Reduction In Pulmonary Artery Pressure Research Articles

Large-bore Aspiration Thrombectomy with the FlowTriever System for the Treatment of Pulmonary Embolism: A Large Single-Center Retrospective Analysis.

Evaluate the outcomes of patients undergoing large-bore aspiration thrombectomy for the treatment of pulmonary embolism at a large university medical center. All patients treated for pulmonary embolism with the FlowTriever System (Inari Medical, Irvine, CA) between September 2019 and January 2023 were retrospectively analyzed. The primary safety and effectiveness outcomes included 7- and 30-day all-cause mortality, major bleeding, procedure-associated clinical decompensation, pulmonary vascular or cardiac injury, and pulmonary artery pressure reduction. Additional outcomes included technical success (completing thrombectomy with the device as intended), changes in hemodynamics and supplemental oxygen requirements, and postprocedural intensive care unit stay. A total of 286 patients were identified. The mean age was 60.5 years, and 90.9% of patients presented with intermediate-risk pulmonary embolism. Technical success was achieved in 96.9% (n = 277) of cases. The average reduction in mean pulmonary arterial pressure was 6.8 mmHg, from 28.7 ± 9.0 to 21.9 ± 8.0 mmHg (p < 0.0001). Two major bleeds (0.7%), 2 pulmonary vascular injuries (0.7%), and 4 (1.4%) procedure-associated decompensations were reported, but no device-related deaths occurred. The mean post-procedure intensive care unit stay was 2.0 ± 4.1 days, and 49.3% of patients had no postprocedural intensive care unit admittance. The overall 7-day and 30-day all-cause mortality rates were 2.4% and 6.7%, respectively, with a 30-day pulmonary embolism-related mortality rate of 3.5%. This non-industry-sponsored single-center analysis of large-bore aspiration thrombectomy in a large population corroborates the findings of other studies and confirms that this approach is safe and effective for the treatment high- and intermediate-risk pulmonary embolism. Retrospective observational study.

Impact of Tafamidis on Delaying Clinical, Functional, and Structural Cardiac Changes in Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy.

Background: This study aimed to evaluate the effect of treatment with tafamidis on clinical, laboratory, functional, and structural cardiovascular imaging parameters at the 12-month follow-up timepoint in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and to assess the response to treatment in terms of disease progression. Methods: Patients with ATTRwt-CM undergoing treatment with tafamidis for >12 months were included. The patients underwent a comprehensive evaluation (including echocardiography, cardiac magnetic resonance imaging, six-minute walking test, assessment of quality of life, and laboratory tests) at baseline and the 12-month follow-up timepoint. Disease progression was assessed using a set of tools proposed by an international panel of experts, evaluating three main domains (clinical, biochemical, and structural). Results: The study cohort consisted of 25 patients (mean age of 75.9 ± 6.1 years, with 92% males). At the 12-month follow-up timepoint, an improvement in quality of life calculated with the KCCQ overall score (64 ± 20 vs. 75 ± 20, p = 0.002) and a reduction in pulmonary artery pressure (34 ± 10 mmHg vs. 30 ± 5 mmHg, p-value = 0.008) and in native T1 time were observed (1162 ± 66 ms vs. 1116 ± 52 ms, p-value = 0.001). Clinical, biochemical, and structural disease progression was observed in 6 (24%), 13 (52%), and 7 (28%) patients, respectively. Overall disease progression was observed in two patients (8%). Conclusions: This study described the impact of tafamidis treatment on clinical, laboratory, and functional parameters. Disease progression, assessed using a multiparametric tool recommended by a recent position paper of experts, was observed in a minority of patients.

Clinical, Functional, and Quality-of-Life Outcomes after Computer Assisted Vacuum Thrombectomy for Pulmonary Embolism: Interim Analysis of the STRIKE-PE Study

PurposeTo report the first interim analysis of the STRIKE-PE study, evaluating the safety and effectiveness of computer assisted vaccum thrombectomy (CAVT) for the treatment of acute pulmonary embolism (PE). Materials and MethodsThis prospective, international, multicenter study will enroll 600 adult patients with acute PE of ≤14 days and a right ventricle (RV)–to–left ventricle (LV) ratio of ≥0.9 who receive first-line endovascular treatment with CAVT using the Indigo Aspiration System (Penumbra, Alameda, California). Primary endpoints are change in RV/LV ratio and incidence of composite major adverse events (MAEs) within 48 hours. Secondary endpoints include functional and quality-of-life (QoL) assessments. ResultsThe first 150 consecutive patients were treated with 12F catheter CAVT. Mean age was 61.3 years, 54.7% were men, 94.7% presented with intermediate-risk PE, and 5.3% presented with high-risk PE. Median thrombectomy and procedure times were 33.5 minutes and 70.0 minutes, respectively, resulting in a mean reduction in systolic pulmonary artery pressure of 16.3% (P < .001). Mean RV/LV ratio decreased from 1.39 to 1.01 at 48 hours, a 25.7% reduction (P < .001). Four (2.7%) patients experienced a composite MAE within 48 hours. At 90-day follow-up, patients exhibited statistically significant improvements in the Borg dyspnea scale score and QoL measures, and the New York Heart Association class distribution returned to that reported before the index PE. ConclusionsInterim results from the STRIKE-PE study demonstrate a significant reduction in pulmonary artery pressure and RV/LV ratio, a median thrombectomy time of 33.5 minutes, a composite MAE rate of 2.7%, and significant improvements in 90-day functional and QoL outcomes.

