bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary inflammation stratifies risk in patients undergoing coronary CT angiography: the Oxford Risk Factors and Non-Invasive Imaging (ORFAN) study
Authors: Chan K , Wahome E , Antonopoulos A , Nicol E , Mittal T K , Rodrigues J , Kardos A , Desai M , West H , Patel P , Tomlins P , Neubauer S , Channon K M , Deanfield J , Antoniades C
Published: October 2024

Background

Patients with chest pain symptoms often undergo coronary CT angiography (CCTA) for the diagnosis of obstructive coronary artery disease (CAD) to guide revascularisation. However, acute cardiac events could occur in the absence of obstructive CAD. Further risk stratification of patients could potentially be useful by quantifying coronary inflammation using the Fat Attenuation Index (FAI) Score, and an artificial intelligence (AI)-assisted prognostic model that captures the inflammatory risk by integrating CCTA-derived metrics (including FAI Score and plaque burden) and the patient’s clinical risk factors.

Purpose

To evaluate the risk of cardiac events among patients without obstructive CAD, and the prognostic value of integrating coronary inflammation in risk stratifying this patient group.

Methods

From the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, patients undergoing CCTA in 7 UK Hospitals (n=40,091) were followed up for the incidence of cardiac mortality over a median(IQR) of 2.7(1.4-5.3) years. In a nested cohort of 3,393 patients with long-term follow up, we evaluated the long-term prognostic value of FAI Score and the performance of AI-Risk algorithm over a median(IQR) follow up of 7.7(6.4-9.1) years. Reclassification of risk category from AI-Risk was compared with contemporary clinical risk score (QRISK3).

Results

Patients without obstructive CAD (n=32,533, 81.1%) accounted for 63.7% of all cardiac deaths (n=1,754) during follow up, highlighting the substantial proportion of cardiac events in absolute terms given a large proportion of patients without obstructive CAD. In the nested cohort with long-term follow up, FAI Score in any of the 3 epicardial coronary arteries was significantly associated with cardiac mortality with or without obstructive CAD. In the whole cohort, the highest quartile of FAI Score in LAD showed 20-times higher risk of cardiac death compared with the lowest quartile (Panel A). Integrating coronary inflammation with clinical risk factors and plaque burden, patients with very-high AI-Risk classification showed 6-fold higher risk of cardiac mortality compared to low/medium risk, with good alignment of the incident predicted events from AI-Risk and observed events. (Panel B) The predicted cardiac mortality from AI-Risk also demonstrated good calibration with the observed events in the whole population. (Panel C) Finally, AI-Risk significantly reclassify the risk above clinical risk factor-based prediction (QRISK3) (Panel D).

Conclusion

Patients with high coronary inflammation measured by FAI Score showed significantly elevated risk for cardiac mortality. The AI-enabled absolute risk prediction algorithm leads to significant reclassification of patients undergoing routine CCTA, and can be used as a precision medicine tool.
A cohort study examining predictors of stroke and bleeding among people with congenital heart disease and atrial fibrillation
Authors: O'shea M , Arunachalam Karikalan S , Ravi S , Baqal O , Van Ligten M , Bacon A , Ibrahim A , Smyth P , Wang W , Alozie N , Marshall C , Girardo M , Egbe A , Majdalany D , El Masry H
Published: October 2024

Background

Congenital Heart Disease (CHD) is associated with development of atrial fibrillation (AF) at an early age. With increased survival of this cohort into adulthood, the prevalence of concurrent CHD and AF is expected to increase over the next several decades. Little is known about the utility of clinical risk factors or prediction models in determining bleeding or stroke rates in adults with CHD and AF.

Purpose

This study aims to measure the performance of the CHADSVASC and HASBLED scores in a cohort of people with CHD. The association between traditional stroke and bleeding risk factors, as well as CHD-specific factors, will be quantified.

Methods

Patients age 18 or older attending one of three centers in the USA were included in this study if they had a history of AF on ECG, holter monitor or device interrogation, in addition to a diagnosis of Tetralogy of Fallot (TOF), Double Outlet Right Ventricle (DORV), or Pulmonary Atresia with Intact Ventricular Septum (PA-IVS). Outcomes were major bleeding event, and stroke rate. Analysis was conducted using cox univariable regression controlling for current age. Receiver operator curve and c-statistics were produced for the CHADSVASC and HASBLED scores respectively.

Results

326 people were included in this study, of whom 161 (49.5%) had TOF secondary to Pulmonic Stenosis, 126 (38.8%) had TOF secondary to Pulmonary Atresia, 25 (7.7%) had DORV, and 155 (47.7%) had PA-IVS. 227 people used warfarin (79.4%), 28 (9.8%) used apixaban, 9 (3.1%) used Rivaroxaban, 3 (1%) used Edoxaban, and 5 (1.7%) used Enoxaparin for a period of at least 30 days during the study. 13 (4.5%) people didn’t receive anticoagulation during the study.

26 people had a stroke (8.8%) while 85 people (28.6%) had a major bleeding event. Only the CHADSVASC score was significantly associated with stroke rates (HR 2.103, 95% CI 1.555 to 2.844, p<0.001). Clinical variables, such as subtype of CHD, prior conduit placement or unifocalization were not associated with stroke or major bleeding events. C-statistic for the CHADSVASC score in predicting stroke events was 0.755 (Figure 1). C-statistic for the HASBLED score in predicting major bleeding was 0.442 (Figure 2).

