Peter A. McCullough M.D.

Goyal, A., K. Chatterjee, R. O. Mathew, M. S. Sidhu, S. Bangalore, P. A. McCullough and J. Rangaswami (2018). “In-Hospital Mortality and Major Adverse Cardiovascular Events after Kidney Transplantation in the United States.” Cardiorenal Med 9(1): 51-60.

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BACKGROUND: Kidney transplantation (KT) is the treatment of choice for end-stage kidney disease. Cardiovascular disease is a major determinant of morbidity and mortality in patients with KT. Temporal trends in perioperative cardiovascular outcomes after KT are understudied, especially in light of an aging KT waitlist population. METHODS: We performed a retrospective observational cohort study using the National Inpatient Sample for the years 2004-2013. All adult patients undergoing KT were identified using the appropriate International Classification of Diseases, 9th Revision, Clinical Modification codes. Demographic and hospital characteristics, discharge disposition, payer status, and major adverse cardiovascular events (MACEs) were summarized using summary statistics. Multivariate logistic regression was used to identify predictors of MACEs in the perioperative period of KT. RESULTS: A total of 147,431 KTs were performed between 2004 and 2013. The mean age at KT went up from 48.1 to 51.8 years from 2004 to 2013. Medicare was the primary payer for 59.6% of the KTs. Overall average perioperative mortality was 0.5%, median length of stay was 5 days, and 6.5% of patients experienced an MACE, 78% of which were heart failures (HFs). Important predictors of perioperative MACEs were age >/=65 years (OR = 2.14), Medicare as primary payer (OR = 1.51), diabetes (OR = 1.46), recreational drug use (OR = 1.72), pulmonary circulation disorders (OR = 3.28), and malnutrition (OR = 1.91). CONCLUSION: Despite increases in age at the time of KT, the absolute risk of perioperative MACEs has remained stable from 2004 to 2013. HF is a major component of postoperative MACEs in KT. Malnutrition and pulmonary hypertension are major nontraditional predictors of perioperative MACE outcomes.

Rangaswami, J. and P. A. McCullough (2018). “Heart Failure in End-Stage Kidney Disease: Pathophysiology, Diagnosis, and Therapeutic Strategies.” Semin Nephrol Nov. 11: 38(6): 600-617.

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Heart failure (HF) is a major comorbidity in patients with end-stage kidney disease (ESKD). The pathogenesis of HF in patients on renal replacement therapy represents the confluence of several traditional and nontraditional vascular risk factors, unique to the milieu of chronic kidney disease and the dialysis modality. The diagnosis of HF with ESKD is complicated by the background of frequent inevitable fluid shifts superimposed on underlying myocardial pump abnormalities and dialysis-induced myocardial stunning. A careful temporal assessment of symptoms and physical findings, cardiac imaging, hemodynamic data, and biomarkers help establish an accurate diagnosis of HF in ESKD. Accurate volume assessment and its tight management remains the cornerstone of treatment in HF in patients on dialysis. A multidisciplinary approach between the cardiologist and nephrologist in optimizing pharmacologic strategies for HF in this population, and dialysis-based options such as frequent dialysis, may help reduce the burden of HF in this vulnerable population. Finally, including patients with ESKD in clinical trials for HF therapies, and designing pragmatic trials that bring targeted strategies for HF into the daily clinical practice of dialysis, will shed light on the optimal management of the dual burden of cardiomyopathy and advanced kidney disease.

McCullough, P. A., T. M. Todoran, E. S. Brilakis, M. P. Ryan and C. Gunnarsson (2018). “Rate of major adverse renal or cardiac events with iohexol compared to other low osmolar contrast media during interventional cardiovascular procedures.” Catheter Cardiovasc Interv Oct 2. [Epub ahead of print].

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OBJECTIVE: This study assessed the rate of major adverse renal or cardiac events (MARCE) when iohexol is used during interventional cardiovascular procedures compared to other low osmolar contrast media (LOCMs). BACKGROUND: Interventional cardiovascular procedures are often essential for diagnosis and treatment, the risk of MARCE should be considered. METHODS: Data were derived from the Premier Hospital Database January 1, 2010 through September 30, 2015. Patient encounters with an inpatient primary interventional cardiovascular procedure with a single LOCM (iohexol, ioversol, ioxilan, ioxaglate, or iopamidol) were included. The primary outcome was a composite endpoint of MARCE, which included: renal failure with dialysis, acute kidney injury (AKI) with or without dialysis, contrast induced AKI, acute myocardial infarction, angina, stent occlusion/thrombosis, stroke, transient ischemic attack, or death. Multivariable regression analysis was performed using the hospital fixed-effects specification to assess the relationship between MARCE and iohexol compared to other LOCMs, while controlling for patient demographics, comorbid conditions and reason for hospitalization. As a sensitivity analysis, direct comparisons of iohexol were made to other LOCMs. RESULTS: A total of 458,091 inpatient encounters met inclusion criteria of which 26% used iohexol and 74% used other LOCMs. Results of multivariable modeling revealed no differences in MARCE rates between iohexol and other LOCMs. When direct comparisons of iohexol vs. ioversol and iopamidol were modeled, no differences in MARCE nor the renal component of MARCE were found. CONCLUSIONS: In this retrospective multicenter study, there were no differences in MARCE events with iohexol compared to other LOCMs during inpatient interventional cardiovascular procedures.

