bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left ventricular early diastolic strain rate and cardiovascular outcome in patients with left ventricular non-compaction phenotype
Authors: Anwer S , Gremminger M , Marchetti A U , Winkler N E , Wilzeck V , Gruner C , Tanner F C 
Published: November 2023

Abstract

Introduction
Speckle-tracking echocardiography is an increasingly important tool for assessing left ventricular non-compaction phenotype (LVNC). This study aims to analyse left ventricular early diastolic strain rate (eSR) in LVNC and explore its association with CV outcome during long-term follow-up.

Methods
Fifty-nine patients meeting prespecified criteria were included from our prospective LVNC cohort. eSR was determined using TomTec ImageArena (Figure A). A combined endpoint (cardiovascular events) was defined including atrial flutter/fibrillation, sustained ventricular arrhythmias, aborted cardiac arrest, and cardiovascular mortality.

Results
Baseline characteristics were comparable between patients reaching the endpoint (16 [27%]) and those without (43 [73%]) except for a higher prevalence of ischemic heart disease in the former (event group: 13%; no-event group: 2%; P=0.019). In the event group, there was a non-significant tendency for a lower LVEF (38 [26–56]% vs 51 [43–56]%; P=0.091) and LVGLS (-12.3 [-16.3 to -9.7]% vs -15.2 [-17.7 to -12.8]%; P=0.111). In contrast, eSR was significantly lower in the event group (0.45 [0.30–0.65]s-1 vs 0.70 [0.39–0.93]s-1; P=0.018; Figure B). Patients with an eSR ≤ 0.70 s-1 (ROC AUC 70%; P=0.005) exhibited a lower event-free probability in Kaplan-Meier survival analysis (P=0.001; Figure C). Inclusion of eSR improved the fitness (ꭓ2) of a multivariable logistic regression model for clinical characteristics (age, gender, and NC:C ratio; Figure D), while LVEF and LVGLS did not (Table). This improvement in ꭓ2 by eSR was significant (ANOVA P=0.033), while that by LVEF or LVGLS was not (P=0.302 and 0.152, respectively).

Conclusions
eSR was lower in LVNC patients with events, differentiated those with events from those without, and was associated with a higher risk of events during long-term follow-up. Outcome association of eSR was independent of age, gender, and NC:C ratio and improved their event prediction. eSR has potential value for functional characterization and outcome prediction in LVNC.
Right ventricular global longitudinal strain is associated with cardiovascular outcome in left ventricular non-compaction phenotype
Authors: Anwer S , Marchetti A U , Winkler N E , Gremminger M , Wilzeck V , Gruner C , Tanner F C 
Published: November 2023

Abstract

Introduction
Speckle-tracking echocardiography is an increasingly important tool for assessing left ventricular non-compaction (LVNC) phenotype. This study aims to analyse right (RV) and left (LV) ventricular global longitudinal strain (GLS) in patients with LVNC and explore their association with CV outcome during long-term follow-up.

Methods
From our prospective LVNC cohort study, 40 patients were identified with a comprehensive echocardiographic examination including strain analysis of both ventricles. Strain was determined using TomTec ImageArena v.4.6. A combined endpoint (CV event) was defined to include: atrial flutter/fibrillation, sustained ventricular arrhythmias, cardiac syncope, thromboembolic event, heart failure progression, aborted cardiac arrest, cardiovascular death or heart transplantation.

