Peter A. McCullough M.D.

McCullough, P.A. (2021). “Anemia of cardiorenal syndrome.” Kidney Int Suppl (2011) 11(1): 35-45.

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Cardiorenal syndrome includes a spectrum of disorders of the kidneys and heart in which loss of function in one organ contributes to reduced function in the other organ. Cardiorenal syndrome is frequently complicated by comorbid anemia, which leads to reciprocal and progressive cardiac and renal deterioration. The triad of heart failure, chronic kidney disease (CKD), and anemia is termed cardiorenal anemia syndrome (CRAS). There are currently no evidence-based recommendations for managing patients with CRAS; however, the treatment of these patients is multifactorial. Not only must the anemia be controlled, but heart failure and kidney injury must be addressed, in addition to other comorbidities. Intravenous iron and erythropoiesis-stimulating agents are the mainstays of treatment for anemia of CKD, addressing both iron and erythropoiesis deficiencies. Since erythropoiesis-stimulating agent therapy can be associated with adverse outcomes at higher doses in patients with CKD and is not used in routine practice in patients with heart failure, treatment options for managing anemia in patients with CRAS are limited. Several new therapies, particularly the hypoxia-inducible factor-prolyl hydroxylase inhibitors, are currently under clinical development. The hypoxia-inducible factor-prolyl hydroxylase inhibitors have shown promising results for treating anemia of CKD in clinical trials and may confer benefits in patients with CRAS, potentially addressing some of the limitations of erythropoiesis-stimulating agents. Updated clinical practice guidelines for the screening and management of anemia in cardiorenal syndrome, in light of potential new therapies and clinical evidence, would improve the clinical outcomes of patients with this complex syndrome.

Lo, K.B., Toroghi, H.M., Salacup, G., Jiang, J., Bhargav, R., Quintero, E., Balestrini, K., Shahzad, A., Mathew, R.O., McCullough, P.A. and Rangaswami, J. (2021). “Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in acute heart failure: invasive hemodynamic parameters and clinical outcomes.” Rev Cardiovasc Med 22(1): 199-206.

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There are limited data regarding the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) in acute heart failure (AHF). The purpose is to determine the patterns of ACEi/ARB use at the time of admission and discharge in relation to invasive hemodynamic data, mortality, and heart failure (HF) readmissions. This is a retrospective single-center study in patients with AHF who underwent right heart catheterization between January 2010 and December 2016. Patients on dialysis, evidence of shock, or incomplete follow up were excluded. Multivariate logistic regression analysis was used to analyze the factors associated with continuation of ACEi/ARB use on discharge and its relation to mortality and HF readmissions. The final sample was 626 patients. Patients on ACEi/ARB on admission were most likely continued on discharge. The most common reasons for stopping ACEi/ARB were worsening renal function (WRF), hypotension, and hyperkalemia. Patients with ACEi/ARB use on admission had a significantly higher systemic vascular resistance (SVR) and mean arterial pressure (MAP), but lower cardiac index (CI). Patients with RA pressures above the median received less ACEi/ARB (P = 0.025) and had significantly higher inpatient mortality (P = 0.048). After multivariate logistic regression, ACEi/ARB use at admission was associated with less inpatient mortality; OR 0.32 95% CI (0.11 to 0.93), and this effect extended to the subgroup of patients with HFpEF. Patients discharged on ACEi/ARB had significantly less 6-month HF readmissions OR 0.69 95% CI (0.48 to 0.98). ACEi/ARB use on admission for AHF was associated with less inpatient mortality including in those with HFpEF.

Kalantar-Zadeh, K., McCullough, P.A., Agarwal, S.K., Beddhu, S., Boaz, M., Bruchfeld, A., Chauveau, P., Chen, J., de Sequera, P., Gedney, N., Golper, T.A., Gupta, M., Harris, T., Hartwell, L., Liakopoulos, V., Kopple, J.D., Kovesdy, C.P., Macdougall, I.C., Mann, J.F.E., Molony, D., Norris, K.C., Perlmutter, J., Rhee, C.M., Riella, L.V., Weisbord, S.D., Zoccali, C. and Goldsmith, D. (2021). “Nomenclature in nephrology: preserving ‘renal’ and ‘nephro’ in the glossary of kidney health and disease.” J Nephrol Mar 13. [Epub ahead of print].