Conclusions

Among people with CHD and AF, the CHADSVASC score can robustly predict stroke events. Other clinical variables are less valuable in predicting either bleeding or strokes. The HASBLED score likely doesn’t have a role in predicting major bleeding episodes in this cohort.
Cardiac resynchronization therapy in adult congenital heart disease: single center cohort study
Authors: Brem O , Rahat O , Yehuda D , Kornowski R , Buturylin K , Golovchiner G , Schamroth Pravda N
Published: October 2024

Introduction

Cardiac resynchronization therapy (CRT) is a recommended therapeutic measure for patients with heart failure. Heart failure is a major morbidity amongst patients with adult congenital heart disease (ACHD). However, the data on the efficacy and safety of CRT amongst ACHD is limited.

Methods

Data was analyzed from a retrospective cohort of patients with a known diagnosis of ACHD and implantation of CRT between 2015-2022. The primary outcome was echocardiographic response to CRT. This was defined as either:1) an increase in systemic ventricular ejection fraction (EF) of ≥5% in patients with EF <50% (therapeutic) or 2) maintenance of EF in patients with EF≥50% (preventative). Secondary outcomes included change in QRS duration, heart failure admissions, death and CIED (cardiovascular implantable electronic devices) infection during follow up. The outcomes were also assessed by subgroup of systemic left or right ventricle systemic ventricle.

Results

Our cohort included 46 patients, 96% male and average age was 54±14 years. 26 patients had a systemic left ventricle (56.6%) and 20 patients had a systemic right ventricle (44.4%). The indication for CRT implantation was 1) Reduced EF with wide QRS (n=10, 22%), 2) Reduced EF and RV (right ventricular) pacing (n=22, 49%), and 3) Normal EF with RV pacing (n=14, 33%). 25 patients (55%) had an implanted defibrillator at baseline. Primary outcome amongst patients with preserved EF at baseline was achieved in 22/32 patients (68.7%) and was achieved in 12/14 patients (85.7%) amongst patients with reduced EF at baseline. During follow up, QRS duration was shortened in 68.7%, 13 patients had heart failure admissions (30%), 4 patients underwent heart transplants/mechanical support device implantation (8.6%), death occurred in 11 patients (24%) and 3 had CIED infection (7%). There was no significant difference in complication or efficacy rates between the left systemic and right systemic group.

Conclusion

CRT is effective in patients with ACHD both as a therapeutic and as a preventative measure for heart failure. There was no difference in clinical response to CRT between patients with SRV compared to SLV. The percentage of patients with a safety outcome was relatively high in this subpopulation due to advanced ACHD.
Outcomes and management of Haemoptysis in the Fontan population
Authors: Sadek Y , Sirakaya M O , Canagarajah H , Jones R , Al-Sakini N , Clift P
Published: October 2024

Background

Patients with a Fontan circulation for palliation of a univentricular congenital heart defect commonly possess pulmonary vascular abnormalities including arteriovenous malformations (AVM), aortopulmonary and venous-venous collaterals (1). These vessels are prone to haemorrhage which may result in life-threatening haemoptysis (2). This risk is increased with oral anticoagulant medication, given to reduce the risk of thromboembolism in Fontan patients (3). Management of these patients is difficult, and strategies vary across institutions.

Purpose

We aim to describe our experience with managing adult Fontan patients presenting with haemoptysis in a tertiary centre with a large Fontan cohort.

Methods

We retrospectively reviewed the records of 410 adult Fontan patients. Individuals admitted to our institution with an episode of haemoptysis were included. Details relating to anticoagulation regimens, interventions and mortality of patients were captured.

Results

From a cohort of 410 Fontan patients, 35 haemorrhagic events were observed in 11 patients (2.68%). The median age at initial haemoptysis was 24.5 years (range 19 to 43 years). 6 of the 11 patients were female (54.5%). Haemoptysis recurred in 8 of the 11 patients (72.7%). 2 out of 11 had a prior history of haemoptysis in childhood. All patients were administered with oral vitamin K antagonists at presentation. 24 of the 35 events were managed conservatively with IV fluids, anticoagulation reversal and tranexamic acid (66.7%). 11 events required catheter-based interventions, with coil and/or plug embolization of bleeding vessels. Prior to intervention, CT successfully identified potential bleeding sites in 10 of the 11 events (90.9%) but could not visualise all vessels that were subsequently embolized. The most common culprits for haemoptysis were aortopulmonary collaterals, followed by AVMs and venous-venous collaterals. In severe cases, more extensive management was required including transfusions, bronchoscopy, intubation, surgical exploration (1 patient) and pneumonectomy (1 patient). 3 patients died following recurrent severe haemoptysis (27.3%), and 2 patients died of subsequent Fontan failure and sudden cardiac death respectively. Total mortality of the cohort is 5 out of 11 (45.5%) with a median follow up of 10.75 years (range 3 days to 27 years).

Conclusions

Haemoptysis is a rare but potentially fatal complication in patients who have undergone a Fontan procedure. The variability in presentation of this condition mandates an individualised approach to management with involvement of a multidisciplinary team. There is a high rate of recurrence following haemoptysis and a comprehensive assessment of all potential bleeding sites is necessary. CT is a useful tool to help facilitate this and guide further management. Our policy is to close all potential sources of bleeding as CT and invasive angiography rarely identifies an active point of bleeding.
Use of chatgpt-4 to explain kawasaki disease to parents and paediatric trainees
Authors: Chik W K B , Chan K L , Tsao S S L , Cheung Y F
Published: October 2024

Background

Paediatric trainees and parents of Kawasaki disease (KD) patients may face challenges when managing the disease due to insufficient accessibility to KD information. Chat Generative Pre-Trained Transformer (ChatGPT) based on large language models may help explain KD information to paediatric trainees and patient parents.

Purpose

This study aims to determine the usefulness of Chat Generative Pre- Trained Transformer -4 (ChatGPT-4) in explaining Kawasaki Disease (KD) and its management to parents and paediatric trainees managing KD patients.

