bluuebunny/crossref_metadata_2025 huggingface dataset:
The MIDA quantitative mortality risk score: prognostic model in floppy mitral valves
Authors: Essayagh B , Benfari G , Antoine C , Grigioni F , Le Tourneau T , Roussel J C , Bax J , Delgado V , Ajmone N , Van Wijngaarden A , Tribouilloy C , Hochstadt A , Topilsky Y , Michelena H , Enriquez-Sarano M
Published: October 2021

Background

The Mitral Regurgitation International Database (MIDA) score is a validated tool for Degenerative Mitral Regurgitation (DMR) management, being able to position a given patient within a continuous spectrum of short and long term mortality. However, whether this score may be applicable and incremental in the entire span of Floppy Mitral Valves (FMV), regardless of DMR severity, remains unsubstantiated.

Methods

The MIDA-Quantitative (MIDA-Q) unprecedented registries include 8187 consecutive patients (age 64±17 years, 45% women, follow-up 5.5±3.4 years) with isolated degenerative mitral valve disease diagnosed at tertiary (European/ North-American/ Middle Eastern) centers in whom DMR severity used both integrative and quantitative grading. The MIDA-Q Score ranged from 0 to 15 depending on accumulating risk factors. Long-term survival overall, under medical management and post-mitral surgery was analysed.

Results

By quantitative grading, MR was no/trivial in 1938 (24%), mild in 1423 (17%), moderate in 2027 (25%) and severe in 2799 (34%), with ERO 0.24±24cm2, RVol 37±35mL, and posterior leaflet prolapse in 49%. MIDA-Q Scores stratified in 8 categories were 0 (score 0, n=851), 1 (score 1–2, n=1301), 2 (score 3–4, n=2043), 3 (score 5–6, n=1581), 4 (score 7–8, n=1273), 5 (score 9–10, n=718), 6 (score 11–12, n=331) and 7 (score 13–15, n=89). In the whole MIDA-Q population (n=8187 patients), 5-year survival under medical management with Scores categories 0–1, 2–4, and 5–7 was 96±1%, 73±1%, and 61±3% respectively (P<0.0001). Five-year mortality ranged from 3% with MIDA Q-score 0 to 95% with MIDA Q-score 13–15 (P<0.0001). After mitral surgery, 1-year mortality with Scores categories 0–1, 2–4, and 5–7 was 0%, 1%, and 6% respectively and 5-year post-operative survival was 99±1%, 94±1%, and 82±2% (all P<0.0001). In models including age, sex and all guideline-provided prognostic markers, the EuroScoreII and the MIDA Score without DMR severity, the MIDA-Q Score provided incremental prognostic information (P<0.001).

Conclusion

This unheard international cohort of patients with FMV and prospective mitral severity quantitative grading, enables for the first time the calculation of a MIDA-Q Score, highly determinant of survival after diagnosis of FMV with any degree of DMR, that may be very useful for mitral valve prolapse management.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Mayo Fundation Figure 1
Socio-economic variations in the clinical presentation, etiology and outcome of infective endocarditis in the ESC-EORP EURO-ENDO (European Infective Endocarditis) registry: a prospective cohort study
Authors: Sengupta S , Prendergast B , Furnaz S , Ronderos R , Almaghraby A , Asch F M , Blechova K , Zaky H , Dworakowski R , Izumi C , Lancellotti P , Habib G ,   the EURO-ENDO Investigators
Published: October 2021

Background

Infective endocarditis (IE) is a life threatening disease associated with high mortality and morbidity worldwide. We sought to determine how socio-economic factors may influence variations in epidemiology, clinical presentation, investigation and management (and their consequence upon clinical outcomes) in a large international multi-centre registry.

Methods

The ESC-EORPEURO-ENDO registry comprises a prospective cohort of 3116 adult patients admitted to 156 hospitals in 40 countries with IE between January 2016 and March 2018. We analysed the complete dataset to assess potentially important determinants of variation according to World Bank economic stratification (high income (Group 1) [73.8%]; upper-middle income (Group 2) [17.1%]; lower-middle income (Group 3)[9.1%]).

Results

Patients in Group 3 were younger (median age [IQR]: Group 1 - 66 [54–75] years; Group 2 - 57 [40–68] years; Group 3 - 33 [26–43] years; p<0.001) with a higher prevalence of smoking, intravenous drug use and human immunodeficiency virus (HIV) infection (all p<0.001). Group 3 patients with IE presented later (median [IQR) days since symptom onset: Group 1 - 12 [3–35]; Group 2 - 20 [6–51]; Group 3 - 31 [12–62]; p<0.001) and were more likely to develop congestive heart failure (13.6%; 11.3%; and 22.6%, respectively; p<0.001), septic shock (8.3%; 11.1%; 13.4%; p=0.007), and persistent fever for greater than 7 days (9.6%; 14.4%; 27.9%; p<0.001) following hospital admission. Surgery was performed less frequently in Group 3 (75.4%, 76.8% and 51.3% in Groups 1, 2 and 3, respectively; p<0.001) and mortality was highest in the poorest countries (14.6%; 23.6% and 23.7%, respectively; p<0.001).

Conclusion

Socio-economic factors influence the clinical profile of patients presenting with IE across the world. Despite being younger, patients from the poorest countries presented with more frequent complications and higher mortality associated with delayed diagnosis and less frequent use of surgery.

