bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural history of MYH7-related dilated cardiomyopathy
Authors: Frutos Seminario F , Ochoa J P , Navarro-Penalver M , Baas A , Bjerre J V , Zorio E , Mendez I , Lorca R , Verdonschot J A J , Garcia-Granja P E , Bilinska Z , Fatkin D , Fuentes-Canamero M E , Garcia-Pinilla J M , Garcia-Pavia P 
Published: October 2022

Abstract

Background
Variants in MYH7 are responsible for disease in 1–5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described.

Objectives
We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression.

Methods
We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% females, 35.6±19.2 years) recruited from 29 international centers.

Results
At initial evaluation, 106 patients (72.1%) had DCM (LVEF 34.5±11.7%). Median follow-up was 4.5 years (interquartile range: 1.7–8.0). 23.7% carriers who were initially phenotype-negative developed DCM. Disease penetrance by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at &lt;18 years. Thirty-six percent of patients with DCM met imaging criteria for LV non-compaction. During follow-up, 28% showed left ventricular reverse remodeling (LVRR). Overall incidence of end-stage heart failure (heart transplantation or heart failure related death) was 11.6% at 5 years. Overall major ventricular arrhythmia rate was low (1.0% at 5 years) even among patients with LVEF ≤35% (2.1% at 5 years). LV non-compaction was more prevalent in patients with variants in head domain (S1) (44.2%) compared with other domains (P&lt;0.001). No differences among domain groups were found regarding LVRR, major ventricular arrhythmias or end-stage heart failure.

Conclusions
MYH7-related DCM is characterized by early age of onset, high penetrance, low rate of LVRR, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, even among patients with severe systolic disfunction.

Funding Acknowledgement
Type of funding sources: None.
Population estimates of obstructive and non-obstructive hypertrophic cardiomyopathy in the UK and Germany
Authors: Schultze M , Zema C , Carroll R , Hurst M , Borchert J , Zhong Y , Krause T , Bluhmki T , Partington H , Osman F , Tome Esteban M 
Published: October 2022

Abstract

Background
While numerous publications have estimated the prevalence of diagnosed hypertrophic cardiomyopathy (HCM), none have quantified the real-world proportion of obstructive and non-obstructive HCM using nationally representative data sources in any European countries.

Purpose
To estimate the prevalence of diagnosed HCM and its subtypes in the UK and Germany.

Methods
Patients with HCM were identified in the UK from 01 Apr 2009 to 30 Oct 2020 and Germany from 2011 to 2019. UK patients with HCM were identified using electronic health records from the Clinical Practice Research Datalink (CPRD) primary care data linked with Hospital Episode Statistics (HES) secondary care data using ICD-10 (I42.1, I42.2), Read, Medcode, SNOMED, and OPCS codes. German patients with HCM were identified using a nationally representative administrative claims data pool (WIG2 Benchmark database) from several German Statutory Health Insurance (SHI)-insurances using ICD-10 and OPS codes. Obstructive HCM was identified as any obstructive HCM diagnosis, any HCM diagnosis with septal reduction therapy, and any HCM diagnosis and left ventricular outflow tract obstruction (LVOTO; not in German claims data). Non-obstructive HCM was any non-obstructive or unspecified HCM diagnosis without evidence of any obstructive HCM. Annual prevalence was calculated for each year in the respective study periods and average annual prevalence across the study period.

Results
The average annual prevalence rate of HCM was 4.15/10,000 in the UK and 8.61/10,000 in Germany, while the average annual prevalence rate of obstructive HCM was 2.84/10,000 in the UK and 4.18/10,000 in Germany (Table). The proportion of HCM that was obstructive HCM was 68% in the UK and 49% in Germany. The prevalence rates of diagnosed HCM and obstructive HCM tended to increase over time (Figure).

