Peter A. McCullough M.D.

Himmelfarb, J., G. M. Chertow, P. A. McCullough, T. Mesana, A. D. Shaw, T. M. Sundt, C. Brown, D. Cortville, F. Dagenais, B. de Varennes, M. Fontes, J. Rossert and J. C. Tardif (2018). “Perioperative THR-184 and AKI after Cardiac Surgery.” J Am Soc Nephrol 29(2): 670-679.

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AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%-79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%-20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients

Rangaswami, J., R. O. Mathew and P. A. McCullough (2018). “Resuscitation for the specialty of nephrology: is cardionephrology the answer?” Kidney Int 93(1): 25-26.

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The specialty of nephrology faces major fellowship recruitment challenges, with ongoing declining interest among internal medicine residents. The field of Cardionephrology can help instill new interest and enthusiasm in choosing nephrology as a career amongst trainee physicians.

Keuffel, E., P. A. McCullough, T. M. Todoran, E. S. Brilakis, S. R. Palli, M. P. Ryan and C. Gunnarsson (2017). “The effect of major adverse renal cardiovascular event (MARCE) incidence, procedure volume, and unit cost on the hospital savings resulting from contrast media use in inpatient angioplasty.” J Med Econ: 1-9.

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OBJECTIVE: To determine the net economic impact of switching from low-osmolar contrast media (LOCM) to iso-osmolar contrast media (IOCM; iodixanol) in patients undergoing inpatient coronary or peripheral angioplasty in the United States (US). METHODS: A budget impact model (BIM) was developed from a hospital perspective. Nationally representative procedural and contrast media prevalence rates, along with MARCE (major adverse renal cardiovascular event) incidence and episode-related cost data were derived from Premier Hospital Data (October 2014 to September 2015). A previously estimated relative risk reduction in MARCE associated with IOCM usage (9.3%) was applied. The higher cost of IOCM was included when calculating the net impact estimates at the aggregate, hospital type, and per hospital levels. One-way (+/-25%) and probabilistic sensitivity analyses identified the model’s most important inputs. RESULTS: Based on weighted analysis, 513,882 US inpatient angioplasties and 35,610 MARCE cases were estimated annually. Switching to an “IOCM only” strategy from a “LOCM only” strategy increases contrast media cost, but prevents 2,900 MARCE events. The annual budget impact was an estimated saving of $30.71 million, aggregated across all US hospitals, $6,316 per hospital, or $60 per procedure. Net savings were maintained across all univariate sensitivity analyses. While MARCE/event-free cost differential was the most important factor driving total net savings for hospitals in the Northeast and West, procedural volume was important in the Midwest and rural locations. CONCLUSIONS: Switching to an “IOCM only” strategy from a “LOCM only” approach yields substantial net global savings to hospitals, both at the national level and within hospital sub-groups. Hospital administrators should maintain awareness of the factors that are likely to be more influential for their hospital and recognize that purchasing on the basis of lower contrast media cost may result in higher overall costs for patients undergoing inpatient angioplasty.

Bilchick, K. C., E. Mejia-Lopez, P. McCullough, K. Breathett, J. L. Kennedy, J. Tallaj, J. Bergin, S. Pamboukian, M. Abuannadi and S. Mazimba (2018). “Clinical Impact of Changes in Hemodynamic Indices of Contractile Function During Treatment of Acute Decompensated Heart Failure.” J Card Fail 24(1): 43-50.

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BACKGROUND: The objective of this work was to determine the impact of improving right ventricular versus left ventricular stroke work indexes (RVSWI vs LVSWI) during therapy for acute decompensated heart failure (ADHF). METHODS AND RESULTS: Cox proportional hazards regression and logistic regression were used to analyze key factors associated with outcomes in 175 patients (mean age 56.7 +/- 13.6 years, 29.1% female) with hemodynamic data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. In this cohort, 28.6% and 69.7%, respectively, experienced the outcomes of death, transplantation, or ventricular assist device implantatation (DVADTX) and DVADTX or HF rehospitalization (DVADTXHF) during 6 months of follow-up. Increasing RVSWI (DeltaRVSWI) from baseline to discharge was associated with a decrease in DVADTXHF (hazard ratio [HR] 0.923, 95% confidence interval [CI] 0.871-0.979) per 0.1 mm HgLm(-2) increase); however, increasing LVSWI (DeltaLVSWI) had only a nonsignificant association with decreased DVADTXHF (P = .11) In a multivariable model, patients with DeltaRVSWI 2-fold risk of DVADTXHF (HR 2.05, 95% CI 1.23-3.41; P = .006). CONCLUSION: Compared with left ventricular stroke work, increasing right ventricular stroke work during treatment of ADHF was associated with better outcomes. The results promise to inform optimal hemodynamic targets for ADHF.

Kovesdy, C. P., L. J. Appel, M. E. Grams, L. Gutekunst, P. A. McCullough, B. F. Palmer, B. Pitt, D. A. Sica and R. R. Townsend (2017). “Potassium homeostasis in health and disease: A scientific workshop cosponsored by the national kidney foundation and the american society of hypertension.” Am J Kidney Dis 70(6): 844-858.

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While much emphasis, and some controversy, centers on recommendations for sodium intake, there has been considerably less interest in recommendations for dietary potassium intake, in both the general population and patients with medical conditions, particularly acute and chronic kidney disease. Physiology literature and cohort studies have noted that the relative balance in sodium and potassium intakes is an important determinant of many of the sodium-related outcomes. A noteworthy characteristic of potassium in clinical medicine is the extreme concern shared by many practitioners when confronted by a patient with hyperkalemia. Fear of this often asymptomatic finding limits enthusiasm for recommending potassium intake and often limits the use of renin-angiotensin-aldosterone system blockers in patients with heart failure and chronic kidney diseases. New agents for managing hyperkalemia may alter the long-term management of heart failure and the hypertension, proteinuria, and further function loss in chronic kidney diseases. In this jointly sponsored effort between the American Society of Hypertension and the National Kidney Foundation, 3 panels of researchers and practitioners from various disciplines discussed and summarized current understanding of the role of potassium in health and disease, focusing on cardiovascular, nutritional, and kidney considerations associated with both hypo- and hyperkalemia.