Funding Acknowledgement

Type of funding sources: None.
The role of right ventricular-arterial coupling in cardiac amyloidosis: a comparison between subtypes and with other genetic and non-genetic hypertrophic cardiomyopathies and prognostic consequences
Authors: Palmiero G , Monda E , Rubino M , Caiazza M , Vetrano E , Di Fraia F , Lioncino M , Dongiglio F , Carciello G , Manganelli F , Ascione L , Caso P , Limongelli G
Published: October 2021

Background

Right ventricular (RV) dysfunction in cardiomyopathies is a consequence of chronic overload (i.e. aortic stenosis) or direct involvement of systemic disorders (i.e. cardiac amyloidosis, CA). The Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure ratio (TAPSE/sPAP) has been recently proposed as a surrogate of RV-arterial coupling (RVAC) in many cardiac disorders.

Purpose

This study aims to compare RVAC between CA subgroups and between CA and other forms of genetic and non-genetic cardiomyopathies with hypertrophic phenotype.

Methods

We enrolled 50 patients with CA (26 pts with AL and 24 pts with wild type ATTR form), 75 patients with LV hypertrophy (LVH) [25 patients with HCM, 25 with hypertensive cardiomyopathy (HypCM), and 25 with aortic stenosis]. We analysed right chambers dimensions and classical and novel parameters of RV function [TAPSE, TAPSE/sPAP, St (S' wave at RV TDI), global (RVGLS) and free-wall (RVFWS) strain].

Results

The ATTR group showed higher right dimensions than AL, without differences in all RV systolic parameters (see Table 1). Compared to the LVH group, CA patients showed no differences in RV dimensions while RV systolic parameters, included the TAPSE/sPAP ratio, were significantly reduced. At ROC curve analysis TAPSE (AUC 0.877; 95% CI: 0.811–0.943; p<0,0001) and TAPSE/sPAP ratio (AUC 0.859; 95% CI: 0.783–0.935; p<0,0001) showed the best ability in discriminating CA among other forms of LVH (cut-off 20,5 mm for TAPSE with a sensibility of 80,5% and specificity of 78,8%; cut-off 0,62 for TAPSE/sPAP ratio with a sensibility of 85,4% and a specificity 81,8%). At Kaplan-Meier estimation, the TAPSE/sPAP ratio showed a significantly reduced survival in the lowest interquartile ranges. Moreover, at multivariate analysis TAPSE/sPAP was the only independent prognostic factor (β −5,644; 95% IC: 0,000–0,522; p<0,027).

Discussion

The RVAC is significantly impaired in CA compared to the LVH group but not between CA subgroups. TAPSE/sPAP proved to be a novel echocardiographic parameter useful in discriminating CA among genetic and non-genetic forms of LVH, and that also show prognostic significance.

Funding Acknowledgement

Type of funding sources: None. Figure 1. K-M for TAPSE/sPAP ratio IQ rangesTable 1
Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease
Authors: Barman H , Atici A , Arabaci H O , Sahin I , Gungor B , Dogan S M
Published: October 2021

Objective

COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet. The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19.

Methods

For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between March 20 - April 20 2020 were collected. Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records. In-hospital clinical outcome was compared between patients with and without cardiac injury.

Results

A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5±14.3 years, and 334 (55%) were male. Cardiac injury was detected in 150 (24.7%) of patients included in the study. Mortality rate was higher in patients with cardiac injury (42% vs. 8%; p<0.01). The frequency of patients who required intensive care unit (ICU) (72% vs.19%), who developed acute kidney injury (AKI) (14% vs. 1%) and acute respiratory distress syndrome (ARDS) (71% vs. 18%) were also higher in patients with cardiac injury. In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury (OR: 10.58, 95% CI: 2.42–46.27; p<0.001) were found to be independent predictors of mortality. In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR: 2.52, 95% CI: 1.17–5.45; p=0.018).

Conclusion

Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.

Funding Acknowledgement

Type of funding sources: None.
Alpha-protein kinase 3 (ALPK3) truncating variants cause an autosomal dominant form of hypertrophic cardiomyopathy
Authors: Rocha Lopes L , Hernandez S G , Lorenzini M , Futema M , Chumakova O , Villacorta E , Garcia-Pavia P , Bilbao R , Sandin-Fuentes M , Pinilla J G , Rasmussen T B , Revilla-Marti P , Elliott D , Monserrat L , Elliott P ,   ALPK3 consortium
Published: October 2021

Background

More than half of hypertrophic cardiomyopathy (HCM) remains genetically unsolved. ALPK3 truncating variants (ALPK3tv) have been described as a cause of autosomal recessive cardiomyopathy in a small number of paediatric cases, but the pathogenicity in heterozygosity as a possible cause of autosomal dominant HCM is unknown.

Aims

To determine the frequency of heterozygous ALPK3tv in patients with HCM and to confirm their pathogenicity by means of burden testing in independent cohorts, family co-segregation studies, and functional analysis of an allelic series of ALPK3tv using human embryonic stem cell-cardiomyocytes (hESC-CM). Phenotype was compared with a cohort of 1679 genotyped HCM patients.

Methods and results

In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv, odds ratio (OR) 16.01 (95% confidence interval (95% CI): 7.89 to 29.74, p<8.36e-11), compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv, OR 16.17 (95% CI: 10.31 to 24.87; p<2.2e-16, compared to gnomAD). Combined logarithm of odds score in 7 families with ALPK3tv was 2.99. In comparison with a large cohort of genotyped HCM patients, the phenotype of 51 HCM patients with ALPK3tv (probands and relatives) was characterised by a higher prevalence of apical/concentric patterns of hypertrophy (60%) compared to both sarcomere-positives or negatives (p<0.001 overall), with the age at diagnosis (56±16ys) and maximum wall thickness (18±4mm) similar to sarcomere-negatives and LV systolic impairment at baseline (6%) and non-sustained ventricular tachycardia (31%) similar to sarcomere-positives. Short PR (10%, p=0.009 overall) and extensive fibrosis>15% of LV segments (49%) were distinctive features. During follow-up (5.3±5.7 years), 4 (9%) patients died of heart failure or had cardiac transplantation (p=0.012 vs sarcomere-negatives and p=0.425 vs sarcomere-positives). Analysis of hESC-CM showed that ALPK3 heterozygotes had phenotypic characteristics of HCM, including increased contractile force and delayed membrane repolarization.

