bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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 >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

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>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

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
Association between epicardial adipose tissue and recurrence after atrial fibrillation catheter ablation
Authors: Lacerda Teixeira B , Jacinto S , Silva Cunha P , Portugal G , Valente B , Coutinho Cruz M , Lousinha A , Veiga J , Delgado A S , Bras M , Paulo M , Guerra C , Fontes I , Teixeira R , Oliveira M
Published: October 2022

Introduction

In patients (pts) undergoing atrial fibrillation (AF) catfheter ablation, up to one third have recurrence of atrial fibrillation after a first ablation. Epicardial adipose tissue (EAT) is closely related to AF and could play a role in the recurrence of AF after catheter ablation.

Objectives

To analyze the association between EAT and recurrence of AF in pts submitted to ablation.

Methods

Single-center retrospective study of consecutive AF pts submitted to ablation between 2011 and 2020, with, at least, one-year follow-up. Epidemiological, clinical, laboratory, echo and angio-CT related data were retrieved. A standardized protocol for quantification of EAT, thoracic adipose volume (TAV) and left atrium volume (LAV) was performed. After comparison of groups using Chi-square and Mann-Whitney analysis, an appropriate Cut Off of EAT for our population was determined, and Kaplan Meier survival curves were used to estimate the risk of events (recurrence of AF).

Results

344 pts (63.1% men) were included, with a mean age of 57.4±10.9 years and a median follow-up time of 22 months. During follow-up, 31.,7% (n=109) of pts had recurrence of AF. Baseline characteristics were similar between groups, except for persistent AF, which was higher in pts with recurrence (25% vs 46%, p=0.011). Recurrence of AF was associated with a higher EAT (p=0.040) and a higher LAV (p<0.001) but not with TAV (p=0.115) nor body mass index (BMI) (p=0.123). In pts with recurrence, values of EAT above a cut-off of 151 cm3 predict the endpoint of time to recurrence (HR 2.05, CI [1.180–3.566], p=0.01), with these pts presenting a median of 11 months survival free from recurrence, comparing to a median of 15 months in pts with EAT values bellow the aforementioned cut-off (log-rank p=0.008).

Conclusion

EAT was predictor of AF recurrence in our population, with pts with a EAT value >151 cm3 presenting a statistically significant lower survival free from recurrence.

Funding Acknowledgement

Type of funding sources: None.
The genetic spectrum of hypertrophic cardiomyopathy in an irish cohort
Authors: Cronin H , Gallagher M , McGorrian C , Galvin J
Published: October 2022

Background

Hypertrophic cardiomyopathy (HCM) has long been described as the archetypal monogenic cardiac disease. It fulfils the criteria for Mendelian inheritance and painstaking early co-segregation studies by Seidman et al in 1990 lead to the discovery that mutations in MYH7 cause HCM. From here, the genetic architecture of HCM has been gradually assembled and thousands of individual mutations discovered. The complexity of HCM genetics continues to evolve to include the gene-negative cohort and those carrying multiple mutations. We sought to describe the genetic spectrum of HCM in an Irish population.

Methods

A retrospective examination of the proband database of a specialist cardiomyopathy clinic was undertaken to select all patients with gene-positive HCM. Their clinical data and cardiac imaging was reviewed. Mutations classified by the American College of Medical Genetics as Class 4 and 5 were considered pathogenic. Variants of uncertain significance (VUS) in candidate genes were also recorded, though not clinically actionable.

Results

The results of genetic testing for 254 HCM patients were reviewed. 94% of patients (n=238) had a single pathogenic HCM gene mutation. 5% of patients (n=13) had digenic disease. The remaining 1% (n=3) had oligogenic disease. MYBPC3 was the most commonly involved gene with 116 patients (45.6%) carrying a pathogenic variant. The p. Arg502Trp missense mutation is the most common mutation observed within the Irish cohort and has a founder effect in England. MYH7 mutations were found in 51 patients (20%). Troponin mutations were found in 20 patients (6.8%). Although formally classified as a VUS, there was an overrepresentation of FHOD3 mutations with 19 patients (7.4%) carrying a variant. 41 patients (16%) had pathogenic mutations in PRKAG2, LAMP2 and mitochondrial genes collectively.

