bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline clinical features in a large-scale registration survey of patient with hypertrophic cardiomyopathy throughout Japan: J-HCM registry study
Authors: Kubo T , Takano H , Takayama M , Doi Y.L , Minami Y , Ebato M , Inomata T , Katoh T , Okamoto R , Chikamori T , Watanabe E , Furugen A , Maekwa Y , Shimizu W , Kitaoka H 
Published: November 2020

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is a most prevalent primary myocardial disorder with heterogeneous clinical features. However, there have been few studies on clinical features of HCM as a prospective cohort. In 2015, we established a large-scale registration survey of patients with HCM throughout Japan, named J-HCM registry study.

Purpose
The aim of this study was to clarify the clinical features of Japanese patients with HCM.

Methods
J-HCM registry study is a prospective, multicenter investigation, consisting of 24 hospitals. This time, we present the baseline clinical characteristics in this survey.

Results
Total 1484 patients were registered. The ages at registration and at diagnosis were 65±15 and 56±17 years, respectively, and 806 patients (54%) were men. Majority of the patients (95%) was NYHA class I or II. With regard to subtypes of HCM, there were 526 patients (36%) in the HCM with left ventricular (LV) outflow tract obstruction, 126 patients (8%) in the mid-ventricular obstruction, 57 patients (4%) in the end-stage phase characterized by LV ejection fraction &lt;50%, and 197 patients (14%) in apical HCM. At registration, 80 patients (6%) had prior successful recovery from sustained ventricular tachycardia or ventricular fibrillation, 162 patients (11%) suffered from heart failure hospitalization, and 64 patients (4%) had history of embolic event. Regarding invasive treatment, 160 patients (10%) had prior septal reduction therapy and 162 patients (11%) had ICD implantation. According to the 2014 European Society of Cardiology Guidelines on sudden cardiac death (SCD) prevention, the study patients were divided into 3 categories by the HCM Risk-SCD calculator: patients distribution, 4% in the high risk group (≥6% calculated HCM Risk-SCD at 5 years), 7% in the intermediate risk group (4% to &lt;6%), 69% in the low risk group (&lt;4%), and 16% in the patients with extreme characteristics (Figure 1).

Conclusions
In this multicenter registration survey of patients with HCM, the baseline clinical characteristics were almost similar to several retrospective large-scale cohorts in Western countries except older age and less symptomatic state. This study will provide important knowledge regarding management of HCM.
Figure 1

Funding Acknowledgement
Type of funding source: None
Expression of miRNA-21 level in hypertrophic cardiomyopathy patients with chronic heart failure and preserved left ventricular ejection fraction: results of a 6-year follow-up
Authors: Davydova V , Bezhanishvili T.G , Filatova M.E , Andreeva S.E , Streltsova A.A , Poliakova A.A , Pyko S.A , Zaraiskii M.I , Gudkova A.Y.A 
Published: November 2020

Abstract

Introduction
Recently it is found that circulating miRNA-21 is associated with chronic heart failure (CHF) and ischemic heart disease. Its clinical significance in hypertrophic cardiomyopathy (HCM) and CHF with preserved left ventricular ejection fraction (LVEF) (≥50%) has to be investigated.

Purpose
The aim of this study was to analyze the expression of miRNA-21 in the peripheral blood of HCM patients and CHF with preserved LVEF (≥50%).

Materials and methods
From 2014 to 2019 years we examined 180 HCM patients. The study population consisted of 60 patients ≥19 years old (51.5 [36.2; 65.7]) with symptomatic HCM and CHF with preserved LVEF (≥50%). The diagnosis of HCM was established according to the guideline of the European society of cardiology on the diagnosis and treatment of HCM, 2014. The control group included 45 healthy donors without cardiovascular diseases and other severe pathologies, matched by age and sex with the studied group. Total RNA was extracted from plasma of patients. MiRNA-21 and reference RNA U6 cDNA was prepared based on StemLoop-technology. Expression was examined using semiquantitative RT-PCR protocol. Calculation of the relative gene expression level of miRNA-21 was done according to the standard procedure 2-ΔCt. IBM SPSS software package and Microsoft Excel 2010 were used for the statistical analysis of the collected data.

