Aaron B Waxman

Publications (50) View all

• Article: The invasive cardiopulmonary exercise test.

  Bradley A Maron, Barbara A Cockrill, Aaron B Waxman, David M Systrom
  Circulation 03/2013; 127(10):1157-64. · 14.74 Impact Factor
• Article: Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies.

  Aaron B Waxman, Roham T Zamanian
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  ABSTRACT: Pulmonary arterial hypertension (PAH), which is a subset of pulmonary hypertension, is a group of diseases distinguished by vascular remodeling of the small pulmonary arteries with associated elevated pulmonary arterial pressure and right ventricular failure. This progressive and sometimes fatal disease occurs as an idiopathic disease or as a component of other disease states. Estimates of the incidence of PAH have varied from 5 to 52 cases/1 million population. Symptoms begin with shortness of breath with exertion and progress to dyspnea with normal activities and, finally, dyspnea at rest. Untreated patients with PAH have a 1-, 3-, and 5-year survival rate of 68%, 48%, and 34%, respectively. Treated, the survival rates improve to 91% to 97% after 1 year and 84% to 91% after 2 years. The current definition of PAH consists of 3 specific hemodynamic assessments confirmed by right heart catheterization findings. One of several important pathophysiologic mechanisms involved in PAH is pulmonary vascular remodeling, which is caused by endothelial and smooth muscle cell hyperproliferation. This is coincident with overexpression of the vasoconstrictor endothelin-1 and a reduction in the vasodilators nitric oxide and prostacyclin, which further impedes proper vasomotor tone, among other effects. Prostacyclin therapies augment the decreased prostacyclin levels in patients with PAH. The currently approved prostacyclins for the treatment of PAH include epoprostenol, iloprost, and treprostinil. Among the 3 medications, the delivery options include intravenous infusion, subcutaneous infusion, and inhaled formulations. Epoprostenol has been shown to have a positive effect on survival in patients with PAH. All prostacyclins have demonstrated improvements in functional class, exercise tolerance, and hemodynamics in patients with PAH. Intravenously and subcutaneously administered formulations of prostacyclins require continuous infusion pump administration, which presents clinical challenges for both the patient and the care provider. Dosing must be individualized and also presents a clinical challenge. Inhaled formulations seem efficacious in moderately symptomatic patients with PAH and might be appropriate when combined with an oral medication. Combination therapies are commonly used in clinical practice, with the decision to do so based on randomized controlled trial data and case study evidence. The present report provides an overview of PAH, the scientific rationale for treatment with prostacyclin therapy, and the benefits and risks of prostacyclin therapy, both as monotherapy and combined with other medications approved for the treatment of PAH.
  The American journal of cardiology 03/2013; 111(5 Suppl):1A-16A. · 3.58 Impact Factor
• Article: Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: Initial clinical experience.

  Jesse J Esch, Pinak B Shah, Barbara A Cockrill, Harrison W Farber, Michael J Landzberg, Mandeep R Mehra, Mary P Mullen, Alexander R Opotowsky, Aaron B Waxman, James E Lock, Audrey C Marshall
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  ABSTRACT: BACKGROUND: Patients with severe pulmonary arterial hypertension (PAH) face significant morbidity and death as a consequence of progressive right heart failure. Surgical shunt placement between the left PA and descending aorta (Potts shunt) appears promising for PAH palliation in children; however, surgical mortality is likely to be unacceptably high in adults with PAH. METHODS: We describe a technique for transcatheter Potts shunt (TPS) creation by fluoroscopically guided retrograde needle perforation of the descending aorta at the site of apposition to the left PA to create a tract for deployment of a covered stent between these vessels. This covered stent-anchored by the vessel walls and surrounding tissue-serves as the shunt. RESULTS: TPS creation was considered in 7 patients and performed in 4. The procedure was technically successful in 3 patients; 1 patient died during the procedure as a result of uncontrolled hemothorax. One acute survivor, critically ill at the time of TPS creation, later died of comorbidities. The 2 mid-term survivors (follow-up of 10 and 4 months) are well at home, with symptomatic improvement and no late complications. The 3 candidate patients in whom the procedure was not performed died within 1 month of consideration, underscoring the tenuous nature of this population. CONCLUSIONS: TPS creation is feasible and may offer symptomatic relief to select patients with refractory PAH. Further study of this innovative approach is warranted.
  The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2013; · 3.54 Impact Factor
• Article: Factors Associated with Adherence to Phosphodiesterase Type 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.

