bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitral annular dynamics after transcatheter edge-to-edge repair for functional mitral regurgitation: comparison with surgical annuloplasty
Authors: Terada M , Kagiyama N , Izumi Y , Higuchi R , Saji M , Kitamura M , Tskamisawa I , Nanasato M , Iwakura T , Isobe M
Published: October 2024

Background

Transcatheter edge-to-edge repair (TEER) is a recently emerged therapeutic option for functional mitral regurgitation (FMR). Although the mitral annular shape and function may play an important role in the pathophysiology of FMR, few reports have evaluated the impact of TEER. We sought to investigate the impact of TEER on the mitral annulus and its motion in FMR compared with that of mitral annuloplasty (MAP).

Methods

Using three-dimensional transesophageal echocardiography, we evaluated the mitral annular morphology and dynamic motion in patients who underwent TEER or MAP before and after the procedures. Mitral annulus analysis was performed by a semi-automatic program to create a dynamic model of the three-dimensional structure, where the end-systolic annular structure was semi-automatically annotated and manually corrected, followed by automatic tracking of the annulus throughout the cardiac cycle . The mitral annular parameters such as mitral annular diameters, area, circumference, and height at all frames were automatically calculated from the model. In order to align the cardiac phase in each patient (i.e. to set the start and the end of diastole and systole at the same time for all patient), data were spline-interpolated to 100 systolic and 200 diastolic frames and then statistically analyzed. The dynamic changes of the parameters during the cardiac cycle were calculated as (maximum – minimum value) / maximum value after the interpolation.

Results

Patients who underwent TEER (n=20, 69±15 years, 40% female) and those who underwent MAP (n=16, 64±11 years, 6% female) had similar echocardiographic characteristics before the procedures. The maximum anteroposterior diameter and annulus area decreased after both TEER and MAP, while the intercommissural diameter decreased only after MAP but not after TEER. After TEER, the dynamic change in anteroposterior diameter throughout the cardiac cycle tended to decrease (p=0.055), while intercommissural change rather increased (p=0.049), resulting in preserved change in annulus area (p=0.74). After MAP, changes in both diameters and area decreased significantly (all p<0.05). MAP was associated with postoperative mitral annulus area immobility after adjustment (p=0.030).

Conclusions

The dynamic motion of the mitral annulus in patients with FMR was better preserved after TEER than after MAP. There was a decreasing trend in anteroposterior motion, which was compensated for by intercommissural motion after TEER. Future studies are needed to determine the association of these results with cardiac function and prognosis.
Prevalence, characteristics and significance of anomalous coronary arteries in adults undergoing cardiac CT scans
Authors: Noman A , Jathanna N , Obafemi M T , Dubois-Marshall S , Marasinghe I , Vithanage T , Rekhraj S
Published: October 2024

Background/introduction

The widespread use of CT coronary angiogram (CTCA) for the evaluation of patients with suspected coronary artery disease has resulted in increased identification of anomalous coronary arteries. These are often incidental findings and their prevalence and significance remains unknown.

Purpose

To identify the prevalence, characteristics and significance of anomalous coronary arteries in patient undergoing cardiac CT for suspected coronary artery disease.

Methods

This is a retrospective analysis of all cardiac CT scans (n= 5727 CTCAs) performed at two tertiary centres in the UK from 2015 to 2022. For the purpose of this study, we excluded separate LAD and circumflex artery coronary origins given it is clinical non-significance.

Results

Eighty three patients (1.45%) were identified as having anomalous coronary arteries. The average age of patients with anomalous coronary arteries was 57 years (range 18 - 86 years) and 36% were female. The most common coronary anomaly was the left circumflex artery arising from the right side (49 patients, 59%) and all had a retroaortic course. This was followed by an anomalous right coronary artery arising from the left side (29 patients, 35%) with 93% of them taking an interarterial course whilst 7% had a subpulmonic course. We also identified an anomalous left main stem (14 patients, 17%) arising from the right side (5 retroaortic, 5 subpulmonic, 2 prepulmonic, 1 anterior and 1 interarterial course). Four patients (5%) had an anomalous LAD arising from the right (2 prepulmonic, 1 subpulmonic and 1 anterior course). Four patients had other coronary anomalies (left circumflex artery arising from right pulmonary artery, OM arising from left ventricle, congenital atresia of left main stem and an ALCAPA). Majority of the patients with an anomalous coronary artery taking an interarterial course underwent a stress test. During a mean follow-up period of 4 years, four patients (5%) underwent cardiac surgery for treatment of anomalous coronary artery (ALCAPA, left main stem atresia and two anomalous right with interarterial course), seven patients underwent cardiac surgery for other reasons (significant atherosclerotic coronary artery disease and/or valve disease), five patients underwent PCI for treatment of atherosclerotic coronary artery disease and two patients died for reasons unrelated to their coronary anomaly.

Conclusion

This study of a large and unselected cohort of CTCA patients demonstrates an overall prevalence of coronary artery anomalies (as defined above) of 1.45%. We also report the prevalence and characteristics of different coronary anomalies and their outcomes. In the majority of patients, coronary artery anomalies are incidental findings and can be managed conservatively.
Improvement of endorgan function following tricuspid edge-to-edge repair
Authors: Jorde U , Benza R , Whisenant B , Makkar R , Tadros P , Naik H , Fam N , Sauer A , Murthy S , Kar S , Von Bardeleben R , Hahn R , Hamid N , Adams D , Sorajja P
Published: October 2024

Background/Introduction

Subjects with severe tricuspid regurgitation (TR) often suffer from impaired endorgan function. The potential to improve endorgan function is an important goal of treatment.

