Exercise Counteracts the Cardiotoxicity of Psychosocial Stress

Physical inactivity and psychosocial stress are prevalent in residents of the United States. The purpose of this article is to review the interaction between these 2 conditions and examine the effects of exercise on stress and cardiovascular (CV) health. A query of scientific references between 1974 to 2018 was performed using the PubMed search engine accessing the MEDLINE database using the search terms psychosocial stress, CV disease (CVD), physical activity, exercise, cardiac rehabilitation, and team sports. Psychosocial stress is a strong independent risk factor for adverse CV events. Conversely, people who experience CV events subsequently have drastically elevated rates of new-onset mental health disorders, including depression and anxiety. Psychosocial stress and CVD often trigger self-reinforcing feedback loops that can worsen mental health and cardiac prognosis. Exercise predictably improves CV health and prognosis and also is effective at lowering levels of psychosocial stress. Group exercise in particular seems to provide social support while at the same time boosting fitness levels and, thus, may be the single most important intervention for patients with concomitant CVD and emotional stress. Collaborative physical activity, such as group exercise, team sports, interactive physical play, and cardiac rehabilitation programs, have the potential to improve mental health and CV prognosis.     

Preoperative Evaluation and Management of Patients With Select Chronic Gastrointestinal,Liver, and Renal Diseases

Patients with chronic gastrointestinal, hepatic, and renal disease are frequently encountered in clinical practice. This is due in part to the rising prevalence of risk factors associated with these conditions. These patients are increasingly being considered for surgical intervention and are at higher risk for multiple perioperative complications. Many are able to safely undergo surgery but require unique considerations to ensure optimal perioperative care. In this review, we highlight relevant perioperative physiology and outline our approach to the evaluation and management of patients with select chronic gastrointestinal, hepatic, and renal diseases. A comprehensive preoperative evaluation with a multidisciplinary approach is often beneficial, and specialist involvement should be considered. Intraoperative and postoperative plans should be individualized based on the unique medical and surgical characteristics of each patient.     

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation,Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD.Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles).ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001].ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.     

Outcomes Following Percutaneous Coronary Intervention in Renal Transplant Recipients: A Binational Collaborative Analysis

ObjectiveTo investigate the clinical and procedural characteristics in patients with a history of renal transplant (RT) and compare the outcomes with patients without RT in 2 national cohorts of patients undergoing percutaneous coronary intervention (PCI).Patients and MethodsData from the National Inpatient Sample (NIS) and British Cardiovascular Intervention Society (BCIS) were used to compare the clinical and procedural characteristics and outcomes of patients undergoing PCI who had RT with those who did not have RT. The primary outcome of interest was in-hospital mortality.ResultsOf the PCI procedures performed in 2004-2014 (NIS) and 2007-2014 (BCIS), 12,529 of 6,601,526 (0.2%) and 1521 of 512,356 (0.3%), respectively, were undertaken in patients with a history of RT. Patients with RT were younger and had a higher prevalence of congestive cardiac failure, hypertension, and diabetes but similar use of drug-eluting stents, intracoronary imaging, and pressure wire studies compared with patients who did not have RT. In the adjusted analysis, patients with RT had increased odds of in-hospital mortality (NIS: odds ratio [OR], 1.90; 95% CI, 1.41-2.57; BCIS: OR, 1.60; 95% CI, 1.05-2.46) compared with patients who did not have RT but no difference in vascular or bleeding events. Meta-analysis of the 2 data sets suggested an increase in in-hospital mortality (OR, 1.79; 95% CI, 1.40-2.29) but no difference in vascular (OR, 1.24; 95% CI, 0.77-2.00) or bleeding (OR, 1.21; 95% CI, 0.86-1.68) events.ConclusionThis large collaborative analysis of 2 national databases revealed that patients with RT undergoing PCI are younger, have more comorbidities, and have increased mortality risk compared with the general population undergoing PCI.     

A Target Antigen–Based Approach to the Classification of Membranous Nephropathy

ObjectiveTo describe the clinical and pathological phenotype of membranous nephropathy (MN) associated with M-type-phospholipase–A₂-receptor (PLA₂R), thrombospondin-type-1-domain-containing-7A (THSD7A), semaphorin 3B (SEMA3B), neural-epidermal-growth-factor-like-1-protein (NELL-1), protocadherin 7 (PCDH7), exostosin 1/exostosin 2 (EXT1/EXT2) and neural cell adhesion molecule 1 (NCAM-1) as target antigens.MethodsA retrospective cohort of 270 adult patients with biopsy-proven MN diagnosed between January 2015 and April 2020 was classified as PLA₂R-, THSD7A-, SEMA3B-, NELL-1–, PCDH7-, EXT1/EXT2-, NCAM-1–associated or septuple-negative MN using serologic tests, immunostaining, and/or mass spectrometry. Clinical, biochemical, pathologic, and follow-up data were systematically abstracted from the medical records, including disease activity of conditions traditionally associated with MN and occurring within 5 years of MN diagnosis.ResultsPatients with PLA₂R-associated MN were predominantly middle-aged white men without associated disease. The presence of associated disease did not affect the clinical and pathologic characteristics of PLA₂R-associated MN, suggesting that they were coincidental rather than causally linked. THSD7A-, NELL-1–, PCDH7-, and NCAM-1–associated MN were rare and SEMA3B-associated MN was not discovered in our cohort. EXT1/EXT2-associated MN was primarily diagnosed in younger women with active systemic autoimmunity. A significant proportion of septuple-negative patients had associated malignancy or systemic autoimmunity.ConclusionThe widely used distinction between primary and secondary MN has limitations. We propose a refined terminology that combines the target antigen and associated disease to better classify MN and guide clinical decision making.     

