bluuebunny/crossref_metadata_2025 huggingface dataset:
Right ventricular-arterial coupling and exercise-induced tricuspid regurgitation
Authors: Mondellini G M , Rusconi I , Giustiniani A , Novello G , Dinardo G , Serrantoni V , Moscardelli S , Torta D , Losito M , Bursi F , Guazzi M
Published: November 2023

Background

Right Ventricular-pulmonary Artery (RV-PA) coupling is prognostic in a variety of cardiovascular disorders, including heart failure with preserved ejection fraction, pulmonary hypertension and severe aortic stenosis. The functional aspects of RV-PA coupling are less investigated than rest ones especially in what is their interaction with tricuspid regurgitation (TR).

Purpose

We sought to understand the association of RV-PA coupling with extent of exercise induced TR by combining gas exchange abnormalities through cardiopulmonary exercise test (CPET) imaging.

Methods

We prospectively studied patients with indication to perform a CPET imaging test due to dyspnoea and underlying heart disease of any left ventricular ejection fraction. Demographics, baseline characteristics, echo and CPET parameters [(e.g. VE/VCO2 slope and peak oxygen consumption (pVO2)] were evaluated across 3 sub-cohorts phenotyped according to TR severity pattern at rest and at peak exercise . Mitral and tricuspid regurgitation degree were adjudicated accordingly to ESC guidelines. RV-PA coupling function was assessed through the ratio between tricuspid annular plane systolic excursion (TAPSE), and non-invasive pulmonary artery systolic pressure (PASP) with echocardiography. Dynamic TR was defined as detection of at least moderate TR grade from rest to stress.

Results

A total of 73 patients (age 67±13 years, 52% men), with a mean LVEF of 50±14% were studied. Overall 50 (69%) patients had less than moderate TR which did not increase during stress (Controls), 11 (15%) patients exhibited a dynamic TR pattern (Group 1), and 12 (16%) already had significant TR at rest (Group 2). TAPSE/PASP at rest and peak exercise were significantly lower in Group 1 and 2 compared to Controls (Figure), while the mean PAP/cardiac output (CO) ratio at rest and at peak exercise were significantly higher (Table). As to gas exchange data, Group 1 and 2 exhibited a lower median peak VO2, while Group 2 patients had also a higher median VE/VCO2 slope compared to Controls (Table). 10 (14%) patients showed at least moderate mitral regurgitation (significant MR) at rest and the prevalence of significant MR at peak was higher in group 1 and 2 compared to Controls (Table). A weak negative correlation was found between TAPSE/PASP slope and E/e’ ratio at peak exercise (r =-0.435, p<0.01).

Conclusion

In presence of exercise dyspnoea, patients with dynamic TR during maximal exercise exhibit a worse degree of RV-PA coupling and gas exchange profile compared to the group without significant exercise-induced TR. Moreover, the exercise-induced TR profile behaves similarly to the one of those presenting with moderate to severe TR already detectable at rest. Phenotyping dynamic TR and RV-PA warrants further evidence on therapies and outcomes prediction in exertional dyspnoea patients.FigureTable
Right ventricular diastolic adaptation to pressure overload in different rat strains
Authors: Axelsen J , Andersen S , Ringgaard S , Nielsen-Kudsk J E , De Man F S , Andersen A
Published: November 2023

Background

Different rat strains are used in various animal models of pulmonary hypertension and right ventricular (RV) failure. No systematic assessment has been performed to test differences in RV response to pressure overload between rat strains.

Purpose

We compared RV adaptation to pulmonary trunk banding (PTB) in Wistar, Sprague Dawley, and Fischer344 rats by hemodynamic profiling focusing on diastolic function.

Methods

Age-matched male rat weanlings were randomized to sham operation (Wistar sham, n=5; Sprague Dawley sham, n=4; Fischer344 sham, n=4) or PTB (Wistar PTB, n=8; Sprague Dawley PTB, n=8; Fischer344 PTB, n=8). RV function was evaluated after five weeks by echocardiography, cardiac MRI, and invasive pressure-volume measurements and RV remodelling assessed by histological analyses.

Results

At end of study, Fischer344 rats weighed 25 % less than Wistar and Sprague Dawley rats. PTB increased RV systolic pressures four-fold, and RV failure was evident by a decrease in cardiac index (Wistar PTB: 1.8±0.2 mL/s/m2 vs. Wistar sham: 3.9±0.2 mL/s/m2, p<0.0001; Sprague Dawley PTB: 1.7±0.1 mL/s/m2 vs. Sprague Dawley sham: 3.0±0.3 mL/s/m2, p=0.0029; Fischer344 PTB: 2.1±0.2 mL/s/m2 vs. Fischer344 sham: 3.8±0.3 mL/s/m2, p<0.0001). There was a 2.4-fold increase in RV end-systolic volume index in Wistar PTB and Sprague Dawley PTB compared with sham, while Fischer344 PTB rats were less affected with only a 2.0-fold increase in RV end-systolic volume index compared with Fischer344 sham. Diastolic and right atrial impairment were evident by increased end-diastolic elastance, filling pressure, and E/e’ in PTB rats compared with sham, again Fischer344 PTB the least affected. PTB increased RV fibrosis in all groups compared with sham, though Fischer344 PTB showed a trend towards a smaller increase in RV fibrosis (Fischer344 PTB: 9.2±0.4 % vs Wistar PTB: 10.7±0.2 %, p=0.0919).

