Health-related quality of life and hospitalizations in chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension: an analysis from the Pulmonary Hypertension Association Registry (PHAR).

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, morbid, potentially curable subtype of pulmonary hypertension that negatively impacts health-related quality of life (HRQoL). Little is known about differences in HRQoL and hospitalization between CTEPH patients and idiopathic pulmonary arterial hypertension (IPAH) patients. Using multivariable linear regression and mixed effects models, we examined differences in HRQoL assessed by emPHasis-10 (E10) and SF-12 between CTEPH and IPAH patients in the Pulmonary Hypertension Association Registry, a prospective multicenter cohort of patients newly evaluated at a Pulmonary Hypertension Care Center. Multivariable negative binomial regression models were used to estimate incidence rate ratios (IRR) for hospitalization amongst the two groups. We included 461 IPAH patients and 169 CTEPH patients. Twenty-one percent of CTEPH patients underwent pulmonary thromboendarterectomy (PTE) before the end of follow-up. At baseline, patients with CTEPH had significantly worse HRQoL (higher E10 scores) (ß 2.83, SE 1.11, p = 0.01); however, differences did not persist over time. CTEPH patients had higher rates of hospitalization (excluding the hospitalization for PTE) compared to IPAH patients after adjusting for age, sex, body mass index, WHO functional class and six-minute walk distance (IRR 1.66, 95%CI 1.04-2.65, p = 0.03). CTEPH patients who underwent PTE had improved HRQoL as compared to those who were medically managed, but patients who underwent PTE were younger, had higher cardiac outputs and greater six-minute walk distances. In this large, prospective, multicenter cohort, CTEPH patients had significantly worse baseline HRQoL and higher rates of hospitalizations than those with IPAH. CTEPH patients who underwent PTE had significant improvements in HRQoL.

Patent foramen ovale: anatomical complexity and long-tunnel morphology related issues.

Patent foramen ovale (PFO) is present in about one-quarter of the population and should be considered an anatomical variant rather than a malformation. The association of PFO with cryptogenic stroke, migraine, peripheral embolism and other pathologies is still controversial. The evaluation of anatomical complexity, and particularly the long-tunnel morphology, is crucial for the assessment of the risk profile and for a targeted therapeutic management. Long-tunnel PFOs seem to be more prone to clot formation and complications related to percutaneous closure procedures. Echocardiography is the most useful method to investigate anatomical complexity, confirm and reinforce the indication to treatment, select the appropriate device and guide the PFO closure towards a successful procedure.

Residence at moderately high altitude and its relationship with WHO Group 1 pulmonary arterial hypertension symptom severity and clinical characteristics: the Pulmonary Hypertension Association Registry.

BACKGROUND: WHO Group 1 pulmonary arterial hypertension is a progressive and potentially fatal disease. Individuals living at higher altitude are exposed to lower barometric pressure and hypobaric hypoxemia. This may result in pulmonary vasoconstriction and contribute to disease progression. We sought to examine the relationship between living at moderately high altitude and pulmonary arterial hypertension characteristics. METHODS: Forty-two US centers participating in the Pulmonary Hypertension Association Registry enrolled patients who met the definition of WHO Group 1 pulmonary arterial hypertension. We utilized baseline data and patient questionnaire responses. Patients were divided into two groups: moderately high altitude residence (home ≥4000 ft) and low altitude residence (home <4000 ft) based on zip-code. Clinical characteristics, hemodynamic data, patient demographics, and patient reported quality of life metrics were compared. RESULTS: Controlling for potential confounders (age, sex at birth, body mass index, supplemental oxygen use, race, 100-day cigarette use, alcohol use, and pulmonary arterial hypertension medication use), subjects residing at moderately high altitude had a 6-min walk distance 32 m greater than those at low altitude, despite having a pulmonary vascular resistance that was 2.2 Wood units higher. Additionally, those residing at moderately high altitude had 3.7 times greater odds of using supplemental oxygen. CONCLUSION: Patients with pulmonary arterial hypertension who live at moderately high altitude have a higher pulmonary vascular resistance and are more likely to need supplemental oxygen. Despite these findings, moderately high altitude Pulmonary Hypertension Association Registry patients have better functional tolerance as measured by 6-min walk distance. It is possible that a "high-altitude phenotype" of pulmonary arterial hypertension may exist. These findings warrant further study.