Purpose

To assess baseline endorgan function and changes in organ function following transcatheter edge-to-edge repair with the TriClip device in subjects with severe TR from the TRILUMINATE Pivotal randomized controlled trial.

Methods

Right heart catheterization was required prior to enrollment; medication history was collected. Changes in biomarkers, including MELD-XI, GGT, eGFR, BUN, and TR and KCCQ overall summary score were assessed at baseline and 12-month follow-up for all enrolled subjects. A 15% improvement in biomarker levels was considered clinically relevant. The odds of achieving a 15% improvement in biomarkers between baseline and 12-month follow-up was compared between the Device and Control groups (presented as OR [95% CI]).

Results

A total of 572 subjects were enrolled and randomized. At baseline, subjects had elevated levels of GGT (83.0±87.7 U/L) and MELD-XI score (10.3±5.2), low eGFR (56.7±21.0 mL/min/1.73m2), and elevated BUN (29.5±16.7 mg/dL). Nearly 90% of subjects were on loop diuretics, with approximately 50% taking these in combination with a thiazide or potassium-sparing diuretic. The average diuretic dosage was 71 mg (furosemide equivalent). Most subjects had normal left ventricle ejection fraction (only 5% with LVEF <40%). Subjects had well-managed blood pressure (systolic: 122±13 mmHg, diastolic: 69±10), slightly elevated central venous pressures (12±6 mmHg), systolic pulmonary artery pressures (40±10 mmHg) and pulmonary capillary wedge pressures (15±4 mmHg), and normal transpulmonary gradients (11±4 mmHg).

The odds of achieving a 15% improvement in liver and renal function was higher in TriClip patients compared to control: MELD-XI score (1.79 [1.22, 2.63]), GGT (1.83 [1.21, 2.77]), and eGFR (1.81 [1.18, 2.77]) - Fig 1.

The favorable changes in organ function observed were also reflected when stratifying subjects by residual TR severity: The odds of a 15% biomarker improvement favored subjects with moderate or less residual TR for MELD-XI score (2.05 [1.39, 3.00]), GGT (1.91 [1.26, 2.90]), and eGFR (1.83 [1.20, 2.80]) compared with subjects who had severe or worse residual TR. Lastly, improvement in these biomarkers also favored subjects with a 15-point or greater improvement in KCCQ compared with subjects with less than a 15-point KCCQ improvement.

Conclusions

Use of TriClip in subjects with severe tricuspid regurgitation was associated with improvement in kidney and liver function, and this improvement was associated with reduction in the severity of TR. These data provide the first objective evidence of the physiologic impact of TR reduction obtained in a randomized clinical trial.
A novel marker of cardiovascular risk stratification: the role of total cardiovascular calcium score using cardiac CT
Authors: Miranda I , Passos M , Gerardo F , Mateus C , Sarmento M , Magno P , Loureiro J , Roque D , Morais C , Augusto J
Published: October 2024

Introduction

It is widely accepted that coronary and valve calcification measured by cardiac CT, individually, are associated with cardiovascular events and mortality. However, the role of an encompassing marker of cardiovascular atherosclerosis could be more representative of the real cardiovascular risk.

Objectives

To determine the prognostic value of a combined coronary, valvular and aortic calcium score to predict long-term major adverse cardiac and cerebrovascular events (MACCE).

Methods

We conducted a single center study on 316 consecutive patients who underwent cardiac CT scan between January 2018 and December 2019. We excluded patients with poor imaging quality, constrictive pericarditis, prosthetic valves and/or devices. The calcium score of coronary arteries (CA), mitral valve (MV), aortic valve (AoV), ascending aorta (AAo) and aortic arch (AAc) were calculated from non-contrast ECG-gated CT using the Agatston method and were combined to derive a valvular (VA=MV+AoV), total cardiac (TC=CA+VA) and total cardiovascular (TCV=TC+AAo+AAc) calcium scores (Fig.1A). The primary endpoint was a composite of MACCE, defined as all-cause death, stroke, myocardial infarction and hospital admission for heart failure.

Results

A total of 275 CT scans were suitable for analysis. Mean age was 59.6±12.3 years, 48.4% were female. A total of 183 (66.7%) patients presented calcification in at least one location. Patients with calcification on any of the prespecified locations had higher prevalence of hypertension, dyslipidemia and type 2 diabetes mellitus (DM) than those without any calcium (p<0.05). After a median follow-up of 3.18 [IQR 2.84-3.69] years, 40 (14.5%) patients had met the primary endpoint. Regression analyses demonstrated that all CA, VA, TC and TCV scores were independent predictors of MACCE (p<0.05 for all). The best prediction models included calcium score (all combinations), age, sex, type 2 DM and smoking status (Fig.1B). The model with TCV score was the most powerful predictor of MACCE (χ2 47.8), followed by TC score (χ2 43.1). Of interest, the model with CA score had the poorest performance (χ2 35.4).