Discussion

This Irish cohort has a similar genetic profile in sarcomeric HCM to published European registry data. There is an overrepresentation in HCM phenocopy/metabolic conditions such as mitochondrial and PRKAG2-associated cardiomyopathy. This represents a genetically homogenous small population in Ireland but also includes one of the largest Danon disease cohorts in Europe.

The genetic architecture of hypertrophic cardiomyopathy is complex and the concept of monogenic sarcomeric disease is an over-simplification. There is significant phenotypic variability due to gene-gene effects and gene-dose effects, as well as elusive epigenetic modifier effects. Our understanding of the genetic complexities continues to evolve.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Mater Foundation
Use of advanced echocardiographic modalities to discriminate preclinical HCM mutation carriers from non-carriers
Authors: Lo A , Ruane L , Mew T , Mew C , Guppy-Coles K , Ng A , McGaughran J , Prasad S , Atherton J
Published: October 2022

Background

It is a challenging goal to identify which family members of patients with hypertrophic cardiomyopathy (HCM) will subsequently develop HCM. Previous studies evaluating the utility of two-dimensional conventional Doppler echocardiography in HCM families with a known pathogenic variant identified on genetic testing have been unable to reliably distinguish preclinical genotype-positive, phenotype-negative (G+P−) individuals from their healthy genotype-negative, phenotype-negative (G−P−) relatives.

Purpose

To determine if advanced echocardiographic modalities can discriminate preclinical HCM mutation carriers (G+P−) from non-carriers (G−P−).

Methods

A total of 199 participants who had undergone genetic testing from HCM families with a known pathogenic variant were included in the study: 39 G−P−; 58 G+P− and 102 overt HCM patients (G+P+). Speckle tracking echocardiography (STE) and colour M-mode were performed on all participants and longitudinal, circumferential and radial strain, and torsion were compared.

Results

Patients with overt HCM had the highest septal, posterior wall thickness, septum/posterior wall (Sep/PW) thickness ratio and left ventricular outflow tract (LVOT) gradient and lowest global longitudinal, circumferential and radial strain, and tissue Doppler-derived myocardial systolic and diastolic velocities. Comparing G−P− and G+P− individuals, there were no significant differences in LV cavity size, wall thickness, LVOT gradient, LVEF and tissue Doppler-derived myocardial systolic and diastolic velocities. However, G+P− individuals had significantly higher peak apical rotation, peak twist and colour M-mode flow propagation velocity (Vp). Multivariate linear regression identified two independent predictors (peak apical rotation and Vp), and a regression equation (using multivariate linear regression) {Mutation carrier prediction value = (0.210×peak apical rotation) − (0.002×Vp) + 0.156; r=0.655)} was derived which allowed reliable discrimination of G+P- individuals with a sensitivity of 95.2% and specificity of 94.1% at the optimal cut-off.

Conclusion

In HCM family members without overt HCM, peak apical rotation and Vp provide good sensitivity and specificity for identifying mutation carriers and may be a clinically useful early marker of HCM before the onset of hypertrophy. Future longitudinal studies involving larger cohorts are required to validate these findings.

Funding Acknowledgement

Type of funding sources: None.
Normal indexed values of left atrial volume by age and gender in a population of 250 healthy subjects: a CT-study
Authors: Alos B , Oresve G , Mergy J , Guillevin R , Christiaens L , Bouleti C
Published: October 2022

Introduction

Left atrial volume (LAV) is predictive of cardiovascular outcomes. Its reference values have been described with 2D-transthoracic echocardiography (TTE) and cardiac MRI but very few data are published regarding cardiac computed tomography angiography (CCTA) values. Recent guidelines have highlighted the role of CT-scan, which is a valuable tool to evaluate cardiac dimensions, by its volumetric approach, with a minimal time acquisition and high reproducibility.

Purpose

We aimed to provide CCTA normal LAV reference values by age and gender in a population of 250 healthy subjects.

Methods

We retrospectively included 250 adults (18–74 years) who underwent a retrospectively ECG-gated CCTA in our institution, in order to rule out coronary disease after an episode of chest pain, without any history of cardiac disease or anomaly on the CT-scan. We divided our population in 5 classes of age (<40; 40–49; 50–59; 60–69; ≥70 years) with 1:1 sex ratio. LAV was evaluated at 40% of RR cycle, corresponding to maximal volume, by 2 different methods: semi-automated volumetric approach (3D) and manual area-length (A-L), as recommended for echocardiography and MRI.

