bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family screening in dilated cardiomyopathy-qualifying screening and need for follow-up
Authors: Vissing C R , Espersen K , Mills H L , Bartels E D , Jurlander R , Skriver S V , Ghouse J , Thune J J , Axelsson Raja A , Christensen A H , Bundgaard H 
Published: October 2022

Abstract

Background
Guidelines recommend family screening in dilated cardiomyopathy to uncover pre-symptomatic disease to improve morbidity and mortality through early treatment. According to patterns of inheritance and incomplete penetrance, less than half of relatives to dilated cardiomyopathy probands will develop disease, but so far, no guidelines provide recommendations on the frequency and intensity of follow-up screening.

Purpose
To investigate the prevalence and incidence and identify predictors of developing familial dilated cardiomyopathy (FDC) in relatives participating in family screening.

Methods
The study was an observational, longitudinal cohort study of families screened and followed from 2006 to 2020, at a regional assembly of clinics for inherited cardiomyopathies in Denmark.

Results
We included 211 families totaling 774 subjects (n=563 relatives, 47% women). At baseline, 124 relatives (22%) were diagnosed with dilated cardiomyopathy, while 43 relatives (8%) not fulfilling FDC criteria were found to carry class IV to V genetic variants. Thus, the combined clinical and genetic yield of screening was 30% at baseline. Relatives not fulfilling diagnostic criteria for FDC at baseline (n=439), were stratified into four groups based on results from genetic screening and clinical work-up at baseline (Figure 1). The risk of developing FDC during follow-up was strongly associated with this classification (see figure 1 and 2). The highest risk of developing FDC was observed in relatives carrying class IV to V genetic variants (n=43, age-adjusted incidence rate of 10% per person-year), while none of the subjects identified as non-carriers of family variants developed disease (n=58). In subjects sub-grouped according to baseline-findings on ECG and echocardiography, relatives with abnormal (n=70) vs normal (n=268) findings had markedly higher incidence rates of FDC (overall 4.7% vs 0.4% per person-year), regardless of age-group (Figures 1 and 2). The relatives with abnormal ECG and/or echocardiographic findings at baseline had a (age-group-adjusted) hazard ratio of 12.9 (CI: 4.8 to 35.1, p&lt;0.001), when compared to relatives with normal findings.

Conclusion
Family screening identified a genetic predisposition to or overt FDC in 30% of screened relatives at baseline. In relatives not fulfilling criteria for FDC at baseline, findings from genetic testing and/or non-diagnostic findings on echocardiography and/or ECG were strongly associated with progression to disease. Importantly, relatives with normal genetic or objective findings had a low incidence rate and overall risk of developing FDC. Thus, baseline-screening identified a large proportion of relatives, in whom follow-up can be considered to be reduced allowing focused follow-up of relatives at higher risk of progression.

Funding Acknowledgement
Type of funding sources: None.
PTX3 as a novel inflammatory biomarker in patients with myocarditis
Authors: Villatore A , Sciorati C , Monno A , Sala S , Della Bella P , Manfredi A A , Peretto G 
Published: October 2022

Abstract

Background
Pentraxin-3 (PTX3) is an acute phase protein, which plays pivotal roles in innate immunity and inflammation. Among cardiovascular diseases, PTX3 was found to be elevated in acute myocardial infarction, chronic heart failure, and cardiac arrest. So far, however, PTX3 has never been investigated in the context of myocarditis.

Purpose
To evaluate PTX3 as a circulating marker of inflammation in patients with suspected myocarditis.

Methods
We enrolled 30 consecutive inpatients with new diagnosis of myocarditis, proven both by the updated Lake Louise criteria on cardiac magnetic resonance (CMR), and by the Dallas criteria on endomyocardial biopsy (EMB) (100%). Circulating serum PTX3 was assessed at the time of EMB, by ELISA technique using a commercial kit. Normal values for PTX3 were considered as &lt;2 ng/mL, as in previous studies. A normal control group (n=10) was used for results validation of PTX3.

Results
In our cohort (77% males, age 50±18 y; median left ventricle ejection fraction [LVEF] 50%, IQR 30–59%), PTX3 levels were assessed in 30 patients. PTX3 levels were elevated in 26/30 (87%) patients with myocarditis (median 4,36 ng/mL, IQR 2,44–6,72, range 1,20–40,0), and in none (0/10) among healthy controls (median 1,28 ng/mL, IQR 1,04–1,36, range 0,77–1,94) (p=0,001). In the study group, the yield of other cardiac biomarkers was lower: 12/30 (40%) for C-reactive protein, 23/30 (77%) for T-troponin, and 20/30 (67%) for NTproBNP. PTX3 was constantly elevated in patients presenting with heart failure (HF) (16/16, 100%), compared with those presenting with acute coronary syndrome-like (8/10, 80%), or arrhythmias (2/4, 50%) (p=0,024). In particular, elevated PTX3 was associated with systolic dysfunction (LVEF &lt;50%) at discharge (16/16 vs. 10/14, p=0,022).

