Axillary mechanical circulatory support improves renal function prior to heart transplantation in patients with chronic kidney disease.

Impaired kidney function is often associated with acute decompensation of chronic heart failure and portends a poor prognosis. Unfortunately, current data have demonstrated worse survival in patients with acute kidney injury than in patients with chronic kidney disease during durable LVAD placement as bridge therapy. Furthermore, end-stage heart failure patients undergoing combined heart-kidney transplantation have poorer short- and long-term survival than heart transplants alone. We evaluated the kidney function recovery in our heart failure population awaiting heart transplantation at our institution, supported by temporary Mechanical Circulatory Support (tMCS) with Impella 5.5. The protocol (#22004000) was approved by the Mayo Clinic institutional review board, after which we performed a retrospective review of all patients with acute on chronic heart failure and kidney disease in patients considered for only heart and kidney combined organ transplant and supported by tMCS between January 2020 and February 2021. Hemodynamic and kidney function trends were recorded and analyzed before and after tMCS placement and transplantation. After placement of tMCS, we observed a trend towards improvement in creatinine, Fick cardiac index, mixed venous saturation, and glomerular filtration rate (GFR), which persisted through transplantation and discharge. The average duration of support with tMCS was 16.5 days before organ transplantation. The median pre-tMCS creatinine was 2.1 mg/dL (IQR 1.75-2.3). Median hematocrit at the time of tMCS placement was 32% (IQR 32-34), and the median estimated glomerular filtration rate was 34 mL/min/BSA (34-40). The median GFR improved to 44 mL/min/BSA (IQR 45-51), and serum creatinine improved to 1.5 mg/dL (1.5-1.8) after tMCS. Median discharge creatinine was 1.1 mg/dL (1.19-1.25) with a GFR of 72 (65-74). None of these six patients supported with tMCS required renal replacement therapy after heart transplantation. Early adoption of Impella 5.5 in this patient population resulted in renal recovery without needing renal replacement therapies or dual organ transplantation and should be further evaluated.

Non-invasive detection of cardiac allograft rejection among heart transplant recipients using an electrocardiogram based deep learning model.

Aims: Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG). Methods and results: Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78-0.90] and 95% (19/20; 95% CI: 75-100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61-0.96) and 100% (2/2; 95% CI: 16-100%) sensitivity. Conclusion: An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.

Controlled temperatures in cold preservation provides safe heart transplantation results.

BACKGROUND: We aimed to investigate the short-term outcomes of heart transplant patients who underwent SherpaPak™ donor organ preservation. METHOD: We prospectively collected the data of patients who underwent heart transplantation using SherpaPak™ system for donor organ transportation from February 2020 to March 2021. Donor and recipient demographic data, preoperative and postoperative echocardiographic and hemodynamic parameters, total ischemic time and SherpaPak temperatures, vasoactive inotropic scores (VIS), primary graft dysfunction (PGD) status, intensive care unit stay, complications, and mortality during follow-up were assessed. RESULTS: A total of 39 consecutive heart transplant patients with SherpaPak system were included in the study. The mean donor age was 32.2 ± 6.7 (range: 16-46). The mean recipient age was 57.5 ± 12 (range: 19-73). The mean preoperative ejection fraction (EF) was 23.7 ± 15.4 (range: 5-75). All recipients underwent a standard bicaval technique for orthotopic heart implantation. The mean total ischemic time was 230.1 ± 41 (range: 149-342) min. The mean Sherpa temperature was 5.6 ± 0.8°C (range: 3.7-7.5). The mean VIS was 10.2 ± 6.5 (range: 2-32). The number of mild PGD was 5 (14.7%), and moderate PGD was 4 (11.8%). There was no severe PGD. The postoperative EF was 64.3 ± 5.5 (range: 50-78). Mean intubation time was 47.4 ± 64 (range: 8-312, median: 22) h. The mean time of intensive care unit stay was 6.3 ± 5 (range: 2-31, median: 5) days. Two patients required chest revision (5.8%), two patients had lung infection (5.8%). Two patients had a stroke (5.8%). There was no mortality. CONCLUSION: Using the SherpaPak system during heart transplantation is safe and not associated with significant recipient morbidity. None of the recipients experienced significant PGD and mortality.

Left ventricular assist devices in the elderly: Marching forward with cautions.

Congestive heart failure is highly prevalent in the elderly population and left ventricular assist device (LVAD) has been increasingly used in this population. LVAD therapy is more costly than medical treatment but it increases the survival and quality of life of the elderly patients with low disease acuity. Therefore careful selection of candidates and implementation of LVAD therapy earlier in the course of the disease is crucial to improve outcomes. With the technical advances and improvement in clinical management, the financial burden of LVAD therapy in the elderly will become less, making this therapy more economically feasible.

