bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;0.001; cohort comparison: p&lt;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

Abstract

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&lt;0.001, r=0.304 p=0.025, r=0.473 p&lt;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

Abstract

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&lt;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&lt;0.80; n=0), mean invasive FFR Adenosine was 0.92±0.06 (FFR&lt;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

Abstract

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 (&lt;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&lt;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

Abstract

Introduction
Medical, surgical, and technological advances over the past decades increased the life expectancy of congenital heart disease (CHD) patients (pts), with &gt;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&lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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