bluuebunny/crossref_metadata_2025 huggingface dataset:
The adding value of fluid challenge and balloon occlusion tests in patients with atrial septal defect
Authors: D'Alto M , Chessa M , Santoro G , Giordano M , Gaio G , Romeo E , Argiento P , Wacker J , D'Aiello F , Sarubbi B , Russo M G , Golino P , Costantine A , Naeije R , Dimopoulos K
Published: October 2021

Background

Careful, step-wise assessment is required in all patients with an atrial septal defect (ASD) to exclude pre-existing pulmonary vascular disease or left ventricular disease. Fluid challenge test (FCT) and balloon occlusion testing (BOT) may unmask left ventricular disease and challenge the pulmonary circulation, but their complementary role in the evaluation of patients with “operable” ASD is not well established.

Aim

To evaluate the haemodynamic changes of the pulmonary circulation by FCT and BOT in ASD patients undergoing percutaneous closure according to the current guidelines.

Methods

Consecutive patients selected for percutaneous ASD closure underwent invasive hemodynamic assessment at baseline and after BOT, FCT and both.

Results

Fifty patients (mean age 47.3±11.7 years, 72% female) were included. All patients had a pulmonary-to-systemic flow ratio (QP/QS) ≥1.5, pulmonary vascular resistance (PVR) <5 WU and pulmonary arterial wedge pressure (PAWP) <15 mmHg. Individuals with a PVR ≥2 WU at baseline were older, more symptomatic, with a higher baseline systemic vascular resistance compared to the lower PVR group (PVR <2 WU; p<0.0001). The response of Qp/Qs to FCT was different between groups (p<0.0001, Figure 1). Patients with a lower baseline PVR experienced an increase in Qp/Qs, which remained above 1.5 in all patients, whereas in almost all (90%) patients with a higher baseline PVR, the Qp/Qs fell to below 1.5.

FCT caused a marked increase in pulmonary blood flow of almost 2 liters (p<0.0001) accompanied by increases in PAWP (p<0.0001). BOT led to a modest increase in PAWP (Δ1.5 [−1.0–7.0] mmHg, p<0.0001). FCT added to BOT caused a further increase in PAWP and Qs (both p<0.0001), while PVR was unchanged (p>0.1).

No difference was observed in the PAWP response to FCT, BOT or both between groups; no patients reached a PAWP ≥18 mmHg following FCT or BOT alone, but 4 (8%) patients did following the addition of FCT to BOT. No acute clinical adverse events were experienced by any patients.

Conclusions

None of the reported ASD patients presented with FCT criteria of post-capillary PH (that is a PAWP >18 mmHg). Even small rises in PVR may have significant implications on cardiovascular haemodynamics. In fact, patients with PVR <2 WU showed an increase in Qp/Qs, which remained above 1.5 in all patients, suggesting that they still had a distensible pulmonary circulation, whereas in almost all patients with a PVR ≥2 WU, the Qp/Qs fell to below 1.5.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Aortic stenosis: correlation of prenatal echocardiography to postmortem histology
Authors: Zwanenburg F , Van Munsteren J C , Wisse L J , De Ruiter M C , Haak M C , Jongbloed M R M
Published: October 2021

Background

Foetal aortic stenosis (AS) is a challenging congenital heart disease considering its potential to progress during the course of pregnancy. Especially at midgestation, it remains extremely difficult to distinguish the cases that end up biventricular from the cases that will develop into an hypoplastic left heart syndrome.

Purpose

To test the hypothesis that the degree of myocardial maturation is a possible predictor of biventricular outcome, we present 4 cases of foetal AS with a varying degree of severity and uniquely correlate differences in myocardial function based on prenatal echocardiography to their post-mortem histopathologic maturation.

Methods

We selected 4 cases with midgestational AS from our tertiary foetal cardiology service between 2018–2020. Speckle tracking recordings of the cardiac four-chamber view were performed during routine foetal echocardiography to quantify myocardial wall motion as a marker for myocardial function. Three cases decided to terminate the pregnancy and donated the cardiac specimen. Immunohistochemical labelling (ICH) against key markers for myocardial maturation (troponin-I, N-cadherin, connexin-43, MLC2A, MLC2V and α-SMA) and fibrosis (Sirius Red) were compared with 2 normal foetal cardiac specimens.

Results

Two cases with critical AS presented extremely decreased global and segmental longitudinal strain (GLS and SLS) values (GLS −2% and −0.9%) in the left ventricle (LV), indicating an impaired myocardial wall deformation. Post-mortem ICH showed overt endocardial fibro-elastosis (EFE) and pathological fibrosis patterns in the subendocardial layer which was remarkably spatially correlated to the EFE. The cardiomyocytes were disorganised with reduced expression of troponin-I and disturbed expression of connexin-43. The remaining 2 cases had normal LV appearance on foetal echocardiography, showing a mild reduction in left ventricular GLS and SLS (GLS −11.8% and −14.2%). Post-mortem ICH of 1 of these cases showed mild EFE with a milder fibrosis pattern. Cardiomyocytes were less disorganised but also showed a disturbed expression of connexin-43. The 4th case continued the pregnancy and had a biventricular outcome.

Conclusions

This is a unique case series showing that myocardial function correlates with high extent to histology. The degree of the reduction in myocardial function corresponded with the amount of pathological fibrosis patterns and disorganisation of the cardiomyocyte network. Myocardial wall motion on foetal echocardiography seems to hold promise as a possible marker for cardiac maturation.