Kidney transplantation on extracorporeal life support for primary cardiac allograft dysfunction.

Patients undergoing heart-kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno-arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno-arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.

High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.

BACKGROUND: A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. METHODS AND RESULTS: Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. CONCLUSIONS: A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance.

Left ventricular hypertrophy, aortic wall thickness, and lifetime predicted risk of cardiovascular disease:the Dallas Heart Study.

OBJECTIVES: To examine whether individuals with low short-term risk of coronary heart disease but high lifetime predicted risk of cardiovascular disease (CVD) have greater prevalence of left ventricular (LV) hypertrophy and increased aortic wall thickness (AWT) than those with low short-term and low lifetime risk. BACKGROUND: Lifetime risk prediction can be used for stratifying individuals younger than 50 years of age into 2 groups: low short-term/high lifetime and low short-term/low lifetime predicted risk of CVD. Individuals with low short-term/high lifetime risk have a greater burden of subclinical atherosclerosis as measured by coronary artery calcium and carotid intima-media thickness. However, >75% of individuals with low short-term/high lifetime risk do not have detectable coronary artery calcium, suggesting the presence of alternative subclinical abnormalities. METHODS: We stratified 1,804 Dallas Heart Study subjects between the ages of 30 and 50 years who had cardiac magnetic resonance into 3 groups: low short-term (<10% 10-year risk of coronary heart disease)/low lifetime predicted risk (<39% lifetime risk of CVD), low short-term (<10%)/high lifetime risk (> or =39%), and high short-term risk (> or =10%, prevalent diabetes, or previous stroke, or myocardial infarction). In those with low short-term risk, we compared measures of LV hypertrophy and AWT between those with low versus high lifetime risk. RESULTS: Subjects with low short-term/high lifetime risk compared with those with low short-term/low lifetime risk had increased LV mass (men: 95 +/- 17 g/m(2) vs. 90 +/- 12 g/m(2) and women: 75 +/- 14 g/m(2) vs. 71 +/- 10 g/m(2), respectively; p < 0.001 for both). LV concentricity (mass/volume), wall thickness, and AWT were also significantly greater in those with high lifetime risk in this comparison (p < 0.001 for all), but LV end-diastolic volume was not (p > 0.3). These associations persisted among participants without detectable coronary artery calcium. CONCLUSIONS: Among individuals 30 to 50 years of age with low short-term risk, a high lifetime predicted risk of CVD is associated with concentric LV hypertrophy and increased AWT.

Association of cystatin C with left ventricular structure and function: the Dallas Heart Study.

BACKGROUND: Cystatin C, a novel marker of renal function, has been associated with heart failure and cardiovascular mortality in older individuals. We tested the hypothesis that cystatin C is associated with preclinical cardiac structural and functional abnormalities in a younger population-based sample. METHODS AND RESULTS: The study included participants in the Dallas Heart Study (ages 30 to 65 years) who had measurements of cystatin C and cardiac MRI. The associations of cystatin C with left ventricular (LV) mass, LV end-systolic and -diastolic volumes, concentricity (LV mass/LV end-diastolic volume), LV wall thickness, and LV ejection fraction were evaluated. Cystatin C levels ranged from 0.46 to 6.55 mg/L. In univariable analyses, increasing levels of cystatin C correlated with higher LV mass, concentricity, and wall thickness (P<0.001), but not with LV end-systolic volume, LV end-diastolic volume, or LV ejection fraction. After adjustment with traditional covariates and estimated glomerular filtration rate by the modification of diet in renal disease formula, log-transformed cystatin C remained independently associated with LV mass (P<0.001), concentricity (P=0.027), and wall thickness (P<0.001). These associations persisted when creatinine or estimated glomerular filtration rate by the Cockcroft-Gault formula were included in the models. CONCLUSIONS: Higher levels of cystatin C were associated with increased LV mass and a concentric LV hypertrophy phenotype. These findings were independent of potential confounding variables including standard measurements of renal function, supporting the hypothesis that cystatin C may be useful to identify individuals with preclinical structural heart abnormalities.

Pancreatic gout masquerading as pancreatic cancer in a heart transplant candidate.

In this report, a case is presented of a patient with advanced heart failure who had asymptomatic pancreatic gout, which masqueraded as metastatic pancreatic cancer. This unusual presentation of gout was important to recognize, as the presence of a pancreatic cancer would have precluded cardiac transplantation in an otherwise suitable candidate.

Utility of routine immunofluorescence staining for C4d in cardiac transplant recipients.

BACKGROUND: Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care. METHODS: This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwent > or = 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection. RESULTS: Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57% (8 of 14, designated C4d+/ACR+) vs 11% (6 of 53, designated C4d-/ACR+; p < 0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p < 0.01 for each). CONCLUSIONS: Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.