Conclusion

Coronary calcium score is a quick way to stratify risk in clinical practice, but its performance is too focused on coronary events. Total cardiovascular calcium score, however, is more encompassing, also quick to measure, and a more truthful depiction of the patient’s cardiac and cerebrovascular risk, potentially allowing a more tailored and timely approach to risk factors in clinical practice.
Feature importance explanation of prosthetic valve endocarditis through machine learning via SHAP
Authors: Matorra L F , Scholtens A M , Traverso S , De Vrey E , Funes F , Aguero R , Cusimano S , Ruijsink B , Geronazzo R , Namias M , Juarez-Orozco L E
Published: October 2024

Introduction

Diagnosing prosthetic valve endocarditis poses a significant challenge in daily clinical practice. Accurately identifying these patients is vital due to its treatment implications. Clinical and imaging assessment of suspected cases yields a substantial number of interrelated variables, which can be analyzed through machine learning techniques in order to improve diagnostic accuracy. Feature ranking facilitates identification and interpretability of relevant clinical and imaging variables in this task.

Purpose

To utilize machine learning feature ranking and modeling in order to improve interpretable identification of patients with prosthetic valve endocarditis.

Methods

89 cases defined by the endocarditis team and 173 controls were analyzed. We implemented the SHapley Additive exPlanations (SHAP) method to evaluate feature importance. 5-fold cross-validated Xgboost models were trained and independently tested with additive clinical, echocardiographic and 18F-FDG PET/CT data. Performance was evaluated through confusion matrices, F1-scores and AUCs. These were compared against conventional logistic regression of the Duke Criteria classification.

Results

Mean age was 59.6 ± 15.7, with 29.7% women. 14 clinical (demographic, laboratory and cultures), 2 echocardiographic, and 5 PET/CT features were included. The XGBoost model trained with all additive features demonstrated an AUC of 0.91±0.1 and outperformed simpler models as well as the Duke classification model (AUC=0.85). The clinical variables alone achieved an AUC of 0.85±0.11, while integration with echocardiography enhanced its performance to 0.90±0.04 (Fig. 1). Feature ranking demonstrated that antibiotic treatment duration, positive blood cultures, valve type, weight and CRP were the most relevant clinical variables, while the presence of vegetation or abscess, and abnormal uptake and uptake focality on PET/CT represented the most relevant imaging variables (Fig. 2).

Conclusion

Machine learning-based feature ranking and modeling may significantly enhance identification of patients with prosthetic valve endocarditis beyond standard clinical criteria. Feature selection offers interpretable performance in identifying these cases, model testing in clinical decision support may be warranted.Fig. 1:Comparative AUC Analysis.Fig. 2:SHAP feature importance.
Development and validation of a smartphone based app to guide the differential diagnosis in patients with primary left ventricular hypertrophy: the Thick Heart App
Authors: Maurizi N , Skalidis I , Fumagalli C , Monda E , Kasky J P , Pieroni M , Limongelli G , Olivotto I
Published: October 2024

Introduction

Patients presenting with primary Left Ventricular Hypertrophy (LVH) suffers from a diagnostic delay quantified in years. They are often misdiagnosed because of both physician-related and disease-related reasons including fragmented knowledge among different specialties and rarity of the conditions.

Purpose

We developed and validate a free digital support tool in the form of an App to provide support and to guide the physician in the differential diagnostic process of patients presenting with primary LVH.

Methods

We studied 712 patients with definitive diagnosis of sarcomeric HCM or one of its genocopies (414 (58%) males, 48±24 years) referred to four tertiary centers in Europe. Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography, echocardiographic and laboratory. Each patient’s characteristics were inserted by two independent and blind investigators on the App of the digital support tool. The possible diagnostic outcome was categorized as follows: (a) most likely diagnosis (age range for the condition, at least 1 extremely specific RFs or >1 specific RF; (b) possible diagnosis (age range, 1 specific RF); (c) less likely diagnosis (outside age range, no RF selected).

Results

Ris were common in patients presenting with a genotyped HCM (2568 RFs, 3.5 per patient). RF on physical examination was associated with non sarcomeric aetiology (318/319 physical examination RF identified in non-sarcomeric HCM), whereas 68% of RF associated with sarcomeric HCM were derived from accurate ECG and echocardiography analysis. Sarcomeric HCM, TTR-amyloidosis, Danon and PRKAG2 cardiomyopathy relied extensively on ECG and echocardiographic systematic analyisis (68%, 69%, 67% and 69% respectively). In contrast, AFD, Friederich’s ataxia, Noonan syndrome with multiple lentiges (NSML), mitochondrial, Pompe and Noonan cardiomyopathy presented red flags potentially identifiable in the general practioner setting by anamnesis, physical examination and routine laboratory (57%, 59%, 52%, 57%, 57% and 58% respectively) in the vast majority of case. A total of 697/712 (97.8%) were correctly categorized in the most likely and possible diagnosis section. The App proved to be sensible for sarcomeric HCM, FD (0.99 and 0.91, NPV 0.98 and 0.83) and extremely capable in the identification of rare causes of LVH (Danon, Friederich’s ataxia, LEOPARD, Pompe, Noonan and PRKAG2 diseases). By design, specificity was not high, in particular for sarcomeric HCM and FD.

Conclusions

The present validation of an App based free digital support tool in the form of an App proved to be extremely sensible in providing the support to the screening of different causes of primary LVH in patients presenting with a HCM phenotype. Further external and multicenter validation is warranted.
Dynamic changes of excessive trabeculation in dilated cardiomyopathy: a longitudinal cardiovascular magnetic resonance study
Authors: Kang Y , Huang S , Xu Y , Qu N , Li Y , Chen Y , Zhang Q
Published: October 2024

Background

A portion of dilated cardiomyopathy (DCM) patients present with left ventricular (LV) excessive trabeculation at diagnosis. It remains unknown if the extent of trabeculation would be reduced after guideline-directed medical therapy (GDMT).

