Peter A. McCullough M.D.

Palazzuoli, A., Ruocco, G., Tecson, K.M. and McCullough, P.A. (2021). “Screening, detection, and management of heart failure in the SARS-CoV2 (COVID-19) pandemic.” Heart Fail Rev Jan 6;1-7. [ Epub ahead of print]. 1-7.

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Observational studies suggest that a heart failure (HF) diagnosis carries a poor prognosis in subjects with severe SARS-CoV2 (COVID-19) infection, but it is unknown whether this association reflects direct myocardial damage due to COVID-19 or the consequence of preexisting cardiac defects and related cardiovascular disease (CVD) risk burden. Although the close relation between CVD and COVID-19 outcomes is well established, contrasting data exists about the occurrence of HF complications during COVID-19 infection. Therefore, a specific algorithm focused on diagnostic differentiation in acute patients distinguishing between acute HF and acute respiratory distress syndrome related to COVID-19 is needed. Further, several concerns exist for the management of patients with an uncertain diagnosis and acute dyspnea, the exact relationship existing between COVID-19 and HF. Therefore, the treatment for subjects with both COVID-19 and HF and which criteria may be defined for domiciliary or hospital management, remain poorly defined. Herein, we describe practices to be adopted in order to address these concerns and avoid further virus spread among patients, l and their familiars involved in such patients’ care.

Roger, S.D., Lavin, P.T., Lerma, E.V., McCullough, P.A., Butler, J., Spinowitz, B.S., von Haehling, S., Kosiborod, M., Zhao, J., Fishbane, S. and Packham, D.K. (2021). “Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study.” Nephrol Dial Transplant 36(1): 137-150.

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BACKGROUND: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1-3 CKD. METHODS: Adults with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24-72 h until normokalaemia (i-STAT K+ 3.5-5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for ≤12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or ≥30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). RESULTS: Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, ≥30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and ≥30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 ≥30 mL/min/1.73 m2 subgroup. CONCLUSIONS: SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.

Procter, B.C., Ross, C., Pickard, V., Smith, E., Hanson, C. and McCullough, P.A. (2020). “Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection.” Rev Cardiovasc Med 21(4): 611-614.

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There is an emergency need for early ambulatory treatment of Coronavirus Disease 2019 (COVID-19) in acutely ill patients in an attempt to reduce disease progression and the risks of hospitalization and death. Such management should be applied in high-risk patients age > 50 years or with one or more medical problems including cardiovascular disease. We evaluated a total of 922 outpatients from March to September 2020. All patients underwent contemporary real-time polymerase chain reaction (PCR) assay tests from anterior nasal swab samples. Patients age 50.5 ± 13.7 years (range 12 to 89), 61.6% women, at moderate or high risk for COVID-19 received empiric management via telemedicine. At least two agents with antiviral activity against SARS-CoV-2 (zinc, hydroxychloroquine, ivermectin) and one antibiotic (azithromycin, doxycycline, ceftriaxone) were used along with inhaled budesonide and/or intramuscular dexamethasone consistent with the emergent science on early COVID-19 treatment. For patients with high severity of symptoms, urgent in-clinic administration of albuterol nebulizer, inhaled budesonide, and intravenous volume expansion with supplemental parenteral thiamine 500 mg, magnesium sulfate 4 grams, folic acid 1 gram, vitamin B12 1 mg. A total of 320/922 (34.7%) were treated resulting in 6/320 (1.9%) and 1/320 (0.3%) patients that were hospitalized and died, respectively. We conclude that early ambulatory (not hospitalized, treated at home), multidrug therapy is safe, feasible, and associated with low rates of hospitalization and death. Early treatment should be considered for high-risk patients as an emergency measure while we await randomized trials and guidelines for ambulatory management.

McCullough, P.A. and Oskoui, R. (2020). “Early multidrug regimens in new potentially fatal medical problems.” Rev Cardiovasc Med 21(4): 507-508.

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The SARS-CoV-2 (COVID-19) pandemic has been the greatest challenge to medical practice in decades. We have witnessed fear, panic, confusion, division, and a wide array of regulatory and public health responses to the crisis (National Institutes of Health, 2020). We believe it is important for all physicians to keep in mind this pandemic is an emergency crisis and is not a usual context for drug development, guidelines, and recommendations for patient practice. In cardiovascular medicine we have had many disruptive forces as the field has evolved and we have witnessed reasonable responses with respect to pharmacotherapy when there was an absence of randomized trials to first guide the approach. [No abstract; excerpt from article].

McCullough, P.A., Alexander, P.E., Armstrong, R., Arvinte, C., Bain, A.F., Bartlett, R.P., Berkowitz, R.L., Berry, A.C., Borody, T.J., Brewer, J.H., Brufsky, A.M., Clarke, T., Derwand, R., Eck, A., Eck, J., Eisner, R.A., Fareed, G.C., Farella, A., Fonseca, S.N.S., Geyer, C.E., Jr., Gonnering, R.S., Graves, K.E., Gross, K.B.V., Hazan, S., Held, K.S., Hight, H.T., Immanuel, S., Jacobs, M.M., Ladapo, J.A., Lee, L.H., Littell, J., Lozano, I., Mangat, H.S., Marble, B., McKinnon, J.E., Merritt, L.D., Orient, J.M., Oskoui, R., Pompan, D.C., Procter, B.C., Prodromos, C., Rajter, J.C., Rajter, J.J., Ram, C.V.S., Rios, S.S., Risch, H.A., Robb, M.J.A., Rutherford, M., Scholz, M., Singleton, M.M., Tumlin, J.A., Tyson, B.M., Urso, R.G., Victory, K., Vliet, E.L., Wax, C.M., Wolkoff, A.G., Wooll, V. and Zelenko, V. (2020). “Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19).” Rev Cardiovasc Med 21(4): 517-530.

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The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.