Conclusion
Our preliminary data suggest PTX3 as a novel biomarker with potential diagnostic and prognostic value for myocarditis and inflammatory cardiomyopathy.

Funding Acknowledgement
Type of funding sources: None.
Relevance of subclinical right ventricular dysfunction measured by feature-tracking cardiac magnetic resonance in non-ischemic dilated cardiomyopathy
Authors: Pozo Osinalde E , Urmeneta Ulloa J , Cabrera J A , Martinez De Vega V , Thuissard I J , Andreu-Vazquez C , Perez De Isla L , Marcos-Alberca P , Cabeza B , Rodriguez-Hernandez J L , Luaces Mendez M , Gomez De Diego J J , Bustos A , Perez-Villacastin J , De Agustin J A 
Published: October 2022

Abstract

Background
Right ventricular (RV) dysfunction is associated with worse prognosis in non-ischemic dilated cardiomyopathy (NIDCM). Cardiac magnetic resonance (CMR) is considered the gold standard for RV evaluation. However, scarce data is available with the new feature tracking (FT) technique, which allows strain evaluation from conventional cine sequences.

Purpose
Our aim is to analyze the prognostic relevance of RV myocardial deformation measured by FT-CMR in NIDCM.

Methods
Consecutive patients with NIDCM diagnosis and CMR at diagnosis were retrospectively included. Global longitudinal strain of RV free wall (GLS-RVFW) and fractional area change (FAC) were obtained from standard CMR cine sequences with a dedicated FT software. Their association with a composite endpoint (heart failure admission, implantable cardioverter defibrillator in secondary prevention, and death) was evaluated using a logistic regression model.

Results
FT derived strain was obtained in 98 patients (68±13 years, 71.4% males) with NIDCM, mostly idiopathic (75.5%). Although our cohort showed a severely impaired left ventricular systolic function (LVEF = 29.5±9.6%, 47% with LVEF ≥30%) the RV function was relatively preserved on average (RVEF 52.2±14.6%, 72% with RVEF ≥45%). During a 3.2 [2.2–4] years follow-up 26.5% presented at least one admission for heart failure (HF), 5.1% received an implantable cardioverter defibrillator in secondary prevention, and 8% died. There was no association of RV-FT parameters with prognosis considering the entire study population. However, in patients with LVEF ≥30%, admissions for HF were associated with worse values of GLS-RVFW (−21.6±6.6% vs −31.3±10%; p=0.006) and FAC (32.8±15.8% vs 47.5±13.9%; p&lt;0.001). Similar differences were observed when only patients with RVEF &gt;45% were considered. An GLS-RVFW cut-off point of −19.5% and FAC of 36.5% showed good prognostic performance. Decreased GLS-RVFW or FAC represented an independent predictor for the composite endpoint in patients with LVEF ≥30%.

Conclusions
In our series of NIDCM decreased values of GLS-RVFW or FAC were able to predict major events independently of RVEF in the subgroup of patients without severe LV dysfunction. Therefore, RV deformation parameters by FT may be early markers of poor prognosis in NIDCM.

Funding Acknowledgement
Type of funding sources: None.
Echocardiographic evolution of patients undergoing 99mTc-DPD scintigraphy for suspected cardiac amyloidosis
Authors: Ramos Lopez N , Ferrandez Escarabajal M , Enriquez Vazquez D , Cn Perez Garcia C N , Wakfie-Corieh C , Islas Ramirez F , Mahia Casado P , Gomez De Diego J J , Vivas D , Vilacosta I , De Agustin Loeches J A 
Published: October 2022

Abstract

Introduction
Cardiac transthyretin amyloidosis (ATTR) is usually associated with thickening of the interventricular septum (IVS), although this finding is not specific and can be attributed to other diseases such as high blood pressure (HBP) or hypertrophic cardiomyopathy. The objective was to evaluate echocardiographic changes over time in patients with ventricular hypertrophy, undergoing 99mTc-DPD scintigraphy (DPD), in order to compare findings between patients with cardiac amyloidosis and other etiologies.