Methods

We created 2 sets of clinical scenarios. In the first set, ChatGPT-4 was instructed to respond to 10 questions based on enquiries from parents of KD patients. Responses were scored in terms of "factual accuracy", "coherence", "comprehensiveness", and "humaneness" by 3 paediatric cardiologists using Likert scale of 0-10. Readability were calculated using Flesch reading-ease test. In the second set, ChatGPT-4 was instructed to respond to 8 KD-related questions based on enquiries from paediatric trainees. Responses are graded based on "relevance", "reliability" and "comprehensiveness" using Likert scale of 0-10 by 3 paediatric cardiologists independently. Reviewers would determine whether major advice from chatGPT-4 would be adopted in clinical judgement.

Results

For parent-targeted responses, ChatGPT-4 achieved the highest scores in ‘humaneness’ (median 9.00, IQR 8.00 to 9.00) and ‘coherence’ (median 8.00, IQR 7.00 to 8.00). Inaccurate information regarding disease prognosis, actions as well as prescription of medications and surgery is found in 80% of scenarios. Missing information regarding long-term coronary complications, antiplatelet management and cardiac assessments is found in all 10 scenarios. Mean readability of parent-targeted responses is 71.70 ± 6.26, a readability level easily understood by 12-year-olds. For paediatrician-targeted responses, ChatGPT-4 achieved the highest scores in ‘relevance’ (median 9.50, IQR 7.25 to 9.0). Inaccurate information regarding coronary interventions, patient education and immunization recommendations is spotted in 37.5% of the scenarios. Missing information regarding patient education and stress imaging is found in 25% of the scenarios. All reviewers would adopt ChatGPT-4’s advice in 87.5% of the scenarios.

Conclusions

ChatGPT-4 has significant limitations in accuracy and lacks salient information when providing KD recommendations for parents and paediatric trainees.Performance in parent-targeted questionsPerformance in trainee-targeted question
Prognostic value of follow-up hemodynamics after initial treatment in pulmonary arterial hypertension
Authors: Dardi F , Ballerini A , Magnani I , Bertozzi R , Donato F , Guarino D , Cennerazzo F , Salvi M , Manes A , Palazzini M , Galie' N
Published: October 2024

Background

Hemodynamic variables such as right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) have consistently been associated with survival in pulmonary arterial hypertension (PAH). The prognostic importance of hemodynamics after treatment initiation seems to be superior to baseline evaluation and stroke volume index (SVI) emerged as an independent prognostic parameter. New PAH treatments are, however, able to improve exercise capacity without increasing CI or SVI.

Purpose

The aim of this work was to define the prognostic role of follow-up hemodynamic parameters in a population of patients with idiopathic, hereditary, drug-induced PAH (I/H/D-PAH) and PAH associated with connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH).

Methods

Treatment naïve PAH patients were assessed at baseline and at 1st follow-up (3-4 months after starting PAH-specific therapy; 1st F-UP) with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC) and right heart catheterization (RHC). Collected hemodynamic parameters were: RAP, systolic, diastolic and mean pulmonary artery pressure (s/d/mPAP), CI, SVI, SvO2, pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), cardiac efficiency (CE), pulmonary arterial elastance (Ea), resistance–compliance product (RC), right ventricular (RV) power, and RV stroke work index (RVSWI). The primary outcome was all cause death. We used stepwise Cox regression to assess variables obtained at baseline and at 1st F-UP.

Results

794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD). A primary outcome occurred in 54% of patients over a median follow-up duration of 5.8 (2.4–11) years. In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis but RAP. At first follow-up RHC (n=706), WHO-FC, 6-minute walk distance, RAP, and Ea were independently associated with death, adjusted for age, gender, and etiology of PAH. Because hemodynamic variables were highly correlated, we compared multivariable Cox regression models adding only variables with a correlation coefficient <0.6. In these models, RAP, Ea, PAC, CE, PVR, SvO2, CI, and SVI at follow-up RHC were independent predictors of death (Table).

Conclusions

Ea and right atrial pressure were the hemodynamic variables independently associated with death at 1st F-UP RHC after initial PAH treatment. These findings suggest that beyond improving RV function, RV afterload reduction can be considered a further treatment target.Table
Long term follow up in pulmonary embolism: can right ventricular strain echocardiographic imaging contribute to refine risk stratification?
Authors: Soulat-Dufour L , Lang S , Evain I , Ederhy S , Chauvet-Droit M , Arnaud C , Fagnen P , Le Bos P , Gerard M , Boccara F , Cohen A
Published: October 2024

Background

In pulmonary embolism (PE), the usual evaluation of early risk of death includes clinical, biological and two-dimensional right ventricular (RV) echocardiographic (TTE) parameters.

Purpose

We hypothesized that myocardial strain analysis could contribute to risk of death prediction at long term follow up.

Methods

We retrospectively analyzed 477 patients hospitalized for acute EP. Usual parameters used to define RV dysfunction were evaluated using TTE (RV dilatation, systolic pulmonary arterial pressure, TAPSE, S’, Fractionnal Area Change (FAC), end diastolic RV diameter and right atrial, RA, area). In addition, we evaluated, left ventricle (LV) longitudinal, left atrial (LA), RA and RV free wall strains. Patients without history of cancer (n=419) were analyzed on the primary outcome of death at long term follow up.

Results

Mean of age was 63.7 ± 17.2 years and 227 (47.6) patients were male. The main clinical and echocardiographic characteristics are displayed in the Table 1. During a mean follow-up was 45.0 ± 16.6 months, the primary outcome occurred in 56 patients. In multivariable analysis, systolic pulmonary arterial pressure, indexed right atrial and left atrial volumes, right ventricle free wall strain, right ventricle global longitudinal strain were the only predictors of death (Table 2).