Results
The serum expression level of miRNA-21 in HCM patients (n=60) varied from 0.13 to 477.7 (4.92 [1.77; 13]) and was significantly higher than those in the control group (0.01 - 9.85 (0.84 [0.55; 1.23]), with statistically significant difference (p=0.001). The HCM group was divided according to CHF severity: I-II functional class (NYHA) (n=42) and III-IV functional class (NYHA) (n=18) subgroups. It was found a significant increase of expression microRNA-21 level in both subgroups HCM patients, compared with control group (p=0.001). The expression level of miRNA-21 also differed between HCM patients and CHF III-IV functional class (NYHA) vs those, who had CHF I-II functional class (NYHA) – 1.1–477.7 (13 [3.88; 41]) vs 0.1–119.4 (3.25 [1.41; 6.06]), respectively (p=0.003). In HCM patients and CHF III-IV functional class (NYHA) (n=18) the expression level of miRNA-21 positively correlated with LVEF (r=0.609; p&lt;0.05).

Conclusion
HCM patients with CHF III-IV functional class (NYHA) and preserved LVEF (≥50%) demonstrated high expression level of miRNA-21.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Almazov Federal Medical Research Centre, Saint-Petersburg, Russian Federation, Pavlov University, L'va Tolstogo str. 6-8, Saint Petersburg, Russian Federation
The role of inflammation in recent-onset dilated cardiomyopathy
Authors: Chaloupka A , Krejci J , Poloczkova H , Hude P , Ozabalova E , Godava J , Zampachova V , Svobodova I , Kubanek M , Piherova L , Spinarova L 
Published: November 2020

Abstract

Background
The aetiology of recent-onset dilated cardiomyopathy (RODCM) includes inflammatory, genetic, toxic and metabolic causes. Delineating the role of inflammation on the genetic background could improve risk stratification.

Purpose
We aimed to ascertain the role of inflammation evaluated by serum CRP immunohistochemical and PCR analysis of endomyocardial biopsy (EMB) in conjunction with genetic testing in left ventricular reverse remodelling (LVRR) in 12-month follow-up.

Methods
83 RODCM patients enrolled in this prospective observational study underwent 12-month echocardiographic follow up whole-exome sequencing, and EMB. Presence of cardiotropic viruses was determined by PCR analysis of the EMB samples. Inflammation was defined according to TIMIC immunohistochemical criteria as the presence of &gt;7 CD3+ lymphocytes/mm2 and/or &gt;14 infiltrating leukocytes (LCA+ cells/mm2). LVRR was defined as an absolute increase in LV ejection fraction &gt; +10% and a relative decrease of LV end-diastolic diameter &gt;−10% at 12 months.

Results
LVRR occurred in 28 (34%) of all cases. PCR analysis uncovered cardiotropic viruses in 55 (66%) patients, with highest prevalence of parvovirus B19 (47%). (Figure 1) EMB analysis detected inflammation in 28 (34%) cases and inflammation significantly positively predicted LVRR (P=0.019). Sequencing identified disease-related gene variants (ACMG class 3–5) in 45 (54%) patients. Carriers of non-titin gene variants showed a lowest probability of 12-month LVRR (19%) P=0.041. Combination of genetic findings and inflammation did not improve the prediction of LVRR in 12 months. (Table 1)

Conclusion
Both myocardial inflammation and disease-causing variants can be identified in a large proportion of RODCM cases. Prognostic value of CRP and virus detection is low. Non-titin disease-related variants carriers of are less likely to reach LVRR. In contrast, myocardial inflammation detected by EMB predicts favourable remodelling in 12 months.
Figure 1

Funding Acknowledgement
Type of funding source: None
Impact of genetic reclassification on ARVC diagnosis based on the 2010 task force criteria
Authors: Costa S , Gasperetti A , Akdis D , Suna G , Medeiros Domingo A , Brunckhorst C , Duru F , Saguner A.M 
Published: November 2020

Abstract

Introduction
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited condition, which is associated with potentially life-threatening ventricular arrhythmias in the young. Approximately 60% of patients carry a possibly disease-causing genetic variant.