Methods
Retrospective registry of 63 patients who underwent DPD due to suspected cardiac amyloidosis in our center between 2018 and 2021. Clinical and echocardiographic characteristics were collected, including 2 echocardiograms per patient, with a minimum separation of one year (echo1, echo2). We compared patients diagnosed with ATTR, with positive scintigraphy grade 2–3 (ATTR group), with patients with negative scintigraphy (grade 0, nATTR group).

Results
The mean age of the patients was 81.3±8.6 years, 67.7% males. 83.9% of patients had HBP, without differences between groups (table1). DPD was positive in 32 (51.6%) patients. Patients with a negative DPD were diagnosed with hypertensive heart disease. The median time between echo1 and echo2 was 3.5 years (IQR 1.2–7), with no differences between groups (4.9 years in nATTR group vs 3.8 years in ATTR group, p=0.2). Results are shown in table1. In echo1, no significant differences were observed in the IVS and biventricular function between both groups. However, in echo3, patients in the ATTR group had significantly greater interventricular septum (IVS) thickness and a worse biventricular function compared to the nATTR group.
A significantly greater growth of the IVS and deterioration of left ventricular ejection fraction (LVEF) between echo1 and echo2 was observed in the ATTR group (table1). The percentage of IVS increase respect to the basal value was also significantly higher in ATTR group. There were no significant differences in the IVS growth per year. In the multivariable analysis LVEF and IVS thickness were independent predictors of a positive DPD.

Conclusions
The increase in thickness of the IVS and deterioration of left ventricular ejection fraction during follow-up of patients with ventricular hypertrophy could be a differential characteristic of ATTR, compared to patients with ventricular hypertrophy of other etiologies. This echocardiographic findings could help to suspect the presence of ATTR.

Funding Acknowledgement
Type of funding sources: None.
Cardiac injury before and after COVID-19. A longitudinal MRI study
Authors: Gonzalez J E , Doltra A , Perea R J , Lapena P , Garcia-Ribas C , Reventos J , Caixal G , Tolosana J M , Guasch E , Roca-Luque I , Arbelo E , Sitges M , Prat S , Mont L , Althoff T F 
Published: October 2022

Abstract

Background
Recent MRI-based studies have raised great concern about frequent cardiac involvement even in mild or asymptomatic COVID-19. However, while signs of myocardial injury were found in large proportions of patients after COVID-19, all studies published to date lack baseline imaging and are therefore unable to discriminate between pre-existing and COVID-19-induced injury.

Purpose
In this longitudinal study, we aimed to assess the true cardiac impact of COVID-19 based on pre- and post-COVID-19 late gadolinium enhancement (LGE)-MRI.

Methods
A prospective registry of patients with serial LGE-MRIs was screened for patients with documented SARS-COV-2 infection after cardiac LGE-MRI. Eligible patients then received a post-COVID-19 LGE-MRI using the same scanner and sequence as in the pre-COVID-19 MRI. Inversion recovery prepared T1-weighted gradient echo sequences were acquired in sinus rhythm using ECG gating and a free-breathing 3D navigator, 15–20 minutes after administering an intravenous bolus of 0.2 mmol/kg of gadobutrol. A TI scout sequence was used in order to determine the optimal TI that nullified the left ventricular myocardial signal. The presence of LGE was independently assessed qualitatively by two experienced investigators blinded to patient information. For quantitative analyses a 3D-reconstruction of the left ventricle was performed using ADAS-3D software. LGE was then automatically quantified based on a prespecified signal intensity threshold of ≥3 SD above the mean of a remote non-enhanced myocardial region.

Results
Pre- and post-COVID LGE-MRI from 31 patients with cardiovascular risk factors that had recovered from mild to moderate COVID-19 (23% hospitalised) were analysed. At a median of 5 months post-COVID-19, LGE-lesions indicative of myocardial injury were encountered in 15 out of 31 patients (48%), which is in line with previous reports. However, intraindividual comparison with the pre-COVID-19 MRI reveiled all of these lesions as pre-existing and thus not COVID-19-related. Quantitative analysis detected no increase in the size of individual LGE-lesions, nor in the global left ventricular LGE-extent. There was no difference in any functional or structural parameter between pre- and post-COVID-19 MRI.

Conclusion
This longitudinal study in a cohort of patients considered at high risk of cardiac involvement, did not find any evidence for COVID-19-induced myocardial injury. The complete absence of de novo LGE lesions in this cohort is reassuring and indicates that cardiac sequelae of COVID-19 are rare and certainly not as common as previously suggested.