Conclusion
The prevalence of HCM, obstructive HCM and the proportion of HCM that is obstructive varied between the UK and Germany. The prevalence of HCM was generally consistent with previously published estimates. Although there are limitations with coding in administrative data, it is important to differentiate obstructive HCM from non-obstructive HCM given their unique treatments and disease progression and management, especially since at least 49–68% of HCM is obstructive.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Bristol Myers-Squibb
Natural history of myocardial fibrosis in dilated cardiomyopathy
Authors: Rubis P , Dziewiecka E , Wisniowska-Smialek S , Banys P , Urbanczyk-Zawadzka M , Krupinski M , Mielnik M , Karabinowska A , Garlitski A 
Published: October 2022

Abstract

Background
It is commonly accepted that myocardial fibrosis (MF) is implicated in the pathology of dilated cardiomyopathy (DCM). However, MF is not a “fixed” abnormality but evolves over time. It is unknown what the natural history of MF is in optimally treated DCM patients.

Methods
This is a prospective, single-center, observational study. Between May 2019 and September 2020, 90 DCM (81 male, mean age 47.2±9.8 years, mean EF 34.5±12.2%) patients underwent cardiac magnetic resonance (CMR). All patients were optimally treated with heart failure approved medications (beta-blockers in 100%, ACE-I/ARNI/ARB – 98%, MRA – 95%). Both, replacement via late gadolinium enhancement (LGE) and interstitial via T1 mapping MF were assessed. Replacement MF was expressed as LGE mass and LGE extent, whereas interstitial MF as extracellular volume (ECV). Left ventricular (LV) matrix and cell volumes were calculated based on LV mass and ECV as: LV matrix volume = (LV mass/1.05 g/mL) × ECV and LV cell volume = (LV mass/1.05 g/mL) × (1 − ECV). After 12 months CMR studies with MF assessment were repeated.

Results
Overall, index LV end-diastolic and end-systolic volumes (LVEDvol, LVESvol) and LV mass significantly decreased, whereas EF increased during follow-up (Table 1). Both, LGE mass (8.7±8.1 vs. 8.6±7.7 g; p=0.6) and LGE extent (4.6±4.2 vs. 4.97±4.6%; p=0.14) were similar between two measurements. There was a trend towards ECV decrease between baseline and follow-up studies but it did not reach statistical significance (28.5±4.9 vs. 27.7±4.1%; p=0.09). LV matrix volume significantly decreased during follow-up (49.1±17.8 vs. 46.1±15.7 ml; p&lt;0.05); however LV cell volume remained unchanged (123.1±35.6 vs. 119.7±39.6 ml; p=0.2).

Conclusions
Beneficial regression of LV volumes and improvement of systolic function is common in DCM over mid-term period (one year). Replacement fibrosis seems to be a “fixed” pathology without much room for improvement. On the other hand, interstitial fibrosis seems to be a subject for substantial change. Left ventricular cells compartment does not change over time. Two types of MF – replacement and interstitial behaved differently during follow-up. Interstitial MF is amenable for treatment, whereas replacement MF does not respond to currently available therapy.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was founded through the National Science Centre, Poland (grant number 2018/29/B/NZ5/02588) and the Department of Scientific Research and Structural Funds of Medical College, Jagiellonian University (grant number K/ZDS/007192)
Significance and distribution of aortic valve calcium score before TAVI
Authors: Viegas J M , Grazina A , Castelo A , Mendonca T , Rodrigues I , Ramos R , Fiarresga A , Cacela D , Ferreira R C 
Published: October 2022

Abstract

Introduction
Aortic valve calcium scoring by multislice computed tomography (MSCT) is an alternative load independent assessment of aortic stenosis severity. Recent studies have further demonstrated that aortic valve calcification load is related to adverse outcomes during and after transcatheter aortic valve implantation (TAVI), however reference values in this population are uncertain. This study aimed to assess aortic valve calcium in P referred for TAVI.

