Frantz, Robert P.

Patient‐reported outcomes are important measures to include in pulmonary arterial hypertension clinical trials but are not widely utilized in clinical practice. Pulmonary Arterial Hypertension—Symptoms and Impact Questionnaire (PAH‐SYMPACT) is the only pulmonary arterial hypertension‐specific patient‐reported outcomes instrument developed and validated in accordance with the US Food and Drug Administration guidance on patient‐reported outcomes development. The PAH‐SYMPACT tool measures pulmonary arterial hypertension‐related symptoms and impact of pulmonary arterial hypertension on daily life. Symptoms are reported each day for seven consecutive days, and the impact of pulmonary arterial hypertension over one week is recalled and reported on day 7; however, daily symptom reporting may overburden patients and healthcare resources, limiting the practicality of PAH‐SYMPACT outside of clinical trials. To determine the practicability of an abridged version of PAH‐SYMPACT for which all reporting is completed on one day, symptom data from the SYMPHONY trial (NCT01841762; PAH‐SYMPACT validation study) were retrospectively analyzed to assess whether symptoms reported on each day correlated with the weekly average and whether one‐day symptom scores were sensitive to disease severity. Correlation coefficients comparing the weekly average and individual day symptom scores were mostly high or very high regardless of the day they were measured. Findings were similar when using either Spearman's rank correlation or weighted kappa method. One‐day symptom scores differentiated well between World Health Organization functional classes II and III/IV pulmonary arterial hypertension and were sensitive to change in disease severity as measured by the Patient Global Assessment of Disease Severity. These data suggest that the one‐day PAH‐SYMPACT is feasible and appropriate for routine implementation in clinical practice.

Background: Invasive hemodynamic evaluation through right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with pulmonary hypertension. Methods: Subjects enrolled in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) program undergo an extensive invasive hemodynamic evaluation that includes repeated measurements at rest and during several provocative physiological challenges. It is a National Institutes of Health/National Heart, Lung, and Blood Institute initiative to reclassify pulmonary hypertension groups based on clustered phenotypic and phenomic characteristics. At a subset of centers, participants also undergo an invasive cardiopulmonary exercise test to assess changes in hemodynamics and gas exchange during exercise. Conclusions: When coupled with other physiological testing and blood -omic analyses involved in the PVDOMICS study, the comprehensive right heart catheterization protocol described here holds promise to clarify the diagnosis and clustering of pulmonary hypertension patients into cohorts beyond the traditional 5 World Symposium on Pulmonary Hypertension groups. This article will describe the methods applied for invasive hemodynamic characterization in the PVDOMICS program. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02980887.

Background The presence of a durable left ventricular assist device ( LVAD ) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation ( HT ). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD . Methods and Results We identified 94 patients who underwent HT after bridging with continuous‐flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT . Patients with and without vasoplegia had similar preoperative LVAD , echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P =0.010), longer LVAD support (odds ratio: 1.06 per month; P =0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P =0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P =0.044) were independent predictors of vasoplegia. After mean follow‐up of 4.0 years after HT , vasoplegia was associated with increased risk of all‐cause mortality (hazard ratio: 5.20; 95% CI, 1.71–19.28; P =0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.

Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real‐world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare costs in pulmonary arterial hypertension patients treated with endothelin receptor antagonists or phosphodiesterase type‐5 inhibitors. From the IQVIA Adjudicated Health Plan Database, patients with pulmonary arterial hypertension were identified based on diagnostic codes and prescriptions for endothelin receptor antagonists (ambrisentan, bosentan, macitentan) or phosphodiesterase type‐5 inhibitors (sildenafil, tadalafil) approved for pulmonary arterial hypertension. Patients were assigned to the class of their most recently initiated (index) pulmonary arterial hypertension therapy between 1 January 2009 and 30 June 2015. Medication adherence was measured by proportion of days covered; patients with proportion of days covered ≥80% were considered adherent. The proportion of adherent patients was higher for endothelin receptor antagonists (571/755; 75.6%) than for phosphodiesterase type‐5 inhibitors (970/1578; 61.5%; P < 0.0001). In both groups, hospitalizations declined as proportion of days covered increased. Among adherent patients, those on endothelin receptor antagonists had a significantly lower hospitalization rate than those on phosphodiesterase type‐5 inhibitors (23.1% versus 28.5%, P = 0. 0218), fewer hospitalizations (mean (standard deviation) 0.4 (0.8) versus 0.5 (0.9); P = 0.02), and mean hospitalization costs during the six‐month post‐index ($9510 versus $15,726, P = 0.0318). Increasing adherence reduced hospitalization risk more for endothelin receptor antagonists than for phosphodiesterase type‐5 inhibitors (hazard ratio 0.176 versus 0.549, P = 0.001). Rates and numbers of rehospitalizations within 30 days post‐discharge were similar between groups. Mean total costs were higher with endothelin receptor antagonists than phosphodiesterase type‐5 inhibitors in all patients ($91,328 versus $72,401, P = 0.0003) and in adherent patients ($88,867 versus $56,300, P < 0.0001), driven by higher drug costs.

BackgroundThe DelIVery for Pulmonary Arterial Hypertension clinical trial was a multi‐center, prospective, single arm, Investigational Device Exemption study utilizing a fully implantable, programmable intravascular delivery system consisting of a pump and a catheter for intravenous treprostinil. The study met its primary endpoint and demonstrated that the intravascular delivery system significantly reduced catheter related complications at 22,000 subject‐days of follow‐up compared with a predefined objective performance criterion. Here we summarize the results obtained during a 6.4‐year follow‐up period.MethodsThroughout study follow‐up, participants had clinic visits and medication refills at least every 12 weeks (dependent on the subjects’ dose). All adverse events and intravascular delivery system complications were evaluated and recorded.ResultsSixty pulmonary arterial hypertension subjects were followed post device implantation for approximately 282 patient‐years (range 87 days to 6.4 years). Of the 60 subjects, 14 died (1 related to intravascular delivery system pump failure), 2 withdrew after lung transplants, and 2 withdrew due to pump pocket infection. No catheter‐related bloodstream infections, catheter thrombosis or occlusions, or catheter kinks occurred through 282 patient‐years. Two participants had adverse events of abdominal pain, rash, due to subcutaneous treprostinil “leaks” after one catheter puncture and one catheter laceration during pump refill and replacement, respectively. Eight pump failure events occurred: seven pump motor stalls and one early replacement (faulty battery).ConclusionDelivery of treprostinil with an intravascular delivery system is a safe alternative to an external delivery system, while providing enhanced life experiences. To preserve the risk–benefit ratio, treatment at specialized pulmonary arterial hypertension centers is recommended until training is disseminated at other sites.