Purpose

To investigate the dynamic change of excessive trabeculation after GDMT in patients with DCM, and its relationship with that in LV structure and function.

Methods

A group of DCM patients with baseline and follow-up cardiovascular magnetic resonance (CMR) examination after 1-2 years of GDMT were enrolled. Trabeculation was assessed by Petersen method as measuring the thickness of the most prominent non-compacted (NC) layer and the corresponding compacted (C) segment at the apical long-axis view at end-diastole. Excessive trabeculation was defined as the NC/C ratio > 2.3, and a regression was reached if it decreased to ≤ 2.3. Major adverse cardiovascular events (MACE) consisted of cardiovascular death, heart transplantation, and heart failure readmission.

Results

Among 218 DCM patients (45 ± 14 years, 67.4% male), 58 (26.6%) met the excessive trabeculation criteria at baseline. Despite a similar LV ejection fraction (LVEF), patients with excessive trabeculation had a higher LV end-diastolic dimension (73.3 ± 9.0 vs. 70.5 ± 8.0mm) and native T1 (1325.3 ± 71.2 vs. 1305.5 ± 65.9mm) (both p<0.05) with a trend of more late gadolinium enhancement (51.7% vs. 39.4% of patients). After 15 months of GDMT, patients with excessive trabeculation (n=58) showed a decreased NC layer (12.7 ± 3.4 vs. 11.3 ± 3.0 mm) and NC/C ratio (3.1 ± 0.9 vs. 2.7 ± 0.9) (both p < 0.05), 25.9% of whom showed a regression of trabeculation. Patients with the regression had a lower NC/C ratio (1.8 ± 0.4 vs. 3.0 ± 0.8, p < 0.001) and LV end-diastolic volume index (LVEDVi) (121.5 ± 40.5 ml/m2 vs. 165.9 ± 67.8ml/m2, p=0.004) compared with those without. The change of (△) NC/C ratio was associated with that of LVEDVi (r = 0.323), and LVEF as well (r = -0.254) (both p < 0.001). Excessive trabeculation at baseline did not differentiate patients with a higher risk of MACE by Kaplan-Meier survival curve (p= 0.208), but its persistent presence at follow-up did (p= 0.004). However, when put △NC/C ratio, △LVEDVi, △LVEF and In NT-proBNP into multivariate cox regression model, only the △LVEDVi (HR, 0.963; 95% CI: 0.942, 0.985; P = 0.001) and In NT-proBNP (HR, 2.016; 95% CI: 1.288, 3.157; P = 0.002) were independent predictors of MACE.

Conclusions

Regression of excessive trabeculation occurred after GDMT in DCM patients that was related somewhat to LV reverse remodeling and not an independent predictor of MACE. It may also indicate the interconnection between LV remodeling and trabeculation.
Radiomics-based multimodality prediction of left atrial appendage thrombus using coronary computed tomography angiography
Authors: Xin R , Yang J , Chen Y
Published: October 2024

Background

Timely detection of thrombus in the left atrial appendage (LAA) may help guide decision-making. However, existing models have challenges in extracting comprehensive image information. It has been shown that radiomics-based prediction models can be used for accurate identification. This study investigates potential radiomic markers and constructs a highly efficient multimodality prediction model for LAA thrombus in patients undergoing coronary computed tomography angiography (CCTA).

Methods

We retrospectively enrolled patients with nonvalvular atrial fibrillation (NVAF) who underwent CCTA and transesophageal echocardiography (TEE) from May 2015 to May 2020. These patients were classified into thrombus or non-thrombus groups based on TEE findings. The data were balanced by resampling and assigned to training or test sets. Radiomics was conducted on the extracted features, and a random forest algorithm was employed for feature selection and importance ranking. We constructed different multimodality thrombus prediction models and compared their performance using the area under the receiver operating characteristic curve (AUC) and other efficacy parameters.

Results

Among 670 patients (60.17±10.98 years, 70.1% male), 5.2% (n=35) had LAA thrombi. A total of 1232 radiomics features were extracted, with 25 features selected using a random forest for modeling. Two radiomics features (Ibp_3D_m1_firstorder Skewness and original_shape_Flatness) ranked the highest. The radiomics-based multimodality prediction model achieved an AUC of 0.964 (95% confidence interval [CI]: 0.947-0.982), an accuracy of 0.926 (95% CI: 0.925-0.926), and an F1 score of 0.924, outperforming other traditional prediction models. Decision curve analysis also indicated that this model provided the best net clinical benefit.

Conclusions

Radiomics facilitates a comprehensive exploration of predictors associated with LAA thrombi. A radiomics-based multimodality prediction model can significantly enhance the efficiency of non-invasively detecting thrombi.Receiver operating characteristic curveDecision curve analysis
The role of 18fluorine-fluorodeoxyglucose positron emission tomography in the diagnosis, follow-up, and regulation of treatment in patients with cardiac sarcoidosis.
Authors: Bobbio E , Cortas N , Bollano E
Published: October 2024

Background

Cardiac sarcoidosis (CS) is a potentially fatal disease, commonly presenting with arrhythmias, heart failure, or sudden death. Diagnostic challenges persist, particularly due to limited sensitivity of endomyocardial biopsy (20-25%). Alternative diagnostic approaches, such as criteria-based diagnosis, have emerged. 18fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has gained prominence in diagnosing CS, monitoring treatment, and serving as a follow-up tool, although its precise role and efficacy remain unclear.