Methods
Retrospective analysis of consecutive patients (P) submitted to TAVI between 2014 and 2020 in a tertiary care centre. Clinical and echocardiographic characteristics, along with MSCT-derived aortic valve calcium score were collected.

Results
A total of 467 P were included, 57% female, median age 83 (9) years (minimum 45 and maximum 95 years-old). The prevalence of hypertension, dyslipidemia and diabetes was 83%, 69% and 36%, respectively. Chronic renal failure was present in 51%, atrial fibrillation in 34% and peripheral artery disease in 14%.
Considering the 346 P with aortic valve calcification quantified by MSCT, median calcium score was 2161 (1761) AU. Age did not correlate with valvular calcification (r=0.043, p=0.422). Male gender showed significantly higher calcium score (2800 (2093) vs 1850 (1584), p&lt;0.001) (Figs. 1 and 2).
11P had bicuspid aortic valve disease, with this population being younger (75 (16) vs 83 (8) years, p=0.001), nonetheless displaying higher aortic valve calcium load (2800 (2599) vs 2112 (1788), p=0.025). A weak but statistically significant correlation between calcium score and maximum (r=0.366, p&lt;0.001) and mean gradients (r=0.387, p&lt;0.001) and aortic valve area (r=−0.120, p=0.047) was demonstrated. Valvular calcification was not significantly different in P with reduced ejection fraction (&lt;50%) (p=0.388).

Conclusion
There are significant differences in aortic valve calcium score between men and women referred for TAVI. Higher maximum and mean gradients were associated with increasing valvular calcification. Age and left ventricle ejection fraction were not related. P with bicuspid aortic valve have distinct calcification characteristics. As calcification burden may influence preprocedural planning, this parameter should be incorporated in the general work-up and reference values in this population should be known.

Funding Acknowledgement
Type of funding sources: None.
Phenotypic variability of FLNC-related cardiomyopathy: insights from a novel Dutch founder variant
Authors: Schoonvelde S A C , Ruijmbeek C W B , Hirsch A , Van Slegtenhorst M A , Wessels M W , Von Der Thusen J H , Verhagen J M A , Michels M 
Published: October 2022

Abstract

Background
Truncating variants in filamin C (encoded by the FLNC gene) are an important cause of dilated cardiomyopathy (DCM). Recently, a new pathogenic FLNC variant c.6864_6867dup, p.(Val2290Argfs*23) was identified in a number of families with DCM in the south of the Netherlands.

Objectives
The aim of this study was to: (i) investigate whether this FLNC variant is a founder variant; and (ii) to evaluate the clinical phenotype of the affected individuals.

Material and methods
Genetic and clinical data from these FLNC carriers were retrospectively collected. To determine a possible founder effect, haplotypes were reconstructed. The geographical distribution and age of the variant were determined. Clinical characteristics and outcomes were retrieved from electronic medical records. Cardiac magnetic resonance imaging (CMR) studies were reviewed.

Results
In total 33 individuals from 9 families carrying this FLNC variant were identified. A shared haplotype spanning 2.1 Mb was present in all subjects that were haplotyped. The variant appears to have originated in the south of the Netherlands between 275 and 650 years ago.
Median age was 53 years (range 20–79). Nine (27%) individuals were male. The clinical presentation is heterogeneous, ranging from the presence of DCM with heart failure with reduced ejection fraction in 11 (33%) subjects (median age 57, range 36–79 years), to presentation with sudden cardiac death (SCD) in 1 subject at 28 years of age with LV dilation and fibrosis on pathology, without prior symptoms. Seven subjects (21%) had left ventricular (LV) dilation with normal LV function, and one had midrange LV function without dilation. Nine (27%) subjects had no cardiac abnormalities, with a median age of 56 (range 26–70).
CMR was available in 18 subjects and showed late gadolinium enhancement (LGE), indicating fibrosis, in 11 subjects (61%), including 2 with preserved LV function. The LGE was extensively present in epicardial and infrequently in the subepicardial LV segments, with ring-like distributions being observed in 4 (22%) of the assessed patients.
During follow-up 1 subject experienced SCD and 3 developed end-stage heart failure and underwent heart transplantation. Six (18%) subjects had asymptomatic non-sustained ventricular arrhythmias detected by Holter monitoring, and 4 (12%) subjects received an implantable cardioverter defibrillator for primary prevention and 1 for secondary prevention.