Purpose
The aim of this study was to investigate the impact of the 2015 American College of Medical Genetics (ACMG) Criteria on ARVC diagnosis based on the 2010 Modified Task Force Criteria (TFC).

Methods
The study included 79 patients from the Swiss ARVC Registry who harbored a genetic variant deemed to be associated with the disease at initial screening, and classified them as definite, borderline or possible ARVC. Every variant found was re-classified on Varsome Genetics, based on the 2015 ACMG Criteria. Clinical information was then assessed at last available follow-up of every patient and ARVC diagnosis was reclassified based on the newest genetic evidence available.

Results
In 42 out of 79 patients (53.2%), genetic variants were reclassified. Out of these, 33 variants (41.8%) were downgraded from pathogenic (P) / likely pathogenic (LP) to either variants of unknown significance (VUS) or benign (B) / likely benign (LB). Three patients (3.8%) were upgraded from VUS / LP to P. Out of the 12 variants initially classified as VUS, 9 (75%) were reclassified as B or LB. Overall, 13 patients (16.5%) were downgraded from their initial diagnosis (11 from definite to borderline and 2 from borderline to possible).

Conclusion
A significant proportion of patients with ARVC diagnosed based on the 2010 TFC were reclassified when the 2015 ACMG Criteria were taken into consideration. These findings may have clinical consequences, particularly for genetic cascade screening of family members of ARVC patients and necessitate reassessment of genetic variants of index patients who were previously diagnosed with ARVC.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): University Hospital Zurich
Filmin-c mutations in arrhythmogenic cardiomyopathy: a peculiar association with left dominat variant and high risk of sudden death
Authors: Bariani R , Celeghin R , Bueno Marinas M , Cason M , Cipiriani A , Rigato I , Pilichou K , Basso C , Perazzolo Marra M , Bauce B 
Published: November 2020

Abstract

Introduction
Arrhythmogenic cardiomyopathy (AC) is characterized by myocyte necrosis and progressive fibro-fatty substitution. Recently, truncated mutations on Filamin C gene have been correlated with AC and a peculiar phenotype characterized by a prominent left ventricular fibrosis and high risk of sudden death.

Purpose
To evaluate clinical and instrumental features of subjects affected by AC in whom genetic study identified presence of truncating and missense mutations on FLNC gene.

Materials and methods
A population of 192 probands affected by AC according to 2010 Task Force Criteria or McKenna's proposed criteria for left dominant AC were evaluated for FLNC variants. In positive probands and families anamnestic and clinical data (ECG, echocardiographic and cardiac magnetic resonance (CMR), twenty-four-hours ECG monitoring) were evaluated.

Results
A total of 19 subjects (9 probands and 10 family members) were identified as carrier of nine different FLNC mutations (5 truncating and 4 missense). In 3 patients (23%) clinical onset was characterized by major arrhythmic episodes and in one (8%) by sudden death. In 6 (46%) ECG was unremarkable and the most common abnormalities were low QRS voltages in peripheral leads (85%), followed by T wave inversion in lateral (15%) and in inferior leads (16%). Twenty-four-hours ECG monitoring revealed a high arrhythmic burden (PVC &gt;500/die) in 6 cases (46%). CMR was performed in all patients. Four of them (31%) showed a LV dilatation, while in 2 cases (15%) a RV dilatation was present. In 8 (61%) a fatty infiltration was detected mainly affecting the left ventricle (6 cases, 46%). Moreover, late enhancement was present in 8 cases (62%), with a LV distribution.

Conclusions
This is the first studied population in which both truncating and missense variants were evaluated as causative of AC, confirming that FLNC gene mutations are rare (4% of probands without known AC causative mutations) and the prevalent clinical expression is a left dominant phenotype with a high degree of electrical instability and recurrence of sudden familial cardiac death.