Purpose

This retrospective cohort study sought to characterize patients with CS who underwent at least one 118F-FDG-PET scan. Primary objectives were to explore the impact of 18F-FDG-PET on both the diagnosis and management of CS. Additionally, this study aimed to investigate any differences in patient outcomes based on the results of their first follow-up 18F-FDG-PET scan.

Methods

Medical records of 69 patients with CS who underwent at least one 18F-FDG-PET scan were analyzed. The study calculated the proportion of 18F-FDG PET scans influencing CS treatment and diagnosis, with 56 patients undergoing at least two scans. Among these, 53 patients were categorized into two groups based on their first follow-up scan results (group 1:no change/progress, group 2:regress). Statistical analyses included independent t-tests, the Mann-Whitney test, and Fisher's exact test. Outcome measures included death, heart transplantation or aborted cardiac death, with survival analyzed by Kaplan-Meier statistics.

Results

Among 69 patients, 204 18F-FDG-PET scans were conducted, with 47% directly influencing treatment decisions. Twenty-five patients were diagnosed with CS through 18F-FDG-PET. While no significant differences were observed regarding demographics and clinical features, the results suggested potential differences in event-free survival (p=0.084;Figure 1) and sex (p=0.08) between the groups.

Conclusions

18F-FDG-PET has emerged as a pivotal tool in regulating treatment, diagnosing, and monitoring CS patients, playing a fundamental role in assessing treatment response. However, further studies are needed.
Cardiac magnetic resonance T1 imaging for the diagnosis of cardiac amyloidosis among patients with symptomatic heart failure
Authors: Gessner R , Unger L , Hagendorff A , Kluge R , Laufs U , Lavall D
Published: October 2024

Background

Cardiac amyloidosis (CA) is a significant cause of heart failure in elderly patients. However, specific signs in cardiac imaging are lacking, hence bone scintigraphy in combination with screening for monoclonal protein, or myocardial biopsy is required for the diagnosis. Cardiac magnetic resonance (CMR) imaging with T1 mapping is a promising diagnostic tool, which may allow to differentiate causes of left ventricular (LV) hypertrophy, particularly CA.

Purpose

The aim of this study was to test the diagnostic accuracy of T1 mapping for the diagnosis of CA in elderly patients with symptomatic heart failure and red flags for CA.

Methods

We prospectively enrolled 120 patients aged above 60 years with symptomatic heart failure NYHA II-IV, LV ejection fraction ≥ 40%, increased LV wall thickness of ≥ 12 mm end-diastolic on echocardiography, and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥ 1,000 ng/L, high-sensitivity cardiac troponin T (hs-cTnT) ≥ 14 ng/L). All patients underwent standardized quantitative CMR with a 3.0T scanner. 99mTc-DPD bone scintigraphy, blood screening for monoclonal protein, and, where applicable, cardiac biopsy, were performed as reference methods in all patients. Primary endpoint was diagnostic accuracy of native T1 mapping for the diagnosis of CA.

Results

112 patients were included in the final analysis. Median age was 81.0 years (interquartile range 74.0–85.0 years), and 45% were female. CA was diagnosed in 38 patients (34%), of which 32 suffered from a Transthyretin (ATTR) and 6 patients from light chain (AL) amyloidosis. The areas under the receiver operating characteristic curves for native T1 were 0.713, 0.772, 0.836 for global, septal short-axis (SAX), and septal 4-chamber (4Ch) view measurements. The corresponding value of extracellular volume fraction (ECV) was 0.904 (Figure 1). Based on these results, we developed a new diagnostic algorithm for the diagnosis of CA including T1 septal 4Ch and ECV, with a sensitivity and positive predictive value of both 92.9% and a specificity and negative predictive value of 95.8% (Figure 2). Thereby, contrast application can be avoided in 33% of patients. A definite diagnosis could be provided in 81%.

Conclusion

CMR with T1 imaging provides a high diagnostic accuracy to diagnose CA in patients with symptomatic heart failure at risk for CA. These data may help to identify underlying causes in heart failure which require specific treatment. An earlier diagnosis of CA may improve outcome of these patients.Figure 1Figure 2
Prevalence of pathogenic variants in cardiomyopathy-associated genes in acute myocarditis: a systematic review and meta-analysis
Authors: Monda E , Bakalakos A , Cannie D , O'mahony C , Syrris P , Kaski J P , Limongelli G , Elliott P M
Published: October 2024

Background

Acute myocarditis is an inflammatory condition that may precede the development of dilated or arrhythmogenic cardiomyopathy.

Objectives

To investigate the reported prevalence of pathogenic/likely pathogenic (P/LP) variants in cardiomyopathy-associated genes in patients with acute myocarditis.

Methods

For this systematic review and meta-analysis, we searched Pubmed and Embase databases on March 04, 2023. Observational studies evaluating the prevalence of P/LP variants in cardiomyopathy-associated genes in patients with acute myocarditis were included. Studies were stratified into adult and pediatric age groups and for the following scenarios: (a) complicated myocarditis (i.e., presenting with acute heart failure, reduced left ventricular ejection fraction, or life-threatening ventricular arrhythmias); (b) uncomplicated myocarditis. The study followed PRISMA guidelines.