The efficacy of the treat-repair-treat strategy for severe pulmonary arterial hypertension associated with congenital heart disease: a meta-analysis

BackgroundThis meta-analysis was conducted to evaluate the efficacy of the treat-repair-treat (TRT) strategy in the treatment of severe pulmonary arterial hypertension with congenital heart disease (PAH-CHD).MethodsPubMed, EMBASE, Cochrane and Web of Science online databases were searched by two independent investigators for studies that used the TRT strategy for PAH-CHD, and the retrieved studies were reviewed by a third investigator. The main outcomes were pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and transcutaneous oxygen saturation (SpO2). The changes were compared between follow-up and baseline. Stata version 14.0 was used for data analysis. A random-effects model was selected for meta-analysis. Subgroup analysis and meta-regression were used to find the source of heterogeneity.ResultsA total of 335 patients from 9 single-arm studies were included. Meta-analysis showed significant reductions in PAP and PVR and improvements in 6MWD and SpO2 (PAP: SMD -2.73 95% CI -2.97, − 2.50 p = < 0.001; PVR: SMD -1.27 95% CI -1.53, − 1.02 p = < 0.001; 6MWD: SMD 1.88 95% CI 1.49, 2.27 p = < 0.001; SpO2: SMD 3.72 95% CI 3.13, 4.32 p = < 0.001). Subgroup analysis showed that younger patients had better efficacy, and the change in SpO2 was an indication for patient selection. The combined mortality rate was 5% at follow-up.ConclusionsIn this meta-analysis, we demonstrated that the TRT strategy may have positive effects on haemodynamics and cardiac function in patients with severe PAH-CHD at short-term follow-up. Our analysis suggests that changes in age and SpO2 may be related to patient prognosis.Trial registrationThe protocol was registered on the PROSPERO website with the registration number CRD42022366552. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced.

Mechanical thrombectomy in intermediate- and high-risk acute pulmonary embolism: hemodynamic outcomes at three months

BackgroundMechanical thrombectomy has been shown to reduce thrombus burden and pulmonary artery pressure (PAP) and to improve right ventricular (RV) function in patients with high-risk or intermediate-high-risk pulmonary embolism (PE). As hemodynamic data after mechanical thrombectomy for PE are scarce, we aimed to assess the hemodynamic effects of mechanical thrombectomy in acute PE with right heart overload.MethodsIn this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after 20 patients completed three months of follow-up.ResultsTwenty-nine patients (34% female) underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients were at high (17%) or intermediate-high (76%) risk and had bilateral PE (79%). Before thrombectomy, systolic PAP (sPAP) was severely elevated (mean 51.3 ± 11.6 mmHg). Mean sPAP dropped by -15.0 mmHg (95% confidence interval [CI]: -18.9 to -11.0; p < 0.001) immediately after the procedure and continued to decrease from post-thrombectomy to three months (-6.4 mmHg, 95% CI: -10-0 to -2.9; p = 0.002). RV/left ventricular (LV) ratio immediately reduced within two days by -0.37 (95% CI: -0.47 to -0.27; p < 0.001). The proportion of patients with a tricuspid annular plane systolic excursion (TAPSE)/sPAP ratio < 0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p = 0.007). There were no procedure-related major adverse events.ConclusionsMechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up.

