Peter A. McCullough M.D.

McCullough, P. A., H. S. Mehta, D. P. Cork, C. M. Barker, C. Gunnarsson, S. Mollenkopf, J. Van Houten and P. Verta (2019). “The healthcare burden of disease progression in Medicare patients with functional mitral regurgitation.” J Med Econ May 20. [Epub ahead of print].

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OBJECTIVE: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. METHODS: We examined Medicare Fee for Service beneficiaries with nsFMR, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. RESULTS: Patients with IHD had higher risk (Hazard Ratio: 1.22 [1.14, 1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD, 1.32; IHD, 1.40) than the non-progression cohort (non-IHD, 0.36; IHD, 0.34) and significantly more annual inpatient hospital days (non-IHD, 13.07; IHD, 13.52) than the non-progression cohort (non-IHD, 2.29; with IHD, 2.08). The progression cohort had over 3.5 times higher costs versus the non-progression cohort, independent of IHD (non-IHD, $12,798 versus $46,784; IHD, $12,582 versus $49,348). CONCLUSION: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

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 8(1): 145-150.

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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.

House, A. A., C. Wanner, M. J. Sarnak, I. L. Pina, C. W. McIntyre, P. Komenda, B. L. Kasiske, A. Deswal, C. R. deFilippi, J. G. F. Cleland, S. D. Anker, C. A. Herzog, M. Cheung, D. C. Wheeler, W. C. Winkelmayer and P. A. McCullough (2019). “Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.” Kidney Int 95(6): 1304-1317.

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The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here.

Ahmad, F. S., M. A. Kallen, K. E. Schifferdecker, K. L. Carluzzo, S. E. Yount, J. M. Gelow, P. A. McCullough, S. E. Kimmel, E. S. Fisher and D. Cella (2019). “Development and Initial Validation of the PROMIS(R)-Plus-HF Profile Measure.” Circ Heart Fail 12(6): e005751.

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Background Bringing together generic and heart failure (HF)-specific items in a publicly available, patient-reported outcome measure may facilitate routine health status assessment for improving clinical care and shared decision-making, assessing quality of care, evaluating new interventions, and comparing groups with different conditions. Methods and Results We performed a mixed-methods study to develop and validate the PROMIS(R)-Plus-HF (Patient-Reported Outcomes Measurement Information System(R)-Plus-Heart Failure) profile measure-a HF-specific instrument based on the generic PROMIS. We conducted 8 focus groups with 61 patients with HF and phone interviews with 10 HF clinicians. The measure was developed via an iterative process of reviewing existing PROMIS items and developing and testing new HF items. In a 600-patient sample, we estimated reliability (internal consistency; test-retest, with n=100 participants). We conducted validity analyses using Pearson r and Spearman rho correlations with Kansas City Cardiomyopathy Questionnaire subscores. In a longitudinal sample, we performed responsiveness testing (paired t tests) with 75 patients with HF receiving interventions with expected health status improvement. The PROMIS-Plus-HF measure comprises 86 items (64 existing; 22 new) across 18 domains. Internal consistency reliability (Cronbach alpha) coefficients ranged from 0.52 to 0.96, with alpha>/=0.70 in 12 of 17 domains. Test-retest intraclass correlation coefficients were >/=0.90. Correlations with Kansas City Cardiomyopathy Questionnaire subscores supported expected convergent (r/rho>0.60) and divergent validity (r/rho<0.30). In the longitudinal sample, 10 of 18 domains had improved (P<0.05) scores from baseline to follow-up. Conclusions The PROMIS-Plus-HF profile measure-a complete assessment of physical, mental, and social health-exhibited good psychometric characteristics and may facilitate patient-centered care and research. Subsets of domains and items can be used depending on the clinical or research purpose.

Zanoli, L., P. Lentini, M. Briet, P. Castellino, A. A. House, G. M. London, L. Malatino, P. A. McCullough, D. P. Mikhailidis and P. Boutouyrie (2019). “Arterial Stiffness in the Heart Disease of CKD.” J Am Soc Nephrol Apr 30. [Epub ahead of print].

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CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.