Conclusions

Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): MRC UK, UCLH BRC
Early onset of heart failure in Japanese ARVC patients with pathogenic desmosomal gene variants
Authors: Sonoda K , Nagase S , Aiba T , Fukuyama M , Kato K , Kusano K , Horie M , Ohno S
Published: October 2021

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy mainly caused by desmosomal gene variants. Although there are a lot of reports regarding to European ARVC patients, the ones in Asian are a few, and the characteristics of Asian ARVC have been still unclear. We have reported that the genetic backgrounds in Japanese ARVC patients were different from those in European ones. In this study, we aimed to examine the phenotype and outcome of Japanese ARVC patients with specific genetic backgrounds.

Methods and results

This study included 104 Japanese ARVC patients who were diagnosed as definite in the 2010 Task Force Criteria for ARVC and received genetic analysis (79 males [76%]; median age at diagnosis, 40 years [IQR 22–53 years].) Fifty-seven patients carried variants in desmosomal genes classified as pathogenic based on ACMG guideline: 30 in DSG2 (29%), 22 in PKP2 (21%), 2 in DSC2 (2%) and 3 in DSP (3%). The median age of diagnosis was significantly younger in the patients with the pathogenic variants than in those without (37 years [IQR 21–49 years] vs. 46 years [IQR 34–58 years], P=0.01). During a median follow-up of 9.3 years (IQR 3.5–20.9 years), 10 patients died and 2 were received heart transplantation. Sixty-two suffered lethal arrhythmic events including cardiopulmonary arrest, ventricular fibrillation, sustained ventricular tachycardia and appropriate shocks by implantable cardioverter defibrillator. Twenty-two were hospitalized for heart failure. There was no difference in these events rate between the two groups. However, survival analysis revealed that patients with pathogenic variants hospitalized for heart failure significantly earlier in their life than those without (P=0.04, log-rank test, Figure 1).

Conclusions

The Japanese ARVC patients with pathogenic variants in desmosomal genes are diagnosed and hospitalize for heart failure at younger age than those without. These findings have not been reported in other ethnics. Our study warns that we should be cautious for not only the prevention of lethal arrhythmic events but also the progress of the heart failure in Japanese ARVC patients with pathogenic variants.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Japan Agency for Medical Research and Development Figure 1
Management strategies for atrial fibrillation and flutter in patients with transthyretin cardiac amyloidosis
Authors: Dale Z , Chandrashekar P , Al-Rashdan L , Kim M , Masri A , Nazer B
Published: October 2021

Background

Atrial fibrillation (AF) and flutter (AFL) are common in transthyretin cardiac amyloidosis (ATTR-CM). Ventricular rate control drugs in ATTR-CM are poorly tolerated but data addressing tolerability and efficacy of rhythm control strategies is limited.

Purpose

We report characteristics and outcomes of AF/AFL in a cohort with ATTR-CM.

Methods

A single center observational study of patients seen at our Amyloidosis Center with wild-type or hereditary ATTR-CM diagnosed between 2005–2019. Treatment was prescribed as per treating cardiologists.

Results

Eighty-four patients with ATTR-CM (average age 74±10 years, 94% male) had mean follow-up of 27.6±22.8 months. AF/AFL occurred in 61 patients (73%). Clinically significant rapid ventricular response (RVR) was common as well attempted rate control with AV node blockers (Table 1). However, discontinuation was frequent (80%), often for adverse effects of hypotension (33%), bradycardia (15%), or presyncope/syncope (10%). Rhythm control was initiated in 64%, most often with cardioversion (DCCV) or ablation (Table 2). Post-DCCV recurrence was common (91%) and time to recurrence did not differ with use of anti-arrhythmic drugs (AAD; 5.8 months (IQR 1.9–12.5) vs without AAD 6.2 months (IQR 1.9–12.5) p=0.83). TEE was performed for 33% of DCCV with thrombus seen in 11% of cases – all patients who were not anticoagulated at the time. TEE was otherwise deferred due to known AF/AFL duration <48 hours (13%) or adequate anticoagulation (54%). Ablation was performed in 23% of patients with AFL (all for typical AFL) with 2 patients (14%) having recurrence after mean of 60.9 months. Pulmonary vein isolation for AF was performed in 12% (86% for persistent AF) with 86% recurrence after median of 6.2 months (IQR 5.6–12.3). Most patients (62%) with rhythm control had subjective improvement (≥1 NYHA class or resolved palpitations). Among AAD, amiodarone was most well tolerated with only 8% of patient discontinuing due to side effects. DCCV and ablation resulted in no direct complications although one patient had a perforation of a previously unknown Zenker diverticulum during TEE pre-DCCV.

Conclusions

In our ATTR-CM cohort, AF/AFL was common. Rate control was poorly tolerated and often abandoned. While rhythm control of AF/AFL had a favorable safety profile and successful conversion to sinus rhythm led to symptomatic improvement in a majority of cases, durable success with rhythm control was limited, often requiring multiple therapies. DCCV is only modestly successful and not significant improved with AAD. Ablation was successful in cases of cavo-tricuspid isthmus dependent AFL but had limited success in AF.