Ambrosy, A. P., H. Mulder, A. Coles, W. E. Krauss, C. S. P. Lam, P. A. McCullough, I. Pina, J. Tromp, D. J. Whellan, C. M. O’Connor and R. J. Mentz (2018). “Renal Function and Exercise Training in AmbulatoryHeart Failure Patients With a Reduced Ejection Fraction.” Am J Cardiol 122(6): 999-1007.

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Patients with chronic kidney disease (CKD) and/or end-stage renal disease are less active and experience significant functional limitations. The impact of a structured aerobic exercise intervention on outcomes in ambulatory heart failure (HF) patients with comorbid CKD is unknown. HF-ACTION enrolled 2,331 outpatients with HF and a reduced ejection fraction (i.e., =35% or less) from April 2003 to February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to the presence of CKD, defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2). A total of 2,091 patients (90%) had serum creatinine measured and were included in the final analytical cohort. The prevalence of CKD was 41% at baseline. In patients with and without CKD, respectively, the incidence of all-cause death and hospitalization was 75% and 63% over a median follow-up of 30 months. After adjusting for potential confounders, CKD was associated with increased risk of the composite of all-cause mortality and hospitalization (hazard ratio 1.18, 95% confidence interval 1.04 to 1.33; p value =0.01 or less). With the exception of a marginally greater improvement in exercise duration in response to aerobic exercise training (estimate +/- standard error: 0.9 +/- 0.2 minutes vs 1.4 +/- 0.1 minutes; p value=0.01), there was no interaction between treatment arm and CKD on functional status, health-related quality of life, or clinical outcomes (p value =0.05 or greater for all interactions). In conclusion, the prevalence of CKD was high in ambulatory reduced ejection fraction patients and was associated with a poorer overall prognosis but not a differential response to aerobic exercise training.

Kluger, A. Y. and P. A. McCullough (2018). “Semaglutide and GLP-1 analogues as weight-loss agents.” Lancet 392(10148): 615-616.

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The increasing global frequency of obesity and its resultant health effects are well documented. Drug development for obesity has been hampered by concerns over cardiovascular safety and a paucity of significant efficacy. One possible pharmaceutical solution to promote weight loss lies in the glucagon-like peptide-1 (GLP-1) analogue class of drugs, one of which is semaglutide and is approved with a dosing schedule of once per a week for the treatment of type 2 diabetes. Reported in The Lancet, Patrick O’Neil and colleagues’ Article5 presents a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial of daily subcutaneous semaglutide (doses ranging from 0·05 mg to 0·4 mg) versus liraglutide (3·0 mg per day) and matched placebo for the treatment of non-diabetic obesity over a 52-week period. The primary endpoint was percentage weight loss at week 52. O’Neil and colleagues found that all semaglutide doses were relatively well tolerated and were associated with reductions in bodyweight from baseline compared with placebo. Placebo was associated with a 2·48 kg weight loss from a baseline of 114·2 kg (estimated mean weight loss of −2·3%), whereas the semaglutide 0·05 mg per day dose was associated with a 6·66 kg weight loss from a baseline of 111·3 kg (estimated mean weight loss of −6·0%), the 0·1 mg per day dose with a 9·34 kg weight loss from a baseline of 111·3 kg (−8·6%), the 0·2 mg per day dose with a 12·30 kg weight loss from a baseline of 114·5 kg (−11·6%), the 0·3 mg per day dose with a 12·45 kg weight loss from a baseline of 111·5 kg (−11·2%), and the 0·4 mg/day dose with a 15·15 kg weight loss from a baseline of 113·2 kg (−13·8%). These treatment differences for all the semaglutide doses versus placebo were significant. (Excerpt from this commentary on O’Neal et al., Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial, Lancet, Volume 392, Issue 10148, 25–31 August 2018, Pages 637-649.)