Funding Acknowledgement

Type of funding sources: None. Speckle tracking and fibrosis patterns
Acute heart failure in congenital heart disease in adults: a single-institution study in Latin-America
Authors: Ortega Zhindon D B , Gonzalez-Pacheco H , Cervantes-Salazar J L , Calderon-Colmenero J , Manzur-Sandoval D , Briseno-Cruz J L , Araiza-Garaygordobil D , Sierra-Lara D , Gopar-Nieto R , Arias-Mendoza A
Published: October 2021

Background

Heart failure in the adult with adult congenital heart disease (ACHD) is a current topic due to its association with high morbidity and mortality and has been implicated as the leading cause of death in these kinds of patients.

Purpose

This study reports experience of patients with ACHD and Acute Heart Failure (AHF) hospitalized at a teaching center specialized in cardiovascular disease in Latin America.

Methods

A retrospective cohort study of patients with AHF who were hospitalized in the coronary care unit of a Latin-American teaching hospital from January 2006 to December 2018. Patients with ACHD were identified and their clinical characteristics and in-hospital evolution were analyzed.

Results

During the study period, of 7,759 patients admitted with AHF, 181 (2.3%) had ACHD. Their median age was 34 years and 53.6% were men. Patients were grouped as follows: (Group I) left to right shunt 51.4%, (Group II) left ventricular outflow tract obstruction 17.7%, (Group III) outflow tract obstruction of the right ventricle 7.2%, (Group IV) conotronchal anomalies 3.9% and (Group V) miscellaneous group 19.9%. In general, history of previous surgery was in 28.2%, the frequency was higher in Group I and Group III (38.5% and 31.3%, respectively). Overall, all-cause in-hospital mortality was higher among patients with AHF- ACHD compared with patients without ACHD with AHF (23.2% vs. 17.8%; p=0.05). Unadjusted in-hospital mortality was not significant different across the five groups (21.5%, 28.1%, 7.7%, 42.9% and 25.0% for Group I, Group II, Group III, Group IV and Group V, respectively; p=0.41) (Figure 1).

Conclusions

Adult patients with congenital heart disease and acute heart failure are a challenge in clinical and surgical management that entails a high in-hospital mortality. A high percentage of these patients are candidates for surgical treatment.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Improving risk stratifcation of pulmonary hypertension patients
Authors: Dias Ferreira Reis J P , Nogueira M , Branco L , Sousa L , Galrinho A , Cruz Ferreira R
Published: October 2021

Background

According to the 2016 ESC/ERS Guidelines on Pulmonary Hypertension (PH), the right atrial area (RAA) and the presence ofa pericardial effusion (PE) are the two main echocardiographic prognostic markers in PH patients (pts).

Aim

To assess the predictive ability of these two parameters.

Methods

Pts with PH were prospectively studied and several clinical/demographic/echocardiographic were retrieved as well as data from six-minute walk test (6MWT) and brain natriuretic peptide (BNP). All-cause mortality was analyzed by PE, RAA and other echocardiographic parameters for positive (PPV) and negative predictive value (NPV) to detect if the current guideline recommended cut-offs can precisely stratify risk in this setting. A survival analysis was performed to evaluate risk stratification (RS) provided by several different cut-offs.

Results

A total of 51 PH pts (mean age 54±46 years, 33.3% male, baseline BNP of 342.4±439.9pg/mL, mean 6MWT distance of 360.3±109.2 meters and baseline pulmonary artery systolic pressure of 78±26mmHg), of which 64.7% had Group I PH (GI) and 35.3% presented chronic thromboembolic pulmonary hypertension. There were no significant differences between these two groups, however pts in GI were significantly younger (p=0.001), achieved a lower 6MWT distance (p=0.038) and had worse values of right ventricular strain (p=0.040). 27 pts (52.9%) died during a mean follow-up of 52 months, with no differences between groups (p=0.756). The presence of a PE had a low NPV and PPV for the primary endpoint (45.0% and 45.5%, respectively), as well as the guideline recommended cut-offs for RAA (18cm2: NPV- 50.0% and PPV– 55.2%; 26cm2: NPV- 51.3% and PPV– 66.7%). A Pulsed Doppler Tei index (TIp) cut-off of 0.40 had a higher NPV (70.8%) and PPV (74.1%). By Kaplan-Meieran alysis, neither the presence of PE (log rank p=0.508) nor the recommended RAA cut-offs provided accurate risk discrimination (log rank p>0.05 for all). Pts below a TIp cut-off of 0.40 presented a significantly lower survival during follow-up (log rank p=0.002)

Conclusion

The currently recommended echocardiographic prognostic markers cannot precisely discriminate risk in PH pts. Markers of Right Ventricular Dysfunction may improve RS in this population.

Funding Acknowledgement

Type of funding sources: None.
Major arterial and venous thromboembolic complications in patients with COVID-19
Authors: Lalor N , Raffaeli A , Bottini F , Scapellato J L , Banos N , Pezzati L , Intile D , Longo F
Published: October 2021

Background

Cardiovascular complications; myocardial infarction (MI), ischemic stroke, and pulmonary embolism (PE), represent an important source of adverse outcomes in COVID-19 disease.

Objectives

To evaluate the incidence of thromboembolic events, specifically PE, MI and stroke; risk factors, management patterns and outcomes in patients who tested positive for COVID-19 through RT-PCR in a regional hospital.

Methods

We included 1125 adults patients admitted for COVID-19 infection between April 1 and October 30, 2020. The total cohort was analyzed by site of care: Intensive care (n=124) and nonintensive care (n=1001).