Conclusions

PTB caused RV failure in all rats subjected to the procedure including signs of diastolic dysfunction. Despite similar increase in RV systolic pressure, Fischer344 PTB rats showed less RV dilatation and where more able to sustain diastolic function compared with Wistar and Sprague Dawley PTB rats. All three rat strains are suitable for PTB and studies of RV failure.
Lung ultrasound, echocardiography and fluid loading for the differential diagnosis of pulmonary hypertension
Authors: D'alto M , Liccardo B , Di Maio M , Del Giudice C , Romeo E , Argiento P , Renon F , Vergara A , Di Vilio A , Bossone E , Rea G , D'andrea A , Gargani L , Golino P , Naeije R
Published: November 2023

Background

There may be interest in combining echocardiography and lung ultrasound for the differential diagnosis between pulmonary arterial hypertension (PAH) and post-capillary pulmonary hypertension on heart failure with preserved ejection fraction (PH-HFpEF).

Methods

Patients referred for PH underwent a right heart catheterization, echocardiography and lung ultrasound before and after rapid infusion of 7 ml/kg of saline. A 7-points echocardiographic score based on cardiac chamber dimensions and estimates of filling pressures was implemented for the prediction of pre-capillary PH. Pulmonary congestion was identified by lung ultrasound B-lines.

Results

The study enrolled 70 patients with PAH and 77 patients with HFpEF. The PAH patients had a higher echocardiographic score (3.5±1.8 v 1.6±1.5, p <0.001).

Figure 1 represents the typical baseline echocardiographic components of pre-capillary pulmonary hypertension prediction score and pre- and post-fluid loading lung ultrasound imaging from patients with PAH and HFpEF respectively. The HFpEF patients had more B-lines both before (8.1±4.2 vs 5.1±3.0; p <0.001) and after fluid loading (14.6±5.4 vs 7.6±3.5; p <0.001), and a more important increase (Δ) of B-lines after fluid loading (6.5±2.9 vs 2.5±1.6; p <0.001). The sensitivity and specificity of the echocardiographic score alone for PAH were 0.91 and 0.49 respectively [area under the curve (AUC) 0.78]. The AUC for PAH was improved by addition of smaller ΔB-lines to the echocardiography prediction score after fluid loading, with significant increase in sensitivity [0.94 (95% CI 0.89;1.00)] and specificity [0.91 (95% CI 0.84;0.97)] and a positive predictive value of 0.90 (CI 0.84;0.97) and a negative predictive value of 0.95 (CI 0.89;1.00).

Figure 2 represents the bar plot of AUC for echocardiographic score, pre- fluid loading B-lines, delta E/e', delta B-lines, post- fluid loading E/e', post- fluid loading B-lines, in ascending order.

Conclusion

Lung ultrasound combined with echocardiography at baseline and after fluid loading has an incremental value for the differential diagnosis between PAH and PH-HFpEF.Figure 1Figure 2
CMR imaging to study biventricular pacing effects on the right ventricle in left bundle branch block patients
Authors: Hopman L H G , Zweerink A , Van De Veerdonk M C , Van Der Lingen A C J , Huntelaar M J , Mulder M J , Robbers L F H , Van Rossum A C , Van Halm V P , Gotte M J W , Allaart C P
Published: November 2023

Background

Cardiac resynchronization therapy (CRT) is an established treatment strategy for selected patients with symptomatic heart failure, left ventricular (LV) systolic dysfunction, and a left bundle branch block conduction abnormality. The effect of CRT on right ventricular (RV) function and possible reverse remodeling however, is less well understood and conflicting data are present. Moreover, the difficulty to accurately measure RV hemodynamics non-invasively may also hamper research on RV function in CRT patients.

Recent development of cardiac magnetic resonance (CMR) conditional CRT-devices allows for proper patient follow-up as BIV-pacing can be performed during the CMR exam. Therefore, this study assesses the effects of BIV-pacing on change in RV volumes and function using CMR.

Methods

Ten patients eligible for CRT-D implantation according to the ESC guidelines were prospectively enrolled in this study. All patients underwent CMR imaging at baseline including cine imaging for volume and function assessment. Six weeks after CRT-D implantation, patients received a follow-up CMR scan which consisted of a two-staged imaging protocol. First, patients were scanned during BIV-pacing and thereafter the CRT was turned off and patients were scanned during intrinsic rhythm. RV end systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (RVEF) were assessed on cine images. RV volumes and function before and after device implantation are compared using paired samples T-tests and results are displayed in the figure.

Results

RV ESV, EDV, and RVEF were not different at CRT-on as compared to baseline (ESV; 94.0±20.3ml vs. 88.9±21.1ml, p=0.44, EDV; 182.4±29.5ml vs. 175.1±22.8ml, p=0.37, and RVEF; 48.6±6.6% vs. 49.6±8.1%, p=0.75). Also, an acute deterioration in RVEF was observed when switching CRT-off (48.6±6.6% vs. 41.1±5.7%, p=0.02). Moreover, RV function was significantly worse during CRT-off compared to baseline in terms of RVEF (41.1±5.7% vs. 49.6±8.1%, p<0.01) and higher volumes (ESV; 119.0±26.4ml vs. 88.9±21.1ml, p<0.001, EDV; 200.8±34.2ml vs. 175.1±22.8ml, p<0.01).

Conclusions

This study showed that RV hemodynamics did not benefit from CRT. Moreover, turning off CRT at follow-up had an instantaneous negative effect on RV function as compared to BIV-pacing, leading to even worse RV hemodynamics as compared to baseline measurements.
Value of exercise right heart catheterization for differential diagnosis of dyspnoea in chronic thromboembolic pulmonary disease
Authors: Huertas Nieto S , Velazquez Martin M V , Sarnago Cebada F , Manerio Melon N , Albarran Gonzalez-Trevilla A , Rivadulla Varela C , Jimenez Lopez-Guarch C , Aguilar Colindres R , Segura De La Cal T , Flox Camacho A , Cruz Utrilla A , Martin De Miguel I , Revilla Ostozala Y , Arribas Ynsaurriaga F , Escribano Subias P
Published: November 2023

Background and Purpose

Chronic thromboembolic disease (CTED) refers to chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but functional limitation attributable to incipient vasculopathy. Our aim is to evaluate the hemodynamic response to exercise in patients with suspected CTED without relevant resting PH.

