Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined. We developed an expert consensus statement on the transition to sGC and other treatment escalations and transitions in PAH using a modified Delphi process. The Delphi process used a panel of 20 physicians with expertise in PAH. Panelists answered three questionnaires on the management of treatment escalations and transitions in PAH. The initial questionnaire included open-ended questions. Later questionnaires consolidated the responses into statements that panelists rated on a Likert scale from -5 (strongly disagree) to +5 (strongly agree) to determine consensus. The Delphi process produced several consensus recommendations. Escalation should be considered for patients who are at high risk or not achieving treatment goals, by adding an agent from a new class, switching from oral to parenteral prostacyclins, or increasing the dose. Switching to a new class or within a class should be considered if tolerability or other considerations unrelated to efficacy are affecting adherence. Switching from a PDE5i to an SGC activator may benefit patients with intermediate risk who are not improving on their present therapy. These consensus-based recommendations may be helpful to clinicians and beneficial for patients when evidence-based guidance is unavailable.

Introduction : Patients with symptomatic heart failure (HF) have an increased incidence of atrial tachycardia/fibrillation (AT/AF). However, the relationship of mean pulmonary artery pressure (mPAP) as a marker for decompensation to AT/AF is unknown. Similarly, whether successful treatment of elevated mPAP reduces AT/AF is unknown. Methods : Patients with an implantable CIEDS in the Cardiomems™ Post-Approval Study (PAS Study) were analyzed for AT/AF burden (episodes of total duration >30 s per day) and incidence of symptomatic AT/AF. The change in mPAP was also evaluated prior to AT/AF episodes. Results : Of the 1189 patients in the PAS study, with baseline mPAP > 10 mmHg, 387 (32.6%) with CIEDS were evaluated. Patients with AT/AF (n = 93) were stratified by baseline mPAP: Group 1: <25mmHg, Group 2: 25-35mmHg, and Group 3: >35mmHg. The mean age was 68 years and 18.3% female. 79.6% had a history of AT/AF and patients with elevated baseline mPAP were much more likely to have history of arrhythmia (54.2%, 90.2% and 85.7% for Groups 1,2 and 3 respectively; p=0.002). However, there was no significant difference in freedom from symptomatic AT/AF over the study f/u of 24 months (figure). Device data revealed 3.5% of total follow-up days with AT/AF, with fewer days in Group 1 versus Groups 2 and 3 (2.0% versus 4.1% and 4.0%; p<0.0001). During the trial period, 49% of AT/AF episodes were associated with an increase in mPAP relative to baseline and was seen more commonly in patients with lower baseline mPAP (75%, 46% and 32% for Groups 1, 2 and 3 respectfully; p=0.008). Change in mPAP relative to baseline, in the 2 weeks prior to an episode, was highest in group1 (area under the curve - median(Q1, Q3) mmHg*days: Group 1: 38.0 (-1.5, 96.0); Group 2: -5.0(-56.5,40.0); Group 3: -29(-98,14)). Conclusions : Despite having a higher incidence of AT/AF at baseline, there was no difference in symptomatic arrhythmia during the PAS study f/u in patients with a CIEDS. Increases in mPAP were associated with 49% of AT/AF episodes, more common in patients with baseline lower mPAP. This supports the notion that chronic management of ambulatory mPAP is associated with reduction in AT/AF and abrupt increases may be associated with acute episodes.