TCT-547 Pulmonary Artery Pressure Reduction With Mechanical Thrombectomy for Pulmonary Embolism Predicts Improved Patient Outcomes Within 48 Hours: Results From the FLASH Registry U.S. Cohort

TCT-547 Pulmonary Artery Pressure Reduction With Mechanical Thrombectomy for Pulmonary Embolism Predicts Improved Patient Outcomes Within 48 Hours: Results From the FLASH Registry U.S. Cohort

Surrogate endpoints in pulmonary arterial hypertension trials

Why don't you just look at the pulmonary artery pressure? This question is frequently asked when we discuss endpoints in pulmonary arterial hypertension (PAH) trials with colleagues from other disease areas. Trials of antihypertensive drugs simply look at blood pressure changes, whereas pivotal trials in PAH use change in 6-min walk distance or time to clinical worsening as primary outcome measures. Why the difference? It is not just the invasiveness of right heart catheterisation but much more a question of validated surrogate endpoints. The US Food and Drug Administration (FDA) and other regulatory agencies approve drugs when they improve how patients feel, function, or survive. 1 Temple R Are surrogate markers adequate to assess cardiovascular disease drugs?. JAMA. 1999; 282: 790-795 Crossref PubMed Scopus (298) Google Scholar In systemic hypertension, lowering blood pressure predicts reductions in major adverse cardiovascular events including stroke, myocardial infarction, and cardiovascular death, and so authorities accept blood pressure reduction as a surrogate endpoint—ie, a substitute for a clinically meaningful endpoint that is expected to predict the effect of a therapy. 1 Temple R Are surrogate markers adequate to assess cardiovascular disease drugs?. JAMA. 1999; 282: 790-795 Crossref PubMed Scopus (298) Google Scholar In PAH, there is no convincing evidence that reductions in pulmonary artery pressure or pulmonary vascular resistance are directly linked to improved exercise capacity or better survival. Hence, change in 6-min walk distance is being frequently used as a primary endpoint assessing the function part of the FDA paradigm. Time to clinical worsening has been applied as well, a composite endpoint based on death, PAH-related worsening, and prespecified reductions in exercise capacity. However, these endpoints have limitations. Improvement in 6-min walk distance reflects better exercise capacity but is no surrogate of better outcomes. 2 Gabler NB French B Strom BL et al. Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation. 2012; 126: 349-356 Crossref PubMed Scopus (185) Google Scholar Time to clinical worsening does not capture clinical improvement, and reducing clinical worsening events does not necessarily lead to better survival. 3 Sitbon O Channick R Chin KM et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015; 373: 2522-2533 Crossref PubMed Scopus (607) Google Scholar , 4 Galiè N Barberà JA Frost AE et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015; 373: 834-844 Crossref PubMed Scopus (750) Google Scholar , 5 Pulido T Adzerikho I Channick RN et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013; 369: 809-818 Crossref PubMed Scopus (981) Google Scholar In addition, studies designed to show improvement in time to clinical worsening require large sample sizes, a challenge in a rare disease like PAH. Hence, there is an ongoing search for surrogate endpoints. Is low-risk status a surrogate outcome in pulmonary arterial hypertension? An analysis of three randomised trialsMulticomponent risk scores have utility for the prediction of outcomes in patients with PAH. Clinical surrogacy for long-term outcomes cannot be inferred from observational studies of outcomes. Our analyses of three PAH trials with long-term follow-up suggest that further study is necessary before using these or other scores as surrogate outcomes in PAH RCTs or clinical care. Full-Text PDF

Reduction in pulmonary artery pressures on right heart cath after percutaneous transmitral commissurotomy.

Objectives: To find out the reduction in pulmonary artery pressures on right heart Cath after percutaneous trans mitral commissurotomy. Study Design: Cross-sectional Observational study. Setting: Catheterization Lab Faisalabad Institute of Cardiology, Faisalabad. Period: April 2022 till October 2022. Material &amp; Methods: After approval from hospital ethical committee 67 patients of severe mitral stenosis having pliable valve suitable for PTMC on TTE followed by TEE to exclude its contraindications and then finalized for PTMC procedure were enrolled in study after informed consent. PTMC was performed through femoral route using INNOUE balloon. Pre PTMC and post PTMC Right ventricle pressures were measured on table in cath lab. Results: Mean age was 33.8 ± 8.4 with 28.4% (n=19) were male, 71.6% (n=48) were females. 79 % patients had NYHA III symptoms of dyspnea. Mean LA diameter was 50.4mm and mean MVA was 1.02 cm2. 65.7% patients had A.fib before PTMC. Others were in sinus rhythm. Majority of patients had severe pulmonary hypertension before PTMC which had significant reduction (mean 23mmHg) in catheterization lab 10 minutes after PTMC procedure. Conclusion: PTMC is quite effective procedure with significant reduction of not only LA pressure but also of right ventricle indicating its effectiveness from the day of procedure.

Learning curve and analysis of curative effects after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

Learning curve and analysis of curative effects after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

Sustained Reduction in Pulmonary Artery Pressures and Hospitalizations During 2 Years of Ambulatory Monitoring

BackgroundTherapy guided by pulmonary artery (PA) pressure monitoring reduces PA pressures and heart failure hospitalizations (HFH) during the first year, but the durability of efficacy and safety through 2 years is not known. Methods and ResultsThe 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 frequency 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. ConclusionsReduction 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.