Conclusion

Atrial volumes and RV strain appeared as strong predictors of death in PE at long term follow up. Right ventricle myocardial strain analysis should be evaluated in each patient hospitalized for PE.
Cardiopulmonary exercise testing in long-term calcium channel blockers responders, does it normalize in the same way as pulmonary vascular resistance?
Authors: Biscotti Rodil B , Segura De La Cal T , Velazquez Martin M , Sarnago Cebada F , Martin De Miguel I , Cruz Utrilla A , Coronel L , Cantero Acedo A , Arribas F , Escribano Subias P
Published: October 2024

Background and aims

Long-term calcium channel blockers (CCB) responders represent <10% of pulmonary arterial hypertension (PAH) patients and are known to have an excellent prognosis on high dose CCB. The few reports of lung histology of these patients suggest a predominant muscular thickening of the precapillary arterioles. Nevertheless, the classic intimal proliferation characteristic of PAH has also been reported, although to a lesser extent. Hence, we hypothesized that long-term CCB responders are likely to exhibit some degree of ventilatory inefficiency as a result of their impaired alveolo-capillary membrane. In this study, we aimed to evaluate the exercise performance of a contemporary cohort of long-term responders to CCB in terms of both exercise capacity and ventilatory efficiency, and whether there are differences depending on the haemodynamic severity.

Methods

We evaluated all long-term CCB responders with regular follow-up at our institution between 1996 to 2024 with at least one cardiopulmonary exercise test (CPET) and a right heart catheterization (RHC) within a three-year period, provided they had remained clinically stable without changes in pulmonary vasodilator treatment. Patients with additional PAH specific treatment were excluded. For data analysis purposes, the population was divided into 2 groups according to pulmonary vascular resistance (PVR). The cut-off point for PVR was set at ≥3.

Results

Twenty-four patients (91,6% female) with complete data were retrospectively enrolled. Baseline characteristics were as follows: median age 45.5 years (59-33) median mean pulmonary artery pressure of 26 mmHg (29-24) and median PVR of 3 WU (3-2.6). Regarding the whole cohort, peak oxygen consumption (pVO2) revealed mild impairment of functional capacity (mean pVO2: 1281 ± 245 ml/kg – 75 ± 15% of predicted). Ventilatory efficiency parameters were also mildy affected with low end-tidal carbon dioxide pressure at the anaerobic threshold (PETCO2@AT) (33.7±3.6mmHg), and increased minute ventilation (VE)/carbon dioxide output (VCO2) slope (33.5±4.5). The subgroup analysis depending on PVR showed no significant differences between groups in terms of pVO2 (1291.9 ±240 Vs. 1150 ±350 ml/kg, p:0.29 / 79%±16 vs 67%±12, p:0.8), VE/VCO2 slope (33 Vs. 34, p:0.21), or PETC02@AT (35 Vs. 33 mmHg, p:0.25). All CPET parameters by subgroups are displayed in Table 1.

Conclusions

Long-term CCB responders exhibit mildly reduced functional capacity. Moreover, they often fail to normalize the ventilatory efficiency parameters in most of the cases, even when PVR reaches close to normal values, suggesting persistent endothelial impairment.Results according to PVR
Metoprolol therapy in patients with Eisenmenger syndrome (MINES) study. A single-centre, double-blinded, randomised, placebo-controlled trial
Authors: Aswin Pius A K , Satyavir Yadav S , Sivasubramanian Ramakrishnan S , Rajiv Narang R , Sandeep Seth S , Saurabh Kumar Gupta S K , Kalaivani M
Published: October 2024

Background

Prevalence of Eisenmenger syndrome is still common in developing countries where early neonatal screening and referral for surgery is seldom possible. Limited number of drugs are available for treatment of this condition. Beta-blockers may improve functional status in these patients. Observational study has shown beta blockers to be safe and effective in improving effort intolerance in patients with Eisenmenger syndrome.

Purpose

To study the safety and efficacy of metoprolol succinate therapy in patients with Eisenmenger syndrome.

Methods

In this double-blind, placebo-controlled study, we randomly assigned 60 patients with Eisenmenger syndrome to receive placebo or to receive 25 mg of metoprolol succinate once daily for 2 weeks followed by 25 mg twice daily for 14 weeks (total of 16 weeks). The primary outcome was mean difference in 6-minute walk test (6MWT) distance. Secondary outcomes were clinical composite outcome (all-cause death, heart failure hospitalization, worsening of heart failure, change in WHO functional class, and new onset syncope), change in resting saturation, Tricuspid Annular Plane Systolic Excursion (TAPSE) and NT Pro BNP level at 16 weeks.

Results

At 16 weeks, the mean difference in 6MWT distance between treatment group and placebo group as per protocol analysis was 6 meters (95% confidence interval, - 7.43 to 19.49; P 0.37), and the mean difference in 6MWT distance as per intention to treat analysis was -1.1 meters (95% confidence interval, - 16.97 to 14.77; P 0.89). Clinical composite outcome occurred more in the treatment group 5(17%) as compared to the placebo group 1(3%) (P 0.197) though it did not reach statistical significance. This was primarily driven by worsening of heart failure in the treatment group. Compared to baseline metoprolol group had 37% increase in NT pro BNP level while placebo group had 13% (-313.69, 88.80) reduction in NT Pro BNP level. There was no difference in TAPSE 0.05 (95% confidence interval -0.62 to 0.72; P 0.88) or resting saturation -0.06 (95% confidence interval -0.88 to 0.75; P 0.87) between the two groups at 16 weeks