Methods

We prospectively included symptomatic patients with persistent pulmonary thrombosis despite optimal anticoagulant therapy for a minimum of 3 months. Patients with left heart disease and abnormal lung function tests were excluded. Patients included had mean pulmonary arterial pressure (mPAP ) ≤25 mmHg, pulmonary vascular resistance (PVR) < 3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg. Exercise right heart catheterization (RHC) was performed via supine cycle ergometry. Exercise precapillary PH was defined as mPAP/CO slope >3 mmHg/l/min and PAWP/CO slope <2 mmHg/l/min. We made a subanalysis of those patients who fulfilled the new definition of resting PH (mPAP>20mmHg & PVR > 2 WU)

Results

We studied 39 patients (mean age 52.7 ± 15.7 years, 36 % women): 12 of them met new resting PH criteria (mPAP > 20 mmHg & RVP > 2 WU) , and 27 had normal resting hemodynamic. Baseline characteristics are summarized in Table 1 and did not reveal differences between groups except for haemodynamic parameters. From the entire cohort, 20 patients developed exercise PH: 14 (36%) with a precapillary pattern, and in 6 (15.4%) patients, the abnormal response was described as an abnormal PAWP/CO relationship during exercise. Exercise precapillary PH was documented in 67% of patients with resting PH according to the new PH criteria versus 37% of those without resting PH (Figure 1).

Conclusion

The functional limitation appears to be attributable to exercise precapillary PH in 36 % of patients with CTED suspicion and absence of significant resting PH. Exercise RHC is a valuable tool for diagnosing CTED and detecting other causes of dyspnoea, such as diastolic dysfunction. New resting PH haemodynamic criteria predict a higher percentage of abnormal exercise response, but one-third of patients develop exPH despite normal haemodynamic at rest.
Comparative investigation of pulmonary vasodilating effects of inhaled Nitric Oxide (NO) gas therapy and inhalation of SIN-1, a new drug formulation containing an NO-donor metabolite
Authors: Olah A , Barta B A , Ruppert M , Sayour A A , Nagy D , Balint T , Nagy G V , Puskas I , Szente L , Szocs L , Zima E , Merkely B , Radovits T
Published: November 2023

Background

The management of acute pulmonary hypertension has recently been in the center of attention as Coronavirus Disease 2019 (COVID-19) might lead to acute respiratory distress syndrome associated with hypoxia-induced pulmonary vasoconstriction. Therefore inhalation therapy has been the object of several clinical trials.

Purpose

In this experimental study we aimed at investigating the hemodynamic effect of inhalative SIN-1a (3-morpholino-syndnonimine, the unstable active metabolite of molsidomine, stabilized by cyclodextrine) administration during physiological and pathological conditions in a large animal model.

Methods

Landrace pigs were randomized into the following experimental groups: iNO (inhaled nitric-oxide, n=3), SIN-1-5 (5 mg, n=3), SIN-1-10 (10 mg, n=3). Hemodynamic parameters were recorded after parallel insertion of PiCCO system and Swan-Ganz catheter. The effect of iNO and SIN-1 inhalation (30 min) was investigated under physiologic conditions and U46619, a thromboxane-receptor agonist induced pulmonary hypertension.

Results

The observed alterations after inhalation therapy were quite similar under physiological and pathological condition. Pulmonary arterial pressure (PAP) was decreased by all of these drugs, SIN-1-10 had similar effect as iNO (physiological contidiont: -36.1% iNO, -23.8% SIN-1-5, -35.5% SIN-1-10; U46619-induced pulmonary hypertension: -30.1% iNO, -22.1% SIN-1-5, -31.2% SIN-1-10). While iNO therapy did not influence the mean arterial pressure (MAP) and systemic vascular resistance (SVR) values, SIN-1 administration resulted in decreased MAP and SVR values. Pulmonary vascular resistance (PVR) was decreased by iNO greater than with using SIN-1. As a result of these alterations, the PVR/SVR ratio decreased markedly in the iNO group, while it was stepwisely increased in the SIN-1-5 and SIN-1-10 group.

Conclusion

The pulmonary vasodilator effect of SIN-1 was dose dependent, and in case of larger dose it was comparable to that of iNO. However, the vasodilatory effects of SIN-1 inhalation was not limited to the pulmonary circulation, a significant and dose-dependent systemic vasodilation could also be documented.
PAH-specific treatment for patients with combined pre- and post-capillary pulmonary hypertension
Authors: Hofbauer T , Gerges C , Skoro-Sajer N , Sadushi-Kolici R , Prihoda M , Ondracek A S , Lang I M
Published: November 2023

Introduction

Pulmonary hypertension (PH) due to left heart disease (PH-LHD) is the most frequent form of PH, constituting approximately 70% of PH patients. Depending on the extent of pressure increase in the pre-capillary bed, PH-LHD is divided into isolated post-capillary PH, where pulmonary vascular resistance (PVR) is ≤2 WU, and combined pre- and post-capillary PH (Cpc-PH), where PVR exceeds 2 WU. Compared to Ipc-PH, Cpc-PH portents substantial morbidity and poor prognosis. Current PH guidelines recommend optimal treatment of underlying pathology, with drugs approved for pulmonary arterial hypertension (PAH) being not recommended; however, therapeutic regimens specifically targeting increases in pre-capillary pressure are urgently required.