Results

Cardiovascular risk factors prevalence in patients with COVID-19 were: hypertension (25.5%), hyperlipidemia (23.2%) and diabetes (12%). Prophylactic anticoagulation and therapeutic anticoagulation was prescribed in intensive care group (91.1% and 33.1%, respectively) versus (84.8% and 12.5%, respectively) in nonintensive care setting. Frequencies of major arterial or venous thromboembolism, pulmonary embolism and myocardial infarction were highest in the intensive care group (29%, 20% and 8%, respectively) than nonintensive care cohort (1.4%, 0.7% and 0,5%, respectively). Hospital mortality was 29% in intensive care group and 1.3% in nonintensive care group.

Conclusions

Patients admitted for COVID-19 had a high risk of major arterial or venous thromboembolism events, especially in the intensive care setting, despite the use of thromboprophylaxis with heparin.

Funding Acknowledgement

Type of funding sources: None.
Use of mechanical pulmonary reperfusion and fibrinolysis in acute massive pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis
Authors: Chopard R , Nielsen P , Ius F , Pilichowski H , Meneveau N
Published: October 2021

Background and objectives

The optimal pulmonary revascularization strategy in acute massive pulmonary embolism (PE) requiring the implantation extra corporeal membrane oxygenation remains controversial, and data are sparse.

Methods

We conducted a systematic review and meta-analysis of available evidence regarding the use of mechanical reperfusion (i.e. surgical or catheter-based embolectomy) and fibrinolytic strategies (i.e. systemic fibrinolysis, catheter-directed fibrinolysis, or as stand-alone therapy) in terms of mortality and bleeding outcomes.

Results

The literature search identified 835 studies, 17 of which were included or a total of 321 PE patients with ECMO. In total, 31.1% were treated with mechanical pulmonary reperfusion, while 78.9% received fibrinolytic strategies. The mortality rate was 23.0% in the mechanical reperfusion group and 43.1% in the fibrinolysis group (Figure). The pooled OR for mortality with mechanical reperfusion was 0.46 (95% CI, 0.213–0.997; I2=28.3%) versus fibrinolysis. The rate of bleeding in PE patients under ECMO was 29.1% in the mechanical reperfusion group and 26.0% in the fibrinolytic reperfusion (OR, 1.09; 95% CI, 0.46–2.54; I2=0.0%) among 10 eligible studies with available bleeding data. The meta-regression model did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy” and “ECMO implantation before pulmonary reperfusion therapy”, and outcomes.

Conclusions

The results of the present meta-analysis and meta-regression suggest that surgical embolectomy yields the best results, regardless of the timing of VA-ECMO implantation in the reperfusion timeline, and regardless of whether fibrinolysis has been administered or not.

Funding Acknowledgement

Type of funding sources: None.
Effectiveness and safety of DOACs for the prevention of recurrent VTE: a prospective cohort study
Authors: Vinci A , Vedovati M C , De Natale M G , Pierpaoli L , Di Filippo F , Agnelli G , Becattini C
Published: October 2021

Background

In the direct oral anticoagulants (DOACs) era, extended anticoagulation after 6–12 months of treatment is an attractive strategy in patients with venous thromboembolism (VTE). Real-life data on the clinical benefit of DOAC over time is lacking.

Purpose

The aim of this study is to assess the effectiveness and safety of DOACs in patients with acute VTE treated for variable periods.

Methods

Data on patients with an objective diagnosis of acute VTE treated with DOACs were included in prospective cohort study. Study outcomes were recurrent VTE and major bleeding (ISTH definition).

Results

Overall, 934 patients were included (mean age 67.0±16.0, male gender 51.4%). Three-hundred and forty-six patients had a deep vein thrombosis (37.0%), 98 (10.5%) had isolated pulmonary embolism and 490 (52.5%) had both. One-hundred and sixty-nine patients (18.1%) had an active cancer, 59 (6.3%) a history of cancer and 365 patients (39.1%) an unprovoked VTE. During DOAC treatment (mean 21.6 months), 7 recurrent VTEs and 25 major bleedings occurred. In 546 and in 98 patients, DOAC was continued with full and reduced doses, respectively. In 290 patients (43.8% unprovoked, 13.8% active cancer, 42.4% associated with non-cancer risk factor), anticoagulants were withdrawn (average treatment duration 8.8 months) and 22 recurrent VTEs occurred over a follow-up off-treatment period of 31.9 months. In these patients, 2 episodes of major bleeding were observed. Overall, 201 patients died; fatal PE occurred in 4 and fatal bleeding in 1 patient. Time course for recurrent VTE according to 2019 ESC risk for recurrence is reported in the Figure.

Conclusions

In this cohort study, DOACs showed a good risk to benefit profile in the extended phase after an acute VTE event.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Cumulative incidence of recurrent VTE
Effectiveness and safety of apixaban vs warfarin among older venous thromboembolism patients: a subgroup analysis of age
Authors: Cohen A , Sah J , Dhamane A , Lee T , Rosenblatt L , Hlavacek P , Emir B , Keshishian A , Yuce H , Luo X
Published: October 2021

Background

Venous thromboembolism (VTE) is the third most common cardiovascular condition in adult patients. Older patients are at an increased risk of VTE. However, they have been underrepresented in clinical trials and evidence on the safety and effectiveness of anticoagulants in older VTE patients, especially very elderly patients (≥80 years), is sparse.