Results

In the overall population, mean LAV was 50.6±12.7 ml/m2 (lower and upper limits 25 and 76 ml/m2 respectively) by 3D method and slightly lower using A-L method (42.8±11.5 ml/m2) (LL and UL 20 and 66 ml/m2 respectively). Normal values were 22–81 ml/m2 (3D) and 17–68 ml/m2 (A-L) in men and 30–70 ml/m2 (3D) and 23–63 ml/m2 (A-L) in women. There was no significant difference across genders, but LAV significantly increased with age by the 2 methods (Table 1). Interobserver agreement was better using 3D than A-L method (Lin's coefficient = 0.89 and 0.67, respectively). Concordance between the 2 methods was good, with overall Pearson's correlation coefficient R = 0.72 (p<0.001) (Figure 1).

Conclusion

This study is the first to establish normal indexed LAV values by gender and age in a large population of healthy adults with 2 methods, 3D volumetric approach being the most reproducible one. More accurate than TTE and more available than CMR, CCTA may become a reference method to evaluate LAV in various cardiac diseases and normal values definition is thus of importance.

Funding Acknowledgement

Type of funding sources: None.
Gender-disparities in patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy
Authors: Lawin D , Stellbrink C , Marx K , Danielsmeier N B , Poudel M R , Lawrenz T
Published: October 2022

Background

Alcohol septal ablation (ASA) improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM) but gender-disparities have only rarely been investigated.

Purpose

To assess gender-disparities regarding outcome and procedure-related aspects in HOCM patients undergoing ASA.

Methods and results

1,367 consecutive ASAs between 2002 and 2020 were retrospectively analyzed for sex-differences. Females (47.2%) had more advanced age at the timing of ASA (66.0 years [IQR 55.0–74.0] vs. 54.0 years [IQR 45.0–62.0]; p<0.0001), had more severe symptoms (NYHA class 2.8±0.6 vs. 2.5±0.8 in males; p<0.0001) and shorter distances walked in 6-min-walk-test at baseline (359.0m [IQR 272.3–442.0] vs. 464.4m [IQR 400.0–524.0] in males; p<0.0001). The baseline interventricular septal diameter (IVSD) was higher in males (21.0mm [IQR 19.0–24.0] vs. 20.0mm [IQR 18.0–23.0] in females; p<0.0001). However, the IVSD was higher in females when it was indexed to the body-surface-area (10.9 mm/m2 [IQR 9.7–12.7] vs. 10.2 mm/m2 [IQR 9.0–11.7] in males; p<0.0001). The resting and exercise-induced left ventricular outflow tract gradients (LVOTG) were lower in females when calculated 1–4 days after ASA (resting: 20.0 mmHg [IQR 12.0–37.5] vs. 22.0 mmHg [IQR 13.0–40.0] in males; p=0.0062; exercise-induced: 55.0 mmHg [IQR 30.0–109.0] vs. 71.0 mmHg [IQR 37.0–115.0] in males; p=0.0006). At 6 months follow-up females had lower exercise-induced LVOTG (34.0 mmHg [IQR 21.0–70.0] vs. 43.5 mmHg [IQR 25.0–74.8]; p=0.0072). More females had complete heart block after ASA (20.3% vs. 13.3% in men; p=0.0005) and, hence, more females (17.4%) than males (10.4%; p=0.0002) needed a pacemaker. There were no differences regarding mortality.

Conclusion

Female HOCM patients had more advanced age, more severe symptoms and a higher IVSD when indexed to BSA at the timing of ASA. However, early hemodynamic response was better in females, but procedure-related complete heart block was more often found in women. Gender-disparities in clinical characteristics and procedural outcome of ASA should be taken into consideration.