Funding Acknowledgement
Type of funding source: None
Regression of cardiac amyloid deposits with novel therapeutics: reaching new frontiers in cardiac ATTR amyloidosis
Authors: Chacko L , Martinez-Naharro A , Kotecha T , Martone R , Hutt D , Lane T , Knight D , Moon J , Kellman P , Hawkins P , Gillmore J , Fontana M 
Published: November 2020

Abstract

Background
Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis.

Methods and results
Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p&lt;0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p&lt;0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline.

Conclusions
These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration.

Funding Acknowledgement
Type of funding source: None
Glucocorticoid therapy rather than the inflammatory state is associated with pulmonary embolism and deep vein thrombosis in cardiac sarcoid
Authors: Kolluri N , Elwazir M , Rosenbaum A , Blauwet L , Abou Ezzeddine O , McBane R , Bois J 
Published: November 2020

Abstract

Background
Sarcoidosis is an infiltrative inflammatory condition affecting multiple organs, with cardiac involvement designated as cardiac sarcoidosis (CS). It has been proposed that inflammatory conditions like sarcoid increase the risk of venous thromboembolism (VTE), defined as pulmonary embolism (PE) and deep vein thrombosis (DVT) due to the hypercoagulable environment created by inflammation.

Purpose
Although previous studies have demonstrated an association with sarcoidosis and VTE, these studies failed to account for steroid use (crucial for sarcoid treatment) as an important confounder. Also, no major studies have been done previously assessing the risk of VTE in CS specifically. The objective of this investigation is to determine the association between CS, steroid treatment for CS, and VTE.

Methods
Patients referred to our institution with concern for sarcoid/CS were retrospectively assessed. Specific variables of interest including general baseline characteristics and those specific to CS were analyzed for their association with VTE development.

Results
Using Heart Rhythm Society guidelines, 649 patients were split into three categories: 235 with no sarcoid (NS), 91 with extra-cardiac sarcoid (ECS) only, and 323 with CS. In univariate analysis, 39 (12%) CS patients developed a PE vs 9 (4%) NS patients (OR 3.44, p=0.0003) and 44 (14%) CS patients developed DVT vs 18 (8%) NS patients (OR 1.90, p=0.02). In multivariate regression analysis however, neither CS nor ECS was an independent risk factor for VTE (p&gt;0.05) but steroid use was a strong predictor of VTE (HR 3.12, p=0.007 for PE, HR 6.17, p&lt;0.0001 for DVT). Also, steroid dose was found to be an independent predictor for both PE (p=0.001) and DVT (p=0.007) in a Cox proportionate hazards model (significance appeared at &gt;17.5 mg daily on a receiver operating characteristic curve).

Conclusion
Contrary to previous studies, the current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, steroid therapy for CS treatment leads to an increased prevalence of VTE, specifically at a dose above 17.5 mg daily. More research is required to clarify this relationship and assess the importance of steroid-sparing immunosuppressive therapy and potentially VTE prophylaxis in CS management.
Steroid use and time to PE/DVT

Funding Acknowledgement
Type of funding source: None
ARVC specific autoantibody identifies cardiac sarcoidosis and correlates with inflammation activity
Authors: Suna G , Kolios A , Chatterjee D , Fatah M , Gasperetti A , Steffel J , Ruschitzka F , Duru F , Hamilton R.M , Saguner A.M 
Published: November 2020

Abstract

Introduction
Cardiac sarcoidosis (CS) is an inflammatory granulomatous disease of unknown origin. CS and arrhythmogenic right ventricular cardiomyopathy (ARVC) are overlapping syndromes. With both, patients are at increased risk of ventricular arrhythmias and sudden cardiac death. However, the diagnosis of CS is challenging, especially in patients with no extracardiac involvement, but correct diagnosis has large therapeutic impact. Recently, a novel diagnostic autoantibody (anti-DSG2 Ab) was identified in ARVC. We sought to identify this antibody in CS patients and correlate its levels with inflammation activity using cardiac positron-emission-tomography (18-FDG-PET).