Hemodynamically-Guided Management of Heart Failure Across the Ejection Fraction Spectrum: The GUIDE-HF Trial

BackgroundHemodynamically-guided management using an implanted pulmonary artery pressure sensor is indicated to reduce heart failure (HF) hospitalizations in patients with New York Heart Association (NYHA) functional class II-III with a prior HF hospitalization or those with elevated natriuretic peptides. ObjectivesThe authors sought to evaluate the effect of left ventricular ejection fraction (EF) on treatment outcomes in the GUIDE-HF (Hemodynamic-GUIDEd management of Heart Failure) randomized trial. MethodsThe GUIDE-HF randomized arm included 1,000 NYHA functional class II-IV patients (with HF hospitalization within the prior 12 months or elevated natriuretic peptides adjusted for EF and body mass index) implanted with a pulmonary artery pressure sensor, randomized 1:1 to a hemodynamically-guided management group (treatment) or a control group (control). The primary endpoint was the composite of HF hospitalizations, urgent HF visits, and all-cause mortality at 12 months. The authors assessed outcomes by EF in guideline-defined subgroups ≤40%, 41%-49%, and ≥50%, within the trial specified pre–COVID-19 period cohort. ResultsThere were 177 primary events (0.553/patient-year) in the treatment group and 224 events (0.682/patient-year) in the control group (HR: 0.81 [95% CI: 0.66-1.00]; P = 0.049); HF hospitalization was lower in the treatment vs control group (HR: 0.72 [95% CI: 0.57-0.92]; P = 0.0072). Within each EF subgroup, primary endpoint and HF hospitalization rates were lower in the treatment group (HR <1.0 across the EF spectrum). Event rate reduction by EF in the treatment groups was correlated with reduction in pulmonary artery pressures and medication changes. ConclusionsHemodynamically-guided HF management decreases HF-related endpoints across the EF spectrum in an expanded patient population of patients with HF. (Hemodynamic-GUIDEd Management of Heart Failure [GUIDE-HF]; NCT03387813)

Ramping Up the Pressure on the Right Ventricle.