Funding Acknowledgement
Type of funding sources: None.
Prognostic prediction of genotype versus phenotype in genetic cardiomyopathies
Authors: Paldino A , Dal Ferro M , Stolfo D , Gandin I , Graw S , Gigli M , Medo K , Gagno G , Zaffalon D , Castrichini M , Mase' M , Merlo M , Taylor M , Mestroni L , Sinagra G 
Published: October 2022

Abstract

Background
In cardiomyopathies (CMPs), the diverse genetic background often leads to phenotypic heterogeneity. Currently, genotype-phenotype studies are founded on clinical phenotype-based classification of CMPs, contributing possible biases due to the exclusion of specific and unascertained phenotypic expressions of CMP genes.

Purpose
We sought to define differences in outcome when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of CMP patients with positive genetic testing.

Methods
In this study, we included the whole spectrum of non-hypertrophic CMP phenotypes, genetically determined: dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), left ventricular arrhythmogenic cardiomyopathy (ALVC) and biventricular ARVC (BiV). The primary and secondary outcomes were: 1) all-cause mortality/heart transplant (D/HT); 2) heart failure-related death/heart transplant/left ventricular assist device implantation (DHF/HT/VAD); and 3) sudden cardiac death/life-threatening ventricular arrhythmias (SCD/MVA).

Results
Two hundred and eighty-one patients (80% DCM) carrying pathogenic or likely pathogenic variants were included in this study. The phenotype was classified as DCM, ARVC, ALVC and BiV according to current consensus criteria. The median follow-up was 188 months. Variants in titin (TTN; 34%) and sarcomeric genes (SARC; 22%) were the most frequent genotypes and almost invariably associated with a DCM phenotype. DSP, LMNA and FLNC displayed more heterogeneous phenotypic presentations, including DCM, ARVC, ALVC, BiV. At survival analysis, the arrhythmic outcome occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA and FLNC variants. However, after adjustment for age and sex, the genotype-based classification but not the phenotype-based classification was predictive of the arrhythmic outcome. LMNA showed the worst trend in term of D/HT and DHF/HT/LVAD.

Conclusions
In genetic cardiomyopathies, genotype is associated with significant phenotypic heterogeneity. Nevertheless, in our study, the genotypic-based classification showed higher precision in predicting CMP patients' outcome in respect to the phenotype-based classification. These findings add to the current understanding of inherited CMPs and may implement the risk stratification of patients with positive genetic testing.

Funding Acknowledgement
Type of funding sources: None.
Impact of myocardial injury on mortality and adverse events in hospitalized patients with influenza: a prospective cohort study
Authors: Valotta A , Biasco L , Klersy C , Valgimigli M , Gabutti L , Della Bruna R , Pagnamenta A , Ruinelli L , Senatore G , Pedrazzini G B 
Published: October 2022

Abstract

Background and aim
Myocardial injury (MINJ) defined as elevated high-sensitivity cardiac troponin level (hs-cTnT) above normal values is a well-recognized prognostic marker in different clinical conditions, nonetheless, its relevance in Influenza remains poorly defined. We aimed to analyse incidence, predictors, short and mid-term prognostic role of MINJ in hospitalized patients (pts) with Influenza.

Material and methods
During 2018–2019 Influenza epidemic, a prospective multicentre observational cohort study was conducted enrolling all hospitalized adult patients with laboratory confirmed Influenza infection. MINJ was prospectively assessed at admission and defined as hs-cTnT &gt;14 ng/L. Primary endpoint was all-cause death at 28-days. Secondary endpoints were all-cause death at 28-days or intensive care unit (ICU) admission/mechanical ventilation and all-cause death at follow up.

Results
145 consecutive pts were enrolled. MINJ was evident in 94 (65.5%) pts. At a 28-days follow up, 7 deaths (4.8%) occurred, all in patients with MINJ at admission (log rank p=0.048). MINJ showed a strong association with the occurrence of death, ICU admission or mechanical ventilation (OR 5.74, 95% CI 1.28–53.29; p=0.015). At a median follow-up of 32.7 months, 15 (10.3%) deaths occurred, all among patients with MINJ at index hospitalization leading to a significantly high mortality rate at follow-up among patients with MINJ (log-rank p=0.003).

Conclusions
Influenza related MINJ is common and identifies patients at higher likelihood of short-term adverse events and midterm mortality.

Funding Acknowledgement
Type of funding sources: None.
Identification of non-calcified coronary plaque characteristics using machine learning radiomic analysis of non-contrast high-resolution CT
Authors: Kruk M , Wardziak L , Kolossvary M , Maurovich-Horvat P , Demkow M , Kepka C 
Published: October 2022

Abstract

Objective
To explore whether machine learning (ML) radiomic analysis of low-dose, high-resolution, non-contrast, ECG gated cardiac CT scan allows identification of non-calcified coronary plaque characteristics.