Results
Over a median follow-up duration of 8 [6–10] years, 23 (58%) of the patients experienced one or more CV event (event group); while the rest (17 [42%]) did not (no event group). Baseline clinical characteristics of the two groups were comparable except for a significantly older age (P&lt;0.01) and a higher BMI (P=0.033) in the event group. RVGLS (Figure 1) was significantly lower in the event group (-13.9[-17.1 – -10.3]%) compared to no-event group (-17.3[-18.8 – -15.1]%, P=0.019). While LVGLS did not show a significant difference (P=0.112), LVEF was significantly lower (P=0.011) in the event group. Other echocardiographic parameters were comparable between the groups. RVGLS &gt; -14.3% (sens. 61%, spec. 88%, AUC 72%; P = 0.010) was applied as cut-off to identify patients with a higher risk of CV events during follow-up. Kaplan-Meier curves revealed a higher probability of CV events when RVGLS was &gt; -14.3% (ꭓ2 = 10.28, P = 0.001; Figure 2). Univariable regression models showed that RVGLS (HR 1.10; P = 0.013), LVGLS (HR 1.23; P = 0.045), and LVEF (HR 0.95; P = 0.005) were associated with an increased risk of CV events. The association of RVGLS (OR 1.19, P = 0.047) remained independent of LV GLS and LVEF in a multivariable logistic regression analysis. When RVGLS was included to the LV function model, a significant improvement was noted (ꭓ2 from 7.31 to 11.58; ANOVA P = 0.009).

Conclusions
RVGLS differentiated LVNC patients suffering a CV event from those who did not and provided incremental value to the association of LV function (LVEF and LVGLS) with an increased risk of CV events. These findings highlight the potential value of RVGLS for evaluating long-term outcome during follow-up of LVNC patients.
The challenge of risk stratification in hypertrophic cardiomyopathy: clinical, genetic and imaging insights from a quaternary referral centre
Authors: Paratz E , Gutman S , Stub D , La Gerche A , Mariani J , Taylor A , Ellims A 
Published: November 2023

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD).

Methods
Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest.

Results
380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p=0.0041), unexplained syncope (33.3% vs 9.4%, p=0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p&lt;0.0001), increased septal thickness (21.5 vs 17.5mm, p=0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p=0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most &gt;60-year-olds having a non-cardiac cause of death (p=0.0223).

Conclusion
This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Utilising newer markers such as cardiac MRI and genetic findings may assist future risk refinement.
Atrial fibrillation in patients with hypertrophic cardiomyopathy
Authors: Zoerner C R , Pallisgaard J L , Schjerning A M , Jensen M K , Toennesen J , Riis-Vestergaard L D , Middelfart C , Rasmussen P V , Gislason G , Hansen M L 
Published: November 2023

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is associated with complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms and increases the risk of stroke. Little is known on which factors contribute to the development of AF in these patients.

Purpose
To determine the incidence of AF in Danish HCM patients and identify risk factors that increase risk of AF.

Methods
Using Danish national registers all patients without previous AF, aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM and incident AF was investigated using multivariable Cox proportional-hazard analysis. Cumulative incidence of AF was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account.

Results
A total of 3,200 HCM patients without prevalent AF were included, median age was 66 years (IQR 55-77) and 48% were female. During the study period, 477 (15%) patients were diagnosed with incident AF. The risk of developing AF was equal between genders and average time from HCM diagnosis to debut of AF was 1260 days. Risk of AF development was increased for patients with prevalent ischemic heart disease (HR 1.33, CI [1.08 – 1. 63]) and hypertension (HR 1.34, CI [1.11 – 1. 63]) as well as for patients classifies as obstructive HCM at diagnosis (HR 1.27, CI [1.06 – 1. 53]). Following AF diagnosis, prescription with oral anticoagulants and antiarrhythmic medication increased markedly.

Conclusion
AF is a common complication in HCM. Patients with obstructive HCM, hypertension and ischemic heart disease were at increased risk of developing AF.Figure 1:CI of AF by genderFigure 2:HR for AF developement
Mechanisms of adaptation to high intensity exercise in hypertrophic cardiomyopathy
Authors: Basu J , Ricci P , Maclachlan H , Miles C , Bhatia R , Parry-Williams G , Sharma S , Tome M , Nikoletou D , Papadakis M , O'Driscoll J 
Published: November 2023

Abstract

Background
Many individuals with hypertrophic cardiomyopathy (HCM) demonstrate exercise limitation. For a proportion this may be related to their overall cardiorespiratory fitness influenced by physical activity habits, body mechanics, or habitus. In others there is evidence of central and/or peripheral pathophysiology. However, some individuals with HCM demonstrate favourable adaptation to exercise. In the SAFE-HCM study, participants who underwent 12 weeks of high intensity exercise showed significant improvement in exercise indices including peak VO2, VO2/kg at anaerobic threshold (AT), time to AT, and overall exercise time compared to a usual care group.