Methods

For this analysis, we included all patients diagnosed with Cpc-PH invluding using right heart catheterization, who presented at the PH outpatient clinic of the Medical University of Vienna, Austria, between 02/2022 and 02/2023. Cpc-PH was defined hemodynamically as an elevated mean pulmonary arterial pressure (mPAP) of >20 mmHg and a PVR >2 WU.

Results

A total of 30 (6.5%) patients were diagnosed with Cpc-PH. Of these, 21 (70%) were female; median age was 75 [70, 76] years. Cardiovascular risk factors were arterial hypertension in 27 (90%), diabetes mellitus in 7 (23%), hyperlipidemia in 22 (73%), atrial fibrillation in 24 (80%), chronic kidney disease in 21 (70%), and coronary artery disease in 13 (43%) patients.

At diagnosis, median mPAP was 42 [36, 53] mmHg, with a PVR of 5.5 [3.4, 5.3] WU. Laboratory evidence of heart failure was illustrated by elevated NT-proBNP levels (2076 [1461, 3959] pg/mL). Transthoracic echocardiography showed mildly, moderately and severely reduced right ventricular (RV) function in 7 (23%), 9 (30%) and 3 (10%) patients. At diagnosis, 6 (20%), 20 (67%) and 4 (13%) patients were in WHO functional class II, III and IV, respectively.

PAH-specific therapy was initiated in 11 (37%) patients: 7 (23%) were put on treprostinil, 4 (13%) on macitentan, 3 (10%) on riociguat, and 3 (10%) on sildenafil. In 3 (10%) patients, combination therapy was started; one (3%) patient received triple therapy. In patients in whom PAH-specific therapy was initiated, PVR at baseline was higher (6.9 [5.4, 9.9] vs. 4.9 [3.1, 5.9] WU, p=0.019). Patients on PAH-specific therapy had a higher rate of improvement in WHO-FC at follow-up (82% vs. 31%, p=0.019).

Conclusions

In patients suffering from Cpc-PH, PAH-specific therapy leads to improvement of symptoms. Further studies are required to extend this finding to a larger patient group to assess whether PAH-specific drugs may also improve hemodynamics, right ventricular function and mortality.
Impact of triple vasodilator therapy on prognosis stratification of pulmonary arterial hypertension associated with congenital heart disease
Authors: Luna R , Segura De La Cal T , Sarnago Cebada F , Salguero R , Arribas F , Escribano Subias P
Published: November 2023

Background

Pulmonary arterial hypertension (PAH) affects 5-10% of congenital heart disease (CHD) patients but there is limited information on the effect of combination therapy in these patients. The aim of this study was to assess the effect of triple therapy (TT) with prostacyclins on the risk status of patients with PAH-CHD.

Methods

A retrospective, longitudinal, cohort study of patients with PAH-CHD under active follow-up in our center. All patients were receiving baseline dual therapy at maximum doses. A simplified global risk assessment according to the 2022 PAH guidelines was performed prior to initiation of treatment, and at subsequent annual follow-up for 2 years, including functional class, 6-minute walk test and NT proBNP.

Results

60 patients were included (median age 41, 31 women 61%). 32 had Eisenmenger syndrome, 9 had coincidental shunts, 18 had postoperative PAH, and 1 had a significant L-R shunt. TT was initiated based on the clinical situation, existence of shunt and ease of administration (epoprostenol 20%, treprostinil 41%, selexipag 32%, iloprost 7%). The use of triple therapy in patients with PAH-CHD demonstrated a significant overall improvement in risk status one year after initiation of treatment (p<0.05), which was maintained two years after initiation (Figure 1). Only four deaths and one lung transplantation occurred within this intermediate-high baseline risk PAH group. The estimated 2-year survival among those who completed treatment was 90%.

Conclusions

The use of triple therapy vasodilator treatment in patients with PAH-CHD demonstrates an overall improvement in risk status maintained over 2 years in line with that observed in other types of PAH.Evolution of the risk situation
Incidence and predictors of in-stent restenosis following intervention for pulmonary vein stenosis due to fibrosing mediastinitis
Authors: Cao C , Jia J , Su S , Jiang J , Wang W , Guo G , Zhu Z , Zhang Z
Published: November 2023

Background

Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis caused by fibrosing mediastinitis (PVS-FM). However, the incidence and predictors of in-stent restenosis (ISR) are elusive.

Purpose

We aim to identify the incidence and predictors of ISR in patients with pulmonary vein stenosis (PVS) caused by extra-luminal compression due to fibrosing mediastinitis (FM).

Methods

We enrolled patients with PVS-FM who underwent PTPV between 2018 and 2022. Patients were divided into ISR and non-ISR groups based on the presence of ISR. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR.

Results

A total of 109 stents were implanted in 102 PVs of 50 patients with PVS-FM. Over a median follow-up of 4.0 months (interquartile range: 3.0 to 11.0 months), there were 47 of 102 PVs suffered from ISR. The cumulative ISR was 3%, 12%, 42%, and 50% at 1-, 3-, 6-, and 12-month follow-up, respectively. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (OR 0.64, 95%CI 0.48-0.86, p = 0.002) and the narrowing severity of the corresponding pulmonary artery (Cor-PA) (severe) independently increased the risk of ISR (OR 6.63, 95%CI 1.82-24.18, p = 0.004), respectively.

Conclusions

ISR is very high in PVS-FM, which is independently associated with Cor-PA stenosis and RVD.
Acute effect of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension
Authors: Yanaka K , Taniguchi Y , Miwa K , Fujii H , Yoneda S , Nakayama K , Emoto N , Hirata K
Published: November 2023

Background

Pulmonary endarterectomy is known to improve hemodynamics in the early postoperative period on chronic thromboembolic pulmonary hypertension (CTEPH). However, there are no reports of early hemodynamic changes after balloon pulmonary angioplasty (BPA) for CTEPH.

