bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of pulmonary hypertension targeted therapy on haemodynamics in pulmonary arterial hypertension associated with adult congenital heart disease: a meta-analysis
Authors: Tsigkriki L , Ntiloudi D , Papanastasiou C , Varrias D , Giannakoulas G 
Published: October 2024

Abstract

Background
Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. There is growing evidence that PAH drugs lead to improved hemodynamics, exercise capacity, quality of life and survival in patients with PAH.

Purpose
The aim of this systematic review and meta-analysis is to evaluate the effects of pulmonary hypertension (PH) medical therapy on the haemodynamic parameters as well as exercise capacity in adult patients with PAH-CHD.

Methods
PubMed and the Cochrane Library databases have been systematically searched. Meta-analysis was conducted using STATA and Review Manager.

Results
Fourteen studies including 575 patients were analyzed. Pulmonary haemodynamics improved in patients receiving PH-targeted therapy. The weighted mean reduction in mean pulmonary arterial pressure (mPAP) was -5.8mmHg (I2=0%, 95% CI [–7.55, –4.06], p&lt;0.001).The weighted mean reduction in right atrial pressure (RAP) was -5.81mmHg (I2=0%, 95% CI [-7.55, - 4,07], p&lt;0.001). The weighted mean reduction in pulmonary vascular resistance (PVR) was 358.5dynes/sec/cm-5 (I2 51%, 95% CI [-566.55, -150.46] and p&lt;0.001). Cardiac index was increased by 0.61L/min/m2 (I2=6%, 95% CI [0.23,1.00], p=0.002). Six-minute walking distance increased by 47.26m, (I2=0%, CI [38.36, 56.16], p&lt;0.001).

Conclusions
PH-targeted therapy improves pulmonary haemodynamics and exercise capacity in adult patients with PAH-CHD.
Ventriculo-arterial coupling parameters by cardiac magnetic imaging are associated with outcome in patients with a systemic right ventricle
Authors: Wustmann K , Burkhardt B , Ruperti-Repilado J , Greutmann M , Schwerzmann M , Rutz T , Bouchardy J , Tobler D , Gabriel H , Stambach D , Schwitter J , Valsangiacomo Buechel E 
Published: October 2024

Abstract

Introduction
Invasive studies have shown that patients with a systemic right ventricle (sRV) due to congenitally corrected transposition of the great arteries (TGA) or complete TGA after atrial switch procedure possess impaired ventriculo-arterial coupling (VAC) parameters. The randomized, placebo-controlled, double-blinded, multi-centre SERVE trial investigated the effect of phosphodiesterase-5 inhibitor tadalafil in sRV patients on RV endsystolic volume (RVESV), with negative results. Aim of this sub-analysis was to evaluate changes of non-invasively assessed VAC parameters over time and for treatment effect. We prospectively analysed whether VAC parameters predict clinical outcome in sRV patients.

Methods
Volumetric RV parameters and aortic flow were assessed by cardiac magnetic resonance (CMR) and analysed (blinded for patient and assessment time and treatment) at baseline, after 3 years, or after 1 year if the study drug was withdrawed. Parameters were compared with clinical outcome at each visit. Effective arterial elastance Ea was calculated as RV endsystolic pressure (RVesp) / aortic forward flow, with RVesp defined as 0.9 x systolic blood pressure. Right ventricular endsystolic elastance Ees was calculated by RVesp / RVESV, and RV VA-coupling ratio was expressed as Ea/Ees. Treatment effect was analysed using ANCOVA with baseline values and FU-time as covariates. Values of &gt; 4th quartile were used as cut-off for Kaplan-Meier analysis on the primary outcome, defined as a composite of all-cause death, clinically relevant arrhythmias and hospitalisation for heart failure.

Results
CMR exams were available for 78 patients at baseline (40±11 years, 33% females) and for 71 patients at follow-up (FU). No effect of tadalafil compared to placebo was evident for effective arterial elastance Ea (p=0.35), ventricular endsystolic elastance Ees (p=0.11), VAC Ea/Ees (p=0.82), RVESVi (p=0.63) and RV ejection fraction (RVEF, p=0.6). Over the 3 years FU-time, Ea (p=0.24) and RVEF (p=0.11) did not change, whereas Ees mildly decreased (p=0.0052, fig. 1 A) and Ea/Ees increased (p=0.013, fig. 1 B). During FU, 14 patients experienced a clinical event. An Ees &lt;0.73 mmHg/ml and an Ea/Ees ratio of &gt;1.94 were associated with adverse clinical outcomes (for both p=0.004, fig. 2).