Introduction In patients with previous heart failure hospitalization (HFH), ambulatory hemodynamic monitoring reduced HFH by 57% in the CardioMEMS Post-Approval Study (PAS), which translated into a 27% reduction in all-cause hospitalization but no change in other causes of hospitalization. We compared the trajectories of pulmonary artery pressures (PAP) before and after breakthrough HFH and the non-HF hospitalizations (non-HFH) that occurred during chronic PAP monitoring. Methods The PAS was a single arm study of 1200 patients with NYHA 3 HF (all EF) and prior HFH within 12 months who underwent implantation of a CardioMEMS PA sensor. An independent clinical events committee adjudicated all hospitalizations with primary cause HF and non-HF. We analyzed PAP changes during the 6 weeks prior and 1 week following hospitalization for all pts with PAP data through the 7 weeks, excluding overlapping analysis periods. Results Analysis was available for 751 hospitalizations, only 199 (26.5%) were HFH and 552 were (73.5%) were non-HFH. The rising trajectory of PAP changes in advance of HFH was distinct from non-HFH with an increase in pressure from baseline beginning approximately 4 weeks prior to HFH and a decrease in pressure observed immediately after HFH but no change observed before or after non-HFH. Conclusion Among patients with chronic HF across a range of EF, PAP rise approximately 4 weeks in advance of HFH and fall by 7 days after, but do not change around non-HFH. These data demonstrate the consistent physiology of rising PAP for breakthrough HFH that occur despite hemodynamic monitoring and the stability of PAP without elevation around the more common hospitalizations for other causes.

Background In the CardioMEMS Post Approval Study (PAS), pulmonary artery (PA) pressure monitoring in patients with NYHA Class III heart failure (HF) reduced HF hospitalizations (HFH) by 57%. Older patients with HF have both higher risks of HFH and the competing risk of all-cause hospitalization (ACH) compared to a younger cohort. We hypothesized that older patients have a decreased benefit from a CardioMEMS device due to the greater prevalence of non-cardiovascular comorbidities and death. Methods The PAS compared the rate of HF hospitalization in the 1 year prior to CardioMEMS implant to the rate in 1 year after implant with an overall 57% reduction in the rate of HFH. Patients were placed in three age categories: <70, 70-80 and >80 years. Baseline characteristics and PA pressures were compared at baseline and the paired change in pressures over 1 year. Hospitalization rates before and after implant were compared using the Andersen-Gill model. Results Older patients were more likely to have EF >40%, ischemic etiology, hypertension and CKD, but diabetes mellitus was less prevalent. The baseline PA diastolic (PAD) pressures were slightly lower in the older group. At 12 months, PA systolic and PAD was lower in all age groups (Table). All age groups had significant reductions in both HFH and all-cause hospitalizations (ACH) at 1 year (p<0.0001 for HFH and ACH, all age groups). Comparison across age groups demonstrated no significant difference in the reduction of HFH, ACH, or in time to first HFH. Conclusions Although older patients with HF have a higher mortality and more comorbidities, the benefit of CardioMEMS in reducing HFH and all-cause hospitalizations was similar across the age categories. The proportion of HFH was decreased after CardioMEMS in all age categories due to a reduction in HFH. In the CardioMEMS Post Approval Study (PAS), pulmonary artery (PA) pressure monitoring in patients with NYHA Class III heart failure (HF) reduced HF hospitalizations (HFH) by 57%. Older patients with HF have both higher risks of HFH and the competing risk of all-cause hospitalization (ACH) compared to a younger cohort. We hypothesized that older patients have a decreased benefit from a CardioMEMS device due to the greater prevalence of non-cardiovascular comorbidities and death. The PAS compared the rate of HF hospitalization in the 1 year prior to CardioMEMS implant to the rate in 1 year after implant with an overall 57% reduction in the rate of HFH. Patients were placed in three age categories: <70, 70-80 and >80 years. Baseline characteristics and PA pressures were compared at baseline and the paired change in pressures over 1 year. Hospitalization rates before and after implant were compared using the Andersen-Gill model. Older patients were more likely to have EF >40%, ischemic etiology, hypertension and CKD, but diabetes mellitus was less prevalent. The baseline PA diastolic (PAD) pressures were slightly lower in the older group. At 12 months, PA systolic and PAD was lower in all age groups (Table). All age groups had significant reductions in both HFH and all-cause hospitalizations (ACH) at 1 year (p<0.0001 for HFH and ACH, all age groups). Comparison across age groups demonstrated no significant difference in the reduction of HFH, ACH, or in time to first HFH. Although older patients with HF have a higher mortality and more comorbidities, the benefit of CardioMEMS in reducing HFH and all-cause hospitalizations was similar across the age categories. The proportion of HFH was decreased after CardioMEMS in all age categories due to a reduction in HFH.