Funding Acknowledgement

Type of funding sources: None.
Left atrial remodelling after septal myectomy is associated with a reduced 5-year risk of atrial fibrillation in hypertrophic cardiomyopathy
Authors: Bataiosu R , Scolari F L , Brahmbhatt D , Hoss S , Chow C , Cooper C , Tsoi M , Rowin E , Maron M S , Billia F , Ralph-Edwards A , Rakowski H , Adler A
Published: October 2022

Background

Left atrial diameter (LAD) is an established predictor of atrial fibrillation (AF) and adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the impact of LAD remodelling after surgical myectomy on the development of late onset AF is still poorly understood.

Purpose

To investigate the association between LAD remodelling and new occurrence of AF in the first five years after surgical myectomy in a large patient population with HCM.

Methods

1177 HCM patients without a history of AF, subjected to surgical myectomy at two referral centres between 2001 and 2020 were retrospectively reviewed. Paired echocardiographic studies before and shortly after surgical myectomy were available in 894 (76%) patients and 889 (75%) patients had complete LAD measurements, defined as the anteroposterior diameter at end-systole from parasternal long axis view. LAD was considered normal when ≤40mm. Late onset AF was determined as AF documented between one month and 5 years follow up after myectomy. Patients were grouped as having normal LAD pre- and post-myectomy (group 1), enlarged pre-myectomy LAD but normal post-myectomy LAD (group 2), and those with enlarged LAD post-myectomy (group 3). Cox proportional hazards models were applied to evaluate the impact of LAD on late onset AF.

Results

Late onset AF was detected in 63 (7%) patients, 56% male, with an incidence of 1%/year. Patients with AF were older (56±13 vs. 52±14 years, p=0.03), had a larger post-surgery LAD (44±7 vs. 41±6 mm, p<0.001) and a lower left ventricular ejection fraction (58±6 vs. 61±6%, p=0.002) compared to patients without AF. Postoperative left ventricular maximal wall thickness (14±4 mm vs. 15±4mm, p=0.53), left ventricular outflow tract obstruction (6% vs. 8%, p=0.49) or moderate/severe mitral regurgitation (13% vs. 9%, p=0.29) were similar between patients with and without late onset AF. Among the 227 patients in group 1, late onset AF occurred in only 5 (3%), in comparison to 8 (5%) of 182 patients in group 2, and in 36 (10%) of the 480 patients in group 3 (p=0.006). Using group 1 as reference, the hazard ratio for developing AF was 2.1 (95% CI 0.7–6.5, p=0.15) for patients in group 2 and 3.5 (95% CI 1.4–9.4, p=0.005) for patients in group 3.

Conclusion

In our study we were able to show that the overall post-myectomy 5-year risk for developing AF was 1%/year. Normal LAD and reverse LAD remodelling correlated with a lower risk for developing late onset AF, whereas a higher risk was associated with enlarged post-myectomy LAD. These results highlight the possible clinical benefit of LAD remodelling after myectomy in reducing late onset AF.

Funding Acknowledgement

Type of funding sources: None.
Promise or peril: the ECG in HCM
Authors: Cronin H , Gallagher M , McGorrian C , Galvin J
Published: October 2022

Introduction

Hypertrophic cardiomyopathy is a complex disease of the myocardium characterised by left ventricular hypertrophy >15mm in any one segment, in the absence of loading conditions. The phenotypic variability and inhomogeneous nature of the condition have resulted in difficulties with diagnosis. Despite the significant progression in cardiac imaging and genetics, the electrocardiogram (ECG) remains the cornerstone of initial evaluation of patients with HCM and in the screening of families. Moreover, the ECG is in widespread use for pre-participation sports screening.

Purpose

Original and contemporary studies indicate that the ECG is normal in only 6–10% of patients with echocardiographic evidence of HCM. We hypothesised that the ECG may be normal in a significant proportion of HCM patients. This study sought to reassess the ECG as a screening tool in a HCM cohort.

Methods

112 patients were selected randomly from the database of a specialist cardiomyopathy clinic. Their most recent ECG, clinical and imaging data were reviewed. All patients had echocardiographic HCM and were carriers of pathogenic sarcomere gene mutations. Patients with phenocopies were excluded. ECG data for 100 age and sex-matched controls was also analysed. ECG interpretation was performed using international criteria.