Purpose

The aim of this study was to clarify early hemodynamic changes of BPA. Furthermore, we investigated whether the early hemodynamic changes were related to the chronic phase hemodynamics after final BPA.

Methods

We retrospectively enrolled 43 consecutive CTEPH patients placed Swan-Ganz catheter for hemodynamic monitoring at first BPA. Hemodynamics were evaluated immediately before (Pre), immediately after (Post), 3 hours, 6 hours, 9 hours, 12 hours, and 1 week after BPA. The hemodynamics in the chronic phase after final BPA were confirmed in each group in which the mean pulmonary artery pressure (mPAP) did not decrease immediately after BPA and 12 hours later.

Results

Although mPAP improved immediately after BPA, no change were observed thereafter and significant improvement were observed after 6 hours (Figure). While, cardiac output rose immediately and reached a peak 6 hours later. Then, it decreased and returned to value of Post after 1 week (Figure). MPAP/CO continued to decrease after BPA until 12 hours later (Figure). There were 16 and 8 cases in which mPAP did not decrease immediately after BPA and 12 hours later. However, mPAP in 16 and 8 cases became less than 20mmHg in the chronic phase (mPAP: Post; 28.5±7.3 to 19.6±5.6 mmHg, P<0.001, 12 hours; 26.0±7.8 to 17.8±3.5, P=0.02)

Conclusion

While mPAP after BPA decreased after 6 hours, there were a temporary rise in CO. Improvement can be obtained in the chronic phase after final BPA even if mean PAP did not decrease during the acute phase.
External validation of PE-SARD bleeding score for early major bleeding in patients with acute pulmonary embolism: Insight from the COMMAND VTE Registry-2
Authors: Nishimoto Y , Chatani R , Kaneda K , Ikeda N , Kobayashi Y , Ikeda S , Kim K , Takase T , Tsuji S , Oi M , Takada T , Otsui K , Watanabe T , Yamada T , Yamashita Y
Published: November 2023

Background/Introduction

The current guidelines and existing bleeding risk scores focus on assessing the risk of anticoagulant-related bleeding in patients with pulmonary embolism (PE) who are candidates for extended anticoagulation therapy. However, there is no consensus on the risk of bleeding in the acute phase. The Syncope, Anemia, Renal Dysfunction (PE-SARD) bleeding score has been developed to predict early major bleeding in acute PE patients. However, the score has not yet been externally validated.

Purpose

The present study aimed to externally validate the PE-SARD bleeding score, using a large-scale multicenter observational database of patients with venous thromboembolism (VTE).

Methods

The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 2722 patients with PE who received anticoagulation therapy during the acute phase and had a calculated PE-SARD bleeding score. The eligible patients were classified into three groups: high-risk group with a PE-SARD score >2.5 points, intermediate-risk group with a score of 1–2.5 points, and low-risk group with a score of 0 point. The discriminatory and calibration ability of the PE-SARD score for 30-day major bleeding were assessed by calculating the area under the receiver operating characteristic curve and creating a calibration plot, respectively.

Results

The high-risk group accounted for 537 patients (20%), intermediate-risk group for 1381 (51%), and low-risk group for 804 (30%). The proportion of thrombolysis use did not significantly differ across the groups. Among the patients who received direct oral anticoagulants (DOACs), the proportion of high-dose DOAC initiation was highest (54%) in the low-risk group and lowest in the high-risk group (29%). During the first 30 days of anticoagulation therapy, major bleeding occurred in 118 patients. The cumulative 30-day incidence of major bleeding substantially increased in the higher risk categories by the PE-SARD bleeding score (high-risk group: 8.2% [95% CI, 6.2%–10.9%], intermediate-risk group: 4.5% [95% CI, 3.5%–5.8%], and low-risk group: 1.8% [95% CI, 1.0%–3.0%], long-rank P<0.001). The discriminating power of the score was modest with a C-statistic of 0.65 (95%CI 0.61–0.70). Based on the calibration plot, the PE-SARD bleeding score was well calibrated. A sensitivity analysis excluding 275 outpatients showed similar results.

Conclusions

The risks of 30-day major bleeding in patients with PE substantially increased in the higher risk categories by using the PE-SARD bleeding score. The score is potentially helpful for management of anticoagulation therapy in the acute phase.The Kaplan-Meier curves
Different impact of each score component in the simplified PESI score on acute mortality of patients with pulmonary embolism in the era of direct oral anticoagulant
Authors: Nishikawa R N , Kaneda K K , Chatani R C , Nishimoto Y N , Ikeda N I , Kobayashi Y K , Ikeda S I , Kim K K , Takase T T , Tsuji S T , Oi M O , Takada T T , Otsui K O , Yamashita Y Y
Published: November 2023

Background

The simplified pulmonary embolism severity index (sPESI) score could help the risk stratification of acute mortality in patients with pulmonary embolism (PE) including identification of low-risk patients for outpatient treatment. The sPESI score consisted of six components such as age, history of cancer, history of chronic cardiopulmonary disease, heart rate, systolic blood pressure (sBP), and O2 saturation. However, the prognostic impact of each score component on acute mortality has not been fully evaluated in the era of direct oral anticoagulant (DOAC).

Methods

The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 centers in Japan between January 2015 and August 2020. In the current study, we evaluated 927 PE patients with the sPESI score 1, and investigated the impact of each score component on acute mortality and detailed causes of deaths.