Funding Acknowledgement

Type of funding sources: None.
Cardiac imaging in tafamidis-treatment patients with transthyretin amyloid cardiomyopathy
Authors: Rettl R , Mann C , Duca F , Dachs T.-M , Binder C , Kronberger C , Schrutka L , Dalos D , Dona C , Kammerlander A , Beitzke D , Charwat-Resl S , Kastner J , Badr Eslam R , Bonderman D
Published: October 2021

Background

Tafamidis kinetically stabilizes the tetrameric form of transthyretin (TTR) and thus may halt disease progression in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). In our explorative analysis, we aimed to investigate the treatment effect on functional capacity and cardiac biomarkers as well as cardiac function and structure using echocardiography and cardiac magnetic resonance imaging (CMR), and to compare patients treated with tafamidis with an untreated control cohort.

Methods

Consecutive ATTR-CM patients either received tafamidis 61mg (n=64) or tafamidis 20mg (n=23) or were assigned to an untreated control cohort (n=54) reflecting the natural history of the disease. Subsequently, we performed clinical, laboratory, echocardiography and CMR follow-up at a median of 9 to 12.5 months.

Results

Main results are summarized in Table 1. In brief, we observed evidence of improvement in functional capacity as measured by the 6-minute walk distance (6MWD) in tafamidis 61mg treated patients (baseline: 377.1m vs. follow-up: 383.2m, p=0.678) compared to a significant decline in mean 6MWD in untreated patients (388.1m vs. 336.4m, p=0.002; cohort comparison: p=0.005). Analysis of cardiac biomarkers revealed evidence of therapeutic response by a decrease in median NT-proBNP levels in patients treated with tafamidis 61mg (2633.0pg/mL vs. 2244.0pg/mL, p=0.366), whereas a significant increase was observed in untreated patients (2798.0pg/mL vs. 3422.0pg/mL, p<0.001; cohort comparison: p<0.001). Echocardiographic findings revealed evidence of approximate stabilization in mean left ventricular (LV) strain (−11.75% vs. −11.58%, p=0.534) and mean right ventricular (RV) strain (−14.18% vs. −13.72, p=0.377) in the tafamidis 61mg treatment cohort compared to significant deterioration of mean LV longitudinal function (−11.71% vs. −10.59%, p=0.001) and mean RV longitudinal function (−14.36% vs. −12.99%, p=0.038) in the untreated cohort (cohort comparison: p=0.030 and p=0.269). Furthermore, cardiac structural assessment by CMR showed a significant increase in mean LV mass (199.1g vs. 214.3g, p=0.040) and mean extracellular volume (50.52% vs. 55.96%, p=0.026) in untreated patients, suggesting increased progression of myocardial amyloid deposition.

Conclusion

Treatment with tafamidis in patients with ATTR-CM results in significant improvements in functional capacity and cardiac biomarkers, and shows marked benefits in functional as well as structural imaging parameters compared with an untreated control cohort.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Pfizer Inc.
Correlations between pathological deposition and non-invasive diagnostic modalities like 99mTc-PYP scintigraphy, cardiac magnetic resonance, GLS in patients with transthyretin cardiac amyloidosis
Authors: Morioka M , Takashio S , Nakashima N , Nishi M , Hirakawa K , Hanatani S , Usuku H , Yamamoto E , Matsushita K , Kaikita K , Tsujita K
Published: October 2021

Background

Although wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) was previously considered a rare disease, recent diagnostic imaging modalities have revealed that it is considerably underdiagnosed among elderly patients with heart failure. The severity of CM is thought to be related to the extent of amyloid deposition in heart.

99mTc-labeled pyrophosphate (99mTc-PYP) scintigraphy, cardiovascular magnetic resonance (CMR), global longitudinal strain (GLS) provide diagnostic and prognostic information in ATTRwt-CM. However, the relevance of these imaging modalities and their association with cardiac amyloid load has not been fully evaluated.

Purpose

The aim of study was to elucidate the associations between pathological amyloid load and cardiac retention evaluated by 99mTc-PYP scintigraphy, CMR, GLS in patients with ATTRwt-CM.

Method

Cardiac amyloid load was calculated as (amyloid deposition area/ total myocardium area)×100 using endomyocardial biopsy specimen. Cardiac retention was quantified by heart to contralateral (H/CL) ratio by 99mTc-PYP scintigraphy. Native T1 and extracellular volume (ECV) were obtained by CMR. GLS was analyzed using the 2D echo at the time of diagnosis.

Result

The mean cardiac amyloid load was 23.0±15.2% (n=57) and correlation with H/CL ratio (1.94±0.36 n=57), native T1 (1426.7±52.5 n=57), ECV (57.9±12.9 n=54), GLS (−9.1±2.4 n=57) were positive (r=0.375 p=0.004, r=0.496 r=0.304 p<0.001, r=0.304 p=0.025, r=0.473 p<0.001).

Conclusion

Increased cardiac amyloid load correlated with an increased 99mTc-PYP positivity, native T1, ECV, and an impaired GLS. These results suggest that imaging parameters may reflect histological and functional changes due to amyloid deposition in the myocardium.