Purpose

To evaluate the risk of recurrent VTE, major bleeding (MB), and clinically relevant non-major (CRNM) bleeding among older VTE patients initiating apixaban or warfarin according to two age sub-groups: 65–79 and ≥80 years.

Methods

Older VTE patients (aged ≥65 years) who initiated apixaban or warfarin were identified from the CMS Medicare database (September 2014–December 2017). To balance the characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting (IPTW) was conducted. Post IPTW, a subgroup interaction analysis was conducted to evaluate if there was any difference in treatment effects between the two age subgroups (65–79 vs. ≥80) on recurrent VTE, MB, and CRNM bleeding. Cox proportional hazard models were used to conduct the interaction analysis, and the statistical significance of the interaction was set to p-value <0.10.

Results

A total of 22,135 apixaban and 45,840 warfarin patients with VTE aged ≥65 years were eligible for analysis. Post IPTW, patient characteristics were balanced between the apixaban and warfarin treatment cohorts. Apixaban patients had significantly lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin patients (Figure). 42,551 (62.6%) were aged 65–79 years and 25,424 (37.4%) were aged ≥80 years. Among apixaban or warfarin patients, those aged 65–79 years had lower Charlson comorbidity index scores (mean 2.7 vs 3.2) and were less likely to have a diagnosis of anemia (34.7–34.9% vs 42.3–42.5%), cerebrovascular disease (14.7–15.7% vs 20.3–20.5%), or dementia (5.0–6.9% vs 20.4–24.6%) compared to patients aged ≥80 years. Across both age subgroups, incidence rates of recurrent VTE, MB and CRNM bleeding were lower for apixaban vs. warfarin. No significant interaction was observed between the treatment and age on recurrent VTE and MB (Figure). There was a significant interaction between treatment and age on CRNM bleeding. Apixaban trended towards a lower risk of CRNM bleeding across both age groups but the treatment effect on CRNM bleeding was larger for patients aged 65–79 years.

Conclusion

The treatment effects of apixaban vs. warfarin on recurrent VTE and MB were consistently observed across both older age groups in this analysis. More studies are needed to evaluate management of VTE in an older and especially the very elderly population.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.
The longitudinal use of EmPHasis-10 and CAMPHOR questionnaire health-related quality of life scores in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
Authors: Hendriks P , Van Thor M C J , Wapenaar M , Chandoesing P P , Van Den Toorn L , Van Den Bosch A E , Post M C , Boomars K A
Published: October 2021

Background

Health-related quality of life (HRQoL) is impaired in patients with pulmonary hypertension (PH). The EmPHasis-10 and CAMPHOR questionnaires are developed to evaluate HRQoL specifically in patients with PH. Data on the longitudinal use of both questionnaires are still limited.

Purpose

This paper will evaluate and compare the longitudinal value of two health-related quality of life questionnaires specific for patients with pulmonary hypertension (CAMPHOR and EmPHasis-10 questionnaires) using a broad spectrum of clinical anchor points. Furthermore we will establish minimal clinically important differences (MCID) for both questionnaires.

Methods

Sixty-one treatment naïve pulmonary arterial hypertension or chronic thromboembolic patients were prospectively included. Patients were treated according to the current ESC/ERS guidelines. We compared EmPHasis-10 and CAMPHOR scores between baseline, 6 and 12 months of follow-up and evaluated the correlation between these scores and a 5-scale symptom severity score, 5-scale overall health score, NYHA-classification, six minute walk test distance (6MWD), NT-proBNP and echocardiographic parameters. MCIDs were calculated using distribution and anchor based calculations.

Results

After one year of treatment a significant reduction in EmPHasis-10 score and CAMPHOR QoL and symptoms domain score was observed. Moderate to good correlations were observed between the questionnaires and the overall-health and symptom severity score and 6MWD. No relevant correlations were seen between the questionnaires and NT-pro-BNP and echocardiographic parameters. EmPHasis-10 scores showed strong correlations with all CAMPHOR domains. The MCID for the EmPHasis-10 questionnaire was −8. The MCIDs for the CAMPHOR domains were: activity −3, symptoms −4, QoL −3.

Conclusion

The EmPHasis-10 and CAMPHOR questionnaires are valid tools for the longitudinal measurement of HRQoL in patients with PH. The much shorter EmPHasis-10 correlates well with the CAMPHOR domain scores and with the clinical endpoints and it may be easier to use in daily practice. We established acceptable MCIDs.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): This research project was supported by an unrestricting grant by Actelion pharmaceuticals.
Cavin-1 modulates BMP/Smad signaling through the interaction of Caveolin-1 with BMPRII in pulmonary artery endothelial cells
Authors: Tomita S , Nakanishi N , Ogata T , Suga T , Tsuji Y , Sakamoto A , Higuchi Y , Matoba S
Published: October 2021

Background

Pulmonary hypertension (PH) is a progressive disease associated with poor outcomes. Caveolin-1 (Cav1) and Cavin-1 are components of caveolae, and Cav1 is identified as a related gene of pulmonary arterial hypertension (PAH). Gene mutations of bone morphogenetic protein type II receptor (BMPRII) is the most common cause of PAH. BMPRII is localized in caveolae and associates with Cav1. However, the role of the Caveolin-Cavin system on the BMP/Smad signaling and the PAH progression has not been well-known.

