half were consistent with the echocardiographic diagnosis (concordant), and half were suggestive of a plausible alternative diagnosis (discordant). Participants were asked for a diagnosis and management plan. The primary outcome was the diagnostic accuracy of the echocardiographic images. The secondary outcome was the management plan. Overall diagnostic accuracy was 63%. If the clinical history was provided before the bedside testing, it significantly improved diagnostic accuracy if it was concordant and it diminished accuracy if it was discordant (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.16-0.80; P = 0.001). Clinical history, whether concordant or discordant, had no significant impact if provided after the images were obtained. Appropriate management was chosen 77% of the time and was chosen less often with discordant compared with concordant histories (OR, 0.25; 95% CI, 0.11-0.57; P = 0.001). Our study suggests a significant downside to clinical information received before echocardiography when the information is discordant, raising the possibility that receiving clinical information after echocardiography may be superior for diagnostic accuracy.

Clustered Emergency Room Visits Following an Acute Heart Failure Admission: A Population-Based Study.

BACKGROUND: While it is well known that heart failure patients presenting to the emergency room (ER) have high short-term mortality after discharge, the outcomes of patients with heart failure with repeated ER visits within a short time are not known. In this study, we aimed to determine whether clustering is associated with an increased risk of death. METHODS AND RESULTS: This is a retrospective, population-based cohort study with an accrual window between 2003 and 2014 and maximal follow-up up to and including March 31, 2015. Data were obtained from administrative databases from Ontario, Canada. Clustering was defined a priori as 3 or more ER visits within a 6-month period. The main outcome of interest was time to death conditional on 6-month survival. A total of 72 810 patients with an index hospitalization for acute heart failure were evaluated. ER clustering was observed in 15.1% of the population. Increased burden of comorbidities, primary rural residence, and lack of primary care provider were identified as factors associated with ER clustering. Age- and sex-adjusted mortality for clustered patients was higher than for nonclustered (hazard ratio [HR] 1.51; 95% confidence interval, 1.47-1.55, P<0.0001). Adjusted mortality risk was also higher for patients with clustered ER visits (HR 1.42; 95% confidence interval 1.38-1.46; P<0.0001). CONCLUSIONS: Clustering, as defined by 3 or more ER visits for any reason within 6 months of index heart failure hospitalization reflects a novel risk factor associated with increased mortality. Future research into the strategies to better manage complex patients with heart failure with recurrent ER visits are warranted.

En-Bloc Transplant of the Liver, Kidney and Pancreas: Experience from a Latin American Transplant Center.

BACKGROUND En-bloc transplantation is a surgical procedure in which multiple organs are transplanted simultaneously. It has some similarities with multi-organ transplantation but offers certain advantages. This report highlights the experience of our interdisciplinary group regarding the treatment and follow-up of patients who received en-bloc transplantation, with the aim of encouraging the development of this surgical technique. CASE REPORT The first case is a 38-year-old patient with type 1 diabetes mellitus, liver cirrhosis, and chronic kidney failure who received an en-bloc transplant of the liver, pancreas, and kidney with no intraoperative complications. He had a prolonged hospital stay due to anemia and systemic inflammatory response syndrome, which were resolved successfully. At follow-up, he had no requirement for insulin or for dialysis, or for new interventions. The second case describes a 48-year-old patient with type 2 diabetes mellitus, renal failure, and liver cirrhosis who received an en-bloc transplant of the liver, pancreas, and kidney with no complications. During the postoperative period, the patient suffered a possible episode of acute tubular necrosis, which evolved towards improvement, with a tendency to normal metabolic and renal functioning, with no additional events. The patient is currently in follow-up and is insulin-independent. CONCLUSIONS En-bloc transplantation is a safe procedure, which is technically simple and which achieves excellent results. This procedure is indicated in patients with end-stage renal disease, cirrhosis, and diabetes mellitus that is difficult to control.

Polyomavirus-associated nephropathy in renal and simultaneous pancreas-kidney transplant recipients: report of three cases.

Infection with polyomavirus (BK virus) is the cause of renal graft losses in more than 50% of the infected cases. There should be a high index of suspicion about this disease, although the incidence is only between 2% and 5% as the future of renal graft depends on the early and appropriate management of the same. Herein, we describe three clinical cases: Two were those of kidney transplant and the third, a combined kidney-pancreas transplant. In these cases, by reducing immunosuppression and, in one case, replacing the calcineurin inhibitor by MTOR (mammalian target of rapamycin) in addition, we were able to preserve of the normal function of the transplanted organs.