Conclusion

Metoprolol succinate therapy did not improve 6-minute walk distance at 16 weeks among patients with Eisenmenger syndrome compared to placebo. Metoprolol succinate therapy was associated with increased clinical composite outcomes, primarily driven by worsening of heart failure.Graphic Abstract of MINES study
Ambrisentan reverses the prosenescent and anti-autophagic effect of high glucose on human pulmonary artery endothelial cells exposed to hypoxia
Authors: Biondi F , Cabiati M , Sgalippa A , Casieri V , Ghelardoni S , Del Ry S , Madonna R
Published: October 2024

Background

Cardiovascular (CV) comorbidities (systemic hypertension, hyperlipidemia, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease) are associated with reduced treatment response to specific drugs for group 1 pulmonary arterial hypertension (PAH). Often this epidemiological evidence is the result of misdiagnosis of group 2 PH associated with left heart disease, but it can also be explained as the intrinsic loss of the ability of pulmonary endothelial cells to respond to specific antiremodeling drugs.

Aims

To evaluate the impact of high glucose and hyperosmolar stress on the responsiveness of human pulmonary artery endothelial cells (hPAECs) to the endothelin receptor antagonist ambrisentan in terms of senescence, autophagic activity, viability and expression of some microRNAs involved in pulmonary arterial remodeling.

Methods

We incubated hPAECs with high glucose (HG, 30.5 mM) or high mannitol (HM, 25 mM), with/without ambrisentan (0.02 nM) in normoxia (N) or hypoxia (H) for 24 h and tested them for cell viability (MTT assay), protein and miRNA levels, autophagy and senescence (β-Gal assay) in vitro.

Results

H induced cell death as compared to N (752 ± 44 vs 701 ± 45 Abs units, p = 0.03). H reduced autophagy (Figure 1A-C) and induced senescence (Figure 1D), an effect further potentiated by HG and HM. Treatment with A in N and H significantly reversed the effect of HG but not HM on autophagy (Figure 1A-C) and senescence (Figure 1D). H increased the abundance of antiapoptotic miR124-3, compared to N in vehicle (V)-treated hPAEC (p=0.008) (Figure 2A), and induced a similar effect on antiapoptotic and proliferative miR191-3p, although not statistically significant (Figure 2B). In N, A potentiated the expression of both miR124-3p (p=0.007) and miR191-3p (p=0.02) in HG-treated hPAEC, and only miR191-3p in HM-treated hPAEC (p=0.01). A induced a similar effect on miR191-3p in hPAEC exposed to H+HG (p=0.02), with a non-statistically significant trend on miR124-3p.

Conclusions

In hPAEC exposed to H, A retains its pro-autophagic and antisenescent effects in an in vitro model mimicking diabetes. miR124-3p and miR191-3p may act as biomarkers of disease and treatment response to specific drugs in patients with PAH.Figure 1:autophagy and senescenceFigure 2:miRNA expression
Endarterectomy in CTEPH: hemodynamic improvement and RV-PA coupling
Authors: Garcia A , Martins M , Oliveira C , Raposo M , Abrantes A , Cazeiro D , Gregorio C , Fonseca J , Jorge C , Guimaraes T , Martins S , Lousada N , Pinto F , Placido R
Published: October 2024

Introduction

Pulmonary artery endarterectomy (PAE) remains the gold standard in treating chronic thromboembolic pulmonary hypertension (CTEPH). Reducing the thrombotic burden and mechanical obstruction of the pulmonary artery (PA) leads to significant hemodynamic improvement, allowing for favorable right ventricular (RV) remodeling.

Methods

Single center retrospective study, including 30 pts submitted to PEA over a 7-year period. Hemodynamic assessment was performed by right heart catheterization (RHC) before PEA, immediately after and at 6-month follow-up (FUP). Echocardiographic assessment of RV function was acquired at baseline and 6m FUP. Mean absolute differences were calculated before and after PEA. Differences between groups were assessed with ANOVA analysis and ROC curve analysis allowed us to define a cut-off point in mPAP reduction to predict favorable RV remodeling.

Results

We included 30 pts with a mean age of 57,9 ± 13 years old and slight predominance of female sex (57%). Regarding risk assessment with the 4 strata tool at baseline, 23% of pts were high risk, 20% intermediate high, 27% intermediate low and 6% at low risk.

Pulmonary hemodynamics improved immediately after PEA, as indicated by a mean reduction of 28,3 ±17 mmHg in mPAP; 44,4±27,6mmHg in sPAP; 8±3,4 Wu in PVR and an increase in CO of 0,5±1 l/min. This improvement was sustained at 6-m post PEA assessment, with a mean reduction of 31,5 ±26,7 mmHg in mPAP; 48,3±41,2mmHg in sPAP; 6,3±6,2Wu in PVR and a 0,5±1 l/min increase in CO.

Regarding RV remodeling at 6m post PEA, an increase of 0.15±0.2mm/mmHg in TAPSE/PSAP ratio and 3±2,8cm/s in Tricuspid S’ were recorded. RV/PA uncoupling, defined as TAPSE/PSAP <0,31 mm/mmHg, was evident in 73% of pts at baseline, 25% of which recovered at 6m follow-up. There were no significant differences between groups, according to the 4 strata risk assessment at baseline, regarding pulmonary hemodynamics and RV remodeling.

Through ROC curve analysis, we were able to define a cut-off point of 37mmHg in immediate mPAP post-op reduction to predict RV-RA coupling normalization at 6-m FUP (sensitivity 70%, specificity 89%).