Results

The distribution of score components of sPESI score were as follows; 80 years or older: 128 patients (14%), history of cancer: 353 patients (38%), history of chronic cardiopulmonary disease: 91 patients (9.9%), heart rate over 110 bpm: 72 patients (7.8%), sBP under 100 mmHg: 18 patients (2.0%), and O2 saturation under 90%: 258 patients (28%). Among the current study population, 736 patients (79%) developed PE out of hospital, and a majority of them (83%) admitted to the hospital with a median length of hospital stay of 14 days. The cumulative 30-day incidence of all-cause death was 2.1%, and the proportions of mortality varied widely depending on different score component of the sPESI (80 years or older: 0.8%, history of cancer: 4.6%, history of chronic cardiopulmonary disease: 1.1%, heart rate over 110 bpm: 0%, sBP under 100 mmHg: 0%, and O2 saturation under 90%: 0.4%). Among all-cause death events, PE-related deaths accounted 1 in patients with history of cancer, 1 in those with history of chronic cardiopulmonary disease, and 1 in those with O2 saturation under 90%.

Conclusions

The risk of acute mortality in patients with sPESI score 1 was relatively low in the era of DOAC, although that could vary widely according to each score component of the sPESI score, which could be useful for the further risk stratification among these patients.
Acute infections and inflammatory biomarkers in patients with acute pulmonary embolism
Authors: Eggers A , Hafian A , Lerchbaumer M , Hasenfus G , Lankeit M , Ebner M
Published: November 2023

Background

Although pneumonia is considered a common complication of acute pulmonary embolism (PE), the true incidence of infections after PE and the effect of infections on patient outcome are insufficiently studied.

Purpose

To investigate incidence and prognostic impact of acute infections and inflammatory biomarkers in patients with acute PE.

Methods

Consecutive PE patients enrolled in a prospective single-centre registry between 09/2008 and 02/2019 were studied. We excluded patients with (1) missing C-reactive protein (CRP) measurements at the time of PE diagnosis, (2) cardiopulmonary resuscitation as the presenting symptom, and (3) other acute cardiopulmonary or infectious disease responsible for the clinical presentation. We evaluated the incidence and impact of infections requiring antibiotic treatment and of inflammatory biomarkers (CRP and procalcitonin [PCT]) on the primary study outcome (hemodynamic insufficiency or in-hospital all-cause death) and the duration of the in-hospital stay.

Results

We analysed data from 749 patients (age 69 [interquartile range (IQR) 56-78] years). The primary study outcome occurred in 65 (8.7%) patients. Of 26 (3.4%) patients who died during the in-hospital stay, 17 (65.4%) deaths were due to PE and 6 (23.1%) due to infections.

During the first 7 days after PE 347 (46.3%) patients required antibiotic treatment; in 79.6% due to pneumonia (Figure). On multivariate logistic regression analyses, antibiotic treatment increased the risk for the primary outcome with an OR of 3.12 (95% confidence interval [CI] 1.70-5.74), similar to an increase in one risk class of the ESC 2019 risk stratification algorithm (OR 3.45 [95% CI 2.24-5.30]). Furthermore, patients requiring antibiotic treatment had a longer duration of in-hospital stay compared to patients with no antibiotic treatment (11.0 vs. 7.0 days, p<0.001).

At presentation, the majority of patients (86.4%) had CRP elevations above the upper limit of normal (median 33.5 [IQR 11.4-71.2] mg/l) and 34.2% had elevated PCT levels (median 0.05 [IQR 0.03-0.10] µg/l). CRP >124 mg/l and PCT >0.25 µg/l predicted the main study outcome with >90% specificity and odds ratios (OR) of 4.64 (95% CI 2.52-8.21) and 6.88 (95% CI 3.48-13.59), respectively. Furthermore, the predictive value associated with elevated inflammatory markers was independent of established risk factors for early mortality such as elevated troponin and the simplified Pulmonary Embolism Severity Index (sPESI).

Conclusion

Clinically relevant infections requiring antibiotic treatment occurred in almost half of patients with acute PE and carried a similar prognostic effect as an increase in one risk class of the ESC 2019 risk stratification algorithm. Furthermore, elevated levels of CRP and PCT were independent predictors of adverse outcome.Indications for antibiotic treatment
Large-bore mechanical thrombectomy for intermediate- and high-risk pulmonary embolism: interim outcomes from the European cohort of the FLASH registry
Authors: Mahfoud F
Published: November 2023

Background/Introduction

Mechanical thrombectomy is utilized for the treatment of acute pulmonary embolism (PE), but reported outcomes are limited in the European patient population.

Purpose

To report interim results from the European cohort of a large, prospective all-comer registry of mechanical thrombectomy for PE treatment.

Methods

The FLASH registry is a multinational, prospective, observational study of safety and effectiveness outcomes for PE treatment using a large-bore mechanical thrombectomy system. FLASH is currently enrolling up to 200 patients in Europe. The primary endpoint is a composite of Major Adverse Events (MAEs) within 48 hours, including device-related deaths, major bleeding, and intraprocedural AEs. Additional assessments include invasive hemodynamics, hospital resource usage, and dyspnea improvement.

Results

Interim results through 48 hours post-thrombectomy are presented for the first 29 patients enrolled in the European cohort across 4 institutions. Mean patient age was 64.9±14.5 years, 51.7% of patients were male, 10.3% were contraindicated for thrombolysis, 51.7% had concomitant deep vein thrombosis, and 79.3% had centrally located thrombus involving one or both main pulmonary arteries. Per ESC guidelines, 58.6% of patients were classified as high-risk. The remaining 41.4% of patients were classified as intermediate-risk, with 31.0% being intermediate-high-risk.

Pre-thrombectomy, the median RV/LV ratio from a composite of computed tomography and echocardiography was 1.31 [IQR: 1.08-1.44], and 38.9% of patients who had cardiac index (CI) measured were in cardiogenic shock (CI ≤2 L/min/m²).