Purpose

Our study aims to investigate the relationship between Caveolin-Cavin system and BMP/Smad signaling pathway in pulmonary artery endothelial cells (PAECs). [Methods] Cav1 knockout mice were used to assess PH, and caveolae in PAECs were observed by electron microscope. After knocking down Cav1 and/or Cavin-1 in human PAECs (hPAECs) using siRNA, we evaluated the phosphorylation of Smad by Western blotting. Apoptosis was explored by flow cytometry. To assess the interaction between Cav1 and BMPRII, and the effect of Cavin-1 for this interaction and BMP/Smad signaling, we performed immunoprecipitation, Co-immunostaining, Proximal Ligation Assay (PLA), GST pulldown assay, and Western blotting.

Results

As in previous reports, Cav1 knockout mice exhibited PH with pulmonary vascular remodeling and right ventricular hypertrophy and PAECs isolated from Cav1 knockout mice showed caveolae disappearance. Cav1 knockdown in hPAECs reduced BMPRII at the plasma membrane and Smad 1/5/9 phosphorylation. Cav1 knockdown also significantly increased hypoxia-induced apoptosis in hPAECs. Co-immunostaining revealed that Cav1 was associated with BMPRII at the membrane of hPAECs. Cavin-1 inhibited the interaction of BMPRII with Cav1 and reduced BMPRII localization on the membrane of hPAECs. GST pulldown assay revealed that Cavin-1 and BMPRII were associated with Cav1 through the scaffolding domain in Cav1. These findings suggest that Cavin-1 and BMPRII are competitively associated with Cav1. Cavin-1 knockdown improved the interaction between Cav1 and BMPRII and inhibited both BMPRII reduction at the plasma membrane and Smad 1/5/9 dephosphorylation.

Conclusions

Cavin-1 affects the interaction of Cav1 with BMPRII at the plasma membrane and modulates BMP/Smad signaling in PAECs. The binding of Cavin-1 to Cav1 enhances the interaction between BMPR2 and Cav1, resulting in stabilization of BMPRII localization at the plasma membrane in PAECs and prevention of BMP/Smad signaling attenuation, which is important for PAH development.

Funding Acknowledgement

Type of funding sources: None.
Family history of aortic dissection is not a risk factor in Marfan syndrome with a FBN1 gene mutation
Authors: Tchitchinadze M , Milleron O , Eliahou L , Jadoui S , Ould Ouali N , Hanna N , Arnaud P , Boileau C , Gouya L , Jondeau G
Published: October 2021

Background

A history family of aortic dissection was considered as a risk factor for aortic dissection in patients with Marfan syndrome with a FBN1 mutation.

Objectives

Evaluate whether a family history of aortic dissection is a risk marker for dissection in this population

Methods

Retrospective study of patients coming to the reference centre between 1996 and 2018, carrying a FBN1 gene mutation. Pedigrees were obtained for each patient, and familial screening actively pursued. Patients with a family history of aortic dissection were compared with patients without family history of aortic dissection.

Results

1700 patients (age 33.2 (±17) years, 51% women) with a FBN1 gene mutation were included. 145 (8,5%) patients underwent aortic dissection at a mean age of 37.9 (±11.4) years and 323 (19%) patients had been operated at 33.8 (±13.9) years.

481 patients had a family history of aortic dissection, including 38 who dissected themselves, and 88 who underwent surgery. 1219 had no family history of aortic dissection, including 107 who dissected themselves, and 235 who underwent surgery.

Therefore, the personal risk for aortic dissection was similar in patients with and without a family history of aortic dissection (38/481, i.e. 7.9% vs 107/1219, i.e. 8.8%), as was the personal risk for prophylactic aortic surgery (88/481, i.e. 18.3% vs. 253/1219, i.e. 17.2%), and the risk for either aortic dissection or prophylactic aortic surgery (118/481, i.e. 24.5% vs. 328/1219, i.e. 26.9%).

Conclusions

In Marfan syndrome with a FBN1 gene mutation, a family history of aortic dissection is not a marker of aortic disease severity.

Funding Acknowledgement

Type of funding sources: None.
Genotype-phenotype correlations in Marfan syndrome patients with FBN1 mutations: a cohort study on 1575 patients
Authors: Arnaud P , Milleron O , Hanna N , Ropers J , Ould Ouali N , Affoune A , Langeois M , Eliahou L , Arnoult F , Renard P , Michelon-Jouneaux M , Cotillon M , Gouya L , Boileau C , Jondeau G
Published: October 2021

Background

Marfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype-phenotype correlations have been found in probands' studies only.

Purpose

The aim of this study is to provide survival curves and genotype-phenotype correlations in all patients with FBN1 mutations, probands and relatives.

Methods

We established survival curves and sought genotype–phenotype correlations in a population of 1575 consecutive MFS patients with pathogenic class 4 or 5 variants in the FBN1 gene. This population represents the most comprehensive clinical database worldwide on MFS.

Results

Global survival was 90% at 60 years. However, lifelong aortic event rate (either dissection or surgery) and survival were impacted by the genotype. Premature termination codons (PTC), resulting in haploinsufficiency, were associated with a shorter life expectancy and a high lifelong risk of an aortic event (83%). Interestingly, these variants were also associated with the highest risk of severe scoliosis (52%) and with a lower risk for ectopia lentis (EL) surgery (13%). Dominant negative in-frame pathogenic variants could be subdivided according to their impact on the cysteine content of fibrillin-1: cysteine loss (–Cys) was associated with high aortic risk (73%) and a higher frequency of EL surgery (43%); cysteine addition was associated with moderate aortic risk (29%) and the highest frequency of EL surgery (48%); unchanged cysteine content was associated with high aortic risk (61%) and lower frequency of EL surgery (23%). No gene-region effect was observed, except for a more severe phenotype for in-frame variants with cysteine loss within the “neonatal region”. Aortic risk was greater for males in all subgroups, and probands were more severely affected.