Conclusion
The c.6864_6867dup, p.(Val2290Argfs*23) pathogenic FLNC variant is a founder variant originating from the south of the Netherlands. The phenotype is characterized by extensive myocardial fibrosis, even in subjects with preserved LV function, making subjects prone to both arrhythmias and heart failure.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation
Myocardial ischaemia in cardiac amyloidosis: a change of perspective
Authors: Ioannou A , Chacko L , Kotecha T , Patel R K , Razvi Y , Porcari A , Venneri L , Martinez-Naharro A , Knight D , Brown J , Hawkins P N , Gillmore J D , Fontana M 
Published: October 2022

Abstract

Introduction
Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis; however many clinical observations are not explained by the concept of replacement of the interstitium by amyloid material. Preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage.

Purpose
This study assesses the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment.

Methods
Ninety-two patients with cardiac amyloidosis (CA) (AL = 41, ATTR = 51) and 97 without CA (3-vessel coronary disease (3VD) = 47, unobstructed coronary arteries = 26, healthy volunteers (HV) = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-six myocardial biopsies and 3 explanted hearts with CA were analysed histopathologically.

Results
Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA = 1.03±0.51 ml/min/g, 3VD = 1.35±0.50 ml/min/g, Unobstructed coronaries = 2.92±0.52 ml/min/g, HV = 3.14±0.69 ml/min/g; CA vs 3VD p=0.008, CA vs Unobstructed coronaries p&lt;0.001, CA vs HV p&lt;0.001). After adjustment for intracellular volume the MBF in patients with CA remained significantly lower than in HV (stress MBF/ICV: AL = 2.24±1.12, ATTR = 2.22±0.93, HV = 4.38±1.06; AL vs. ATTR p=1.000, AL vs HV p&lt;0.001, ATTR vs. HV p&lt;0.001). Myocardial perfusion reserve (MPR) was severely reduced in CA patients, compared to HV and patients with unobstructed coronary arteries, with the degree of reduction being comparable only to patients with 3VD (CA = 1.55±0.60, 3VD = 1.54±0.51, unobstructed coronaries = 2.78±0.70, HV = 4.08±0.86; CA vs 3VD p=1.000, CA vs unobstructed coronary arteries p&lt;0.001, CA vs. HV p&lt;0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p&lt;0.05). Biopsies demonstrated diffuse hypoxia with abnormal VEGF staining in cardiomyocytes and endothelial cells. Amyloid infiltration in intramural arteries was associated with severe lumen reduction in 20% of vessels, and severe reduction in capillary density.

Conclusion
CA is associated with severe myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Funding Acknowledgement
Type of funding sources: None.
Utility of advanced echocardiographic deformation measures to delineate cause of pathological left ventricular hypertrophy: value of a multiparametric approach
Authors: Lo A , Ruane L , Mew T , Mew C , Guppy-Coles K , Dahiya A , Ng A , Prasad S , Atherton J 
Published: October 2022

Abstract

Background
Early diagnosis of cardiac amyloidosis (CA) is warranted to initiate specific treatment and improve outcomes. Conventional echocardiography is unable to reliably differentiate CA from other causes of increased left ventricular (LV) wall thickness.

Purpose
To demonstrate the value of a multiparametric approach utilising both standard and advanced echocardiographic measures to distinguish CA from other pathological causes of increased LV wall thickness.

