Citations

Abstract Aims The effects of obesity on Fontan haemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive haemodynamics and exercise capacity. Methods and results Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity [body mass index (BMI) > 30 kg/m2] and overweight/normal BMI (BMI ≤ 30 kg/m2). There were 18 individuals with obesity (BMI 36.4 ± 3 kg/m2) and 59 with overweight/normal BMI (BMI 24.1 ± 3.6 kg/m2). Peak oxygen consumption (VO2) on non-invasive cardiopulmonary exercise testing was lower in patients with obesity (15.6 ± 3.5 vs. 19.6 ± 5.8 mL/kg/min, P = 0.04). At rest, systemic flow (Qs) [7.0 (4.8; 8.3) vs. 4.8 (3.9; 5.8) L/min, P = 0.001], pulmonary artery (PA) pressure (16.3 ± 3.5 vs. 13.1 ± 3.5 mmHg, P = 0.002), and PA wedge pressure (PAWP) (11.7 ± 4.4 vs. 8.9 ± 3.1 mmHg, P = 0.01) were higher, while arterial O2 saturation was lower [89.5% (86.5; 92.3) vs. 93% (90; 95)] in obesity compared with overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7 ± 6.5 vs. 24.7 ± 6.8 mmHg, P = 0.01) and PAWP (23.0 ± 6.5 vs. 19.8 ± 7.3 mmHg, P = 0.047), but lower arterial O2 saturation [82.4 ± 7.0% vs. 89% (85; 92), P = 0.003]. Conclusion Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared with those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve haemodynamics and outcomes requires further study.

AbstractMultiple risk factors are important predictors in the development of diabetic nephropathy (DN). Once DN has developed, it progresses steadily to renal failure. To determine the rate of renal function decline and the parameters that influence the rate of decline, we retrospectively reviewed the charts of patients with DN who had undergone dialysis or kidney transplantation at the Mayo Clinic from 1983 to 1993. Forty patients were found to have two or more iothalamate clearance (IothmCl) measurements where a slope of renal function decline over time, expressed as mL/ min/month/1.73 m2, can be calculated. The parameters examined included age of onset and duration of diabetes (DM), age at initial presentation, insulin dosage, glycosylated hemoglobin level, proteinuria, blood pressure (BP), number of antihypertensive medications (HTM), use of ACE inhibitors, creatinine, and initial IothmCl. The mean overall decline of clearance was 1.36±1.1 mL/min/month, corrected. Univariate regression analysis showed that only systolic and mean BP (p<0.05), use of HTM (p=0.02), and the number of HTM used (p=0.0001) correlated with the rate of clearance decline. No other parameter was significant. The decline of IothmCl was 0.72±0.41, 1.20±0.9, and 2.34±1.38 mL/min/month, for patients taking no HTM, <3 HTM, and ≥ 3HTM, respectively. Of the eight patients on HTM who presented with initial IothmCl of <30 mL/min/1.73 m2, seven (88%) had clearance of <10 mL/min/1.73 m2 within 1 yr. We conclude that hypertension is an important marker of DN progression, and that the more HTM required for control of BP, the faster the decline of renal function. We recommend that a suitable transplant candidate with DN who presents with hypertension requiring HTM and a clearance of <30 mL/min should be placed on the transplant waiting list.

AbstractIntroductionCytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high‐risk recipients. However, delayed‐onset post‐prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post‐HSCT.MethodsRetrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event.ResultsAmong 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty‐six (15.7%) developed a breakthrough csCMVi. Delayed‐onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed‐onset csCMVi (OR 0.23).ConclusionsHaving a matched unrelated donor, a CMV donor negative/recipient positive status, and a non‐AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients. image

AbstractBackgroundIgA Nephropathy (IgA N) is one of the most common glomerulopathies and may lead to renal failure in 10–20% of cases. After renal transplantation, IgA N has a strong tendency to recur in the graft. Initially considered a benign condition, graft losses from recurrent IgA N have been reported over the last 20 yr, casting doubt on the initial premise. Since large single‐center studies of the fate of renal allografts in IgA N are rare and the Mayo Clinic transplant experience for IgA N is extensive (dating back to 1970), a review of these issues appeared worthwhile.MethodsA retrospective study was done of all renal transplant patients who had had biopsy‐proven IgA N as underlying disorder. We extracted data on the underlying disease, history leading to renal transplantation, factors affecting transplant outcome, and on the course after transplantation with special attention to rejection activity and recurrence of the primary disease. Standard statistical methods were employed.Results53 renal allografts were transplanted to 51 biopsy‐proven IgA N patients: 12 were cadaveric (CAD) grafts, 3 HLA‐mismatched living related donor (LRD) kidneys, 29 one haplotype‐matched LRD and 9 HLA‐identical LRD organs. Five‐year actuarial graft survival was 100% in HLA‐ identical LRD, 88% in one haplotype‐matched LRD, and 74% in CAD grafts. All three HLA‐mismatched LRD kidneys were functioning up to 1.6 yr (longest follow‐up). Only one patient died after acute rejection of the CAD graft. There were 3 early graft losses from acute rejection and 4 late losses. IgA N recurred in 26% of allografts and led to significant loss of graft function in 10 of the 14 patients (71%) over a long period of observation. Three of four late graft losses were in patients with recurrent IgA N. Recurrence was not related to the type of graft, i.e. CAD vs. LRD, nor to the extent of HLA‐matching in LRD transplantation.ConclusionRenal transplantation in patients with IgA N has excellent patient and graft survival. There is a high rate of recurrence of the primary glomerulopathy in the renal allograft, and this event is by no means inconsequential. Loss of renal function and even graft loss occur over prolonged periods of time. There is no disadvantage getting a well matched LRD in regard to incidence of recurrent IgA N. Thus, we encourage LRD transplantation in IgA N.

We examined the value of thallium‐201 myocardial perfusion scintigraphy in noninvasive assessment of cardiac risk in 36 insulin‐dependent (type 1) diabetic patients being evaluated for pancreas or combined pancreas/kidney transplantation. An extensive cardiovascular evaluation including electrocardiogram was performed in all patients, and most patients were also evaluated by two‐dimensional and Doppler echocardiography. Exercise thallium studies were performed in 31 patients. Five patients were unable to exercise and underwent dipyridamole‐thallium study. The thallium images were abnormal in 12 patients, 10 of whom underwent coronary arteriography. Significant coronary artery disease was found in 7 of these patients. Nineteen patients underwent pancreatic (3 patients) or pancreato‐renal (16) transplantation without any occurrence of cardiac death or nonfatal myocardial infarction peri‐operatively or on follow‐up ranging from 7 months to 21 months. In contrast, 3 cardiac events occurred in 12 patients not approved for transplantation, each of whom had an abnormal thallium study exhibiting significant ischemia. Resting left ventricular global and regional function was not helpful in determining perioperative risk. Thus, thallium‐201 myocardial perfusion scintigraphy may be useful in identifying diabetic patients at low risk for pancreas transplantation and may obviate the need for routine coronary angiography in these patients.