HomeCirculation: Heart FailureVol. 15, No. 6Ramping Up the Pressure on the Right Ventricle Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessResearch ArticlePDF/EPUBRamping Up the Pressure on the Right Ventricle Simone L. Savaris, MD, MSc, Isaac S. Chang, PhD, Stephen P. Wright, MSc, PhD and Susanna Mak, MD, PhD Simone L. SavarisSimone L. Savaris Correspondence to: Simone L. Savaris, MD, MSc, Division of Cardiology, Mount Sinai Hospital, 600 University Ave, Toronto, ON M5G 1X5, Canada. Email E-mail Address: [email protected] https://orcid.org/0000-0002-9049-1805 Division of Cardiology, Mount Sinai Hospital, Toronto, ON, Canada (S.L.S., S.M.). Search for more papers by this author , Isaac S. ChangIsaac S. Chang Mount Sinai Hospital, Toronto, ON, Canada (I.S.C.). Search for more papers by this author , Stephen P. WrightStephen P. Wright Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Kelowna, Canada (S.P.W.). Search for more papers by this author and Susanna MakSusanna Mak https://orcid.org/0000-0003-2193-602X Division of Cardiology, Mount Sinai Hospital, Toronto, ON, Canada (S.L.S., S.M.). Search for more papers by this author Originally published21 Apr 2022https://doi.org/10.1161/CIRCHEARTFAILURE.122.009671Circulation: Heart Failure. 2022;15Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: April 21, 2022: Ahead of Print A 49-year-old man underwent Heartmate 3 left ventricular assist device implantation as bridge to transplant candidacy for cardiogenic shock due to an ischemic cardiomyopathy which was complicated by a flail mitral valve leaflet resulting in severe regurgitation.Right heart catheterization was performed to assess residual pulmonary hypertension. Right ventricular (RV) and pulmonary artery (PA) pressures were recorded continuously. At baseline, mean PA pressure was 24 mm Hg and pulmonary vascular resistance was 3.0 WU at a speed of 5600 rpm. PA wedge pressure was altered by adjusting speed from 4600 to 5800 rpm. Further increases in speed did not change hemodynamics. Vasoreactivity testing with sodium nitroprusside was also used, based on recent evidence that even mildly elevated PA loading confers increased mortality risk.1,2 Pmax, a theoretical maximal RV systolic pressure derived by extrapolating the isovolumic portions of the waveform, was averaged over 10 cardiac cycles to calculate a single-beat estimate of RV end-systolic elastance, along with PA elastance and the end-systolic elastance:elastance ratio.3The incremental decline in the PA wedge pressure with attenuation of the V wave can be seen as left ventricular assist device speed was increased, and then with infusion of the vasodilator sodium nitroprusside (Figure and Table from left to right). Concomitant reductions in PA pressure and elastance were associated with shortening of the time to peak RVSP, and improved RV-PA coupling as reflected by increasing end-systolic elastance:elastance ratio. Importantly, mixed venous O2 saturation, stroke volume, and cardiac output increased steadily with afterload reduction.Table. Hemodynamics and Values Derived From Single-Beat Estimation of the Ees:Ea RatioUnsupportedRelatively unsupportedBaselineSNP (0.75 μg/kg per min)SNP (1.5 μg/kg per min)Speed4600 rpm5000 rpm5600 rpm5600 rpm5600 rpmMAP, mm Hg9492969065PAWP (a/v/mean), mm Hg18/37/1817/35/1710/24/1011/28/115/9/3PAP (S/D/M), mm Hg51/14/3047/13/2941/10/2441/9/2432/5/17RAP, mm Hg44320PVR, d/s per cm5192200240176168SVR, d/s per cm51532143613781193765MVO2, %61.663.365.168.573.3CO, L/min4.74.95.45.96.8SVi, mL/m2 per beat3941454955RVSP, mm Hg4946424334Time to RVSP, ms318226221210146Pmax, mm Hg166136143147142Ea, mm Hg/mL0.60.470.370.340.2Ees:Ea ratio2.72.73.63.76.7CO indicates cardiac output; Ea, pulmonary artery arterial elastance; Ees, RV end-systolic elastance; MAP, mean arterial pressure; MVO2, mixed venous oxygen saturation; PAP, pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; Pmax, maximal predicted RV pressure; PVR, pulmonary vascular resistance; RAP, right atrium pressure; RV, right ventricle; RVSP, right ventricle systolic pressure; SNP, sodium nitroprusside; SVi, stroke volume index; and SVR, systemic vascular resistance.Download figureDownload PowerPointFigure. The figure shows that with alterations in speed and with a vasodilator challenge (from left to right), pulmonary artery wedge pressure (PAWP) and pulmonary artery pressure (PAP) declined, with measurable changes in the morphology of the right ventricular pressure (RVP) waveform. Pmax, the theoretical maximal RVP, and graphical representations of the coordinates employed for single-beat estimation of RV end-systolic elastance (Ees) are also illustrated. Ea indicates pulmonary artery arterial elastance; Pes, estimated end-systolic pressure; Pmax, maximal predicted RVP; RVSP, right ventricle systolic pressure; SNP, sodium nitroprusside; and SV, stroke volume.This case reinforces the effect of systemic vasodilation and venodilation to optimize hemodynamics in the setting of heart failure with reduced ejection fraction, mitral regurgitation, and a continuous flow left ventricular assist device. The upstream effects of adequate unloading of the left ventricle to improve the function of the RV-PA circulatory unit are also illustrated.Article InformationSources of FundingNone.Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 645.Correspondence to: Simone L. Savaris, MD, MSc, Division of Cardiology, Mount Sinai Hospital, 600 University Ave, Toronto, ON M5G 1X5, Canada. Email simonelouise.[email protected]ca

Efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn: a Metaanalysis.

To systematically evaluate the efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn (PPHN). Chinese Journal Full-text Database, Weipu Database, Wanfang Data, China Biology Medicine disc, PubMed, Web of Science, Embase, and Cochrane Library were searched for literature on bosentan in the treatment of PPHN published up to August 31, 2021. A total of 8 randomized controlled trials were included for Meta analysis. The results of the Meta analysis showed that compared with the control group, the bosentan treatment group had a significantly lower treatment failure rate (RR=0.23, P<0.001), a significantly greater reduction in pulmonary artery pressure [mean difference (MD)=-11.79, P<0.001)], significantly greater increases in oxygen partial pressure (MD=10.21, P=0.006) and blood oxygen saturation (MD=8.30, P<0.001), and a significantly shorter length of hospital stay (MD=-1.35, P<0.001). The descriptive analysis showed that the bosentan treatment group had a lower degree of tricuspid regurgitation than the control group after treatment. The main adverse reactions of bosentan treatment included abnormal liver function, anemia and edema. The results of subgroup analysis based on treatment regimen, research area, and drug dose were consistent with those before stratification. Bosentan is effective in the treatment of PPHN. However, when using bosentan, attention should be paid to adverse reactions such as abnormal liver function.