Conclusions

PEA remains a cornerstone of CTEPH treatment. It’s impact on improving pulmonary hemodynamics is immediate and maintained at 6-month FUP. This improvement may be expected regardless of risk assessment at baseline. Reducing RV afterload allows favorable remodeling and an immediate post operative reduction of mPAP > 37mmHg may predict normalization of RV-PA coupling.
EPAS-1 as a potential D-dimer alternative in pulmonary embolism evaluation
Authors: Sahin A T , Icli A , Alsancak Y , Tatar S , Sertdemir A L , Celik M , Akilli H
Published: October 2024

Background and Objectives

We aimed in this study was to determine the changes in EPAS-1 levels, which is a biomarker proven to increase with hypoxia, at the time of diagnosis and after treatment in addition to the laboratory parameters and scoring systems examined at the time of admission in patients with pulmonary thromboembolism.

Methods

Our study included 60 pulmonary embolism patients followed in the Cardiology clinic and 60 control groups with similar demographic characteristics. Laboratory parameters determined at the time of admission were examined. Pulmonary embolism risk and severity scores were applied and EPAS-1 levels were also studied. To determine the response, EPAS-1 levels were checked 3 days later and compared with the control group.

Results

There was no difference between the two groups in terms of demographic characteristics and comorbidities.EPAS-1 levels were found to be higher at the time of diagnosis compared to the control group ((3.6±1.42/1.57±0.45), p<0.001). It showed a statistically significant positive correlation with PESI severity score and risk score in the patient group. EPAS-1 levels were shown to decline with the treatment of the patients and the tendency to decline was different according to the types of treatment. In patients who died, EPAS-1 levels continued to increase despite treatment (p:0.014).

Conclusions

Our study is important in that EPAS-1 levels, which are correlated with scoring systems and other laboratory parameters used in pulmonary embolism patients, can be used as a predictive value in the diagnostic process of the disease and play a complementary role in the evaluation of treatment response.
Intracranial haemorrhage following treatment for pulmonary embolism: analysis of the german nationwide inpatient sample
Authors: Christodoulou K C , Farmakis I T , Mohr K , Valerio L , Muenzel T , Lurz P , Gori T , Uphaus T , Jaegersberg M , Hobohm L , Konstantinides S V , Keller K
Published: October 2024

Background

Intracranial haemorrhage (ICH) can be a life-threatening complication of pulmonary embolism (PE) and its treatment during the acute phase.

Purpose

To characterize patients hospitalized with PE and ICH by identifying risk factors across different treatment groups, and to detect temporal trends in a large nationwide sample.

Methods

The German nationwide inpatient sample was screened for patients admitted with PE during the period 2005-2020. All hospitalizations were stratified based on the occurrence of ICH and accordingly, risk factors for ICH were investigated (source: Research data center [RDC] of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations).

Results

Overall, 816,653 hospitalizations were included in the present study; among them, 2516 (0.3%) experienced an ICH event and 84,810 (10.4%) died in-hospital. The annual number of hospitalizations of patients admitted due to PE increased steadily from 38,749 in 2005 to 54,966 in 2020, whereas the incidence of ICH remained, despite annual fluctuations, largely stable over time, both in the entire study population and in the subgroup of patients with severe PE as defined by clinical and haemodynamic parameters (n=270,980 [33.2%]). ICH was overall more frequent after the seventh decade of life but, interestingly, no correlation with age was found amongst patients with severe PE (Figure 1). ICH in hospitalized PE patients was associated with an aggravated comorbidity burden mirrored by a higher Charlson Comorbidity Index (5.0 [interquartile range 4.0-7.0] vs. 4.0 [2.0-5.0], P<0.001). This was mainly driven by the higher prevalence of heart failure (27.3% vs. 19.4%, P<0.001) and acute or chronic kidney disease (27.6% vs. 18.1%, P<0.001) in patients with ICH. In addition, severe PE (OR 3.09 [95% CI 2.84-3.35], P<0.001), acute kidney injury (OR 3.60 [3.09-4.18], P<0.001), and particularly ischaemic stroke (OR 14.64 [12.61-17.00], P<0.001) were identified as independent predictors of ICH by multivariable logistic regressions. Overall, 27% of the ICH cases were related to systemic thrombolysis. In PE patients treated with systemic thrombolysis, age ≥70 years as well as female sex were independent predictors of ICH. Finally, ICH was independently associated with a substantial increase in case-fatality in patients hospitalized with PE (univariate OR: 5.38 [4.97-5.84], P<0.001; multivariable OR: 6.16 [5.64-6.72], P<0.001).

Conclusions

In this healthcare dataset of the German nationwide inpatient sample, the overall incidence of ICH remained low at 0.3% over the 15-year study period. Severe PE, age, comorbidity burden, kidney disease, heart failure and ischaemic stroke were independent risk factors for ICH.
The role of comorbidities for hospital outcome of patients with severe acute pulmonary embolism treated with thrombolytic therapy
Authors: Ruzicic D R , Dzudovic D Z B , Subotic S B , Salinger S S , Mitrovic M B , Kos K L J , Benic B M , Jevtic J E , Svircev S M , Mitevska M I , Bozovic B B , Neskovic N A , Obradovic O S
Published: October 2024

Background

The association between the outcome of severe acute pulmonary embolism treated with thrombolytic therapy and the presence of common comorbidities is fairly known.

Methodology

In this study we investigated the influence of common comorbidities (arterial hypertension, atrial fibrillation, heart failure, coronary disease, diabetes mellitus, active malignant disease, chronic obstructive lung disease, chronic renal failure, anemia and previous stroke) to hospital mortality and the composite of major and clinically relevant non-major bleeding at 7 days from hospital admission in patients with severe acute PE treated with thrombolytic therapy enrolled in the Regional PE Registry from the 4 west-Balkan countries. Univariate and multivariable regression analysis (adjusted to age and the presence of arterial hypotension – systolic blood pressure below 90 mmHg) was used to establish association between comorbidities and hospital outcome of acute PE treated with thrombolysis.