Procedural characteristics included a median thrombectomy time of 39 minutes [IQR: 26-49]. Extracorporeal membrane oxygenation was used in 6.9% of patients. Post-thrombectomy, the median length of stay in the intensive care unit (ICU) was 1 overnight [IQR: 0-2], and 48.1% of patients required no overnight ICU stay. In addition, hemodynamic variables, vitals, dyspnea symptoms, and reliance on supplemental oxygen all improved significantly post-thrombectomy (Table 1).

Acute safety and mortality outcomes were highly favorable following the procedure (Table 2). All patients survived through 48 hours post-thrombectomy. There were no MAEs (0%), no major access site complications (0%), and no device-related Serious AEs (0%) through 48-hour follow-up.

Conclusions

Interim results from the first 29 patients in the European cohort of the FLASH registry suggest that large-bore mechanical thrombectomy can be safely performed in both intermediate- and high-risk PE patients, with no MAEs or mortalities observed through 48 hours. Significant improvements observed in multiple hemodynamic and dyspnea-related variables further suggest that thrombectomy can offer effective reperfusion treatment for acute PE.
Associated factors and clinical implications of dynamic changes in late gadolinium enhancement after acute myocarditis
Authors: Bohbot Y , Sanguineti F , Renard C , Hovasse T , Limouzineau I , Unterseeh T , Di Lena C , Boukefoussa W , Tawa C , Duhamel S , Garot P , Tribouilloy C , Garot J
Published: November 2023

Background

Although follow-up cardiac magnetic resonance (CMR) is often performed after acute myocarditis (AM), the prognostic implications of dynamic changes in late gadolinium enhancement (LGE) are unknown.

Purposes

To determine the prognostic implications of dynamic LGE changes after acute AM.

Methods

In a two-centre study, 204 consecutive hemodynamically stable patients (mean age 35±16 years, 78.9% males) with a CMR-based diagnosis of AM were included and underwent repeat CMR 3-12 months after diagnosis. Quantitative LGE was expressed as percent of left ventricular (LV) myocardium. The primary endpoint was the occurrence of major adverse cardiac events (MACE) at median 7.3[IQR:5.7-8.7] years.

Results

Compared to index CMR, there was an increase in LV ejection fraction (EF) (59% vs. 55%,p<0.001) and a decrease in LGE extent (7.6% vs. 12.0%,p<0.001) at follow-up (mean 5.7±2.6 months after index CMR). LGE persisted in 175 patients at follow-up (85.8%). LGE decreased by ≥50% from baseline in 94 patients (46%), by <50% in 86(42%) and increased in 24(12%). Female gender (OR[95%CI]=3.27[1.17-9.12],p=0.023), low baseline LVEF (OR[95%CI]=0.93[0.88-0.98] per %,p=0.010) and LGE involving both septal and lateral walls (OR[95%CI]=4.64[1.77-12.17],p=0.002) were independently associated with increased LGE. By multivariate Cox analysis, only acute heart failure at inclusion (HR[95%CI]=3.11[1.02-9.20],p=0.044), baseline LVEF (HR[95%CI]=0.95[0.89-0.99] per %,p=0.028), a <50% LGE decrease (HR[95%CI]=2.17[1.23-3.88],p=0.021) and an increase in LGE (HR[95%CI]=4.12[1.47-11.52],p=0.004) were significantly associated with MACE.

Conclusion

After AM, LGE persists at 6 months in the vast majority of patients but tends to decrease. A <50% decrease or an increase in LGE are associated with MACE, indicating that follow-up CMR is relevant for risk stratification.SUMMARY OF THE STUDY
Effectiveness and safety of catheter-directed thrombolysis for pulmonary embolism in key patient subgroups: results of an individual patient level analysis
Authors: Fumagalli R , Fuerbringer Schwarz A , Catalani F , Farmakis I , Kucher N , Konstantinides S , Barco S
Published: November 2023

Background

The effectiveness of catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE) has been rarely investigated in subgroups of patients at a higher risk of complications. Furthermore, this group of patients has been excluded from prior and ongoing phase 3 trials with CDT.

Purpose

To assess the efficacy and safety of catheter-directed thrombolysis for pulmonary embolism among specific patient subpopulations.

Material and methods

We conducted an individual patient-level analysis of patient data from 16 cohort studies and randomized trials of CDT for intermediate- and high-risk acute PE. Studies were identified on the basis of a systematic review of the literature. We focused on early clinical outcomes, including haemodynamic decompensation, intracranial bleeding, major bleeding, and death, as well as on the changes in the mean pulmonary artery pressure (mPAP) before and after CDT. We predefined three subgroups of at-risk patients: (i) older age (i.e. ≥75 years), (ii) active cancer, and (iii) surgery in the prior 4 weeks.

Results

We studied 1244 patients, of whom 586 (47.1%) were women. The median age was 61 (Q1-Q3; 50-71) years. There were 202 (16.3% of total available) patients aged 75 years or older, 101 (10%) with active cancer, and 108 (14.8%) with prior surgery. A total of 946 (89.3%) patients had intermediate-risk PE, and 113 (10.7%) were classified in the high-risk group. Patients aged ≥75 years more frequently suffered haemodynamic decompensation (7.5% vs 1.6% aged <75 years; p< 0.001), major bleeding (12.7% vs 4.5%; p<0.001), and death (9.2% vs 2.2%; p<0.001); Table 1. In a multivariable logistic regression model, age remained associated with death, major bleeding, and haemodynamic decompensation after adjustment for a key prognostic factor (high-risk PE). The same, except for decompensation, was observed after conditioning for sex, high-risk PE, and cancer status. Patients with active cancer showed a tendency to a higher 30-day case fatality when compared with patients with no active cancer, without reaching statistical significance; Table 1. Recent surgery did not appear to influence the outcome rate in this cohort. No differences were found among the three subgroups regarding the reduction of the mPAP following CDT ; Table 2.

