Peter A. McCullough M.D.

McCullough, P. A. and W. C. Roberts (2016). “Influence of Chronic Renal Failure on Cardiac Structure.” J Am Coll Cardiol 67(10): 1183-1185.

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It has been long recognized that patients with end-stage renal disease (ESRD) have an approximate 10-fold increase in mortality compared to age-matched individuals in the general population. Approximately one-half of this mortality is attributable to cardiovascular disease in the large domains of coronary artery disease, valvular abnormalities, arrhythmias, and cardiomyopathy. Our understanding of “structural heart disease” among those with ESRD has come from autopsy studies describing abnormalities including increased cardiac and left ventricular (LV) mass, mitral and aortic calcium, and marked calcific deposits in atherosclerotic plaques in the coronary arteries, aorta, and peripheral arteries. Morphological studies have also demonstrated high rates of pericardial disease (thickening and calcium) as well as myocardial hemosiderosis in ESRD. Physiological derangements over the course of many years, including pressure overload, volume overload, and derangements in myocyte function, also play a central role in the development of morphological abnormalities seen in ESRD. Cardiac ultrasonography has added to our understanding that these morphological changes have physiological consequences including impairment in LV systolic and diastolic function, chamber dilation and wall thickening, abnormal flow acceleration, and in some cases valvular stenosis. Coronary angiographic analysis has found in general that epicardial coronary arterial disease is more diffuse with more extensive calcium than those with normal renal function. The rate of coronary calcific deposition is more rapid than in the general population and is not reversible or able to be attenuated with any form of therapy we are presently aware of. (Excerpt from text, p. 1183; no abstract.)

Roberts, W. C., S. A. Hall, J. M. Ko, P. A. McCullough and B. Lima (2016). “Atrophy of the Heart After Insertion of a Left Ventricular Assist Device and Closure of the Aortic Valve.” Am J Cardiol 117(5): 878-879.

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Described are findings in a 70-year-old man who had heart transplantation 4 years after treatment with a left ventricular assist device, and surgical closure of his previously replaced aortic valve. The result was a totally nonfunctioning left ventricle resulting in severe atrophy.

Anker, S. D., M. Kosiborod, F. Zannad, I. L. Pina, P. A. McCullough, G. Filippatos, P. van der Meer, P. Ponikowski, H. S. Rasmussen, P. T. Lavin, B. Singh, A. Yang and P. Deedwania (2015). “Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial.” European Journal of Heart Failure 17(10): 1050-1056.

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Aims Hyperkalaemia in heart failure patients limits use of cardioprotective renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS-9) is a selective potassium ion trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract as early as the duodenum following oral administration. ZS-9 previously demonstrated the ability to reduce elevated potassium levels into the normal range, with a median time of normalization of 2.2 h and sustain normal potassium levels for 28 days in HARMONIZEa Phase 3, double-blind, randomized, placebo-controlled trial. In the present study we evaluated management of serum potassium with daily ZS-9 over 28 days in heart failure patients from HARMONIZE, including those receiving RAASi therapies. Methods and resultsHeart failure patients with evidence of hyperkalaemia (serum potassium 5.1 mmol/L, n = 94) were treated with open-label ZS-9 for 48 h. Patients (n = 87; 60 receiving RAASi) who achieved normokalaemia (potassium 3.5-5.0 mmol/L) were randomized to daily ZS-9 (5, 10, or 15 g) or placebo for 28 days. Mean potassium and proportion of patients maintaining normokalaemia during days 8-29 post-randomization were evaluated. Despite RAASi doses being kept constant, patients on 5 g, 10 g, and 15 g ZS-9 maintained a lower potassium level (4.7 mmol/L, 4.5 mmol/L, and 4.4 mmol/L, respectively) than the placebo group (5.2 mmol/L; P<0.01 vs. each ZS-9 group); greater proportions of ZS-9 patients (83%, 89%, and 92%, respectively) maintained normokalaemia than placebo (40%; P < 0.01 vs. each ZS-9 group). The safety profile was consistent with previously reported overall study population. ConclusionCompared with placebo, all three ZS-9 doses lowered potassium and effectively maintained normokalaemia for 28 days in heart failure patients without adjusting concomitant RAASi, while maintaining a safety profile consistent with the overall study population.