Funding Acknowledgement

Type of funding sources: None.
Comprehensive non-invasive and invasive functional assessment of anomalous coronary arteries with anatomical high-risk features
Authors: Bigler M R , Spano G , Boscolo Berto M , Ueki Y , Otsuka T , Huber A T , Raeber L , Graeni C
Published: October 2021

Background

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital disease associated with an increased risk of myocardial ischemia. In AAOCA, the occurrence of ischemia is based on the extent of a fixed and a dynamic component, each attributed to different anatomical high-risk features (i.e., acute take-off angle, slit-like ostium, proximal narrowing, elliptic vessel shape and intramural course). Coronary computed tomography angiography (CCTA) is the primary non-invasive imaging method to depict the presence and quantitatively assess anatomical high-risk features while invasive physiologic evaluation under maximal dobutamine-volume challenge is the gold standard to unravel the hemodynamic relevance of AAOCA.

Methods

We included all consecutive AAOCA patients with anatomical high-risk features from our prospective, open-label registry. The objective is to quantify anatomical high-risk features in the CCTA and to measure hemodynamic relevance using invasive fractional flow reserve with maximal dobutamine-volume challenge (gradually increasing dose of dobutamine max. 40 μg/kg per body weight/min, max. 3000 mL ringer lactate and max. 1mg atropine). Pathological invasive FFR was defined as FFR Dobutamine<0.80. Additionally, CCTA-data were processed to assess computational fluid dynamics (CT FFR) and intravascular ultrasound (IVUS) was used to determine minimal lumen area (MLA) during baseline and maximal stress conditions.

Results

A total of 11 patients were included between 05/19 and 11/2020. Mean age was 59±13 years (range: 40–79), 10 patients showed a right-AAOCA and one patient showed a single right coronary artery. All patients had either one (i.e., in 1 patient) or more than one anatomical-high risk features (i.e., in 10 patients). Mean invasive FFR Dobutamine was 0.88±0.07 with n=2 (18%) being pathological. Mean non-invasive CT FFR was 0.89±0.04 (FFR<0.80; n=0), mean invasive FFR Adenosine was 0.92±0.06 (FFR<0.80; n=1; 9%). There was a significant decrease in IVUS MLA between rest (7.93±2.79mm2) and under dobutamine-volume challenge (6.57±3.20mm2, p=0.008). Mean percentage of MLA reduction was 19±18%.

Conclusion

Our preliminary results provide evidence that relevant myocardial ischemia seems to be often absent in a middle-aged population with AAOCA and anatomical high-risk features. However, in a minority of cases hemodynamic relevance could be depicted, especially when stressing with dobutamine-volume challenge. The presence of a dynamic component in AAOCA is represented by the reduced minimal lumen area under stress conditions. Comprehensive diagnostic evaluation should be performed to prevent unnecessary guideline recommended open-heart surgery in a middle-aged population with AAOCA.

Funding Acknowledgement

Type of funding sources: None.
Increased incidence of Persistent Pulmonary Hypertension of the Newborn following third trimester maternal COVID-19 infection
Authors: Ishqeir A , Nir A , Aptowitzer I , Godfrey M ,   Pediatric Cardiology Unit, Shaare Zedek Medical Center, Jerusalem, Israel
Published: October 2021

Background

Novel coronavirus (COVID-19) has been a world concern since December 2019. The knowledge about vertical transmission and fetal morbidity and mortality from maternal COVID-19 infection is limited. We detected an increase in the number of cases of term and near-term neonates with persistent pulmonary hypertension (PPHN) during the COVID-19 pandemic in 2020.

Methods and results

We collected data on all newborns with PPHN born between 2018 and 2020. We excluded premature infants (<34+0 weeks) and infants with other significant pathology or genetic syndromes. Compared to 5 cases of PPHN of 22930 live births in 2018, and 6 cases of PPHN of 22270 live births in 2019 (2-year average 0.02%, 95% CI 0.013%-0.043%), there were 16 PPHN cases from 22323 live births in 2020 (0.07%, 95% CI 0.044%-0.12%), a 3 fold increase (p<0.01). We report 5 cases of term and near-term neonates born to mothers who had highly suspected (2) and PCR proven (3) COVID-19 infection during the third trimester of pregnancy, who presented with PPHN during COVID-19 pandemic in 2020. All had otherwise unexplained pulmonary hypertension, right ventricular hypertrophy (RVH) and dilatation. Two patients needed endotracheal intubation, one was supported by nasal continuous positive airway pressure (CPAP) without intubation, two needed O2 support by nasal cannula only ant two newborns (one of them was intubated) needed Nitric oxide (NO) as pulmonary vasodilator therapy. No patient required Extracorporeal membrane oxygenation (ECMO) or died, and no prolonged residual cardiovascular or pulmonary morbidity was recorded during a median follow up of 4.8 months (range 4–6 months).

Conclusions

The increase in the incidence of PPHN during the COVID-19 pandemic, and the cases presented, suggest an intrauterine effect of maternal COVID-19 infection on the fetal pulmonary circulation. It is possible that the maternal infection affected the fetal pulmonary vascular resistance, or altered the normal decline in the resistance after birth. The right ventricular hypertrophy and dilatation with reduced function may be secondary to this hypothetical increased afterload or a direct effect of the infection. Further studies are warranted to elucidate the pathogenesis and clinical implications of this phenomenon.

Funding Acknowledgement

Type of funding sources: None.
Trends in mortality of adult congenital heart disease patients in the last 4 decades
Authors: Mano T , Viegas J , Bras P , Rito T , Agapito A , Pinto F , Cruz Ferreira R , De Sousa L
Published: October 2021

Introduction

Medical, surgical, and technological advances over the past decades increased the life expectancy of congenital heart disease (CHD) patients (pts), with >90% reaching adulthood. Nonetheless, mortality for adults with CHD (ACHD) is still higher than for the general population.

Purpose

To analyse trends in mortality and causes of death of ACHD.