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Background: Therapy guided by pulmonary artery (PA) pressure monitoring reduces PA pres-sures and heart failure hospitalizations (HFH) during the first year, but the durability of effi-cacy and safety through 2 years is not known.Methods and Results: The CardioMEMS Post-Approval Study investigated whether benefit and safety were generalized and sustained. Enrollment at 104 centers in the United States included 1200 patients with NYHA Class III symptoms on recommended HF therapies with prior HFH. Therapy was adjusted toward PA diastolic pressure 8-20 mmHg. Intervention fre-quency and PA pressure reduction were most intense during first 90 days, with sustained reduction of PA diastolic pressure from baseline 24.7 mmHg to 21.0 at 1 year and 20.8 at 2 years for all patients. Patients completing two year follow-up (n = 710) showed similar 2 -year reduction (23.9 to 20.8 mmHg), with reduction in PA mean pressure (33.7 to 29.4 mmHg) in patients with reduced left ventricular ejection. The HFH rate was 1.25 events/patient/year prior to sensor implant, 0.54 at 1 year, and 0.37 at 2 years, with 59% of patients free of HFH during follow-up.Conclusions: Reduction in PA pressures and hospitalizations were early and sustained during 2 years of PA pressure-guided management, with no signal of safety concerns regarding the implanted sensor. (J Cardiac Fail 2023;29:56-66)

The implanted system for treprostinil has been described in previous publications. There is no information published about how to handle this system around lung or heart-lung transplantation. We present the experience from the DelIVery for Pulmonary Arterial Hypertension study. Seven subjects from five pulmonary arterial hypertension centers were included in this retrospective chart review. All subjects were participating in the previously described DelIVery for pulmonary arterial hypertension study. Seven subjects with implanted pumps have been listed for lung or heart-lung transplant. Six subjects underwent lung or heart-lung transplantation and one remains on the transplant list. Three different methods of patient management for transplant were used. In three subjects, the implanted system was filled with saline prior to transplantation and treprostinil was infused via an external system. Three subjects had their drug-filled implanted pump and catheter system explanted at the time of transplant. One patient had the drug-filled implanted system removed prior to being listed for transplantation. Four subjects were hospitalized while waiting for transplantation. In conclusion, the implanted system for treprostinil is an important advance in the care of pulmonary arterial hypertension subjects. The experience described here provides three effective strategies for managing the implanted system around lung or heart-lung transplantation. The optimal strategy will depend on patient characteristics and lung transplant program preferences and wait list times.

Background Patients with recurring heart failure (HF) following cardiac resynchronization therapy fare poorly. Their management is undecided. We tested remote hemodynamic‐guided pharmacotherapy. Methods and Results We evaluated cardiac resynchronization therapy subjects included in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association Class III Heart Failure Patients) trial, which randomized patients with persistent New York Heart Association Class III symptoms and ≥1 HF hospitalization in the previous 12 months to remotely managed pulmonary artery (PA) pressure‐guided management (treatment) or usual HF care (control). Diuretics and/or vasodilators were adjusted conventionally in control and included remote PA pressure information in treatment. Annualized HF hospitalization rates, changes in PA pressures over time (analyzed by area under the curve), changes in medications, and quality of life (Minnesota Living with Heart Failure Questionnaire scores) were assessed. Patients who had cardiac resynchronization therapy (n=190, median implant duration 755 days) at enrollment had poor hemodynamic function (cardiac index 2.00±0.59 L/min per m2), high comorbidity burden (67% had secondary pulmonary hypertension, 61% had estimated glomerular filtration rate <60 mL/min per 1.73 m2), and poor Minnesota Living with Heart Failure Questionnaire scores (57±24). During 18 months randomized follow‐up, HF hospitalizations were 30% lower in treatment (n=91, 62 events, 0.46 events/patient‐year) versus control patients (n=99, 93 events, 0.68 events/patient‐year) (hazard ratio, 0.70; 95% CI, 0.51–0.96; P=0.028). Treatment patients had more medication up‐/down‐titrations (847 versus 346 in control, P<0.001), mean PA pressure reduction (area under the curve −413.2±123.5 versus 60.1±88.0 in control, P=0.002), and quality of life improvement (Minnesota Living with Heart Failure Questionnaire decreased −13.5±23 versus −4.9±24.8 in control, P=0.006). Conclusions Remote hemodynamic‐guided adjustment of medical therapies decreased PA pressures and the burden of HF symptoms and hospitalizations in patients with recurring Class III HF and hospitalizations, beyond the effect of cardiac resynchronization therapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00531661.