Conclusions

MFS genotype-phenotype correlations related to pathogenic FBN1 variants exist for aortic and extra-aortic features. This leads us to propose new tools to refine the prognosis in this population. Preventive therapy with β-blockers and restricted exercise should be proposed regardless of the aortic diameter in the high aortic risk groups (PTC and –Cys variants). These results have major consequences on genetic counseling and personalized medicine for patients carrying a FBN1 mutation. This study also improves the overall understanding of the role of FBN1 in various organs.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Fondation Coeur et Recherche, Paris, FranceFédération Française de Cardiologie, Paris, France Patients with PTC vs. in-frame mutationsDifferences within in-frame mutations
Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with risk for thromboembolic complications and mortality in patients with COVID-19
Authors: Luo S , Samelko B , Du-Fay-De-Lavallaz J M , Gomez J M D , Zemke A M , Suboc T , Williams K A , Fugar S , Simmons J A , Volgman A S , Hayek S , Reiser J
Published: October 2021

Background/Introduction

The high prevalence of thromboembolism in patients with COVID-19 causes significant morbidity and mortality. The soluble urokinase-type plasminogen activator receptor (suPAR), a known inflammatory and immune mediator in several renal and cardiovascular conditions, has recently been shown to correlate with acute kidney injury and severe respiratory failure in COVID-19. To date, no study has investigated the association between suPAR and thromboembolism in COVID-19.

Purpose

To evaluate associations between suPAR, thromboembolic complications, and mortality in COVID-19.

Methods

We conducted a retrospective cohort study of a random sample of 109 patients among those hospitalised at a tertiary medical centre comprising three hospitals between March and June 2020 for COVID-19 who had blood samples collected and stored on admission. Serum suPAR was measured using a commercially available enzyme immunoassay. Baseline (hospital admission) variables extracted from electronic medical records included age, sex, race/ethnicity, body mass index (BMI), history of cardiovascular disease (including deep venous thrombosis [DVT] and pulmonary embolism [PE]), serum creatinine, serum D-dimer, incident DVT/PE, and death during hospitalization. Patients were subsequently grouped by suPAR quartiles. Associations between suPAR, thromboembolic complications (PE and/or DVT), and overall mortality were evaluated using multivariable logistic regression.

Results

Among the 109 patients, mean age was 56 (standard deviation [SD], 16) years, 34 (39%) were women, mean BMI was 35 (SD, 8) kg/m2, 78 (71%) had coexisting cardiovascular disease, median creatinine level was 1.2 (interquartile range [IQR]: 0.8–2.3) mg/dl, median D-dimer level was 1.5 (IQR, 0.8–6.4) μg/ml, and median suPAR level was 10.1 (IQR: 4.1–14.4) pg/mL. Seven (6%) patients were found to have PE, 18 (17%) developed PE/DVT, and 22 (20%) died during the admission (Table). Per quartile higher suPAR level, there was higher risk for PE or DVT (OR=2.02, 95% CI 1.07–3.83, p=0.03). Compared to those in the lowest suPAR quartile, patients in the highest quartile had 11.1 times higher risk for PE/DVT (OR=11.1, 95% CI 1.51–81.8, p=0.02, Figure). SuPAR is also associated with overall mortality, with 2.25 times higher risk of death seen per quartile increase in suPAR level (OR= 2.25, 95% CI 1.24–4.06, p=0.007).

Conclusion

Higher suPAR levels at the time of hospital admission is associated with higher risk for thromboembolic complications i.e., PE and DVT, as well as mortality in patients with COVID-19.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Rush University Medical Center
Impact of peripheral angioplasty on wound oxygenation measured with near-infrared spectroscopy in patients with critical limb ischemia
Authors: Foerster R , Stern M , Heinen Y , Baasen S , Sansone R , Heiss C , Kelm M , Busch H L
Published: October 2021

Impact of peripheral angioplasty on wound oxygenation measured with near-infrared spectroscopy in patients with critical limb ischemia

Abstract

Background

Near-infrared Spectroscopy (NIRS) has been proposed as a promising noninvasive tool for the assessment of hemoglobin oxygen saturation (StO2) in complex wounds in patients with critical limb ischemia (CLI).

Objective

Up today, NIRS measurements are undertaken at single points near the wound, but not in the wound.

Methods

In this prospective, single center study, 34 patients with PAD Rutherford stage 4–6 were included. We analyzed StO2 maps in and around the wound at baseline one day before and one day after angioplasty using a NIRS camera; macrovascular function was assessed by Doppler ultrasound with spectral analysis including ankle-brachial index (ABI).

Results

Baseline StO2 of the wound area was 63% (± 3.66 [SE]) and 34% in the wound (± 4.8 [SE]). After successful angioplasty, wound area StO2 significantly increased to 71% (± 3.09 [SE]; p<0.001) and wound StO2 increased even more pronounced to 42% (± 4,77 [SE]; p<0.001). Likewise, ABI increased in the treated leg (before 0.74±0.03 [SE]; after 0.87±0.02 [SE]; p=0.008).