The effects of adeno/tonsillectomy on cardiopulmonary function based on echocardiography indices in children with primary snoring and mild obstructive sleep apnea

BackgroundThe goal of this study was to evaluate the effects of adenotonsillectomy on heart function based on echocardiography indices in children with primary snoring (PS) and mild obstructive sleep apnea due to adenotonsillar hypertrophy (ATH). Methods55 children (aged 7 to 11 years old) with PS and ATH who were a candidate for adenotonsillectomy from August 2018 to June 2019 evaluated. A history of Upper Respiratory Tract Obstruction was obtained, clinical examination was performed and the cases suspicious for moderate to severe degrees of Obstructive Sleep Apnea Syndrome were excluded. Echocardiography was performed one week before and 3–6 months after surgery. All data were analyzed by SPSS version 19 and P-value<0.05 was considered significant. ResultsFrom 55 enrolled cases, 42 [30 boys (71.5%) and 12 girls (28.5%)] completed the study course. Tricuspid Annular Plane Systolic Excursion (TAPSE), Ejection Fraction (EF), Right Ventricular Peak Systolic Myocardial Velocity (RVSM), Right Ventricular Fractional Area Change (RVFAC) were increased significantly and Isovolumic Contraction Time (IVCT) index was decreased significantly after surgery (P-value<0.05). The difference of indices between the two sexes was not significant after surgery (P-value>0.05). ConclusionAdenotonsillectomy can improve cardiac function indices in patients with PS due to ATH especially in terms of right ventricle (RV) function and reduction in pulmonary artery pressure. So, although “subclinical”, it is better to be considered PS not just as annoying noise for roommates before significant clinical cardiac problems happen.

Safety, tolerability, and pharmacokinetics (PK) of treprostinil palmitil inhalation powder (TPIP): a phase 1, randomised, double-blind, single- and multiple-dose study

Abstract Background/Introduction Use of treprostinil in the treatment of pulmonary arterial hypertension (PAH) is limited by a short half-life and dose-limiting adverse events. TPIP, a dry powder formulation of the treprostinil prodrug treprostinil palmitil, is under investigation for PAH. In preclinical models, TPIP provided sustained treprostinil release in the lung and demonstrated sustained reduction of pulmonary arterial pressures. Purpose To examine the safety, tolerability, and PK of single- and multiple-dose administration of once-daily (QD) TPIP in healthy volunteers. Methods In this phase 1 study, healthy adults (aged 18–45 years) were randomised to receive single or multiple QD inhalation doses of TPIP. Single-dose participants received TPIP 112.5, 225, 450, or 675 μg (n=6 per dose) or placebo (n=2). Multiple-dose participants received TPIP 225 μg QD for 7 days (n=6), 112.5 μg QD for 4 days followed by 225 μg QD for 3 days (n=6), or placebo for 7 days (n=4). Results Of 42 randomly assigned participants who received ≥1 dose, 41 (97.6%) completed the study. Of the single-dose TPIP–treated participants, 70.8% (n=17/24) experienced a treatment-emergent adverse event (TEAE) vs 0% (0/2) of placebo-treated participants; the most common TEAEs (≥15%) among TPIP-treated participants were cough (45.8%), dizziness (29.2%), throat irritation (20.8%), nausea (16.7%), and hypotension (16.7%). Of the multiple-dose TPIP–treated participants, 83.3% (n=10/12) experienced a TEAE vs 50.0% of placebo-treated participants (2/4); the most common TEAEs were cough (58.3% TPIP vs 50.0% placebo), headache (50.0% vs 0%), nausea (33.3% vs 0%), and dizziness (25.0% vs 0%). Overall, 69.0% of participants (29/42) experienced mild TEAEs and 16.7% (7/42) experienced moderate TEAEs; no severe or serious TEAEs occurred. TEAEs were more frequent with increasing TPIP doses. Participants titrated from TPIP 112.5 μg QD to 225 μg QD experienced fewer TEAEs than those who received 225 μg QD at treatment initiation; all TEAEs were mild. After single-dose TPIP treatment, treprostinil exposure was dose proportional, with mean (CV%) Cmax = 78.4–717 pg/mL (38.6-72.9%) and AUC(0–∞) = 1.09–5.48 h·ng/mL (11.5–30.0%). At steady-state (225 μg), the mean (CV%) of Cmax, Cmin, and AUC(0–t) were 193–228 pg/mL (32.9–46.4%), 17.6–22.8 ng/mL (43.7%-64.4%) and 1.68–1.82 ng·h/mL (28.7–36.6%), respectively. No steady-state accumulation was observed. Elimination t1/2 was 8.7–11.6 h after a single dose and 6.8–8.8 h at steady state. Plasma concentrations of treprostinil palmitil were below the limit of quantification (100 pg/mL) at all time points measured. Conclusions In this phase 1 study, single and multiple TPIP dosing was generally well tolerated in healthy volunteers, with a PK profile that supports QD dosing. TEAEs were dose related; most were mild, none were severe or serious, and a titration schedule improved tolerability. These results support further examination of TPIP in patients with PAH. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Insmed Incorporated