Results

Of 732 studies identified, 8 met the inclusion criteria, providing data for 586 patients with acute myocarditis. A total of 89 P/LP variants in cardiomyopathy-associated genes were reported in 85 patients. In uncomplicated myocarditis the pooled prevalence was 4.2% (95% CI 1.8-7.4%, I2 1.4%), while in complicated myocarditis pooled prevalence was 21.9% (95% CI 14.3-30.5%, I2 38.8%) and 44.5% (95% CI 22.7-67.4%, I2 52.8%) in adults and children, respectively. P/LP variants in desmosomal genes were predominant in uncomplicated myocarditis (64%), while sarcomeric gene variants were more prevalent in complicated myocarditis (58% in adults and 71% in children).

Conclusions

Genetic variants are present in a large proportion of patients with acute myocarditis. The prevalence of genetic variants and the genes involved vary according to age and clinical presentation.Central Illustration
Mavacamten in a real-world hypertrophic cardiomyopathy population: how many may be eligible?
Authors: Lima M R L , Bello A R B , Maltes S M , Laranjeira T L , Cunha G C , Adragao P A , Rocha B R , Aguiar C A
Published: October 2024

Introduction

Mavacamten is a newly approved drug for obstructive hypertrophic cardiomyopathy (oHCM) and is currently being studied in non-obstructive HCM (nHCM). Our goal was to evaluate how often patients with oHCM and nHCM in a real-world cohort would be eligible for the main mavacamten trials: EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM.

Methods

Single-centre retrospective study enrolling consecutive patients with confirmed HCM, as per the 2023 ESC Guidelines, with at least yearly follow-up in our center, from 2017-2023. Key inclusion criteria from the three trials were considered: NYHA class II-III for all; obstructive forms (defined as peak left ventricle outflow tract [LVOT] gradient ≥50 mmHg at rest, after Valsalva manoeuvre or exercise) for EXPLORER-HCM and VALOR-HCM; left ventricular ejection fraction (LVEF) ≥55% for EXPLORER-HCM and MAVERICK-HCM; LVEF ≥60% and formal criteria for septal reduction therapy for VALOR-HCM, and NT-proBNP ≥300pg/mL for MAVERICK-HCM. Key exclusion criteria (estimated glomerular filtration rate [eGFR] <30mL/kg/1.73m2, QTc using the Fridericia’s formula >500ms, paroxysmal or intermittent atrial fibrillation present on screening electrocardiograph) were also considered.

Results

Overall, 410 patients were diagnosed with HCM, of whom 361 (88%) were alive at follow-up and included in the analysis: mean age of 63 ± 16 years, 196 (54%) were male, 272 (75%) with septal HCM and 60 (17%) with oHCM. According to the criteria of EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM, 35 (10%), 6 (2%) and 27 (7%) patients would be eligible for enrolment, respectively. In patients with oHCM, 35 (58%) would be eligible for the EXPLORER-HCM trial. In the overall cohort, 65 (18%) would have criteria for at least one of the trials. The main reasons for exclusion were as follows: 191 (53%) NYHA I, 43 (12%) with NYHA IV, 12 (3%) had a LVEF <55%, 8 (2%) had both HCM and infiltrative myocardial disease and/or moderate-to-severe aortic stenosis and 8 (2%) had an eGFR <30mL/kg/1.73m2. In patients with nHCM, 16 (5%) would have been excluded due to NT-proBNP <300pg/mL and 8 (3%) due to paroxysmal atrial fibrillation.

Conclusion

In a real-word HCM cohort, we found that approximately 1 in every 5 patients would have criteria for either of the mavacamten trials, with more than half of oHCM being potential candidates for the EXPLORER-HCM. The main reasons for non-eligibility were NYHA I and LVEF <55%.
Assessing the alignment of obstructive hypertrophic cardiomyopathy pharmacological treatments with ESC guidelines in Germany
Authors: Sedaghat-Hamedani F , Zema C , Schultze M , Garcia T , Kossack N , Hernandez E M , Bluhmki T , Krause T , Schmoelders J , Meder B
Published: October 2024

Introduction

The European Society of Cardiology (ESC) recently updated treatment guidelines for hypertrophic cardiomyopathy (HCM).

Purpose

The aim of this study was to describe the treatment of obstructive HCM in Germany and assess alignment with the 2014 and 2023 ESC guidelines.

Methods

Adults with HCM were identified using a nationally representative administrative claims dataset (WIG2 Benchmark database) from several German Statutory Health Insurances between 2012 and 2018. Obstructive HCM was identified as any obstructive HCM diagnosis (ICD-10: I42.1) or any HCM diagnosis (I42.2, I42.9) with septal reduction therapy. The index date was defined as the date where the patient met all eligibility criteria for HCM. Minimum follow-up time was set to one year. Patients had at least 1 year of baseline data prior to the index HCM diagnosis and were followed up for at least 1 year after the diagnosis (or until death within 1 year). Patients with phenocopies were excluded. ESC guideline-directed pharmacological treatments for HCM included beta-blockers (BB), calcium channel blockers (CCB), disopyramide, and/or mavacamten (approved by EMA June 2023). While the 2014 ESC Guidelines on Diagnosis and Management of HCM were applicable during the study, recommendations pertaining to the use of non-vasodilating BBs and non-dihydropyridine (DHP) CCBs did not change in the 2023 ESC Guidelines for the Management of Cardiomyopathies; thus, this study applies to both.