Results

18% of patients with a clinical diagnosis of HCM by conventional diagnostic standards (LV wall thickness >15mm) had a normal ECG. A further 7% had a normal ECG with a mild HCM phenotype (LV wall thickness of 13–14mm). The most common abnormality observed was T wave inversion (TWI) in 28%. An additional unexpected finding in the HCM group was isolated TWI in lead aVL. This occurred in 27% of patients in the absence of any other repolarisation abnormalities, compared with 1% of controls. The significance of this finding is unclear. 27% of HCM patients displayed voltage criteria for left ventricular hypertrophy by either Cornell or Sokolow-Lyon criteria, with just 4% meeting criteria for both. 13% of HCM patients had corrected QT prolongation, in the absence of medications responsible for this.

Conclusion

The ECG continues to play a pivotal role in HCM diagnosis but its sensitivity to detect disease has been over-estimated. Up to a quarter of patients with HCM have a normal ECG. This is significantly higher than previously reported. The ECG in isolation therefore is not a reliable tool for screening for HCM in the general population and especially unreliable in at-risk subjects.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Mater Foundation
Augmented risk of ischemic stroke in hypertrophic cardiomyopathy patients without documented atrial fibrillation
Authors: Choi Y J , Kim B S , Rhee T M , Lee H J , Lee H , Park J B , Lee S P , Han K D , Kim Y J , Hk K I M
Published: October 2022

Background

Ischemic stroke is a common complication in patients with hypertrophic cardiomyopathy (HCM) (1). Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke in HCM, the risk of ischemic stroke in patients with HCM without documented AF is less recognized (1, 2). This study aimed to determine the risk of ischemic stroke and identify its risk factors in patients with HCM without documented AF.

Methods

This nationwide population-based cohort study used the Korean National Health Insurance database. After excluding patients with a prior history of AF, thromboembolic events, cancer, or the use of anticoagulants, we identified 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls. The clinical outcome was an incident ischemic stroke.

Results

During a mean follow-up of approximately 6 years, ischemic stroke occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. Among individuals who developed ischemic stroke, the proportion of AF concomitantly detected accounted for 26.5% (87/328) and 5.8% (26/443) in the HCM and control groups, respectively. The overall incidence of ischemic stroke was 0.716/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.643; 95% CI, 1.424–1.895; P<0.001, Figure 1). The subgroup analysis according to age, sex, and comorbidities (chronic heart failure, hypertension, dyslipidemia, and vascular disease) consistently demonstrated a higher risk of ischemic stroke in the HCM group (P for interaction >0.05). In the HCM group, age ≥65 years (adjusted hazard ratio [HR] 2.741; 95% confidence interval [CI], 2.156–3.486; P<0.001) and chronic heart failure (adjusted HR 1.748; 95% CI, 1.101–2.745; P=0.018) were independent risk factors for ischemic stroke. Overall incidence was 1.360/100 in patients with HCM aged ≥65 and 2.315/100 person-years years in those with chronic heart failure, respectively. Also, compared to controls aged <65 years and without CHF, adjusted HR for ischemic stroke was 4.756 (95% CI 3.807–5.867) in patients with HCM aged ≥65 years and 2.539 (95% CI 1.638–3.936) in those with CHF, respectively (Figure 2).

Conclusions

Patients with HCM without documented AF are at a higher risk of ischemic stroke than the propensity score-matched general population. Age ≥65 years and chronic heart failure are two strong independent risk factors for ischemic stroke in this population.

Funding Acknowledgement

Type of funding sources: None.
CT analysis of left ventricular function predicts short term survival in patients following transcatheter aortic valve implantation: 1-year outcome data
Authors: Ijgua M , Arnold M , Eckstein M , Smolka S , Bittner D , Ammon F , Kondruweit M , Moshage M , Achenbach S , Marwan M
Published: October 2022

Introduction

Contrast-enhanced cardiac CT routinely performed prior to transcatheter aortic valve implantation (TAVI), allows assessment of cardiac morphology and function. We assessed left ventricular function in CT as a predictor of survival following TAVI.