Conclusion
In sRV patients, treatment with tadalafil had no effect on VAC parameters compared to placebo. CMR-derived ventricular endsystolic elastance (Ees) and Ea/Ees ratio changed over the FU of 3 years and were associated with adverse clinical outcome.Figure 1Figure 2
Cardiovascular comorbidities and risk stratification in normotensive acute pulmonary embolism patients with right ventricular dysfunction and normal cardiac troponin: insights from a regional registry
Authors: Dzudovic B , Djuric I , Subotic B , Matijasevic J , Kovacevic-Preradovic T , Neskovic A , Mitevska I , Miloradovic V , Bozovic B , Obradovic S 
Published: October 2024

Abstract

Background
Acute pulmonary embolism (PE) management guidelines categorize normotensive patients with right ventricle dysfunction (RVD) and normal cardiac troponin (cTn) as intermediate low risk. This study explores the prevalence of cardiovascular comorbidities and their impact on risk stratification in this specific cohort.

Purpose
To investigate the characteristics of normotensive acute PE patients with RVD and normal cTn, emphasizing the role of pre-existing cardiovascular diseases in determining the intermediate-low risk status.

Methods
A total of 1675 PE patients from a regional registry were screened, excluding high-risk and intermediate-high-risk cases. Among the remaining 400 normotensive patients with RVD, 353 with echocardiography and normal cTn were included. Patients were categorized into low or intermediate-low risk based on RVD presence. Cardiovascular comorbidities were assessed, and logistic regression analyzed their association with intermediate-low risk.

Results
Intermediate-low-risk patients (n=137) exhibited significantly higher rates of chronic heart failure, arterial hypertension, coronary artery disease, diabetes, and atrial fibrillation compared to low-risk patients (n=216). A substantial 77.4% of intermediate-low-risk patients had at least one cardiovascular comorbidity, significantly elevating the risk of RV dysfunction (adjusted OR 2.954, p&lt;0.001). The all-cause hospital mortality was 5.1% in intermediate-low-risk and 1.4% in low-risk PE.

Conclusions
Normotensive acute PE patients with RVD and normal cTn are predominantly burdened with chronic cardiovascular conditions. The majority of intermediate-low-risk patients have at least one cardiovascular comorbidity, indicating an increased risk of death during hospitalization compared to low-risk patients. This study underscores the necessity for nuanced risk stratification considering pre-existing cardiovascular diseases for tailored and effective management. These findings have important implications for optimizing treatment strategies and improving outcomes in this high-risk population.
Diagnostic performance of computed tomography-derived fractional flow reserve in patients with severe aortic stenosis
Authors: Kido S , Okayama H , Kurokawa T , Kazatani T , Aono T , Matsuda K , Kawamura G , Kawada Y , Hiasa G , Yamada T 
Published: October 2024

Abstract

Background
Computed tomography-derived fractional flow reserve (FFR-CT) is a clinical modality for assessing coronary artery disease; however, its use has not been validated in patients with severe aortic stenosis (AS).

Purpose
This study assessed the diagnostic performance of FFR-CT in patients with severe AS.

Methods
Retrospectively recruited patients with severe AS underwent standard-protocol invasive fractional flow reserve (FFR) and coronary CT angiography. The FFR-CT values were compared with the invasive FFR values (ischemia defined as invasive FFR ≦0.80).

Results
Among 46 patients (105 vessels), the mean age was 82.8 ± 5.9 years (37% male). Mean invasive FFR and FFR-CT values were 0.86 ± 0.11 and 0.83 ± 0.10, respectively. In a per-vessel analysis, there was a positive correlation between invasive FFR and FFR-CT values (Pearson correlation coefficient, R= 0.64; P&lt;0.0001). In addition, the sensitivity, specificity, positive predictive, and negative predictive values were 100%, 86%, 43%, and 100% with 88% diagnostic accuracy, respectively. The Bland-Altman plot showed that the mean bias between invasive FFR and FFR-CT values was 0.031 (-0.146 to 0.209). The per vessels area under the receiver-operating characteristic curve analysis was 0.97 (95 % CI: 0.94-1.00, P&lt;0.0001). Importantly, among another 58 patients who deferred invasive coronary angiography (ICA) because the FFR-CT value was negative (&gt; 0.80), none experienced deterioration of condition during transcatheter aortic valve replacement (TAVR) or major adverse cardiac events (all-cause death, myocardial infarction, and unplanned hospitalization with urgent revascularization) within 30 days after TAVR.