Background: Ambulatory hemodynamic monitoring with an implantable pulmonary artery (PA) sensor is approved for patients with New York Heart Association Class III heart failure (HF) and a prior HF hospitalization (HFH) within 12 months. The objective of this study was to assess the efficacy and safety of PA pressure-guided therapy in routine clinical practice with special focus on subgroups defined by sex, race, and ejection fraction. Methods: This multi-center, prospective, open-label, observational, single-arm trial of 1200 patients across 104 centers within the United States with New York Heart Association class III HF and a prior HFH within 12 months evaluated patients undergoing PA pressure sensor implantation between September 1, 2014, and October 11, 2017. The primary efficacy outcome was the difference between rates of adjudicated HFH 1 year after compared with the 1 year before sensor implantation. Safety end points were freedom from device- or system-related complications at 2 years and freedom from pressure sensor failure at 2 years. Results: Mean age for the population was 69 years, 37.7% were women, 17.2% were non-White, and 46.8% had preserved ejection fraction. During the year after sensor implantation, the mean rate of daily pressure transmission was 76±24% and PA pressures declined significantly. The rate of HFH was significantly lower at 1 year compared with the year before implantation (0.54 versus 1.25 events/patient-years, hazard ratio 0.43 [95% CI, 0.39–0.47], P <0.0001). The rate of all-cause hospitalization was also lower following sensor implantation (1.67 versus 2.28 events/patient-years, hazard ratio 0.73 [95% CI, 0.68–0.78], P <0.0001). Results were consistent across subgroups defined by ejection fraction, sex, race, cause of cardiomyopathy, presence/absence of implantable cardiac defibrillator or cardiac resynchronization therapy and ejection fraction. Freedom from device- or system-related complications was 99.6%, and freedom from pressure sensor failure was 99.9% at 1 year. Conclusions: In routine clinical practice as in clinical trials, PA pressure-guided therapy for HF was associated with lower PA pressures, lower rates of HFH and all-cause hospitalization, and low rates of adverse events across a broad range of patients with symptomatic HF and prior HFH. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02279888.

Introduction: Effective management of ambulatory heart failure (HF) requires active patient (pt) participation. In telemonitoring of weights and symptoms, pt adherence to transmission is often halved within 6 months (M). Although ambulatory pulmonary pressure-guided management decreases hospitalizations and improves quality of life, the time course of pt perception of illness and sense of security in relation to monitoring frequency is not known. Hypothesis: Pts will perceive decreased impact of their HF during pulmonary pressure-guided management, which may contribute to their engagement in transmission of ambulatory PAP. Methods: The post-approval study for the implanted PA sensor was amended to include serial measurements of pt reported outcomes, (PRO, n=143), including the Brief Illness Perception Questionnaire (BIPQ). Treatment was adjusted to a target PA diastolic pressure 8 to 20 mmHg and adherence to transmitting pressure data from home was collected. Results: In the PRO cohort, mean age was 68 years, 58% were male, and 55% with HFpEF. Negative illness perception (BIPQ) decreased during each measurement interval. Pts reported improvement in symptoms, sense of security, sense of control and less impact of illness on their emotions at each time point, equally with HFpEF or HFrEF. In this cohort pt adherence to transmitting pressures was high throughout 24 M, Fig.1. Perception of illness was most favorable at 2 years, at which time there was a slight decline in transmission frequency. Conclusions: Pt perception of HF was positively impacted during ambulatory hemodynamic monitoring including improvement in symptoms, less emotional effect of illness, improved sense of security and control over their HF throughout follow-up. This was associated with high-level pt adherence to pressure data transmission. The optimal level of chronic monitoring for stable pts to maintain clinical benefit while minimizing disease awareness beyond 2 years is still unknown.