Purpose
There have been no studies investigating the mechanistic adaptation(s) to exercise in HCM. This sub-study aimed to identify whether the observed improvements in exercise indices were attributable to central or peripheral adaptation.

Methods
Eighty patients with HCM (45.7±8.6 years) underwent baseline clinical, quality of life and psychological assessment. Individuals were randomised to a 12-week high intensity exercise programme (n=40) or usual care (n=40). Baseline evaluation was repeated at 12 weeks. The Fick equation (oxygen uptake (VO2) = cardiac output (CO) X (arterial-venous oxygen content (a-vO2 difference)) was used to assess whether central and/or peripheral adaptation was responsible for observed improvements. 2D speckle tracking imaging was utilised to calculate left ventricular longitudinal strain from the apical 2-, 3- and 4 chamber views (EchoPAC, V202, GE Healthcare).

Results
12-weeks of high intensity exercise training produced a statistically significant increase in CO (1.1±0.4 L/min, CI (0.2,2.0), p=0.016) compared with the usual care group. There was no difference in the change in a-vO2 difference between groups (p=0.682) suggesting central adaptation to high intensity exercise. This was driven by an increase in stroke volume (SV) (6.1±3.0ml, CI (0.1,12.2), p=0.047) rather than an increase in heart rate (0.6±3.6 bpm, CI (-6.6,7.7), p=0.874). However, there was no change in resting myocardial deformation to account for the observed improvement in CO. Analysis of strain data demonstrated no difference in resting regional 4Ch (-0.7±0.6, CI (-1.9, 0.5), p=0.270) 3Ch (-1.1±0.9, CI (-2.8, 0.6), p=0.201), 2Ch (-1.3±0.9, CI (-3.1, 0.5), p=0.162) or average global longitudinal strain (0.9±0.6, CI (-2.2,0.3), p=0.144) between groups at 12 weeks.

Conclusion
Favourable central adaptations, predominantly driven by an increase in SV, enable improvements in exercise capacity following a high intensity exercise programme. Further studies are required to understand the physiological processes underlying this adaptation including assessment of myocardial deformation at peak exercise
Genotipe-phenotype correlation in alpk3 null variants. an extended analysis
Authors: Garcia Hernandez S , De La Higuera Romero L , Fernandez X , Perez Barbeito M , Cazon Varela L , Peteiro Deben R , Gomez Diaz I , Valverde Gomez M , Amor Salamanca A , Cardenas I , Sanchez Flores M , Cabrera D , Ortiz-Genga M , Ochoa J P 
Published: November 2023

Abstract

Introduction
ALPK3 null variants (ALPK3nv) in simple heterozygosis represent an established and emerging genetic cause for hypertrophic cardiomyopathy. Some studies have indicated that this genetic substrate would be associated with a disease of late-onset disease and incomplete penetrance.

Purpose
To perform an extended genotype-phenotype correlation analysis with respect to simple heterozygous ALPK3nv carriers, focusing on age at diagnosis, maximum wall thickness and survival analysis, performed on the largest available released cohort to date.

Methods
ALPK3 gene was included in an extended NGS panel in 16,780 probands from a reference multicentric genetic laboratory, of whom 6,505 were referred with a HCM phenotype. We collected a composite cohort of ALPK3nv (considering frameshift, nonsense and splice-site predicted frameshift variants), including index and familial cases referred to this laboratory, but also cases reported in the literature. Phenotypic behavior was analyzed, mainly considering age at diagnosis, maximum LV wall thickness, and a composite of events (heart failure and arrhythmia-related endpoints).