Methods

500 consecutive patients referred for CT assessment of aortic root anatomy prior to TAVI were screened for inclusion in this analysis. All CT data sets were acquired using a third-generation dual source system. For assessment of aortic root anatomy, acquisitions were acquired using ECG-gated retrospective spiral acquisition and multiphase reconstructions in 10% increments of the cardiac cycle were rendered (slice thickness 0.75, increment 0.4 mm). left ventricular endocardial contours were automatically traced by a dedicated software (syngo. via, Siemens Healthineers, Forchheim, Germany) throughout the cardiac cycle and manually adjusted if required. Global left ventricular function parameters (end-diastolic and end-systolic volumes, stroke volume, cardiac output and ejection fraction) were derived by volumetric assessment.

Results

Out of 500 patients, 439 patients (mean age 80±6 years, 56% males, and Log EuroScore 23±14%) were included in this analysis (61 patients were excluded due to poor CT image quality or missing outcome data). Previous cardiac surgery had been performed in 15% of the patients, 50% had obstructive CAD with previous interventional or surgical revascularisation and 18% had a previous acute coronary syndrome. One-year survival was 83% (366/439 patients). Parameters of left ventricular function were as follows: mean LVEDV 172±56 ml, mean LVESV 78±62 ml, mean LV ejection fraction 59±18%, mean LV stroke volume index 51±22 ml/m2, mean LV cardiac output 6.6±3.3 L/min and LV cardiac index 3.5±1.7 l/min/m2. Cluster analysis of multiple LV-function surrogate parameters identified a group of patients with higher 1-year mortality, with LVEF identified as a predictor of 1-year survival with a cut-0ff of ≥37% associated with an OR 0f 0.52 (95% CI 0.27 to 0.98).

Conclusion

Assessment of left ventricular function using functional CT data sets is feasible and allows risk stratification of patients following TAVI. Among LV functional parameters, CT derived LV-ejection fraction with a cut-off ≥37% identifies patients with better short-term outcome.

Funding Acknowledgement

Type of funding sources: None.
Influence of sex on cardiovascular outcomes in RBM20 variant carriers
Authors: Cannie D , Protonotarios A , Syrris P , Sengupta A , Bilinska Z , Arana Achaga X , Barriales-Villa R , Garcia-Pavia P , Gimeno J , Merlo M , Wahbi K , Fatkin D , Mogensen J , Rasmussen T B , Elliott P
Published: October 2022

Background

Variants in the RBM20 gene cause dilated cardiomyopathy and may be associated with a poor prognosis.

Objectives

To determine disease penetrance, the risk of adverse events and the influence of sex on outcomes in RBM20 variant carriers.

Methods

Consecutive probands and relatives carrying pathogenic or likely pathogenic RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary endpoint was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF endpoints were also analysed separately and males and females compared.

Results

Longitudinal follow-up data were available for 163 RBM20 variant carriers (82 male, median age 36.5 years, median follow-up 77.6 months). 10/163 had an MVA event at baseline. 30/153 without baseline MVA (19.6%) reached the primary endpoint with a trend towards worse outcomes in males (p=0.08). 16/153 (10.5%) had new MVA with no difference between males and females (p=0.92). 20/163 (12.2%) developed ESHF (17 males and 3 females; p<0.001).

By the end of follow-up, 114 patients (70%) had either left ventricular systolic dysfunction (LVSD) or had experienced MVA. 22 patients received a first diagnosis of LVSD during follow-up. Disease penetrance in individuals over 40 years of age was 78.5% by last evaluation.

Eleven patients that reached the MVA endpoint had a left ventricular ejection fraction (LVEF) available within 6 months of the event. Median [IQR] contemporary LVEF was 30% [23.75, 40%]. 5/11 patients had a contemporary LVEF >35%. 1/11 had a contemporary LVEF >45% (a female, 1st degree relative presenting with sustained ventricular tachycardia and an LVEF of 65%).

Conclusions

RBM20 variants are highly penetrant. The risk of MVA in male and female RBM20 variant carriers is similar but male sex is strongly associated with ESHF. MVA events occur in patients with LVEF >35%.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship
ACE values in the diagnosis of sarcoidosis
Authors: Kawai H , Naruse H , Sarai M , Kato Y , Sato Y , Motoyama S , Ishii J , Morimoto S , Izawa H
Published: October 2022

Background

In clinical practice, we often encounter the patients with sarcoidosis showing relatively high in the normal range of serum angiotensin-converting enzyme (ACE) value.