Methods

Retrospective analysis of pts followed in an ACHD outpatient clinic, in one tertiary center, who died between 1980 and December 2020. Data relating to the cardiac diagnosis, symptoms, interventions, comorbidities, and causes of death were analysed.

Results

During a median follow-up of 8.9 years (IQR 2.2–17), 251 pts of 3725 (6.7%) died during the study period: 127 males (51%), mean age at death 44.9±18.1 years, 54% with severe CHD. The majority of these death was CHD-related (171 pts – 68.1%) with no statistically significant differences over the years vs non-cardiovascular death (Table 1). However, a paradigm shift was noticed: in the first years the main cardiac cause was sudden-death that was replaced by heart failure in the last decade. Also, the mean age at death increased over the years (33±14.9 years until 2000 vs 52.3±17 years after the year 2010, p<0.001) as the number of implantable devices (4 vs 20, p=0.05).

Conclusion

Causes of death of ACHD patients are in the majority still CHD-related. However, in the last decade, according to the increase in life expectancy, heart failure became the leading cause of death.

Funding Acknowledgement

Type of funding sources: None.
Right ventricular function in Marfan patients remains stable despite (multiple) cardiac interventions
Authors: Mihalj M , Ferro C , Yildiz M , Nucera M , Mosbahi S , Heinisch P P , Schoenhoff F
Published: October 2021

Background

Left-sided heart lesions, namely aortic root aneurysm, mitral valve prolapse and intrinsic left ventricular (LV) dysfunction are an essential part of the cardiovascular phenotype of Marfan syndrome (MFS). While recent data stresses the need for concomitant tricuspid valve repair (TVR) when addressing left-sided heart lesions in non-MFS patients, data on tricuspid valve disease and right ventricular (RV) function in MFS is scarce.

Purpose

We sought to determine changes in RV function, tricuspid valve regurgitation and need for TVR in MFS patients throughout their lifetime, from day of first contact.

Methods

We retrospectively analyzed 183 MFS patients fulfilling Ghent criteria seen at our institution between 1995 and 2019. In this patient population, 136 patients (74%) underwent 170 procedures with cardioplegic arrest. Aortic root surgery was performed in 90% and mitral valve surgery (MVR) in 19% of patients undergoing surgery. TVR was performed in 3.7% of all patients undergoing surgery and 18.5% of patients undergoing MVR. Mean age at time of first intervention was 37.8±14.4 years. Mean age in the group of patients without history of surgery was 20.6±17.5 years. Right ventricular function was evaluated using tricuspid annular plane systolic excursion (TAPSE) by echocardiographic assessment at baseline (defined as most recent exam before surgery, or first available exam in patients without history of surgery), and at last available follow-up (defined as last available exam after surgery, or last available exam prior to subsequent surgery). Mean follow-up (FU) was 7.2±7.1 years.

Results

Patients that underwent surgery with cardioplegic arrest did not experience a significant decrease in RV function over time (mean TAPSE at baseline 22.3±4.7 mm, mean difference −4.0±6.7 mm at last FU after surgery). The same was true for patients undergoing MVR with a mean TAPSE at baseline of 21.5±5.2 mm and a mean difference of −5.6±8.05 mm at last available FU (p=0.664). Freedom from impaired RV function (defined as TAPSE ≤15mm) at 5-, 10- and 15-years FU was 78%, 77%, 73%, respectively. Freedom from severe TR was 100% up to 15 years, and freedom from TVR at 5-, 10- and 15-years FU was 96%. Actuarial survival of all patients at 5-, 10- and 15-years FU was 95.6%, 94.5%, and 91.8%, respectively.

Conclusions

Current data suggests that right-sided heart lesions in MFS patients are rare. RV function remains stable over time despite (multiple) cardiac interventions. Furthermore, the need for TVR is low, independently of whether MVR was performed or not.

Funding Acknowledgement

Type of funding sources: None.
BMPR2 variants in pulmonary arterial hypertension. Are they really worrisome?
Authors: Cruz Utrilla A , Gallego N , Cristo Ropero M J , Perez Olivares-Delgado C , Tenorio Castano J A , Lapunzina P , Lopez Meseguer M , Martinez Menaca A , Arribas-Ynsaurriaga F , Escribano Subias P
Published: October 2021

Background

Pulmonary arterial hypertension (PAH) is a rare and severe disease. The discovery of the gene encoding Bone Morphogenetic Protein Receptor Type 2 (BMPR2) in 2000 was the first evidence of an association between genetics and PAH. BMPR2 mutation carriers are younger and have higher haemodynamic severity, determining higher risk than sporadic cases. In the last few years, novel genetic variants have been identified. The risk of mortality of the currently known mutations is scarce.

Purpose

To describe the role of gene variants regarding long-term survival in a cohort of PAH patients.

Methods

We included patients diagnosed with PAH between January 2011-December 2020, following the ESC/ERC Guidelines recommendations. At least one genetic study was available in included individuals. Pulmonary venooclusive disease, PAH associated with congenital heart disease, or connective tissue disorders were excluded. Three groups were compared: no mutation, BMPR2 carriers and other genetic variants. Comparison of qualitative and quantitative variables was done by Chi-square test and ANOVA test, respectively. Crude and adjusted Log-rank test was performed for the evaluation of mortality.

Results

361 were finally included. The most frequent gene variant was BMPR2. Among the eight other gene variants, there were 2 cases of KCKN3, 2 of ACVRL1, and 1 case of KCNA5, TBX4, CPS1, and GDF2.