Results

2068 patients enrolled with computed tomography pulmonary angiography proven acute, symptomatic PE, and of them 645 patients had features of intermediate-high PE (right ventricle dysfunction with positive biomarkers without severe hypotension) and 283 patients had high-risk PE with arterial hypotension. Of them, 394 (42.5%) were treated with thrombolytic therapy (245 with intermediate-high and 149 with high-risk PE). Overall hospital mortality was 17.0% and the composite of major and clinically relevant non-major bleeding at 7 days was 17.5% (11.2% was major bleeding). Among all tested comorbidities, only 3-staged renal failure (OR 3.56, 95%CI 1.78-7.15, p<0.001 for creatinine clearance 30-59 ml/min compare to clearance ≥ 60 ml/min; and OR 6.01, 95%CI 2.35-15.37, p<0.001 for creatinine clearance <30 ml/min versus ≥ 60 ml/min), and the presence of either paroxysmal or chronic atrial fibrillation had significant higher risk for hospital mortality adjusted to age and the presence of arterial systolic hypotension (OR 2.11, 95% 1.03-4.29, p=0.04). Between all presented comorbidities only the presence of diabetes mellitus type 2 was independently associated with the higher risk for bleeding on thrombolytic therapy OR adjusted to age 2.03, 95%CI 1.126-3.659, p=0.019.

Conclusion

Creatinine clearance and atrial fibrillation were the independent predictors of hospital death and diabetes mellitus type 2 for bleeding in patients with severe acute PE who were treated with thrombolysis.
Prognostic impact of the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio in acute pulmonary embolism
Authors: Kultursay B , Keskin B , Tanyeri S , Kulahcioglu S , Hakgor A , Mutlu D , Bulu C , Tokgoz H C , Yucel E , Sekban A , Sirma D , Karagoz A , Tanboga I H , Ozdemir N , Kaymaz C
Published: October 2024

Background

Currently available risk stratification models for acute pulmonary embolism (PE) include hemodynamic status, cardiac biomarkers, right ventricle (RV) dysfunction on imaging, and clinical scores. Focusing on length-tension relationship of the ventricle might have a superior predictive capability over RV dysfunction in terms of mortality and classification of patients with acute PE. In this study, our hypothesis suggests that tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio has superior predictive capability for in-hospital mortality in patients with acute PE compared to TAPSE or sPAP as distinct measures.

Methods

This single-center study comprised retrospectively evaluated 703 patients referred to our tertiary cardiovascular center with acute PE. We divided patients into quartiles by TAPSE/sPAP ratio. Different models were developed to quantify the predictive relationship between in-hospital death and echocardiographic measurements. A base model was created with variables including risk status and RV/LV ratio >1. Then, to evaluate the predictive contribution of each measurement; TAPSE/sPAP, TAPSE, and sPAP were sequentially added to the base model. After that, the performance of each model was evaluated.

Results

Predictive and discriminative power was the highest in model containing TAPSE/sPAP. There was still a significant inverse association between TAPSE/sPAP and risk of in-hospital death even after adjusting by risk status and RV/LV ratio >1. ROC curve analysis for TAPSE/sPAP revealed the best cut-off value as 0.34.

Conclusion

The outcomes of our study reveals that the ratio of TAPSE/sPAP serves as a more potent predictor of mortality than either of the two measurements taken separately. The interpretation and utilization of the TAPSE/sPAP cut-off value in acute PE can assist in identifying patients at risk of deterioration and guide the consideration of more intensive treatment options across all risk groups.
Efficacy and safety of reduced-dose and slow-infusion intravenous alteplase regimen in patients with acute pulmonary embolism at intermediate-high-risk
Authors: Kultursay B , Keskin B , Sekban A , Hakgor A , Tokgoz H C , Tanyeri S , Sirma D , Bulus C , Karagoz A , Tanboga I H , Kulahcioglu S , Ozdemir N , Kaymaz C
Published: October 2024

Background

In patients with intermediate-high-risk (IHR) pulmonary embolism (PE), full-dose systemic thrombolytic treatment (STT) has been documented to lower the risk of hemodynamic decompensation and mortality, at the expense of an elevated risk of life-threatening bleeding. In this study, we aimed to evaluate the safety of reduced-dose STT regimen while maintaining effective reperfusion.

Methods

This single-center study comprised 124 retrospectively evaluated patients (female 58.9 % and mean age 55.4+15.8 years) diagnosed with acute PE at IHR status in accordance with European Society of Cardiology (ESC) 2019 acute PE guidelines in whom intravenous (i.v.) alteplase treatments were utilized. Patients fulfilling at least one of the following criteria have been included in the study: systolic blood pressure ≤ 110 mm Hg, heart rate > 100 bpm, SaO2 < 90 % on room air, respiratory rate > 20 breaths per minute, or serum lactate > 2 mmol/L. Exclusion criteria were any contraindication for STT and symptom onset > 14 days. Standard protocol for initial STT was i.v. infusion of alteplase of 25 mg over 4-6 hours. After completion of the infusion, a second STT in the same manner if one of the following criteria were present; heart rate > 100 bpm, SaO2 < 90 % or signs of organ hypoperfusion.

Results

Syncope and concomitant deep vein thrombosis were documented in 27.4 % and 49.2 % of patients, respectively. Baseline vital measures were as follows; heart rate: 112 +16.6 bpm, systolic blood pressure: 123+14.9 mm Hg, SaO2: 89 % (85-93), serum lactate 2.35 (1.6-2.9) mmol/L. Median alteplase dose and infusion duration were 50 (25-50) mg and 6 (4-10) hours, respectively. There were significant improvements in clinical parameters, pulmonary thrombus burden, pressure strain and right ventricular size and function as assessed by computed tomography and echocardiography (p< 0.001 for all). Minor and major bleeding events occurred in 3.2 % and 4.8 % of patients, respectively. One major bleed was due to cerebellar hemorrhage, but did not require surgery and patient was discharged without sequela. There were 6 (4.8 %) in-hospital deaths in which 2 were attributed to major hemorrhages and 4 due to hemodynamic decompensation.