Parenteral prostanoids are effective for improving outcomes in patients with pulmonary arterial hypertension. However, subcutaneous or intravenous delivery via an external pump places a significant burden on patients. Consequently, the Implantable System for Remodulin© (treprostinil) was developed and is associated with a low rate of complications (United Therapeutics (Research Triangle Park, NC) in collaboration with Medtronic, Inc. (Mounds View, MN)). The current real-world experience study evaluated pulmonary arterial hypertension patients' perceptions of their quality of life, ability to perform activities of daily living, perceptions on the benefits and risks of the implantable system, and their social interactions before and after receiving the implantable system. Pulmonary arterial hypertension patients who had been transitioned from an external infusion pump to the implantable system completed a mix of quantitative and qualitative questions administered online over the course of a six-day period. A total of 20 patients completed the study. All patients reported that their quality of life, confidence out in public, and ability to travel long distances had improved. Over 90% of patients reported that their overall level of independence was better since receiving the implantable system, and most patients indicated that their ability to independently perform specific activities of daily living had improved. Responses to the qualitative questions suggested that the implantable system saved time, improved interpersonal relationships, and increased freedom. Results from this real-world patient experience study suggest this novel delivery system provides improvements in factors that are of substantial importance to patients.

Introduction Heart Failure (HF) undermines daily quality of life even when not severe enough to warrant hospitalization. Ambulatory pulmonary pressure-guided management decreases hospitalizations across all ranges of EF. This management improves HF symptom scores, but it is not known whether it improves health expectations and perceptions of disease control as reported directly by patients. Hypothesis Patients with prior HF hospitalization and NYHA class III symptoms will report improved health expectations and an increased sense of control over their HF disease progression. Methods Patient-reported outcomes were explored in a substudy of 286 class III CHF patients during the post-approval study for the implanted pulmonary artery pressure sensor. Patients completed validated measures of key appraisals of their cardiac disease and health expectations (e.g. 8-item Brief Illness Perception Questionnaire (BIPQ)) and the 24-item Cardiac Health Security Survey (CHSS) at baseline, 6 months and 12-month timepoints. All patients continued to receive optimal guideline directed medical therapy during ambulatory hemodynamic monitoring with a target PAD pressure of 8-20 mmHg. Results In this substudy, age was 69 ± 11 years and 62% were male, 53% with preserved ejection fraction. From the Baseline BIPQ of 46 ± 10.5, illness perception was reduced by 3.3 and 4.4 points at 6 and 12 months, respectively (p< 0.0001 both). Individual item analysis indicated significant benefits across perceptions of disease control, symptom reduction, and emotional and disease concerns (p<.05). Health expectations scores from the CHSS were not significantly different at any timepoint. Subjects’ perceptions about the use of the CardioMEMS™ system from the CHSS after both 6 and 12 months of use indicated high levels of satisfaction, security, and ease of use of the hemodynamic monitoring system. Conclusion Patient management guided by ambulatory pulmonary pressure monitoring was associated with improved patient perception of illness spanning sense of control, symptom reduction, and reduced concerns about their illness over time. The lack of change in health expectations likely reflects patient understanding regarding chronicity of HF on recommended therapies. Patients reported high levels of end user satisfaction and benefit with the hemodynamic monitoring system itself. This technology offers sustained benefits to patients beyond reduction of hospitalizations.