Conclusions

Our results point to age as a strong predictor of early mortality and decompensation in patients undergoing CDT, even after adjusting for the higher rate of high-risk PE in the elderly. The clinical net benefit of CDT in the elderly when accounting for bleeding and the risk of haemodynamic decompensation remains unclear.Efficacy and safety outcomes of CDTmPAP values before and after CDT
Macitentan tadalafil Fixed Dose Combination (FDC) in treatment-naive and prior monotherapy patients with Pulmonary Arterial Hypertension (PAH): insights from A DUE
Authors: Gruenig E , Jansa P , Fan F , Friberg M , Lassen C , Pannaux M , Rofael H , Chin K
Published: November 2023

Background

Combination therapy is recommended for the management of pulmonary arterial hypertension (PAH). The A DUE study showed that M/T FDC, a fixed dose combination (FDC) of the endothelin receptor antagonist (ERA) macitentan 10mg (M) and the phosphodiesterase type 5 inhibitor (PDE5i) tadalafil 40mg (T), led to a clinically relevant improvement in pulmonary vascular resistance (PVR) vs macitentan and tadalafil monotherapies in PAH patients. A clinically meaningful trend for improvement in 6-minute walk distance (6MWD) in favor of M/T FDC vs macitentan and tadalafil was observed.

Purpose

Here we analysed the effect of M/T FDC in the subgroups of treatment-naïve and prior monotherapy patients.

Methods

In A DUE 187 adult PAH patients in WHO functional class II / III were randomised 2:1:1 to M/T FDC, macitentan or tadalafil if treatment-naïve, 2:1 to M/T FDC or macitentan if on prior ERA, and 2:1 to M/T FDC or tadalafil if on prior PDE5i. The treatment effect of M/T FDC vs macitentan and M/T FDC vs tadalafil was calculated using ANCOVA models for PVR (geometric mean ratios [95% CL]) and for 6MWD (mean change [95% CL]) in treatment-naïve patients and in patients on prior monotherapy (ERA or PDE5i) at randomisation.

Results

Treatment effects for M/T FDC versus macitentan and versus tadalafil on the change in PVR and 6MWD are reported in the table for each subgroup, along with those for the overall population. The safety profile of M/T FDC was in line with the safety profiles of macitentan and tadalafil.

Conclusions

In A DUE, the effect of M/T FDC vs both monotherapies on PVR and 6MWD in treatment-naïve and prior ERA/PDE5i patients was consistent with that observed in the overall population.
A comprehensive CMR analysis improves risk stratification in left ventricular noncompaction
Authors: Casas G , Rodenas E , Gonzalez-Del-Hoyo M , Barriales R , Garcia-Pavia P , Villacorta E , Zorio E , Jimenez-Jaimez J , Bayes A , Ripoll T , Gimeno J R , Guala A , Limeres J , Ferreira-Gonzalez I , Rodriguez-Palomares J F
Published: November 2023

Background

Left ventricular noncompaction (LVNC) is a heterogeneous and controversial entity. Risk assessment by cardiovascular magnetic resonance (CMR) remains poorly defined.

Purpose

To develop a CMR prediction model of major adverse cardiovascular events (MACE) in LVNC.

Methods

We conducted a retrospective longitudinal multicentre cohort study of LVNC patients with core-lab CMR analysis. The endpoint was a composite of MACE: heart failure, ventricular arrhythmias, systemic embolisms and all-cause death. The effect of variables on the endpoint was analysed by Cox regression and variables were dichotomized according to their association with the outcome. Three sequential prediction models were developed: a "traditional model" based on LV ejection fraction (LVEF); a "clinical model" based on daily-practice CMR variables (e.g.: LVEF, right ventricular (RV) EF, and late gadolinium enhancement (LGE)); and a "research model" including advanced parameters (e.g.: global longitudinal strain (GLS) and hemodynamic forces (HDF)). The best prediction models were chosen based on C-statistic and Akaike information criterion (AIC). A risk score was developed based on the third model, and according to proportional hazard ratios.

Results

A total of 348 patients were included, age was 46 (19) years and 150 (43%) were female. LVEF was 48 (14) % and 32 (10%) had LGE. During a median follow-up of 3.9 (1.8-6.1) years, 54 (16%) patients developed MACE: 27 (8%) heart failure, 32 (9%) ventricular arrhythmias, 2 (1%) systemic embolisms and 6 (2%) deaths. Figure 1 shows the association of the main CMR variables with the endpoint.

The "traditional model" (dichotomic LVEF with cut-off point at 40%) had an AUC of 0.71 (95% CI: 0.64-0.78). The best "clinical model" was a combination of LVEF, RVEF (cut-off point 35%), left atrium (LA) volume index (cut-off point 53 mL/m2) and percentage of LGE mass (LGE%, cut-off point 5%), with an AUC of 0.77 (95% CI: 0.70-0.85; p=0.006 compared to the first model). The best "research model" included LVEF, RVEF, LGE%, LA GLS (two cut-off points 17% and 28%), and lateral-septal HDF (cut-off point 3%), with an AUC of 0.85 (95% CI: 0.80-0.90; p=0.007 compared to the second model) (Figure 2a).

Subsequently, a risk score was developed: 1 point was assigned to LVEF<40%, RVEF<35%, LGE% >5% and LA-GLS <28%, 2 points to LA-GLS <17% and 4 points to HDF<3%. The score was accurate at identifying both low- (0-4 points), intermediate- (5-7 points) and high-risk (8-9 points) patients (Figure 2b).

Conclusions

A comprehensive CMR evaluation in LVNC allows for precise risk stratification. Our proposed prediction model could be used to individualise patients’ management, which might improve long-term outcomes.CMR characteristics according to MACEPrediction models of MACE and risk score