Conclusion

In patients with acute IHR PE, reduced-dose and slow-infusion i.v. alteplase regimen seems to be a clinically relevant and safe reperfusion alternative to full-dose STT protocols associated with well-known major bleeding risks.
Recent secular trends of catheter-directed therapy for treatment of pulmonary embolism: a retrospective cohort study based on German national data
Authors: Oettinger V , Von Zur Muehlen C , Hilgendorf I , Wolf D , Rilinger J , Gauchel N , Maier A , Wessinger M , Kaier K , Westermann D , Olivier C
Published: October 2024

Background

Various approaches exist for treatment of pulmonary embolism, including systemic lysis, catheter-directed therapy, or anticoagulation.

Purpose

This study aimed to describe recent secular trends of treatment strategies for patients with pulmonary embolism.

Methods

Data were interrogated from the Research Data Centre of the German Federal Statistical Office by ICD- and OPS-codes. 800,119 patients with pulmonary embolism, who were treated in German hospitals between 2007 and 2021, were analyzed and grouped according to the therapeutic strategy: no lysis or intervention, systemic lysis, ultrasound-assisted thrombolysis, catheter-directed lysis without ultrasound, retriever system, other transluminal thrombus removal, or surgical thrombectomy. In-hospital outcomes were investigated with focus on the last 8 years.

Results

Of all patients examined, 37,885 were treated with systemic lysis, 1,383 with ultrasound-assisted thrombolysis, 2,520 with catheter-directed lysis without ultrasound, 181 with a retriever system, 695 with other transluminal thrombus removal, and 1,037 with surgical thrombectomy. There was an increase in all catheter-directed therapies between 2007 and 2021 (from 102 to 735 procedures per year) with more than twice as many procedures from 2019 to 2021 (from 343 to 735 procedures). Between 2014 and 2021, 453,893 patients with main diagnosis of pulmonary embolism were included in the analysis. Mean age was 58.4-68.1 years in the observed groups. 42.5-52.2% were female. Highest rates of cor pulmonale were observed in patients undergoing surgical thrombectomy (87.7%) and systemic lysis (80.1%), which also applied to shock (26.2% and 25.7%), while both rates were lowest in patients without lysis or intervention (cor pulmonale: 25.4%, shock: 1.8%). The overall in-hospital mortality rate was 8.3%, ranging between 6.5% in the ultrasound-assisted thrombolysis group and 38.4% in the systemic lysis group. In catheter-directed therapies, the rate of major bleeding (>5 units of red blood cells) was 4.9%, ranging from 3.1% for catheter-directed lysis without ultrasound to 10.1% for other transluminal thrombus removal. The rate of intracerebral bleeding was 1.4%, with 0.0% for ultrasound-assisted thrombolysis and 4.4% for treatment with a retriever system.

Conclusion

In recent years, the use of catheter-directed therapy for pulmonary embolism has steadily increased. Rates of in-hospital major bleeding events and intracerebral bleeding were low.
Types of pulmonary hypertension and prognosis in COVID-19: 18-months analysis of BNP-PL national database
Authors: Mamzer A , Waligora M , Kurzyna M , Mroczek E , Mularek-Kubzdela T , Pruszczyk P , Gasior M , Lewicka E , Karasek D , Kusmierczyk-Droszcz B , Mizia-Stec K , Ptaszynska K , Jachec W , Kopec G , Kasprzak J D
Published: October 2024

Introduction

The COVID-19 pandemic significantly increased mortality in the group of patients (pts) with pulmonary hypertension (PH). However, there is no data whether specific types of this disease, such as PAH associated with connective tissue diseases, were more likely to have a poor prognosis.

Aim

To assess mortality in the course of COVID-19 among pts diagnosed with PH, treated under the Polish ministry therapeutic program and registered in the national BNP-PL database, according to the type of PH.

Methods

We analyzed the records of the complete population of Polish pts treated under the National Drug Program of PH (PAH and CTEPH) and registered in the national database of BNP-PL from 01 March 2020 to 31 August 2022. The clinical severity of COVID-19 course and mortality were reviewed. Clinical characteristics of infected and deceased patients were compared in relation to the type of PH.

Results

The analysis included 143 pts with SARS-CoV-2 infection (mean age 61 ± 15 years; 60% female). Mortality rate was 24% (34/143, including 20 out-of-hospital deaths) vs. 2.6% for estimated in the general population. The highest mortality was observed in the group of pts with idiopathic PAH (33%), slightly lower among pts with connective tissue diseases [CTD] (29%). Patients with congenital heart diseases had a fairly good prognosis [CHD] (81% recovered), and the best survival was recorded in those with CTEPH (84%). CTD and IPAH were found to represent "high-risk" subset with mortality risk ~ 32% vs. ~ 17% in others (p=0.032). Etiologic categories had significant trend for different COVID-19 outcomes according to chi2 test for trend (p=0.039).

Conclusions

The SARS-CoV-2 infection in pulmonary hypertension pts was related to high mortality, with pts with IPAH had the worst prognosis, folloved by pts with CTD who might already have had lung involvement. Interestingly, the best survival was recorded in one of the oldest group - patients with CTEPH. This may be related to the chronic anticoagulant treatment used in this group, as significant disorders of coagulation pathways have been observed in SARS-CoV-2 infection.