BMPR2 and the rest of mutation carriers were younger at diagnosis and had worse haemodynamic parameters than non-carriers. Nevertheless, these patients tended to perform higher distances in the 6-minute walk test. Interestingly, BMPR2 patients had higher DLCO values at diagnosis (table).

After 104.1±77.2 months of follow-up, there was a tendency for BMPR2 carriers toward lower crude free survival of mortality or lung transplantation. Nevertheless, this survival benefit disappears when adjusted by age (Table, figure).

Conclusions

The diagnostic yields of genetic analysis for pathogenic or likely pathogenic variants in idiopathic PAH are approximately 11%. BMPR2 is the most frequent causal gene. These patients are associated with marked haemodynamic impairment. Nevertheless, its younger age probably determines the better long-term results regarding mortality or lung transplantation observed when comparing these results with sporadic patients or those carrying other mutations.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Rio Hortega grant. Instituto de Salud Carlos III (ISCIII), Ministry of Science and Innovation, Spanish Government.
Covid-19 morbidity and outcomes among the patients observed in the pulmonary hypertension reference center
Authors: Sirenko Y , Zhyvilo I , Radchenko G
Published: October 2021

Background

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive condition with high mortality rate despite modern pharmacotherapy. There is no reliable data concerning influence of Covid-19 infection on PAH and CTEPH morbidity and mortality.

Aim

To evaluate influence 12-month Covid-19 pandemic presence on morbidity and mortality in patients with PAH and CTEPH observed in PH reference center.

Methods

During the 12 months (from March 2020 to March 2021) we closely follow-up the condition of 404 initially alive patients with on PAH and CTEPH with specific PH therapy who were observed in our reference center for adults. All information was checked and confirmed with proper medical documents and Covid-19 diagnosis was confirmed with positive PCR or/and serological tests. We finished our database with the vaccination beginning.

Results

Main data are presented in table. Among 404 patients symptomatic Covid-19 infection was documented in 44 (10,9%) cases. Only 9 (20,5%) of them were hospitalized because this reason, 4 patients of them (9,1% from all Covid-19 diagnosis and 44,4% from hospitalized) needed ICU because severe circulatory and respiratory failure. All of them needed the ventilator support. Unfortunately, despite of the necessary measures all of the ICU admitted patients died shortly during couple of days (mean 2,5±1,8). There was no difference in demographic, diagnosis and initial condition between hospitalized and ambulatory treated patients. The small numbers of died patients did not allow to make any statistically significant assumption.

Conclusion

During 12-months Covid-19 pandemic presence 11% of PAH and CTEPH patients had symptomatic COVID-19 infection, roughly 20% of them needed hospital admission and 10% needed ICU and ventilator support. The mortality in ICU was 100%.

Funding Acknowledgement

Type of funding sources: None. Table 1. Covid-19 morbidity and mortality among PAH and CTEPH patients
Predictors of unfavourable outcome in clinically stable, low risk acute pulmonary embolism patients (sPESI 0)
Authors: Karolak B K , Skowronska M S , Plywaczewska M P , Furdyna A F , Machowski M M , Pacho S P , Uchacz K U , Kurnicka K K , Pruszczyk P P , Ciurzynski M C ,   Department of Internal Medicine and Cardiology, Infant Jesus Teaching Hospital, Medical University of Warsaw, Poland
Published: October 2021

Introduction

Nowadays one of the most challenging tasks is to identify, within the large group of normotensive and clinically stable acute pulmonary embolism (APE) patients, those who are at “sufficiently low” risk to permit early discharge and home treatment. Current ESC guidelines suggest, that troponin measurement is optional in sPESI 0 patients.

Aim

The aim of this study was to assess whether right ventricular dysfunction (RVD) in transthoracic echocardiographic examination (TTE) and/or elevated plasma troponin level improves in-hospital risk stratification in sPESI 0 patients.

Methods

Post-hoc analysis of a prospective study of 1191 patients with at least segmental APE confirmed in computed tomography (CT). Among this group 434 patients (208 F, age median = 52 yrs [39; 67]) were classified to low risk group according to sPESI. TTE and TnT concentration were assessed within the first 24-hours from admission. Echocardiographic criteria for RVD were RV/LV ratio≥1 or tricuspid regurgitant pressure gradient ≥31 mmHg. The sPESI score was calculated from patient records. The combined endpoint (CE) included in-hospital death of any cause and/or haemodynamic deterioration requiring catecholamines i.v., rescue thrombolysis, cardio-pulmonary resuscitation, cardiac surgical intervention or percutaneous catheter-directed treatment.

Results

Among 434 sPESI 0 patients, cardiac troponin plasma level was assessed in 409 individuals, 136 results were above the normal limit. CE occurred in 6 patients with elevated and 0 with non-elevated troponin concentration (p=0,0013).

In 253 cases high-sensitive troponin (hsTnT) assays were used. Median hsTnT concentration was significantly higher in patients with CE (0,032 ng/ml [0,024; 0,127] vs 0,09 ng/ml [0; 0,025])

SPESI and hsTnT assessment showed AUC ROC=0.834 (0.727–0,941; p=0.000) for the CE with suggested threshold 0,024 ng/ml (Fig. 1).

Interestingly, no statistically significant differences in RV/LV ratio or TRPG between CE and non-CE group were observed. Furthermore, CE did not occur more often in patients with RVD (7 vs 1; p=0,067).

Conclusion

SPESI combined with normal cardiac troponin plasma concentration may be used for predicting favourable outcome in patients with APE and thus select candidates for home treatment. We suggest to assess plasma troponin levels in all normotensive patients early, before discharge to home treatment. However, due to relatively low number of endpoints, these findings need to be confirmed in further studies enrolling more patients.