SESSION TITLE: Wednesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Because of a relatively short half-life, oral or inhaled prostacyclin therapy for PAH oscillates between high peak and relatively low trough levels between doses. We conducted the BEAT study to test the hypothesis that combination of two different prostanoids, esuberaprost (ESU) and inhaled treprostinil (iTRE) delivered by distinct routes (oral and inhaled), would benefit patient outcomes by approximating parenteral prostanoid delivery. METHODS: The BEAT study was a phase 3 trial of prognostically-enriched (i.e. WHO FC III and IV) PAH patients conducted at 77 sites in the US and Israel. All patients were receiving background iTRE at the time of randomization to ESU or placebo (PBO), and background oral PAH therapy was allowed (e.g. endothelin receptor antagonists and/or phosphodiesterase-5 inhibitors/soluble guanylate cyclase stimulators but no other prostanoids). Eligible patients were randomized 1:1 to ESU (fixed dose of 30 μg 4 times a day) or PBO. The primary endpoint, confirmed by an independent endpoint adjudication committee, was to compare the effects of ESU vs PBO as measured by time to clinical worsening (TtCW), i.e., from randomization to the 1st occurrence of any one of the following events: death (all causes), hospitalization due to worsening PAH, use of parenteral prostacyclin, disease progression, or unsatisfactory long-term clinical response. Secondary endpoints included changes in: six-minute walk distance (6MWD), Borg dyspnea score, WHO FC, and N-terminal pro-brain natriuretic peptide. RESULTS: A total of 273 patients were randomized; 271 received study drug (136 in ESU and 135 in PBO arms, respectively). Demographics and baseline characteristics were similar in both arms. The addition of ESU to iTRE was not statistically significant between the two arms (p=0.62; Hazard Ratio 0.9 [0.6-1.3]); subgroup analyses did not identify factors favoring a treatment effect for ESU. Overall, ESU was safe and well-tolerated. Despite enriching the study with only WHO FC III/IV patients for increasing the likelihood of higher event rates, the observed overall event rate at 1-year was 19% (relative to ∼15% seen in other non-enriched WHO FC II/III trials that used TtCW as an endpoint). Based on the observed event rate trend, the calculated median TtCW (∼4.5 y) was higher than the expected 1.2y for the enriched patient demographic studied. CONCLUSIONS: Combining ESU with iTRE in stable but advanced PAH patients on non-prostanoid background PAH therapy did not delay TtCW compared to PBO or provide added clinical benefit in the secondary end points evaluated. CLINICAL IMPLICATIONS: The background rate of TtCW events seen in this FC III/IV enriched study was lower than anticipated, possibly due to the use of an inhaled prostanoid in both arms, and potentially reduced the ability to discern a difference between ESU and PBO. DISCLOSURES: Speaker/Speaker's Bureau relationship with actelion Please note: $20001 - $100000 by Sonja Bartolome, source=Web Response, value=Honoraria Removed 06/18/2019 by Sonja Bartolome, source=Web Response Consultant relationship with actelion Please note: $5001 - $20000 by Sonja Bartolome, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Gilead Please note: $5001 - $20000 by Sonja Bartolome, source=Web Response, value=Honoraria Removed 06/18/2019 by Sonja Bartolome, source=Web Response Consultant relationship with Gilead Please note: $5001 - $20000 by Sonja Bartolome, source=Web Response, value=Consulting fee Removed 06/18/2019 by Sonja Bartolome, source=Web Response Speaker/Speaker's Bureau relationship with Bayer Please note: $1001 - $5000 by Sonja Bartolome, source=Web Response, value=Honoraria Removed 06/18/2019 by Sonja Bartolome, source=Web Response Consultant relationship with Bayer Please note: $5001 - $20000 by Sonja Bartolome, source=Web Response, value=Consulting fee Consultant relationship with medscape Please note: $1001 - 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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.

Aims Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00-1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24h for 180-day all-cause mortality was 1.01 (95% CI 1.00-1.03; P= 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h. Conclusions In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients.