Repeat angiography in patients undergoing conventional catheter-directed thrombolysis for submassive pulmonary embolism: a large single-center experience

Purpose Few studies have examined conventional catheter directed thrombolysis (CDT) for the treatment of submassive pulmonary embolism (PE). Moreover, angiographic resolution of thrombus burden following CDT has infrequently been characterized. This study describes a single-center experience treating submassive PE with CDT while utilizing repeat angiography to determine treatment efficacy. Methods A retrospective analysis of 140 consecutive patients who underwent CDT for submassive PE from December 2012 to June 2019 was performed. Angiographic resolution of thrombus burden after CDT was reported as high (>75%), moderate (51-75%), low (26-50%), or insignificant (≤25%). All angiograms were reviewed by two interventional radiologists. Secondary endpoints included reduction in pulmonary artery pressure (PAP) and clinical outcomes. Bleeding events were classified according to the Society of Interventional Radiology (SIR) adverse event criteria. Results CDT was performed in 140 patients with a mean rtPA dose of 25.3 mg and a mean treatment time of 26.0 hours. Angiographic resolution of thrombus burden was high in 70.0%, moderate in 19.3%, low in 5.7%, and insignificant in 3.6%; in 2 patients (1.4%) repeat angiography was not performed. Systolic PAP was reduced (47 vs. 35 mmHg, p Conclusion In patients with submassive PE undergoing CDT, angiographic resolution of thrombus burden is a safe and directly observable metric that can be used to determine procedural success. In this study, CDT with repeat angiography was associated with a 5.7% bleeding event rate and thirty-day mortality of 1.4%.

Evaluation of the Results of Balloon Pulmonary Angioplasty in Patients with Chronic Distal Pulmonary Thromboembolic Disease and Pulmonary Hypertension

Abstract Introduction The gold standard curative treatment for chronic pulmonary thromboembolic disease and pulmonary hypertension (CTEPH) is pulmonary thromboendarterectomy (PTE). Balloon pulmonary angioplasty (BPA) is emerging for distal CTEPH patients, where lesion is inaccessible for surgery. This is the first study conducted in Indian patients for evaluating the impact of BPA in patients with distal CTEPH. Aims and Objectives To evaluate the effect of BPA in patients with distal CTEPH with the help of New York Heart Association (NYHA) functional class and 6-minute walk distance (6MWD). To study decrease in pulmonary artery pressure and improvement in right atrial and right ventricular function with the help of echocardiography. Material and Methods Study population—CTEPH patients presenting to the hospital during the study interval of 16 months from January 2017 to April 2018. A. Method: This was an observational retrospective and prospective follow-up study. All distal CTEPH patients after meeting inclusion and exclusion criteria were taken for study. B. Detailed case records containing information on demographics, clinical features and necessary blood and imaging investigations, ventilation/perfusion (V/Q) scan, computed tomography pulmonary angiography (CTPA), right heart catheterization (RHC) study, pulmonary angiogram, and BPA procedure details were obtained for all participants. C. After 8 weeks of last BPA session, patients were assessed clinically and then 6-minute walk test, blood investigations and echocardiography were done. Data Analysis Statistical analysis was performed by using the software SPSS 22.0 version. We used paired t-test to test the significant difference in the mean pre- and post-BPA. p-value &lt; 0.05 will be considered as statistically significant. Results In our study, mean age of presentation was 39.81 ± 12 years. Out of 11 patients, 5 were females and 6 were males. Mean duration of symptoms was 40.5 months. The total number of BPA sessions performed were 30. The minimum number of BPA sessions undergone was 1 and maximum number of BPA sessions undergone by one patient was 5, with 45% of patients undergoing 2 BPA sessions. The total number of segmental arteries dilated was 104. Segmental vessels dilated per each session was 3.46. There was statistically significant improvement in NYHA class and 6MWD after BPA. 6MWD increased from 299 m to 421 m (p-value &lt; 0.001). This improvement in functional capacity is strongly associated with the improvement in right ventricular (RV) function (tricuspid annular plane systolic excursion [TAPSE] from 15.3 mm to 18.9 mm) and with the reduction in pulmonary artery systemic pressure (PASP) (from 92 mm Hg to 60 mm Hg). Conclusion In patients with distal CTEPH who undergo BPA, there was statistically significant improvement in 6MWD. These changes correspond to a treatment-induced reduction in pulmonary artery pressure and lend support to use of BPA in patients with distal CTEPH. ECHO and 6MWD can be used for evaluating BPA efficacy and monitoring disease progression.

