bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical features and natural history of RASopathy-associated hypertrophic cardiomyopathy in children
Authors: Boleti O , Field E , Norrish G , Dady K , Summers K , Lord E , Smyth S , Thompson E , Cervi E , Kaski J P 
Published: October 2021

Abstract

Background
The RASopathies are a group of genetic disorders caused by germline mutations in genes encoding components of the RAS/MAPK signalling pathway and frequently associated with hypertrophic cardiomyopathy (HCM). The clinical features and outcomes of RASopathy-related HCM are incompletely understood and most published studies are limited by relatively small numbers and incomplete clinical characterisation.

Purpose
To describe the clinical features outcomes in a large, single-centre cohort of patients with RASopathy-associated HCM diagnosed &lt;18 years.

Methods
Data from 105 patients [68 (64.8%) males] diagnosed in childhood with RASopathy-associated HCM at a single specialist centre between 1985 and 2020 were retrospectively analysed.

Results
The RASopathy diagnosis was Noonan syndrome in 69 patients (65.7%); NSML in 10 (9.5%); CFC in 6 (5.7%); Costello in 5 (4.8%) and 15 patients (14.2%) had another Noonan-like variant. 72 patients (68.6%) had a pathogenic/likely pathogenic variant in a RAS-MAPK gene, most commonly PTPN11 [n=25 (34.7%)], followed by RAF 1 [n=13 (18.1%)]. 100 patients (95.2%) were probands, 9 (8.6%) had family history of cardiomyopathy and 2 (1.9%) family history of sudden cardiac death (SCD). 52 (49.5%) had concomitant congenital heart defects (CHD) [ASD 13 (25%), VSD 6 (11.5%), PDA 1 (1.9%), &gt;1 CHD 32 (61.5%)]. 29 (27.6%) had symptoms at baseline assessment and 56 (53.3%) were on cardiac medication. The distribution of left ventricular hypertrophy (LVH) was concentric in 47 (44.7%); 32 (30.5%) had asymmetric septal hypertrophy (ASH), and undocumented in 25 patients (23.8%). 45 patients (42.9%) had biventricular hypertrophy (BVH). Resting left ventricular outflow tract obstruction (LVOTO) was present in 39 (37.1%) with haemodynamically significant LVOTO (≥50mmHg) in 23 (21.9%). Resting right ventricular outflow tract obstruction (RVOTO) was present in 21 (20%). Over a median follow up time of 6 years, 19 patients (18.1%) died [1 (5.3%) SCD; 2 (10.5%) due to Heart Failure-related death; 1 (5.3%) due to another CVS cause; 5 (26.3%) due to a non-CVS cause and for 10 (52.6%) cause of death was unknown]. Incidence rate of death was calculated at 2.7 deaths per 100 person-years. Surgical septal myectomy was performed in 9 patients (8.6%) and 3 (2.9%) underwent cardiac transplantation. 14 patients (13.3%) suffered arrhythmic events [atrial tachycardia 6 (42.9%), Non-Sustained Ventricular Tachycardia 4 (3.8%), and Ventricular Tachycardia/Ventricular Fibrillation 4 (3.8%)].

Conclusion
To our knowledge, this is the largest cohort of RASopathy-associated HCM. The findings show a heterogeneous clinical presentation with a high prevalence of morbidity and mortality. Further work is needed to determine predictors of outcome in this population.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Onassis Foundation
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

Abstract

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) &lt;5 WU and pulmonary arterial wedge pressure (PAWP) &lt;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 &lt;2 WU; p&lt;0.0001). The response of Qp/Qs to FCT was different between groups (p&lt;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&lt;0.0001) accompanied by increases in PAWP (p&lt;0.0001). BOT led to a modest increase in PAWP (Δ1.5 [−1.0–7.0] mmHg, p&lt;0.0001). FCT added to BOT caused a further increase in PAWP and Qs (both p&lt;0.0001), while PVR was unchanged (p&gt;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 &gt;18 mmHg). Even small rises in PVR may have significant implications on cardiovascular haemodynamics. In fact, patients with PVR &lt;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

Abstract

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

Abstract

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

Abstract

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&gt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt;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.