Introduction: The CHAMPION trial demonstrated a significant reduction in heart failure (HF) hospitalizations (HFH) in New York Heart Association (NYHA) functional Class III patients managed with the PA pressure (PAP) guided HF management (CardioMEMS HF™ System). The system uses a percutaneously implanted sensor that allows for remote monitoring and management of PAP and is approved by the Food and Drug Administration (FDA) for use in the United States. A post approval study (PAS) was initiated to assess the safety and efficacy of the CardioMEMS HF system in a commercial setting in the United States. Purpose: The purpose of this analysis is to report on the 6 month outcomes in the first 300 patients enrolled into the PAS. Methods: The PAS is a prospective, multi-center, open-label trial being conducted at up to 150 sites in the United States. Study population is comprised of NYHA Class III HF patients experiencing at least 1 HF hospitalization in the past year, who undergo implantation of the CardioMEMS sensor. Definitions for HFH were consistent with the CHAMPION trial, and were adjudicated by an independent clinical events committee (CEC). Results: From January 2015 to March 2016, 300 patients were enrolled into the PAS at 53 sites. Average age was 69 ± 12 years, 62% were male, 41% had preserved EF and 47% had ischemic cardiomyopathy. There were 56 HF hospitalizations post sensor implantation for a HFH rate of 0.20 events/patient-6 months (95% CI: 0.15–0.26) and 0.40 events/patient year [eppy] (95% C.I.: 0.30 - 0.52 eppy). These were consistent and less than the rate observed in the treatment arm of the CHAMPION trial (0.32 events / patient-6 months, unadjusted P < .01) and were significantly lower that observed in the control arm of the CHAMPION trial (0.44 events / patient-6 months, unadjusted P < .0001). Device related complications occurred in only 1 patient (0.3%), and there were no sensor failures. Conclusions: Preliminary analysis of the CardioMEMS HF™ PAS demonstrates that outcomes in a commercial setting are consistent with those observed in the CHAMPION trial, with a reduction in HF hospitalization rates post sensor implantation.

Introduction: New access to pulmonary artery pressures for home hemodynamic monitoring should trigger active intervention to establish optimal pressures, but it is not known how the need for intervention decreases during real-world pressure-guided management as both providers and patients learn from patterns of response. Hypothesis: The pulmonary artery pressures and frequency of interventions will decrease to a plateau by 180 days after implantation of a pressure sensor (Cardiomems HF system) to guide HF management. Methods: The post approval study for the implanted pressure sensor is a prospective, multi-center, open-label trial in 53 U.S. sites. Enrolled pts have NYHA Class III symptoms and ≥1 HF hospitalization in the prior year, with intent to exclude pts approaching refractory Stage D HF. HF medication changes (HFMC) made in response to PAP changes in the first 300 patients were analyzed during the first 180 days and per pt per month. Results: The first 300 HF patients were enrolled from Jan 2015 through March 2016, average age 69 yrs, 38% women, and 41% with preserved ejection fraction. At implant, mean pulmonary artery wedge pressure was 20 mm Hg with cardiac index 2.2 L/min/m2. Pulmonary pressures declined most rapidly during the first 60 days (fig). During 180 days, 1252 HFMC occurred in 246 (82%) patients with an average of 1.11 HFMC/pt/month. Diuretics accounted for 82% of HFMC, direct vasodilators for 10%, and neurohormonal antagonists for 7%. HFMC rate averaged 1.41/pt/month during the first 3 months, then declined to average 0.80/pt/month for the next 3 months (P = .005), with 14.5% patients hospitalized during total 6 months. Conclusion: The intensity of interventions is focused in the first 60–90 days of pulmonary pressure-guided management, after which pulmonary pressure reduction levels out and pts undergo fewer than one medication adjustment per month. This may reflect not only medication adjustment but also the benefit of rapid feedback to pts to empower improved adherence to Na restriction and medications. This suggests that 90 days may be a reasonable time-frame after which to incorporate referring physicians and patients into local long-term management.