Efficacy of treat-and-repair strategy for atrial septal defect with pulmonary arterial hypertension

ObjectiveTherapeutic strategies for atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) are controversial. This study aimed to evaluate the efficacy of PAH-specific medications and subsequent transcatheter closure (ie,...

Remote Hemodynamic Monitoring Equally Reduces Heart Failure Hospitalizations in Women and Men in Clinical Practice: A Sex-Specific Analysis of the CardioMEMS Post-Approval Study.

Response to pharmacological and device-based therapy for heart failure (HF) may vary by sex. We examined sex differences in response to ambulatory hemodynamic monitoring in clinical practice using the CardioMEMS PAS (Post-Approval Study). The CardioMEMS PAS was a prospective, single-arm, multicenter, open-label study of 1200 adults with New York Heart Association class III HF and at least 1 HF hospitalization (HFH) within 12 months who underwent pulmonary artery pressure sensor implantation between 2014 and 2017. Changes in pulmonary artery pressure over time were stratified by ejection fraction <40% and sex. Clinical outcomes including HFH rate at 12 months, 1-year mortality, and quality of life were examined in women and men. Four hundred fifty-two women (38% of total) enrolled in the PAS were less likely to be White (78% versus 86%) and more likely to have nonischemic cardiomyopathy (44% versus 34%) and had significantly higher SBP (132 versus 124 mm Hg), mean ejection fraction (44% versus 36%), and pulmonary vascular resistance (3.2 versus 2.6 WU) than men (P<0.001 for all). There were similar reductions in pulmonary artery pressure from baseline to 12 months in both men and women for the whole cohort and for subgroups with HF with reduced ejection fraction and HF with preserved ejection fraction. Both sexes experienced significant decreases in HFH over 12 months (men: HR, 0.46 [95% CI, 0.40-0.52]; women: HR, 0.39 [95% CI, 0.33-0.46]). In adjusted models, there were no significant differences in change in HFH between men and women (interaction P=0.13) or all-cause mortality at 1 year (adjusted HR, 1.25 [95% CI, 0.88-1.77]). Women and men enrolled in the CardioMEMS PAS had similar reductions from baseline in pulmonary artery pressure over 1 year and experienced similar reductions in HFH. Hemodynamic monitoring provides similar benefit with regard to HF events in both women and men. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02279888.

Cardiopulmonary Adaptations and Maladaptations to the Chronic Intermittent Hypoxia Associated With Repetitive Apnea Diving

Hypoxia (low oxygen) induces a reversible form of pulmonary hypertension which can be studied to elucidate the etiology of pulmonary hypertension and right heart dysfunction. Breath-hold divers (BHD) routinely place themselves into extremely hypoxemic (low blood oxygen) conditions and therefore repeatedly expose themselves to acute intermittent hypoxia and bouts of pulmonary hypertension and increased right heart work. The purpose of this study was to 1) determine if pulmonary arterial pressure and right heart dysfunction in hypoxia were greater in BHD compared to controls, and 2) determine the role of a pulmonary vasodilator in alleviating the increased pulmonary pressure in response to hypoxia. The hypotheses under hypoxic conditions were as followed 1) Right heart dysfunction will be the most severe amongst subjects with the greatest degree of pulmonary hypertension, regardless of group and 2) Sildenafil administration will result in a reduction of pulmonary arterial pressure compared to a placebo during hypoxia, regardless of group. Subjects (n=24, 12 BHD, 12 Control) completed two 30-minute isocapnic normobaric hypoxic breathing challenges, after receiving either 50mg sildenafil or placebo, with a 48-hour minimum washout period between visits. Pulmonary arterial systolic pressure (PASP) and right heart function via tricuspid anular plane systolic excursion (TAPSE) measures were made using Doppler ultrasound, and total pulmonary resistance (TPR) was calculated as PASP / cardiac output (Qt). Compared to placebo, BHD had a reduction in TPR with sildenafil in normoxia placebo (312.5 ± 92.8 vs 385 ± 122.6 dynes/sec/cm-5, respectively, p = .04). Compared to normoxia, PASP was increased with hypoxia in BHDc with placebo (22.9±6.0 vs. 32.4±8.9 mm Hg, respectively, p=0.0002) but not with sildenafil. Conversely, BHD had no changes in PASP with placebo, but had an increase in PASP from normoxia to hypoxia with sildenafil (22.3±4.8 vs. 31.5±6.9 mm Hg, respectively, p=0.0002). There was no effect of group or treatment on TAPSE. Our data suggests breath hold divers may have a previously unrecognized chronic pulmonary vasoconstriction in room air that is prevented with administration of sildenafil.