Purpose

We aimed to examine the serum ACE value of the patients with sarcoidosis and determine the new cut-off value for detecting the patients with sarcoidosis.

Methods and results

We retrospectively examined all 3781 subjects (51.1% men, 60.1±17.0 y.o.) in whom ACE was measured for any reasons including suspected sarcoidosis between 2009 and 2020 in our hospital. Of 293 patients with sarcoidosis, 101, 212, 84, and 88 were diagnosed as sarcoidosis in heart, lung, skin, and eyes, respectively. After excluding 477 patients taking ACE inhibitor and/or immunosuppression agent or those with any diseases affecting serum ACE levels, we analyzed 3304 subjects including 215 with sarcoidosis. Serum ACEs were 19.6 IU/L [IQR, 15.1–31.5] in the subjects with sarcoidosis and 10.7 [8.4–16.5] in those without (P<0.01). In ROC curve analysis of ACE for diagnosis of sarcoidosis, the cut-off point was 14.7 IU/L and the AUC was 0.865. When we used the current cut-off of 21.4 or new cut-off value of 14.7, sensitivity, specificity, PPV, NPV, and accuracy were shown in Table. Finally, they were divided into four groups based on the presence of cardiac and/or extra cardiac sarcoidosis, ACE values in Group A, B, C, and D were 17.9, 20.9, 18.6, and 10.7, respectively (Figure 1).

Conclusion(s)

In the current cut-off value of serum ACE, sensitivity for detecting sarcoidosis was comparatively low, though positive predictive value was low when the new-cut-off value was used in our study. Further examinations may be needed for the patients suspected sarcoidosis with relatively high ACE in the normal range.

Funding Acknowledgement

Type of funding sources: None.
Valve disease in cardiac amyloidosis: an echocardiographic score
Authors: Aimo A , Fabiani I , Maccarana A , Vergaro G , Chubuchny V , Pasanisi E M , Petersen C , Poggianti E , Giannoni A , Spini V , Taddei C , Castiglione V , Passino C , Fontana M , Emdin M
Published: October 2022

Background

Cardiac amyloidosis (CA) may affect all cardiac structures, including the valves.

Methods

From 423 patients undergoing a diagnostic workup for CA we selected 2 samples of 20 patients with amyloid transthyretin (ATTR-) or light-chain (AL-) CA, and age- and sex-matched controls. We chose 31 echocardiographic items related to the mitral, aortic and tricuspid valves, giving a value of 1 to each abnormal item.

Results

Patients with ATTR-CA displayed more often a shortened/hidden and restricted posterior mitral valve leaflet (PMVL), thickened mitral chordae tendineae and aortic stenosis than those with AL-CA, and less frequent PMVL calcification than matched controls. Score values were 15.8 (13.6–17.4) in ATTR-CA, 11.0 (9.3–14.9) in AL-CA, 12.8 (11.1–14.4) in ATTR-CA controls, and 11.0 (9.1–13.0) in AL-CA controls (p=0.004 for ATTR- vs. AL-CA, 0.009 for ATTR-CA vs. their controls, and 0.461 for AL-CA vs. controls). Area under the curve values to diagnose ATTR-CA were 0.782 in patients with ATTR-CA or matched controls, and 0.773 in patients with LV hypertrophy.

Conclusions

Patients with ATTR-CA have a prominent impairment of mitral valve structure and function, and higher score values. The valve score is quite effective in identifying patients with ATTR-CA among patients with CA or unexplained hypertrophy.

Funding Acknowledgement

Type of funding sources: None.
Indexing calcium score of the aortic valve to the annulus area improves the grading of aortic stenosis severity in patients within the grey zone of aortic valve calcification
Authors: Gomes D , Reis Santos R , Freitas P , Presume J , Mendes G , Coutinho Santos A , Guerreiro S , Abecasis J , Ribeiras R , Andrade M J , Campante Teles R , Saraiva C , Mendes M , M Ferreira A
Published: October 2022

Introduction

Calcium score of the aortic valve (CaScAoV) is recommended as a supporting tool to assist in the grading of aortic stenosis (AS) severity when echocardiographic assessment is inconclusive. However, a significant proportion of patients have CaScAoV values within a “grey zone” between the “unlikely” and “likely” thresholds. The purpose of this study was to assess the potential usefulness of indexing CaScAoV to the area of the aortic annulus, in order to improve the discriminative power of CaScAoV in this subset of patients.