Results

Out of 6793 patients with HCM analysed in the period 2012-2018, 1,141 had obstructive HCM. The average follow-up was 5 years. Patients were mostly male (62%) with a mean age of 60 years. Hypertension, hyperlipidaemia, coronary artery disease, heart failure, and atrial fibrillation were among the most common comorbidities; the mean Charlson Comorbidity Index score was 2.3. At index, 46% of patients were on BB monotherapy, 23% were on CCB monotherapy, <1% were on a combination of BBs or a combination of CCBs, 9% were on a combination of BBs and CCBs, and as many as 22% received no HCM treatment. Patients experienced 1615 unique treatment combinations throughout the study across all lines of therapy (Table 1). The most common treatments were bisoprolol (24%), metoprolol (19%), amlodipine (12%), and verapamil (12%). The use of propranolol was negligible (1%). 43% of pharmacological treatments were not in line with ESC guidelines. The most common reason for not aligning was using DHP-CCBs or vasodilating BBs.

Conclusion

This study shows that 57% of obstructive HCM treatments received by patients during the study were aligned with recommendations from the 2023 ESC guidelines on cardiomyopathies. Research is needed to investigate barriers and enablers to implementing the guideline including awareness of recommended treatments, as well as the management of comorbidities.
Effect of trimetazidine dihydrochloride therapy on myocardial external efficiency in preclinical individuals with an HCM sarcomeric gene mutation
Authors: Van Driel B , Schoonvelde S , Borodzicz-Jazdzuk S , Huurman R , Visch J , Robbers L , Van Den Aardweg J , Germans T , Michels M , Van Der Velden J
Published: October 2024

Background

Hypertrophic cardiomyopathy (HCM) is frequently caused by pathogenic gene variants, i.e. mutations in genes encoding sarcomere proteins. Previous studies have shown that preclinical asymptomatic individuals with a heterozygous sarcomere mutation have decreased myocardial external efficiency (MEE), which is thought to be a key pathomechanism in the onset and progression of HCM.

Purpose

In the ENERGY trial, preclinical individuals with an HCM sarcomere gene mutation without hypertrophy were treated with the metabolic anti-anginal drug trimetazidine (TMZ) to determine whether the reduced MEE can be corrected at an early pre-hypertrophic disease stage.

Methods

40 MYBPC3 and MYH7 asymptomatic mutation carriers without hypertrophy were treated for eight weeks with TMZ or placebo in a double-blind randomized study design. Directly before and after treatment, study participants underwent an [11C]-acetate PET/CT-scan and cardiac magnetic resonance imaging to measure MEE. A cardio-pulmonary exercise test was performed to measure the influence of TMZ on exercise parameters.

Results

Eight weeks of treatment with TMZ 20mg three times daily did not significantly alter MEE compared to placebo. The mean MEE changed from 30.3±3.8 percent to 29.8±4.3 percent in the placebo group and from 30.1±4 percent to 29.1±4 percent in the TMZ group. After adjustment for baseline, the TMZ group did not have a significantly different MEE (95% CI, -2.863 to 1.986, P=0.68) compared to placebo. Exercise parameters VO2max and respiratory exchange ratio were not significantly altered by treatment with TMZ.

Conclusion

The ENERGY trial is the first proof-of-concept randomized controlled trial with well-matched (age, sex, mutation) groups to test the hypothesis that TMZ improves MEE at a preclinical disease stage. We conclude that metabolic therapy does not correct reduced MEE in an early disease stage of HCM.methodsprimary outcome
Phenotype progression in pediatric RASopathy-associated hypertrophic cardiomyopathy
Authors: Boleti O , Monda E , Norrish G , Field E , Cervi E , Limongelli G , Kaski J P
Published: October 2024

Background

RASopathy syndromes represent the second most common cause of hypertrophic cardiomyopathy (HCM) in children. RASopathy associated HCM (Ras-HCM) has been shown to differ both in cardiac phenotype and long-term outcomes from sarcomeric HCM. However, there is a lack of knowledge from large cohort studies of how the cardiac phenotype of Ras-HCM changes over time.

Aim

To describe cardiac phenotype changes over time in children with Ras-HCM

Methods

Retrospective data from 148 patients diagnosed with Ras-HCM aged <18 years with ³2 follow-up visits were included. Clinical and echocardiographic data were collected at baseline assessment, 1, 2, and 5 years of follow up. Separate analyses were performed for patients who survived, versus patients who died or had a heart transplant (censoring events).

Results

One-hundred-and-two (68.9%) patients with Noonan syndrome, 25 (16.9%) with Noonan-syndrome with multiple lentigines, 10 (6.8%) with Costello syndrome, 9 (6.1%) with cardio-facio-cutaneous syndrome and 2 (1.4%) patients with Noonan-like syndrome with a median age of diagnosis 0.16 years (0.01-0.89) were seen at a median baseline age of 1.41 years (0.37-5.71) and followed up for a median of 12.1 years (4.8-17.4). During follow up, 18 patients (12.2%) died at a median age of 1.8 years (0.5-8.7) and 17 (12.5%) had a left ventricular myectomy, at a median age of 7.0 years (3.1-12.7). At baseline evaluation, patients who died compared to those who survived had a lower median age [0.4 years (0.1-0.8) versus 2.3 years (0.5-7.6), p<0.001], a higher proportion of them had a NYHA class>I (54.5% vs 15.1%, p<0.001), a higher maximal left ventricular wall thickness (MLVWT) z-score [13.4 (7.5) vs 9.6 (6.2), p=0.04], a higher proportion of left ventricular outflow tract obstruction (LVOTO) [64.7% vs 43.8%, p=0.087] and a higher proportion of biventricular hypertrophy [75% vs 49.2%, p=0.045]. For survivors, the MLVWT z-score improved over follow up [+9.6(6.2) at baseline vs. +7.9(5.5) at 5 years, p=0.072], and the proportion of patients with LVOTO (43.8% at baseline vs. 27.9% at 5 years, p=0.019) and biventricular hypertrophy (49.2% at baseline vs. 35.5% at 5 years, p=0.012) decreased over follow up.