Conclusions
FFR-CT values were significantly correlated with invasive FFR values and had a high negative predictive value in patients with severe AS. Patients with a negative FFR-CT value and deferred ICA had an excellent short-term prognosis after TAVR. FFR-CT is expected to serve as a gatekeeper for unnecessary ICA prior to TAVR.
Impact of new definition on the prognosis of patients with pulmonary hypertension compared to classic definition
Authors: Lee S , Jung H 
Published: October 2024

Abstract

Background
The recent European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 pulmonary hypertension (PH) guidelines have updated the definition of PH from a mean pulmonary arterial pressure (mPAP) ≥ 25mmHg to &gt; 20mmHg, and the pulmonary vascular resistance (PVR) threshold for pre-capillary PH (Pre-PH) from &gt; 3 wood units (WU) to &gt; 2 WU. Little is known regarding the implication of this new criteria in all PH subgroups in Asia.

Purpose
In this study, we aim to evaluate the impact of the new PH definition on the prevalence and prognosis of PH subgroups in as Asian cohort.

Methods
A retrospective analysis of a single-center RHC registry (April 2016 - July 2023) was conducted. 314 patients (median age 62.5, 50.3% men) were included. Patients were categorized into PH subgroups as defined by both the classic and new criteria. The primary outcome included cardiovascular mortality or heart failure hospitalizations, assessed over a maximum follow-up period of 5 years. Clinical outcomes of different PH subgroups using the classic and new definitions were compared using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models. Continuous parameters were analyzed using restrictive cubic splines within Cox models.

Results
Based on the new cutoffs (mPAP &gt; 20mmHg, PVR &gt; 2 WU), 76 patents (24.2%) were reclassified. PH increased to 233 (+ 41, +13.1%), Pre-PH increased to 92 (+ 30, +9.6%), Ipc-PH decreased to 27 (- 21, -6.7%), and Cpc-PH increased to 108 (+33, +10.5%). Over a median follow-up of 238.5 days, 65 primary outcomes occurred. Under the new PH definition, 5-year survival rates for Pre-PH, Ipc-PH, and Cpc-PH are 73.2%, 57.5%, and 47.0%, improved from 67.0%, 53.3%, and 44.3% in the classic definition. In the Cox regression analysis, using the Non-PH as a reference, the risk of primary outcome for PH subgroups was lower in the new definition compared to the classic definition (Table 1). Using the classic mPAP cut-off [&lt;25 vs. ≥25 mmHg], patients with PH had a significantly higher risk for primary outcome (HR 2.25, 95% CI 1.26-4.00, p=0.006) compared with patients without PH. However, using the new mPAP cut-off [&lt;20 vs. ≥20 mmHg], it didn’t show significant difference between two groups (HR 1.62, 95% CI 0.86-3.04, p=0.132). Spline analyses suggested a linear relation between the risk of primary outcome and mPAP considering mPAP between 20 and 45mmHg, and a plateau of events for mPAP values over 45mmHg. In patients with PVR &gt; 2 WU, we observed a linear relation between PVR and events for values and a plateau of events for PVR values over 7.5 WU (Figure 1).

Conclusion
The new definition increased the diagnosis of PH, particularly in Pre-PH and Cpc-PH. This definition faciliates earlier diagnosis, encompassing milder disease states, and demonstrated better prognosis in PH subgroups. However, it dose not identify additional patients at increased risk of primary outcomes.Table 1Figure 1
Efficacy of specific drug class therapy in pulmonary arterial hypertension associated with HIV, portal hypertension or both: a single Center experience
Authors: Dardi F , Cennerazzo F , Guarino D , Ballerini A , Magnani I , Salvi M , Donato F , Bertozzi R , Manes A , Palazzini M , Galie' N 
Published: October 2024

Abstract

Background
Pulmonary arterial hypertension (PAH) is a rare complication of both HIV infection (HIV-PAH) and portal hypertension (Po-PAH); it can occur in patients with both diseases (HIV/Po-PAH). The use of the PAH-specific drug classes (prostanoids, endothelin-1 receptor antagonists [ERA] and phosphodiesterase-5 inhibitors [PDE5-i]) is largely justified by retrospective and observational case reports since, to date, there are no randomized clinical trials except for the PORTICO trial which demonstrated the efficacy of macitentan in Po-PAH.