Long-term results of the DelIVery for Pulmonary Arterial Hypertension trial.

BACKGROUND: The 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. METHODS: Throughout 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. RESULTS: Sixty 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). CONCLUSION: Delivery 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.

Role of Two-Dimensional Speckle-Tracking Echocardiography Strain in the Assessment of Right Ventricular Systolic Function and Comparison with Conventional Parameters.

Despite the already well-known role the right side of the heart plays in many diseases, right ventricular (RV) function has only recently been carefully considered. Echocardiography is the first-line diagnostic technique for the assessment of the right ventricle and right atrium, whereas cardiac magnetic resonance is considered the gold standard but is limited by cost and availability. According to the current guidelines, systolic RV function should be assessed by several conventional measurements, but the efficacy of these parameters as diagnostic and prognostic tools has been questioned by many authors. The development in recent years of myocardial deformation imaging techniques and their application to the right heart chambers has allowed deeper evaluation of the importance of RV function in the pathophysiology of a large number of cardiovascular conditions, but the real value of this new tool has not been completely clarified. The aim of this review is to provide a wide and careful analysis of findings available in the literature about the assessment of RV systolic function by strain measurements, comparing them with conventional parameters and evaluating their role in several clinical settings.

Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System: Results of the DelIVery for PAH Trial.

BACKGROUND: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion. METHODS: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature. RESULTS: Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 ± 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 ± 1.7 hours per week preimplantation, and this time decreased to 0.6 ± 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions. CONCLUSIONS: The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov.

Treatment of a nonhealing saphenous vein harvest graft with treprostinil sodium.

Impaired healing of saphenous vein harvest sites is a serious but under-recognized complication of coronary artery bypass grafting surgery, particularly in the presence of peripheral arterial disease. We report the use of a continuous subcutaneous infusion of treprostinil sodium, an analog of prostacyclin, to treat a limb-threatening, nonhealing saphenous vein harvest incision site after myocardial revascularization.

Dose proportionality of treprostinil sodium administered by continuous subcutaneous and intravenous infusion.

This study assessed the relationship between dose and plasma concentration following administration of treprostinil sodium infusion therapy in pulmonary arterial hypertension patients. This was a multicenter, open-label, multiple-cohort, steady-state, pharmacokinetic study in subjects with pulmonary arterial hypertension receiving treprostinil by continuous intravenous or subcutaneous infusion at doses between 10 and 125 ng/kg/min. A blood sample was obtained from each patient at steady state and analyzed via a liquid chromatography/tandem mass spectrometry method. Forty-nine subjects receiving treprostinil were enrolled. Treprostinil doses ranged from 12.1 to 125 ng/kg/min; treprostinil plasma concentrations ranged from 14.9 to 18 248 pg/mL. Linear regression analysis revealed a correlation between treprostinil dose and treprostinil plasma concentration with an R2 value of 0.561. Using a power model to assess dose proportionality, the estimated nonproportionality parameter was 0.641 (95% confidence interval: 0.083-1.199), reflecting consistency with dose proportionality. Subset linear regression analysis, which excluded 2 subjects with anomalous treprostinil plasma concentrations, increased the R2 value to 0.796. Using a power model to assess dose proportionality of this subset, the estimated nonproportionality parameter was 0.941 (95% confidence interval: 0.809-1.073). This study supports previous findings of linearity at lower doses up to 15 ng/kg/min and demonstrates linearity at treprostinil doses up to 125 ng/kg/min.