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A recently published nomenclature by a “Kidney Disease Improving Global Outcomes” (KDIGO) Consensus Conference suggested that the word “kidney” should be used in medical writings instead of “renal” or “nephro” when referring to kidney disease and kidney health. Whereas the decade-old move to use “kidney” more frequently should be supported when communicating with the public-at-large, such as the World Kidney Day, or in English speaking countries in communications with patients, care-partners, and non-medical persons, our point of view is that “renal” or “nephro” should not be removed from scientific and technical writings. Instead, the terms can coexist and be used in their relevant contexts. Cardiologists use “heart” and “cardio” as appropriate such as “heart failure” and “cardiac care units” and have not replaced “cardiovascular” with “heartvessel”, for instance. Likewise, in nephrology, we consider that “chronic kidney disease” and “continuous renal replacement therapy” should coexist. We suggest that in scientific writings and technical communications, the words “renal” and “nephro” and their derivatives are more appropriate and should be freely used without any pressure by medical journals to compel patients, care-partners, healthcare providers, researchers and other stakeholders to change their selected words and terminologies. We call to embrace the terms “kidney”, “renal” and “nephro” as they are used in different contexts and ask that scientific and medical journals not impose terminology restrictions for kidney disease and kidney health. The choice should be at the discretion of the authors, in the different contexts including in scientific journals.

Rahimi, G., Tecson, K.M., Elsaid, O. and McCullough, P.A. (2021). “Role of Ischemic Heart Disease in Major Adverse Renal and Cardiac Events Among Individuals With Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial).” Am J Cardiol 142: 91-96.

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Despite improvements in the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), established therapy for heart failure patients with preserved ejection fraction (HFpEF) is lacking. Additionally, ischemic heart disease adversely impacts the clinical course of HFrEF patients; however, its role in HFpEF is not fully understood. We conducted a post hoc analysis of propensity score matched patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial to compare HFpEF patients with versus without myocardial ischemia in terms of major adverse renal and/or cardiac events (MARCE). Of 3,445 participants, the prevalence of ischemia was 59%. For this analysis, we included 1,747 ischemic patients and 1,207 propensity matched nonischemic patients. Ischemia was associated with a 20% increased risk (HR = 1.20, 95% confidence interval [CI] = 1.042 to 1.382, p value = 0.0112) of major adverse renal and/or cardiac events (MARCE) in adjusted analyses. Other important predictors of MARCE were diabetes (hazard ratio [HR] = 1.60, 95% CI = 1.38 to 1.87, p <0.0001), dyslipidemia (HR = 1.30, 95% CI = 1.10 to 1.52, p = 0.001) and smoking (HR = 1.33, 95% CI = 1.04 to 1.69, p = 0.0197). Revascularization was not significantly associated with MARCE in the subgroup of ischemic HFpEF patients. Future work is warranted to develop tailored interventions for patients with both HFpEF and ischemic heart disease to mitigate the risk of MARCE .

Aldujeli, A., Hamadeh, A., Tecson, K.M., Krivickas, Z., Maciulevicius, L., Stiklioraitis, S., Sukys, M., Briedis, K., Aldujeili, M., Briede, K., Braukyliene, R., Pranculis, A., Unikas, R., Zaliaduonyte, D. and McCullough, P.A. (2021). “Six-Month Outcomes for COVID-19 Negative Patients with Acute Myocardial Infarction Before Versus During the COVID-19 Pandemic.” Am J Cardiol Feb 23;S0002-9149(21)00161-2. [Epub ahead of print].

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The Coronavirus disease 2019 (COVID-19) pandemic has changed the way patients seek medical attention and how medical services are provided. We sought to compare characteristics, clinical course, and outcomes of patients presenting with acute myocardial infarction (AMI) during the pandemic compared with before it. This is a multicenter, retrospective cohort study of consecutive COVID-19 negative patients with AMI in Lithuania from March 11, 2020 to April 20, 2020 compared with patients admitted with the same diagnosis during the same period in 2019. All patients underwent angiography. Six-month follow-up was obtained for all patients. A total of 269 patients were included in this study, 107 (40.8%) of whom presented during the pandemic. Median pain-to-door times were significantly longer (858 [quartile 1=360, quartile 3 = 2,600] vs 385.5 [200, 745] minutes, p <0.0001) and post-revascularization ejection fractions were significantly lower (35 [30, 45] vs 45 [40, 50], p <0.0001) for patients presenting during vs. prior to the pandemic. While the in-hospital mortality rate did not differ, we observed a higher rate of six-month major adverse cardiovascular events for patients who presented during versus prior to the pandemic (30.8% vs 13.6%, p = 0.0006). In conclusion, 34% fewer patients with AMI presented to the hospital during the COVID-19 pandemic, and those who did waited longer to present and experienced more 6-month major adverse cardiovascular events compared with patients admitted before the pandemic.