Results
A heterozygous ALPK3 null variant was identified in 110 probands out of 6,505 index cases diagnosed with HCM in our center (1.7% of HCM cases). For genotype-phenotype analysis, in total 189 heterozygous carriers were included, considering relatives and cases from the literature; 21 carriers had biallelic involvement (were homozygous or compound heterozygous for two ALPK3Knv).
Among ALPK3nv heterozygous carriers, mean age at diagnosis was 53.4 (±15.2) years; mean left ventricular thickness was 17.7 (±4.9) mm, and morphological profile was mainly apical (42%) and/or concentric (26%). Males tended to be diagnosed at an earlier age than females (median age of diagnosis was 56 vs 71 years, respectively, p &lt;0.01). Five events were observed in this group (four males and one female) all of them related to heart failure, and occur in carriers older than 45 years. The clinical profile was drastically different in cases with biallelic involvement, with a mean age at diagnosis of 22.2±9.3, mean LV wall thickness of 24 mm (±8.6), with LV dysfunction observed in 25%. Nine events were observed in this group, also mostly associated with HF (70%).

Conclusions
ALPK3 null variants in simple heterozygosis can explain 1.7% of HCM. They were associated with late-onset disease, especially in females, predominance of apical and/or concentric forms, and a phenotype that was not particularly severe, both morphologically and in terms of survival.
Risk stratification in patients with structurally normal hearts: does fibrosis type matter?
Authors: Gil K , Mikrut K , Mazur J , Lowery Black A , Vien T , Smart S , Zareba K M 
Published: November 2023

Abstract

Background
The clinical relevance of tissue abnormalities identified by CMR in patients with structurally normal hearts remains unclear.

Purpose
The study sought to assess the prognostic significance of nonischemic myocardial fibrosis (MF) on cardiovascular magnetic resonance (CMR) – both macroscopic MF assessed by late gadolinium enhancement (LGE) and diffuse microscopic MF quantified by extracellular volume fraction (ECV) – in patients with structurally normal hearts.

Methods
Consecutive patients undergoing CMR were screened for inclusion to identify those with LGE imaging and structurally normal hearts. ECV was calculated in patients with available T1 mapping. The associations between myocardial fibrosis and the outcomes of all-cause mortality, new-onset heart failure [HF], and an arrhythmic outcome were evaluated.

Results
In total 525 patients (mean age 43.1±14.2 years; 30.5% males) were included. Over a median follow-up of 5.8 years, 13 (2.5%) patients died and 18 (3.4%) developed new-onset HF. Nonischemic midwall (Figure 1B-C)/subepicardial LGE (Figure 1D) was present in 278 (52.9%) patients; isolated RV insertion fibrosis was present in 80 (15.2%) patients (Figure 1A). In 276 patients with available T1 mapping, the mean ECV was 25.5 ± 4.4%. There was no significant association between LGE and all-cause mortality (HR: 1.36, CI: 0.42-4.42, p=0.61), or new-onset HF (HR: 0.64, CI: 0.25-1.61, p=0.34). ECV (per 1% increase) correlated with all-cause mortality (HR: 1.19, CI: 1.04-1.36, p=0.009), but not with new-onset HF (HR: 0.97, CI: 0.86-1.10, p=0.66)(Figure 2). There was no significant association between arrhythmic outcomes and LGE (p=0.60) or ECV (p=0.49). In a multivariable model after adjusting for covariates, ECV remained significantly associated with all-cause mortality (HR per 1% increase in ECV: 1.26, CI: 1.06-1.50, p=0.009).

Conclusion
Nonischemic LGE in patients with structurally normal hearts is common and does not appear to be associated with adverse outcomes, whereas elevated ECV is associated with all-cause mortality and may be an important risk stratification tool.
Does aetiology of dilated cardiomyopathy impact the outcome in Eastern Europe?
Authors: Dziewiecka E , Wisniowska-Smialek S , Winiarczyk M , Karabinowska-Malocha A , Robak J , Kaciczak M , Baranowski F , Rubis P 
Published: November 2023

Abstract

Introduction
There are regional variations (West vs. East vs. North vs. South) in aetiology and outcomes in patients with cardiomyopathies according to EORP Registry. However, those preliminary observations have not been systematically verified. Here we report on the large cohort of dilated cardiomyopathy (DCM) patients managed in a tertiary centre in Eastern Europe.

Purpose
Analysis of all-cause mortality in DCM patients with different aetiology.