Background
Novel imaging and analysis techniques may provide the ability to detect non-calcified or high risk coronary plaques on a non-contrast CT scan, advancing cardiovascular diagnostics.

Methods
We prospectively enrolled 125 patients with a non-calcified plaque and an adverse plaque characteristic (APC), and 25 controls without visible atherosclerosis on coronary CT angiography (CCTA). All patients underwent the non-contrast CT exam prior to CCTA. 419 radiomic features were calculated to identify: presence of any CAD, obstructive CAD (stenosis&gt;50%), plaque with ≥2 APC, degree of calcification and specific APCs. ML models were trained on a training set (917 segmentations) and tested on a separate (validation) set (292 segmentations).

Results
Among the radiomic features 88.3% was associated with any plaque, 0.9% with obstructive CAD and 76.4% with presence of at least two APCs. Overall, 80.2%, 88.5% and 36.5%, of features were associated with calcified, partially calcified, and noncalcified plaques, respectively. Regarding APCs, 61.1%, 61.8%, 84.2%, and 61.3%, of features were associated with low attenuation (LAP), napkin-ring sign (NRS), spotty calcification (SC), and positive remodeling (PR), respectively. ML models outperformed conventional methods for the presence of plaque, obstructive stenosis, presence of 2 APC, as well as for noncalcified plaque and partially calcified plaque, but not for calcified plaque. ML models also significantly outperformed identification of LAP and PR, but neither NRS nor SC.

Conclusions
Radiomic analysis of non-contrast CT heart exams may allow identification of specific non-calcified coronary plaque characteristics which could aid cardiovascular risk stratification or pre-screening of individuals prior to contrast enhanced CCTA exam.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Center
Genetic characterization of biopsy-proven myocarditis: a pilot study
Authors: Bueno Marinas M , Baritussio A , Cason M , Celeghin R , Giordani A , Tarantini G , Rizzo S , Marcolongo R , Basso C , Iliceto S , Pilichou K , Caforio A L P 
Published: October 2022

Abstract

Background
Myocarditis is characterized by the presence of an inflammatory infiltrate in the myocardium with degenerative/necrotic changes of cardiomyocytes, not-related to ischemic damage. Its clinical presentation is extremely heterogenous1. Endomyocardial Biopsy (EMB) is the diagnostic gold standard and provides etiopathogenetic diagnosis. Biopsy-proven myocarditis may be infectious, mainly viral, toxic o non-infectious immune-mediated/autoimmune. A complex interplay between genetic factors, environmental triggers (i.e. viral infection) and the immune response of the host is postulated at the basis of different disease evolution2.

Purpose
To determine the prevalence of pathogenic/likely pathogenic (P/LP) variants in cardiomyopathy-related genes in a well-characterized cohort of biopsy-proven myocarditis.

Methods
Sixty-six biopsy-proven myocarditis-affected patients (mean age 51±9, 41 males) underwent screening of 200 genes related to inherited cardiomyopathies. Definite/moderate gene association with Dilated Cardiomyopathy (DCM)3 and Arrhythmogenic Cardiomyopathy4 was based on the ClinGen framework. Variant prioritization was carried out using American College of Medical Genetics and Genomics rules5. Correlation with presence of virus on endomyocardial biopsy by polymerase chain reaction, family history and serum anti-heart autoantibodies (AHA) and/or aintiintercalated-disk autoantibodies (AIDA) was appraised.

Results
Nineteen of the 66 biopsy-proven myocarditis patients (28%) carried a P/LP variant in cardiac-related genes. Titin (TTN) was the most overrepresented gene accounting for 11% of cases (7/66), followed by Myosin Heavy Chain 7 (MYH7) and Myosin Binding Protein C3 (MYBPC3) each accounting for 3% of cases (2/66), respectively. Of note, 29 of the 66 of index cases (44%) referred family history for cardiomyopathy and/or sudden cardiac death. However only 13/29 patients with family history were genotype-positive (45%), indicating that other immunogenetic factors might contribute to triggering myocarditis. Circulating AHA and/or AIDA were detected in 31% of our genotype-positive cohort (6 of 19); a virus positive diagnosis was obtained in 15% of cases.

Conclusion
The prevalence of clinically actionable P/LP variants in cardiomyopathy-related genes is nearly one third of biopsy-proven viral or autoimmune myocarditis patients, most of them associated with DCM. On the other hand, positive family history (44%) in the absence of known cardiomyopathy-related genes indicates that additional immunogenetic factors might contribute to disease pathogenesis.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministero della Salute - Italy - Ricerca Sanitaria Finalizzata