Conclusion

This is the first study to assess oxygenation in the wound using a NIRS camera after peripheral angioplasty. NIRS monitoring of wound oxygenation in patients undergoing endovascular treatment is a promising tool to monitor tissue perfusion.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Pulmonology, and Vascular Medicine, University Duesseldorf, Medical Faculty, Duesseldorf, Germany
Impact of polyvascular disease on the prognosis of acute coronary syndrome
Authors: Laraba N , Menzou F , Aitali M , Krim M , Berrah A
Published: October 2021

The polyvascular disease reflects a diffuse atherosclerotic disease. By a prospective and descriptive study, recruiting three hundred thirty-six inpatient coronary care unit for acute coronary syndrome, the aim is to estimate the prevalence, to identify predictors factors and to assess the impact of the polyvascular disease in term of mortality and cardiovascular events (MACE 4points) at one, six and twelve months after discharge.

The polyvascular disease is defined by the presence of cerebrovascular disease or peripheral artery disease. The cerebrovascular disease is defined in patients with documented stroke or carotid stenosis assessed by ultrasound; the peripheral artery disease is defined by an anchle brachial index (ABI) inferior to 0.9.

The prevalence of polyvascular disease in patients with acute coronary syndrome (Men = 69,0%; mean age = 63,3y) is 28.9%. In our study population, 20.8% have cerebrovascular disease. A significant carotid stenosis is seen in 57 patients (16,7%), half of which have bilateral stenosis. 16.1% of patients have a peripheral artery disease. an ABI less than 0.45 is found in 7 patients (2,1%). 1.8% of patients have abdominal aortic aneurysm.

Many factors statistically associated with the polyvascular disease are identified. High blood pressure, thinness, advanced age, prolonged smoking and diabetes are the most powerful predictors. On admission, the polyvascular patients have more likely a KILLIP than or equal to two, anemia and kidney failure. They have an ejection fraction of the left ventricle lower than patients with only coronary artery disease. Their coronary artery disease appears more severe and extensive in coronary angiography.

Polyvascular disease appears as an independent and powerful predictor of mortality and cardiovascular events in the short and medium term in patients with acute coronary syndrome. The hazard ratio of polyvascular disease mortality at day 30, 6 months and 12 months of hospitalization are respectively 6.16, 4.44 and 5.91. The hazard ratio for disease polyvascular for cardiovascular events at 6 months and 12 months of hospitalization are 2.79 and 2.90 respectively.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): University hospital of Bab ElOued AlgiersUniversity hospital of Douéra Algiers
Derivation and validation of a pretest probability score for deep vein thrombosis before surgery
Authors: Hamamoto Y , Tokushige A , Yuasa T , Horizoe Y , Yasuda H , Kubozono T , Ikeda Y , Ohishi M
Published: October 2021

Background

Venous thromboembolism represents a crucial perioperative complication and causes morbidity and mortality. It is important to predict deep vein thrombosis (DVT) before surgery under general anesthesia.

Purpose

We developed a pretest probability score for predicting DVT with perioperative clinical and laboratory variables.

Methods

Total 7435 patients were planed surgery under general anesthesia between 2017 and 2018. 1313 patients were performed whole leg ultrasonography suspected DVT using cutoff point of D-dimer ≥1μg/ml. We excluded age <18 years, ongoing anticoagulant therapy, other thrombosis, protein C deficiency, disseminated intravascular coagulation, central venous catheter, pregnancy and aneurysm. We enrolled 971 patients, we divided into the derivation cohort or the validation cohort. The association of DVT with multiple variables was characterized in a derivation cohort of 651 patients. The score validated in an independent cohort of 322 patients from the same study. We also performed a validation of this model in an independent cohort of patients derived from the same observational study.

Results

We found 6 clinical and 1 laboratory parameters that predicted DVT in patients before surgery. The prediction rule for DVT assigned 2 points for D-dimer more than 1.44 μg/ml and 1 point for age ≥60 years, female, ongoing steroid, active cancer with high risk of DVT, prolong immobility and antipsychotic drug. In derivation and validation cohorts, area under the curve was 0.73 and 0.70, respectively. New preoperative risk model with these parameters stratified patients into 3 individual categories corresponding to the risk of DVT. Rates of DVT in the derivation and validation cohorts, respectively, were 6% and 7% in low-risk (score 0–2), 22% and 21% in intermediate-risk (score 3–4), and 49% and 47% in high-risk (score ≥5) category. Rates of fresh DVT were 1% and 3% in low-risk, 10% and 9% in intermediate-risk, and 33% and 19% in high-risk category.

Conclusion

This score stratifies perioperative DVT risk and may detect effectively DVT. The findings should be considered with the further prospective research.

Funding Acknowledgement

Type of funding sources: None. Rate of DVT
Association of rs12122341 polymorphism with the development of acute cerebrovascular event
Authors: Chernova A , Nikulina S , Nikulin D
Published: October 2021

Purpose

To study SNP rs12122341 (C> G) with development of Acute Cerebrovascular Event in the patients with cardiovascular pathology and risk factors of its development who are representatives of the east Siberian population.

Material and methods

260 patients with Acute Cerebrovascular Event participated in a research (age [57.0; 51.0–62.0]) and 272 patients of control group (age [55.0; 51.0–62.0].). Among the patients who transferred Acute Cerebrovascular Event, 157 men and 103 women. The control group included 170 men and 102 women. Inspection of the main group included: collecting complaints, anamnesis, clinical examination, computer tomography of a brain, electrocardiography, echo, ultrasonic of arteries, daily monitoring of arterial blood pressure and cardiac rhythm, analysis of a coagulant system of blood. Patients of the main group had the following cardiovascular pathology and risk factors: arterial hypertension, supraventricular tachycardia, dislipidemiya, atherosclerosis brachiocephalic of arteries, disturbances of a system of a hemostasis. The control group is examined within the international HAPIEE project. The molecular and genetic research was conducted by PCR method in real time. Statistical processing of material was carried out with use of set of the Statistica for Windows 7.0, Excel and SPSS 22 application programs.

