Peter A. McCullough M.D.

McCullough, P. A., T. M. Todoran, E. S. Brilakis, M. P. Ryan and C. Gunnarsson (2019). “Rate of major adverse renal or cardiac events with iohexol compared to other low osmolar contrast media during interventional cardiovascular procedures.” Catheter Cardiovasc Interv 93(2): E90-e97.

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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.

McCullough, P. A. (2019). “Treatment of Orthostatic Hypotension Due to Autonomic Dysfunction (Neurogenic Orthostatic Hypotension) in a Patient with Cardiovascular Disease and Parkinson’s Disease.” Cardiol Ther Jan 9. [Epub ahead of print].

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INTRODUCTION: The prevalence of neurogenic orthostatic hypotension (nOH) increases with age and is associated with autonomic failure in neurodegenerative diseases (e.g., Parkinson’s disease). Symptoms can interfere with daily activities that require standing or walking and can increase risk of falls and related morbidity. Many patients with nOH have or develop cardiovascular comorbidities that can predate nOH symptoms or may arise as a result of autonomic dysregulation. In this report, we describe a complicated case of a patient with cardiovascular disease and Parkinson’s disease who presented with orthostatic symptoms. CASE REPORT: A 78-year-old man with a history of coronary heart disease, class III heart failure, cardiac cachexia, long-standing persistent atrial fibrillation (AF), Hodgkin’s lymphoma, and Parkinson’s disease presented with weakness, dizziness, presyncope, fatigue, and inability to stand. Orthostatic blood pressure (BP) measurements revealed a seated BP of 120/70 mmHg that decreased to 60/40 mmHg upon standing, accompanied by a slight increase in heart rate from 70 to 74 beats per minute. He was diagnosed with nOH and prescribed droxidopa (titrated to 600 mg three times daily). Treatment with droxidopa improved the patient’s ability to stand and his orthostatic BP. CONCLUSION: Droxidopa is approved by the US Food and Drug Administration to treat symptomatic nOH and is not contraindicated in patients with cardiovascular conditions. In this case, treatment with droxidopa improved the patient’s orthostatic tolerance and, importantly, did not change the patient’s rate-controlled AF or his symptoms of class IV heart failure. Because symptoms associated with nOH can be detrimental to patient safety and mobility, it is critical to screen for and treat patients with nOH, even when there are cardiovascular comorbidities. FUNDING: Editorial support and article processing charges were funded by Lundbeck. Plain language summary available for this article.

Roberts, W. C., S. P. McCullough and A. Vasudevan (2018). “Characteristics of Adults Having Aortic Valve Replacement for Pure Aortic Regurgitation Involving a Congenitally Bicuspid Aortic Valve Unaffected by Infective Endocarditis or Aortic Dissection.” Am J Cardiol 122(12): 2104-2111.

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Few reports have appeared describing patients with a purely regurgitant congenitally bicuspid aortic valve (BAV) unassociated with active or healed infective endocarditis or with acute or healed aortic dissection. This report describes a large group of such patients who had replacement of the purely regurgitant BAV with or without concomitant resection of the ascending aorta. Operatively excised purely regurgitant BAVs were examined and then their clinical records were examined to confirm that the valves indeed were purely regurgitant. The patients were aged 21 to 86 years (median 50). Of the 133 patients, 114 (86%) were men. The degree of aortic regurgitation (AR) ranged from 1+ to 4+/4+. Of the 133 patients, 52 (39%) had simultaneous resection of the ascending aorta, its frequency varying inversely with the degree of AR. Histologic study of sections of the operatively excised aortas disclosed that 28 (54%) had a normal or nearly normal aorta (0-1+ loss of medial elastic fibers) and that 24 (46%) had an abnormal loss (grade 2+ -4+/4+). In conclusion, the congenitally BAV, unassociated with either infective endocarditis or aortic dissection, is a common cause of pure AR in adults in the Western World undergoing AVR for AR. About half the patients had a dilated ascending aorta and those resected were histologically abnormal half the time. Why one BAV becomes stenotic, another purely regurgitant, another the site of infective endocarditis, and another functions normally for an entire lifetime remains unclear.

Haase, V. H., G. M. Chertow, G. A. Block, P. E. Pergola, E. M. deGoma, Z. Khawaja, A. Sharma, B. J. Maroni and P. A. McCullough (2019). “Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.” Nephrol Dial Transplant 34(1): 90-99.

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Background: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. Methods: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7-8) and end-of-trial (Weeks 15-16) and was analyzed using available data (no imputation). Results: Overall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations-analyzed using available data-remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat. Conclusions: Vadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis.

Goyal, A., K. Chatterjee, R. O. Mathew, M. S. Sidhu, S. Bangalore, P. A. McCullough and J. Rangaswami (2019). “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.