Methods
Recombinant human desmoglein-2 (DSG2) proteins on western blots were exposed to sera as well as purified IgG of 14 patients with sarcoidosis (all confirmed by histology) and 6 controls (1 ARVC patient (positive control) and 5 healthy control subjects (negative control)). Clinical patient characteristics were correlated to detected antibody intensity levels.

Results
The sarcoidosis cohort comprised 43% (6/14) male patients and the average age was 50±12 years. Anti-DSG2 Abs were identified in 43% (6/14) and were detected faintly (below cut off level) in 21% (3/14) of all sarcoidosis patients. Antibody was also present in the ARVC patient (1/1) and was absent in all control subjects (5/5). Myocardial inflammation was present in 18-FDG PET imaging in all CS patients with positive anti-DSG2 Abs, corresponding to an average SUV (standardized uptake value) of 8.1±4.2. In patients with faint or no antibody, the SUV values were significantly lower with 1.2±2.1 and 3.2±4.0, respectively (P=0.044, one-way ANOVA). The Pearson correlation coefficient (R) was 0.6 (P=0.037) for SUV vs. higher antibody levels assessed by pixel count of the western blot bands for purified IgG.

Conclusions
Anti-DSG2 Abs are not only a specific biomarker for ARVC, but are also found in CS, suggesting a similar pathophysiological mechanism in these overlapping syndromes, both involving cardiac inflammation and myocyte cell death. Moreover, antibody levels correlate with disease activity on cardiac PET imaging. Larger cohorts are necessary to confirm these findings.

Funding Acknowledgement
Type of funding source: None
Myocardial constructive work is impaired in cardiac amyloidosis, eases the differential diagnosis and predicts the prognosis among patients with left ventricular hypertrophy
Authors: Palmiero G , Rubino M , Monda E , Caiazza M , Pafundi P.C , Caso V.M , Pacileo G , Caso P , Limongelli G 
Published: November 2020

Abstract

Background
Myocardial Work (MW) is a novel non-invasive echocardiographic method for myocardial performance assessment. MW is abnormal in patients with many forms of left ventricular hypertrophy [hypertrophic cardiomyopathy (HCM), hypertensive cardiomyopathy (HypCM), aortic stenosis (AS)] while little is known about cardiac amyloidosis (CA).

Purpose
We aimed to evaluate the role of MW in myocardial performance assessment, diagnostic significance and prognostic relevance in CA patients.

Methods
25 patients with CA (10 AL pts and 15 ATTRwt pts) and 75 patients with LVH (25 HCM pts, 25 HypCMP pts, 25 pts mild AS pts) were enrolled. Beside routine measurements, deformation parameters [GLS (Global Longitudinal Strain), EFSR (Ejection Fraction on Strain Ratio), RRSR (Relative Regional Strain Ratio)], and MW parameters [MWI (Myocardial Work Index), GCW (Global Constructive Work), GWW (Global Wasted Work), GWE (Global Work Efficiency)] for LV function evaluation were analysed.

Results
LV and RV function evaluated with classical and novel parameters were significantly impaired in CA group (see table). Among all these parameters, GCW showed the best performance to discriminate CA from other forms of LVH (AUC 0.90; 95% CI: 0.80–0.99; P&lt;0,0001), with a cut-off value &lt;1141 mmHg% showing good sensitivity and specificity (90% and 82%, respectively). At Kaplan-Meier estimation of cardiovascular mortality there were 9 deaths in the CA group and none in LVH group, showed significantly higher mortality at follow-up (p=0,0001). At multivariate analysis GCW (β=1,006; 95% CI: 1,003–1,009; P&lt;0,0001) was the only prognostic parameter associated with cardiovascular mortality.

Discussion
Myocardial performance was reduced in CA group. GCW was able to discriminate CA from other forms of LVH and showed to be an independent prognostic factor. In our pilot study GCW seems a promising novel diagnostic and prognostic factor in CA.
Kaplan-Meier curve

Funding Acknowledgement
Type of funding source: None