Methods
500 DCM patients (aged 53.1±13.6 years, 81% male, LVEF 26.6±10.4%, LVEDd 65.9±10.3mm, symptoms duration 38.6±61.2 months) from 2010-2021 with complete baseline and follow-up data were included retrospectively. DCM aetiology was diagnosed according to medical documentation as: idiopathic, inflammatory, toxic: alcohol-induced or other (including chemotherapy and drug-induced), arrhythmic and familial or genetic (ref genetic). After mean follow-up (FU) of 45.6±31.0 months, the all-cause mortality and composite endpoint (all-cause mortality, heart transplant – HTX, left ventricle assist device implantation - LVAD) were assessed.

Results
Out of 500 DCM patients no clear aetiology was found in 41% of patients (idiopathic DCM). The most common was inflammatory DCM, followed by alcohol-induced, arrhythmic, and genetic DCM (Figure 1-A). The least common was toxic DCM (18 - after chemotherapy, 2 – drug-induced).
During FU there were 97 (19%) patients with the following events: 88 (18%) patients died, 7 (1%) had LVAD and 15 (3%) had HTX (Figure 1-B). Statistically, all groups did not differ in terms of events (all p&gt;0.05), however on the Kaplan-Meier plot patients with toxic DCM (chemotherapy or drug-induced) had the worst outcome while patients with inflammatory DCM had the best outcome during 6-years FU (Figure 1-C, 1-D).

Conclusion
More than one-third of DCM patients were diagnosed with idiopathic DCM. Toxic DCM was the second most prevalent aetiology and was diagnosed in nearly a quarter of patients. Alcohol-induced DCM was present in every fifth of patients. Although statistically no difference in outcome was found, according to Kaplan-Meier curves, patients with inflammatory DCM have the best prognosis and those with chemotherapy- or drug-induced – the worst.Figure 1.
High intensity plaque in carotid artery on magnetic resonance imaging predict long term major adverse cardiac and cerebrovascular events
Authors: Fujtia A , Miura H , Asaumi Y , Morita Y , Oota Y , Fukuda T , Noguchi T , Iihara K 
Published: November 2023

Abstract

Background
Cardiocerebrovascular diseases remain the major cause of death in the world. The presence of carotid plaque is a surrogate marker for systemic atherosclerosis. High intensity plaque (HIP) in carotid artery on magnetic resonance imaging (MRI) was reported to be associated with the ipsilateral ischemic stroke as well as coronary artery disease. However, few studies have examined the impact of carotid HIP on long-term prognosis of cardiocerebrovascular disease.

Purpose
We investigated whether HIP in carotid artery associated with long term major adverse cardiac and cerebrovascular events (MACCE).

Method
We retrospectively analyzed 241 patients suspected carotid artery stenosis and underwent MRI at our hospital between January 2002 and December 2004. Plaque imaging was performed with non-contrast T1 imaging, and we defined as HIP if plaque-to-myocardium signal-intensity ratio (PMR) ≥2.0. Patients were divided into the HIP group (n=134) or non-HIP group (n=107). The outcome of this study was first incidence of ischemic cardiac or cerebrovascular events. Cardiovascular events were defined as cardiac death (sudden death, fetal myocardial infarction) and non-fetal myocardial infarction. Cerebrovascular events were defined as cerebral infarction. We compared the cumulative incidents of MACCE between with or without HIP groups using Kaplan-Meier method and log-rank test. Multivariate Cox regression analysis was carried out to assess whether HIP could be independent predicter of MACCE.

Results
Median age of study patients was 70 (inter quartile range; 65-75) and 215 (88.1%) patients were male, 185 patients (76.6%) had established vascular diseases. The median follow-up periods were 8.6 years (inter quartile range; 4.0-14.2 years). The presence of HIP was associated with MACCE (p&lt;0.001). Multivariate analysis shows that the presence of HIP was an independent predicting factor for MACCE. When we analyzed incidence of each cardiovascular and cerebrovascular event, the presence of HIP was significantly associated with cerebrovascular events (p=0.004) and cardiovascular events(p=0.03), respectively.

Conclusion
The presence of carotid HIP was associated with long term prognosis for MACCE. Our findings indicate that carotid HIP is a surrogate marker for vulnerable patients with cardiocerebrovascular disease.