Results

As a result of a research gender differences in functions of genotypes of SNP rs12122341 are set (C> G). So, for males risk factor of Acute Cerebrovascular Event is the genotype of CC, for female persons – CG genotype. In the general group of patients with Acute Cerebrovascular Event and also in subgroups of patients with different cardiovascular pathology and risk factors of statistically significant differences in frequencies of genotypes and alleles it is not revealed.

Conclusion

A genotype of the CC SNP rs12122341 (C> G) the risk of development of Acute Cerebrovascular Event in males in comparison with genotypes of CG and GG (p=0.009 raises; OR 1.83, 95% of CI: 1.16–2.91). The genotype of CG performs protective function concerning development of Acute Cerebrovascular Event in males. At female persons risk factor of development of Acute Cerebrovascular Event is CG genotype.

Funding Acknowledgement

Type of funding sources: None.
Distal versus conventional transradial access for coronary angiography and intervention: a systematic review and meta-analysis
Authors: Mhanna M , Beran A , Nazir S , Al-Abdouh A , Barbarawi M , Sajdeya O , Srour O , Burmeister C , Malhas S , Eltahawy E
Published: October 2021

Introduction

Distal transradial artery access (DTRA) has recently gained attention due to potential benefits in terms of local complications and risk of superficial palmar arch ischemia in case of radial artery occlusion.

Purpose

In this meta-analysis, we aimed to evaluate the utility of DTRA compared to conventional transradial artery access (CTRA) for coronary angiography and intervention.

Method

We performed a comprehensive literature search using multiple databases from inception through February 2021 for all the studies that evaluated the efficacy and safety of DTRA for coronary angiography and intervention. The primary outcome of interest was access success rate. The secondary outcomes were periprocedural local complications (site hematoma, radial artery occlusion or spasm) and procedural characteristics (cannulation, fluoroscopy, and radial artery compression times). All meta-analyses were conducted using a random-effect model.

Results

A total of 8 studies including 1630 patients (805 underwent DTRA vs. 825 with CTRA), were included in the final analysis. Three of the included studies were randomized controlled trials (RCTs), and the remainder were observational studies. The access success rate was similar in the two groups (odds ratio (OR): 0.61; 95% confidence interval (CI): 0.18–2.09; P=0.43; I2=72%). Similarly, no difference was observed in the overall periprocedural local complications rate (OR 0.63, 95% CI 0.38–1.04, P=0.07, I2=25%). On subgroup analysis, the rate of radial artery occlusion was significantly lower in DRTA group (OR 0.33, 95% CI 0.13–0.82, P=0.02, I2=0%). Regarding the procedural characteristics, the two approaches were different only in the cannulation time favoring the CTRA group (mean difference in minutes [MD] 0.96, 95% CI 0.16–1.76; P=0.02).

Conclusions

The DTRA represents an alternative site for radial artery access for coronary angiography and interventions, with a high success rate accompanied by a low risk of complications. Although the cannulation time was longer for the DTRA, this can potentially improve with training, practice, and utilization of ultrasound-guided punctures. The major advantage provided by the DTRA is the trend toward a lower risk of radial artery occlusion, which is frequently observed with the conventional approach. Further adequately powered RCTs are needed to confirm the safety and efficacy of this approach.

Funding Acknowledgement

Type of funding sources: None. Central illustration
Refined prediction and validation of individual risk using machine learning in transcatheter aortic valve implantation: TAVI Risk Machine (TRIM) scores
Authors: Leha A , Huber C , Friede T , Bauer T , Beckmann A , Bekeredjian R , Bleiziffer S , Herrmann E , Moellmann H , Walther T , Kutschka I , Hasenfuss G , Ensminger S , Frerker C , Seidler T
Published: October 2021

Background

Given the recent option for treatment using TAVI irrespective of surgical risk, general surgical risk scores have become less relevant, while TAVI-specific scores require refinement. Additionally, post-TAVI risk models are lacking; however, such risk models can support decision between post-TAVI treatment approaches, such as early discharge or close surveillance.

Purpose

This study aimed to predict 30-day mortality following transcatheter aortic valve implantation (TAVI) based on machine learning (ML) using data from the German Aortic Valve Registry.

Methods

Mortality risk was determined using a random forest ML model that was condensed in the newly developed TAVI Risk Machine (TRIM) scores, designed to represent clinically meaningful risk modelling before (TRIMpre) and after (TRIMpost) TAVI. Algorithm was trained and cross-validated on data of 24,452 patients and generalisation was examined on data of 5,889 patients.

Results

TRIMpost demonstrated significantly better performance than traditional scores (C-statistics value, 0.79; 95% confidence interval [CI] [0.74; 0.83]). An abridged TRIMpost score comprising 25 features (calculated using a web interface) exhibited significantly higher performance than traditional scores (C-statistics value, 0.74; 95% CI [0.70; 0.78]).

Conclusion

TRIM scores have high performance for risk estimation before and after TAVI. Together with clinical judgement, they may support standardised and objective decision-making before and after TAVI.

Funding Acknowledgement

Type of funding sources: None.