  Aaron Waxman, Shih-Yin Chen, Luke Boulanger, Jay A Watson, Gil Golden
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  ABSTRACT: Abstract OBJECTIVES: To assess factors associated with adherence to phosphodiesterase type 5 inhibitors (PDE5Is) in the management of pulmonary arterial hypertension (PAH). Methods: We analyzed pharmacy benefit claims of naïve Adcirca and Revatio users between 01/01/2008 and 12/31/2010. Patients were considered adherent if their proportion of days covered (PDC) was ≥80% over a 6-month period. Logistic regressions were estimated to assess the factors associated with adherence. Analyses were stratified by use of a specialty pharmacy or retail pharmacy. A sensitivity analysis was performed by excluding individuals with 90-day supply. Results: Of the total of 2,143 patients included, 46.8% were adherent. Adherence was higher among 930 specialty pharmacy users (65.6%) than 1,213 retail pharmacy users (32.3%, p<0.001). Adherence was higher among Adcirca users (60.7%; approved dose 40mg once-daily) than Revatio users (44.3%, p<0.001; approved dose 20mg thrice-daily). Among retail pharmacy users, adherence was higher in patients using Adcirca (OR= 2.59; 95% CI: 1.60-4.22) and patients with an index prescription given by pulmonologists (OR= 1.70; 95% CI: 1.15-2.50) while lower in patients with higher copayment ($51-$250: OR=0.61, 95% CI: 0.42-0.90; $251+: OR=0.57, 95% CI: 0.39-0.83). Among specialty pharmacy users, only high copayment ($251+: OR=0.56, 95% CI: 0.35-0.90) was found to be a significant factor for non-adherence. After excluding individuals with 90-day supply, adherence rate was 29.6% in retail pharmacy and 57.9% in specialty pharmacy (p<0.001), and regression results were similar. LIMITATIONS: Diagnosis of PAH was not confirmed without access to medical claims. Pharmacy refill records might not reflect actual consumption. Adherence evaluated for 6 months might not be generalizable to longer periods. Conclusion: Adherence to PDE5Is for PAH is suboptimal. Our findings suggest that adherence to PDE5Is in patients with PAH is associated with the use of specialty pharmacy, simpler dosing frequency, a lower financial barrier, and a prescription given by pulmonologists.
  Journal of Medical Economics 12/2012;
• Article: Plasma aldosterone levels are elevated in patients with pulmonary arterial hypertension in the absence of left ventricular heart failure: a pilot study.

  Bradley A Maron, Alexander R Opotowsky, Michael J Landzberg, Joseph Loscalzo, Aaron B Waxman, Jane A Leopold
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  ABSTRACT: AIMS: Elevated levels of the mineralocorticoid hormone aldosterone are recognized as a modifiable contributor to the pathophysiology of select cardiovascular diseases due to left heart failure. In pulmonary arterial hypertension (PAH), pulmonary vascular remodelling induces right ventricular dysfunction and heart failure in the absence of left ventricular (LV) dysfunction. Hyperaldosteronism has emerged as a promoter of pulmonary vascular disease in experimental animal models of PAH; however, the extent to which hyperaldosteronism is associated with PAH in patients is unknown. Thus, the central aim of the current study is to determine if hyperaldosteronism is an unrecognized component of the PAH clinical syndrome. METHODS AND RESULTS: Plasma aldosterone levels and invasive cardiopulmonary haemodynamic measurements were obtained for 25 patients referred for evaluation of unexplained dyspnoea or pulmonary hypertension. Compared with controls (n = 5), patients with PAH (n = 18) demonstrated significantly increased plasma aldosterone levels (1200.4 ± 423.9 vs. 5959.1 ± 2817.9 pg/mL, P < 0.02), mean pulmonary artery pressure (21.4 ± 5.0 vs. 45.5 ± 10.4 mmHg, P < 0.002), and pulmonary vascular resistance (PVR) (1.41 ± 0.6 vs. 7.3 ± 3.8 Wood units, P < 0.003) without differences in LV ejection fraction or pulmonary capillary wedge pressure between groups. Among patients not prescribed PAH-specific pharmacotherapy prior to cardiac catheterization, a subgroup of the cohort with severe pulmonary hypertension, aldosterone levels correlated positively with PVR (r = 0.72, P < 0.02) and transpulmonary gradient (r = 0.69, P < 0.02), but correlated inversely with cardiac output (r = -0.79, P < 0.005). CONCLUSIONS: These data demonstrate a novel cardiopulmonary haemodynamic profile associated with hyperaldosteronism in patients: diminished cardiac output due to pulmonary vascular disease in the absence of LV heart failure.
  European Journal of Heart Failure 10/2012; · 4.90 Impact Factor