Purpose
the aim of the study was to evaluate the efficacy of PAH-specific drugs, both monotherapy and dual oral upfront therapy (ERA + PDE5i started within 1 month apart), in patients with Po-PAH, HIV/Po-PAH and HIV-PAH.

Methods
Between 1998 and 2023 we enrolled patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to our Center and undergoing monotherapy with prostanoid, ERA and PDE5-I or dual upfront oral therapy. The efficacy of the drugs was assessed by comparing clinical parameters (NYHA functional class), exercise capacity (six-minute walking test) and hemodynamic parameters at baseline and after a treatment period of 3-6 months. The data are expressed as mean and standard deviation and were compared with Student's t-test for paired data.

Results
128 patients were enrolled (83 Po-PAH, 23 HIV/Po-PAH and 22 HIV-PAH). 20 were treated with ERA monotherapy, 90 with PDE5-I, 13 with prostanoids and 5 treated with dual oral upfront therapy.

Conclusions
Prostanoids, ERAs and PDE5-Is, both in monotherapy and as dual upfront oral therapy, are associated with a significant improvement in functional class, exercise capacity and hemodynamic parameters. The effect of such drugs is similar to patients suffering from other forms of PAH.
Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH) study
Authors: Rothman A , Villar S , Middleton J , Law M , Varian F , Zafar H , Kiely D G , Roussakis A , Howard L , Toshner M , Wort J , Wilkins M 
Published: October 2024

Abstract

Introduction
Pulmonary arterial hypertension (PAH) is characterised by pre-capillary pulmonary vascular remodelling. Imatinib, a tyrosine kinase inhibitor, was the first treatment investigated in PAH patients with the primary aim of targeting vascular remodelling. A Phase 3 study showed that imatinib 400mg daily reduces pulmonary vascular resistance and increases exercise capacity but only 43% of patients continued the drug for 6 months. Concerns about safety prevented regulatory approval.

Purpose
To identify a safe and tolerated dose of oral Imatinib and evaluate efficacy in the dose range 100-400mg daily.

Methods
Oral Imatinib was added to the background therapy of 17 patients with PAH; prior intracranial haemorrhage was excluded by cross sectional imaging and none were receiving an anticoagulant. The first patient started on 100mg daily. The next 12 patients were recruited serially at a minimum of 4 week intervals and started on 200mg, 300mg or 400mg, according to a Bayesian adaptive design (Continuous Reassessment Method, CRM). Patients 14-17 were recruited as an extension cohort to better understand the safety and tolerability of the 100mg and 200mg doses. The primary endpoint was safety and tolerability at 4 weeks. Imatinib was continued for up to 24 weeks. Thirteen patients had implanted devices that provided remote daily measurements of cardiopulmonary haemodynamics and heart rate and rhythm and physical activity. Non-invasive measures of systemic blood pressure, weight and oxygen saturations were made remotely. We compared the time-haemodynamic response relationship with that produced by licensed treatments in a similar patient cohort.

Results
The recommended starting dose from the CRM was 200mg daily. The most common side effect was nausea. Imatinib reduced mean pulmonary artery pressure (P&lt;0.01), increased cardiac output (P=0.08) and reduced total pulmonary resistance (TPR, P&lt;0.001, Figure). There was a clear dose-TPR response relationship (r2=0.52, p&lt;0.01). A reduction in TPR was evident within the first week and plateaued at 4-5 weeks. Withdrawal of Imatinib led to an increase to baseline in TPR over 4-5 weeks. This contrasts with a sharp fall in TPR with licensed therapy and rapid increase on treatment withdrawal. There was a small reduction in systemic vascular resistance (P&lt;0.05) with Imatinib that reached plateau before TPR.