Funding Acknowledgement

Type of funding sources: None. Figure 1. hsTnT ROC
Right ventricular myocardial work characterisation in patients with pulmonary hypertension: association with invasive haemodynamic parameters
Authors: Butcher S C , Feloukidis C , Kamperidis V , Stassen J , Fortuni F , Vrana E , Mouratoglou S A , Boutou A , Giannakoulas G , Playford D , Ajmone Marsan N , Bax J J , Delgado V
Published: October 2021

Background

Non-invasive evaluation of indices of right ventricular (RV) myocardial work derived from RV pressure-strain loops may provide novel insights into RV function in pre-capillary pulmonary hypertension.

Purpose

This study was designed to evaluate the association between the indices of RV myocardial work and invasive haemodynamic parameters in a patient cohort with pulmonary arterial hypertension (Group I) or chronic thromboembolism pulmonary hypertension (Group IV).

Methods

The non-invasive analysis of echocardiography-derived RV myocardial work (Figure 1, upper panel) was completed in 51 patients (mean age 58.1±12.7 years, 31% male) with Group I (78%) or Group IV (22%) pulmonary hypertension. Conventional echocardiographic measurements of RV systolic function, RV global work index (RV GWI), RV global constructive work (RV GCW), RV global wasted work (RV GWW) and RV global work efficiency (RV GWE) were compared with parameters derived invasively during right heart catheterisation (RHC).

Results

The median RV GWI, RV GCW, RV GWW and RV GWE were 620 (443 to 857) mmHg%, 830 (650 to 1206) mmHg%, 105 (54 to 169) mmHg% and 87 (82 to 93)%, respectively. Compared to pulmonary artery systolic pressure and conventional echocardiographic parameters of RV systolic function (RV global longitudinal strain [GLS], tricuspid annular plane systolic excursion and RV fractional area change), RV GCW and RV GWI correlated more closely with invasively-derived RV stroke work index (R=0.63, P<0.001 and R=0.60, P<0.001, respectively) (Figure 1, lower panels). Invasively-derived pulmonary vascular resistance (PVR) correlated with RV GWW (R=0.63, P<0.001), RV GWE (R=0.48, P<0.001) and RV GLS (R=0.58, P<0.001). RV GLS correlated more closely with invasively-derived stroke volume index (R=−0.57, P<0.001) than RV GCW, RV GWI and RV GWE (R=0.34, P=0.016, R=0.48, P<0.001 and R=0.47, P<0.001, respectively).

Conclusions

In a patient cohort with Group I and Group IV pulmonary hypertension, indices of RV myocardial work were more closely correlated with invasively-derived RV stroke work index and PVR than conventional echocardiographic parameters of RV systolic function.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Method and correlations
Modified FAST score as a predictor of fibrinolysis in normotensive patients with acute pulmonary embolism
Authors: Devesa Neto V , Pires I
Published: October 2021

Introduction

Intermediate risk pulmonary embolism (PE) encompass a heterogeneous group of patients with very distinct prognosis. While some patients will only need anticoagulation, in others fibrinolytic therapy (FT) should be considered in order to prevent further hemodynamic decompensation. It is very important to identify the subgroup of intermediate risk PE patients at highest risk of an adverse outcome in whom FT may be needed. Modified FAST score was developed to identify non-high risk PE patients at highest risk of early PE-related complications. This study aims to evaluate if modified FAST score is a predictor of necessity of FT.

Methods

A retrospective analysis of 178 patients admitted for acute PE was performed. Modified FAST score evaluates the presence of syncope (1.5 points), troponin I elevation (1.5 points) and heart rate ≥100bpm (2 points), ranging from 0–5 points (<3 points low risk and ≥3 points intermediate-high risk for adverse in-hospital outcome). PESI score was also calculated for each patient. The Mann-Whitney U was used for comparisons between groups. Binary logistic regressions were used to obtain the odds ratio (OR) for FT of the various variables. ROC curves allowed the comparison of modified FAST and PESI scores.

Results

Mean age was 63±18 years; 61% were female; 8.5% had previous history of venous thromboembolism; 48% of patients had a precipitating factor identified; 58% had signs of right ventricle dilation on echocardiography (echo) and/or chest computed tomography (CCT). 47% had low risk (LR) and 53% had intermediate-high risk (IHR), according to modified FAST score. Mean FAST score was 2.22±1.4.

There were no differences between patients with LR or IHR regarding age, sex and precipitating factor. IHR was associated with dyspnea (p=0.002), lower arterial systolic pressure at admission (p=0.007), higher levels of D-dimer (p=0.013), S1Q3T3 pattern (p=0.001) and right bundle branch block pattern (p=0.005) in electrocardiography and higher right ventricle diameter in echo and CCT (p=0.006).

During hospitalization patients with IHR had more worsening of renal function (p=0.015).

Patients with IRH were submitted more frequently to FT than patients with LR (65% vs 39%; p=0.001). Modified FAST score was a predictor of FT (OR 2.9; 95% CI 1.5–5.5; p<0.001) and was independent of PESI score (OR 2.9; 95% CI 1.5–5.6; p=z0.001). ROC curve analysis revealed a higher area under the curve for modified FAST score comparing to PESI score (0.659 vs 0.497).

Conclusion

IHR modified FAST score was associated with characteristics of poor prognosis in PE. Furthermore, modified FAST score was a predictor of FT in normotensive patients with PE, and was independent of PESI score. Therefore, this score may be useful to select patients with PE that will benefit from FT.

Funding Acknowledgement

Type of funding sources: None.