Results
Patients with HCM had the highest septal thickness, maximum LV wall thickness, septum/posterior wall (Sep/PW) thickness ratio and left ventricular outflow tract (LVOT) gradient and lowest PW thickness (p&lt;0.0001) among all groups. Patients with CA had the lowest global longitudinal strain (GLS), tissue Doppler-derived myocardial systolic and diastolic velocities and LV ejection fraction (EF) (p&lt;0.0001). EF strain ratio (EFSR=LVEF/GLS) and LV longitudinal strain (apex/base) ratio were highest (largest number) in CA patients (p&lt;0.0001). Multivariate linear regression identified 5 independent predictors (PW thickness, Sep/PW thickness ratio, LVOT gradient, LV longitudinal strain (apex/base) ratio and GLS) that discriminated CA from other causes of increased LV wall thickness. A regression equation (using multivariate linear regression) {CA prediction value = (0.230*LS apex/base) − (0.002*LVOT gradient) − [0.068*(Sep/PW ratio)] + (0.007*PW thickness) + (0.022*GLS) + 0.189; r=0.667)} was derived which allowed reliable distinction of CA with a sensitivity of 92.3% and specificity of 91.2% at the optimal cut-off.

Conclusion
PW thickness, Sep/PW thickness ratio, LVOT gradient, LV longitudinal strain (apex/base) ratio and GLS are independent predictors of CA. We developed a multiparametric regression equation which allowed discrimination of CA from other causes of increased LV wall thickness. Future studies involving larger cohorts are required to validate these findings.

Funding Acknowledgement
Type of funding sources: None.
Incidence and risk factors for pacemaker implantation in light chain and transthyretin cardiac amyloidosis
Authors: Porcari A , Rossi M , Cappelli F , Canepa M , Musumeci B , Cipriani A , Tini G , Varra' G G , Argiro' A , Sessarego E , Sinigiani G , Di Bella G , Rapezzi C , Sinagra G , Merlo M 
Published: October 2022

Abstract

Background
The incidence and risk factors of pacemaker (PM) implantation in patients with cardiac amyloidosis (CA) are largely unexplored.

Purpose
We sought to characterise the trends in the incidence of permanent PM and to identify baseline predictors of future PM implantation in light chain (AL) and transthyretin (ATTR) CA.

Methods
Multicentre, retrospective, observational study. Consecutive patients with AL and ATTR-CA diagnosed or referred at participating Centres between 2017 and 2020 were included. Clinical data recorded within ± 1 month from baseline evaluation were collected from electronic medical records. The primary outcome of the study was the need for clinically-indicated PM implantation. Reversible causes of conduction system disease were systematically ruled out before PM implantation. Patients with PM (n=41) and/or permanent defibrillator in situ (n=13) at the time of CA diagnosis were excluded.

Results
The study population consisted of 405 patients: 29.4% AL, 14.6% variant ATTR and 56% wild-type ATTR; 82.5% were males, with median age 76 years. During a median follow-up of 33 months (interquartile range 21–46), 36 (8.9%) patients experienced the primary outcome: 10 patients with AL-CA, 2 with variant ATTR-CA and 24 with wild-type ATTR-CA (p=0.08). At multivariable analysis, history of atrial fibrillation (hazard ratio [HR] 3.80, p=0.002), PR interval (HR 1.013, p=0.002) and QRS &gt;120 ms (HR 4.7, p=0.001) on baseline ECG were independently associated with PM implantation (Figure 1). In the individual patient, the contemporary presence of these 3 factors yielded the highest risk of PM implantation (HR 6.26, p=0.003).

Conclusion
In a large cohort of AL and ATTR-CA, the incidence of PM implantation was high accounting for ≈9% of patients in the 3 years following the diagnosis. History of atrial fibrillation, longer PR interval and QRS &gt;120 ms identified CA patients at high-risk of future PM implantation (Figure 2).
CA patients with these features might need close monitoring during follow-up for the development of conduction system disease requiring PM implantation.

Funding Acknowledgement
Type of funding sources: None.