Conclusion

While at baseline evaluation Ras-HCM has a high burden of symptoms, biventricular hypertrophy and LVOTO for patients who die or have a heart transplant, we have demonstrated that for survivors, over follow up, the phenotype becomes milder.Table 1
The obesity paradox in patients with hypertrophic cardiomyopathy: A Korean nationwide cohort study
Authors: Soh M , Park J H , Park B H , Lee G N
Published: October 2024

Background

In cardiomyopathies, obesity is known to affect the cardiac remodeling and is associated with a poor prognosis. However, in hypertrophic cardiomyopathy, which is included in the category of heart failure with preserved ejection fraction, the risk of underweight has been suggested, and its impact in practice is controversial.

Purpose

The aim of this study was to investigate the potential relationship between obesity and cardiovascular outcomes in patients diagnosed with hypertrophic cardiomyopathy.

Methods

We conducted a retrospective national cohort study from 2013 to 2020 utilizing administrative claims data and health check-up database from the Korean National Health Insurance Service. Patients newly diagnosed with hypertrophic cardiomyopathy from January 2015 to December 2019 were included. Body mass index was stratified into five groups based on the World Health Organization's recommended criteria for Asian populations, and patients were followed until the date of each outcome or the end of the study period. Predefined clinical outcomes included heart failure hospitalization events, fatal arrest events, all-cause death, and composite clinical outcomes.

Results

A total of 6,361 patients were included in the study, with a mean age was 60 ± 13 years and 32.6% female. During a median follow-up of 3.0 years (interquartile range, 1.8 to 4.3), 921 heart failure hospitalization, 185 fatal arrest, and 340 deaths occurred. The underweight group had higher adjusted hazard ratios for heart failure hospitalization, fatal arrest, all-cause death, and the composite outcome compared to the normal range body mass index group (HR 1.69, 95% CI 1.16-2.47; HR 2.29, 95% CI 1.06-4.93; HR 2.74, 95% CI 1.77-4.24; HR 1.77, 95% CI 1.28-2.45). In addition, the adjusted hazard ratios for the composite outcome were lower in the overweight and obese I group compared to the normal range (HR 0.80, 95% CI 0.68-0.95; HR 0.84, 95% CI 0.72-0.98).

Conclusions

Among patients with hypertrophic cardiomyopathy, those classified as underweight had an increased risk of heart failure hospitalization, fatal arrest, all-cause death, and composite outcomes compared with normal weight patients, while those classified as overweight and obese had a decreased risk of composite outcomes.
Hemodynamic effects of right and biventricular pacing during exercise in hypertrophic obstructive cardiomyopathy
Authors: Ahmed T A , Ross S , Helle-Valle T , Gude E , Holm T , Lyseggen E , Andreassen A K , Broch K , Ravnestad H , Almaas V M , Haugaa K H , Edvardsen T , Kongsgaard E , Stokke M K , Dejgaard L A
Published: October 2024

Background

One third of patients with hypertrophic cardiomyopathy present with dynamic left ventricular outflow tract obstruction (LVOTO), referred to as hypertrophic obstructive cardiomyopathy (HOCM). Symptomatic treatment aims at reducing LVOTO with either medications, invasive septal reduction, or pacing. The importance of pacing site is unclear, and effects of pacing during physical activity have not been investigated.

Purpose

To determine the effect of right ventricular (RV) and biventricular (BiV) pacing, respectively, on LVOTO and cardiac output (CO) during exercise in patients with HOCM.

Methods

Patients with symptomatic HOCM, sinus rhythm, and no bundle branch block, scheduled for alcohol septal ablation (ASA), were eligible for inclusion. The day before ASA, we placed temporary pacing leads in the right atrium, the RV apex, and on the left ventricle’s lateral wall via the coronary sinus. LVOTO was assessed by echocardiography, and CO was measured by thermodilution with a pulmonary artery catheter. Patients performed supine cycling for 2 minutes until heart rate (HR) increased ≥20 bpm. We measured LVOTO and CO in sinus rhythm, and during cycling with atrial sensed RV pacing, and atrial sensed BiV pacing. The order of pacing sites was randomized, and the personnel performing echocardiography and CO measurements were blinded to the order of pacing.

Results

We included six patients (54±15 years) with a mean maximal left ventricular wall thickness of 16.7±1.8 mm. Resting LVOTO was 55.7±30.9 mmHg. The figures show LVOTO and CO in sinus rhythm (HR 85±10 bpm), RV pacing (HR 90±10 bpm), and BiV pacing (HR 91±9 bpm) during supine cycling. The LVOTO declined from 56±34 mmHg in sinus rhythm to 27±12 mmHg and 25±5 mmHg respectively for atrial sensed RV and BiV pacing. CO remained unchanged during sinus rhythm (9.0±1.2 L/min), atrial sensed RV pacing (9.0±1.7 L/min), and BiV pacing (8.9±1.5 L/min).

Conclusion

In this ongoing study evaluating cardiac pacing in HOCM, preliminary data indicate that both RV and BiV pacing are effective in reducing LVOTO during exercise, without compromising CO.