Methods

Consecutive patients evaluated at a single center TAVI program were retrospectively identified and included in the analysis if cardiac CT and echocardiography were performed within a 6-month timeframe. Those with LVEF <50%, indexed stroke volume <35 ml/m2, rheumatic heart disease, or bicuspid aortic valves were excluded. Severe AS was defined as mean transvalvular gradient ≥40 mmHg. The likelihood of severe AS assessed by CT was categorized according to the guideline-recommended sex-specific CaScAoV thresholds. Patients were considered to be in the “grey zone” if their CaScAoV values were between 800–1200 for women, and between 1600–2000 for men.

Results

A total of 655 patients were included (282 men (43.1%), median age 83 years [IQR 79–86]). AS was considered severe by echocardiographic criteria in 587 patients (89.6%), and moderate in the remainder. Median transvalvular gradient was 49 mmHg (IQR 43–59), and median CaScAoV values were 3329 (IQR 2356–4500) for men, and 1995 (IQR 1462–2781) for women.

Overall, 77 patients (11.7%) had CaScAoV values in the “grey zone”, of which 24 (31.2%) had moderate AS (Figure 1). Patients within this region of uncertainty were no different form the others in terms of age, sex, annulus size and body surface area.

In this subset of patients, indexing CaScAoV to aortic annulus area showed good discriminative power to identify severe AS (AUC 0.69, 95% CI 0.56–0.81, p=0.008). Using previously established thresholds (>300 AU/cm2 for women and >500 AU/cm2 for men), 48 patients (62.3%) were correctly reclassified (net reclassification index of 0.45, p=0.03). These findings were similar for both sexes.

Conclusion

In patients undergoing cardiac CT for known or suspected severe AS with CaScAoV values within the “grey zone”, indexing CaScAoV to the area of the aortic annulus improves the classification of AS severity and may decrease diagnostic uncertainty.

Funding Acknowledgement

Type of funding sources: None.
Association of cardiac amyloidosis with valvular heart diseases – a nationwide analysis
Authors: Seri A , Baral N , Kambalapalli S , Kattubadi A , Htwe K , Kunadi A , Moza A , Volgman A
Published: October 2022

Background

Association of cardiac amyloidosis (CA) with aortic stenosis (AS) is well known. There is limited data on the association of CA with other valvular heart diseases like aortic regurgitation (AR), mitral stenosis (MS), mitral regurgitation (MR), tricuspid stenosis (TS), tricuspid regurgitation (TR), pulmonary stenosis (PS) and regurgitation (PR).

Purpose

To assess the associations between valvular heart diseases and cardiac amyloidosis.

Methods

This is a retrospective observational study from hospitalizations between January 1, 2016, and December 31, 2019, using the National Inpatient Sample (NIS), the largest all-payer public database of hospital care data in the United States. We looked into associations between valvular heart diseases (VHD) and CA.

Results

From 2016 to 2019, a total of 4999 patients with a history of CA, 16,711 MS, 361,864 MR, 380,072 AS, 89,452 AR, 194 TS, 104,151 TR, 853 PS, 13,277 PR were identified. Compared to those without any history of CA, those with a history of CA had significantly higher associations with MR (6.4% vs 1.3%, p<0.001), AS (3.6% vs 1.3%, p<0.001), AR (1% vs 0.3%, p<0.001), TS (0.02% vs 0, p<0.033), TR (2.7% vs 0.4%, p<0.001), PR (0.4% vs 0.1%, p<0.001). Mean age of patients with history of CA in MS (73.7 years), MR (75.2 years), AS (81.4 years), AR (77.1 years), TS (82 years), TR (77.3 years), PR (78.1 years). Compared to males, females had higher incidence of MS (0.1% vs 0.03%, p<0.001) and lower incidence of AS (1.2% vs 1.6%, p<0.001) and AR (0.3% vs 0.4%, p<0.001).

Conclusion

There was a significantly higher association between CA and MR, AS, TR. Comparatively, patients with CA and MS were younger than those with other VHD.

Funding Acknowledgement

Type of funding sources: None.