Conclusions
Oral Imatinib 200mg daily is well tolerated and effective as an add-on treatment in PAH. The time course of the initial haemodynamic response and the gradual return to baseline on withdrawal distinguishes Imatinib from licensed treatments and is supportive of a mechanism of action beyond reliance on vasodilation. Remote monitoring enables the safe evaluation of the withdrawal of an investigational drug in patients established on best medical therapy.Figure 1.
Mitigating health disparities by improving access to catheter-based therapies for vulnerable patients with acute pulmonary embolism
Authors: Bailey E , Zhang R , Keller N , Yuriditsky E , Elbaum L , Greco A , Postelnicu R , Hena K , Mukherjee V , Hall S , Alviar C , Bangalore S 
Published: October 2024

Abstract

Introduction
This study explores the implementation and outcomes of catheter-based thrombectomy (CBT) in acute pulmonary embolism (PE) within a safety-net hospital (SNH), addressing a critical gap in the literature concerning CBT in underserved and vulnerable populations.

Methods
This is a retrospective study of patients undergoing CBT between October 2020 and January 2024 at a SNH. The primary outcome was 30-day all-cause mortality.

Results
A total of 107 patients (47.6% female, mean age 58.4 years) underwent CBT for acute PE, with 23 (21.5%) high-risk and 84 (78.9%) intermediate-risk PE. Demographically, 64% identified as Black, 10% White, 19% Hispanic or Latino, and 5% Asian. In terms of insurance coverage, 50% had private insurance or Medicare, 36% had Medicaid, and 14% were uninsured. Notably, 67% of the patients resided in high poverty rate zip codes and 11% were non-citizen non-residents. Markers of risk severity, such as biomarkers (troponin, BNP), PE risk classification (high versus intermediate-risk), rates of low CI, lactate level, CPES/sPESI score, and rates of RV dysfunction did not vary significantly across race/ethnic groups, insurance status, level of poverty and citizenship status. Over a median follow up period of 30 days, 6 (5.6%) patients expired (all high-risk PE), 3 of which presented with cardiac arrest. No patients who presented with intermediate-risk PE died at 30 days. There was no difference in 30-day mortality based on race, insurance type, poverty level or citizenship status.

Conclusion
The findings emphasize the feasibility and success of implementing PERT and CBT at a SNH, offering a potential model to address healthcare disparities in acute PE on a broader scale.
Ultrasound assisted, catheter-directed thrombolysis for acute intermediate-high and high risk pulmonary embolism: focus on safety for oncological patients
Authors: Colombo C , Lorenzo Tua L T , Luca Villanova L V , Giovanna Viola G V , Marco Solcia M S , Antonio Rampoldi A R , Chiara Tognola C T , Francesco Musca F M , Nicolo Capsoni N C , Filippo Russo F R , Mario Iannaccone M I , Fabrizio Oliva F O , Andrea Garascia A G , Alice Sacco A S 
Published: October 2024

Abstract

Background
Catheter-based revascularization procedures have been developed as an alternative to systemic thrombolysis or surgical embolectomy for intermediate-high and high risk pulmonary embolism (PE) patients with. Little is known about the outcomes of oncological patients, who are notably at higher bleeding risk, undergoing such procedure.

Purpose
The USAT IH-PE registry is a retrospective and prospective multicenter registry of patients treated with ultrasound-facilitated, catheter-directed thrombolysis. We sought to determine whether patients with active cancer experience more bleeding complications and need for transfusions.
Methods: Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate–high-risk PE (86%), mostly female (57%), with a mean age of 63.7 ± 14.5 years. Most patients (77.8%) had a bilateral involvement of the main pulmonary arteries on CT scan and 9 patients (8.8%) had at least one prior episode of PE. 28.4% had active cancer. We compared the oncological and non-oncological subpopulations. The primary endpoints were bleeding complications (defined as BARC &gt; IIIa) and need for transfusion.

Results
Overall, 12% of patients experienced bleeding complications, of which 4.9% were BARC ≥ 3. When comparing bleeding complications, defined as BARC &gt; IIIa or the need for transfusion, no significant difference was found between patients with active cancer and those without (OR 0.61, 95% CI 0.01-6.62, p=1, and OR 2.43, 95% CI 0.61-9.48, p=0.18, respectively).

Conclusions
In the USAT IH-PE registry, where a significant proportion of patients have active cancer, no significant difference in bleeding complications was observed in these subjects. This finding confirms the safety of the procedure, even in a subpopulation traditionally considered at higher risk for bleeding.