Renal Neoplasia in Tuberous Sclerosis: A Study of 41 Patients

ObjectiveTo study the clinical features and identify unique renal neoplasia subtypes and their prognostic implications in individuals with tuberous sclerosis complex (TSC).Patients and MethodsThe Mayo Clinic nephrectomy registry included 37 patients with TSC diagnosed between 1970 and 2018. Four additional patients were identified from the pathology consultation and autopsy files. All available renal tumors were further characterized using immunohistochemistry and fluorescence in situ hybridization. Clinicopathologic features and follow-up were obtained from the medical record. The American Association for Cancer Research Project GENIE registry was accessed using cBioPortal for molecular profiling of angiomyolipoma (AML).ResultsA total of 276 renal tumors from 41 patients were analyzed. Renal tumors were classified into 9 distinct morphological subtypes, with AML predominating (238 [86%]). Interestingly, all these tumors acted in a benign fashion except one renal cell carcinoma with clear cells and fibromyomatous stroma and one epithelioid AML that metastasized. Molecular profiling studies revealed that epithelioid AMLs were enriched for alterations of TP53, RB1, and ATRX. Eight patients died of direct complications of TSC, including 3 of end-stage renal disease. To date, none have died of a renal epithelial neoplasm.ConclusionThe identification of unique renal neoplasia subtypes may provide important clues to establish a diagnosis of TSC, and in the somatic setting, this finding has important implications for accurate prognostication. These tumors tend to be indolent, and only 2 of 276 tumors in our study exhibited metastatic behavior. Our results support multidisciplinary management with a focus on preservation of renal function.     

Lower Extremity Arterial Disease as a Predictor of Incident Atrial Fibrillation and Cardiovascular Events

ObjectiveTo evaluate the relationship between peripheral arterial disease (PAD) and incident atrial fibrillation (AF) and its clinical and pathophysiologic implications on ischemic stroke and all-cause mortality.Patients and MethodsWe identified all adult patients in the Mayo Clinic Health System without a previous diagnosis of AF undergoing ankle-brachial index (ABI) testing for any indication from January 1, 1996, to June 30, 2018. Retrospective extraction of ABI data and baseline echocardiographic data was performed. The primary outcome of interest was incident AF. The secondary outcomes of interest were incident ischemic stroke and all-cause mortality.ResultsA total of 33,734 patients were included in the study. After adjusting for demographic and comorbidity variables, compared with patients who had normal ABI (1.0 to 1.39), there was an increased risk of incident AF in patients with low ABI (<1.0) (adjusted hazard ratio, 1.14; 95% CI, 1.06 to 1.22) and elevated ABI (≥1.4) (adjusted hazard ratio, 1.18; 95% CI, 1.06 to 1.31). The risk was greater in patients with increasing severity of PAD. Patients with abnormal ABIs had an increased risk of ischemic stroke and all-cause mortality. We found that patients with PAD and incident AF have certain baseline echocardiographic abnormalities.ConclusionIn this large cohort of ambulatory patients undergoing ABI measurement, patients with PAD were at increased risk for incident AF, ischemic stroke, and mortality. In these high-risk patients with abnormal ABI, particularly severe PAD and cardiac structural abnormalities, routine monitoring for AF and management of cardiovascular risk factors may be warranted.     

Kidney Microstructural Features at the Time of Donation Predict Long-term Risk of Chronic Kidney Disease in Living Kidney Donors

ObjectiveTo determine whether microstructural features on a kidney biopsy specimen obtained during kidney transplant surgery predict long-term risk of chronic kidney disease in the donor.Patients and MethodsWe studied kidney donors from May 1, 1999, through December 31, 2018, with a follow-up survey for the results of recent blood pressure and kidney function tests (estimated glomerular filtration rate [eGFR] and proteinuria). If not recently available, blood pressure and eGFRs were requested from a local clinic. Microstructural features on kidney biopsy at the time of donation were assessed as predictors of hypertension and kidney function after adjusting for years of follow-up, baseline age, sex, and clinical predictors.ResultsThere were 807 donors surveyed a mean 10.5 years after donation. An eGFR less than 45 mL/min/1.73 m² in 6.4% (43/673) of donors was predicted by larger glomerular volume per standard deviation (odds ratio [OR], 1.48; 95% CI, 1.08 to 2.04) and nephron number below the age-specific 5th percentile (OR, 3.38; 95% CI, 1.31 to 8.72). An eGFR less than 60 mL/min/1.73 m² in 42.5% (286/673) of donors was not predicted by any microstructural feature. Residual eGFR (postdonation/predonation eGFR) was predicted by nephron number below the age-specific 5th percentile (difference, ?6.07%; 95% CI, ?10.24% to ?1.89%). Self-reported proteinuria in 5.1% (40/786) of donors was predicted by larger glomerular volume (OR, 1.42; 95% CI, 1.08 to 1.86). Incident hypertension in 18.8% (119/633) of donors was not predicted by any microstructural features.ConclusionLow nephron number for age and larger glomeruli are important microstructural predictors for long-term risk of chronic kidney disease after living kidney donation.