bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose escalation pre-clinical trial of novel DOK7-AAV in mouse model of DOK7 congenital myasthenia
Authors: Cossins Judith , Kozma Imre , Canzonetta Claudia , Hawkins Al , Beeson David , Sepulveda Patricio , Dong Yin Yao
Published: January 2025

Congenital myasthenic syndromes are a group of inherited disorders characterized by defective neuromuscular transmission and fatigable muscle weakness. Causative mutations have been identified in over 30 genes, including DOK7, a gene encoding a post-synaptic protein crucial in the formation and stabilization of the neuromuscular junction. Mutations in this gene are one of the leading three most prevalent causes of congenital myasthenia in diverse populations across the globe. The majority of DOK7 congenital myasthenic patients experience varying degrees of disability despite receiving optimized treatment (usually salbutamol), necessitating the development of improved therapeutic approaches. Here, we executed a dose escalation pre-clinical trial using a DOK7 congenital myasthenic syndrome mouse model to assess the efficacy of AMP-101, an innovative recombinant adeno-associated viral gene replacement therapy. This mouse model harbours a duplication in the Dok7 gene that corresponds to the mutation most commonly found in DOK7 congenital myasthenia patients, c.1124-1127dupTGCC. The model has a much more severe phenotype than patients, and lives for only a few days. AMP-101 is based on AAVrh74 and contains human DOK7 cDNA under the control of a muscle-restricted promoter. Three doses of AMP-101 (2 × 1013 vg/kg, 6 × 1013 vg/kg or 1 × 1014 vg/kg) were administered intraperitoneally at 4 days of age. We show that the two higher doses of 6 × 1013 vg/kg and 1 × 1014 vg/kg generated enlarged neuromuscular junctions and rescued the very severe phenotype of the model. Treated mice became at least as strong as wild-type littermates, as demonstrated by using an inverted screen hang test, a rotarod test and a grip strength test. EMG showed that the treated model mice had decrement of compound muscle action potential on repetitive nerve stimulation, which indicates defective signalling at the neuromuscular junction. However, male models treated with 1 × 1014 vg/kg showed the least decrement that was not statistically different from wild-type littermates. Western blot analysis demonstrated robust expression of DOK7 in the diaphragm and tibialis anterior muscles. These data show that AMP-101 is an effective treatment in a mouse model for DOK7 congenital myasthenia, and suggests that AMP-101 is a promising candidate to move forward to clinic trials as a gene therapy for patients.
Inference for local projections
Authors: Inoue Atsushi , Jordá Óscar , Kuersteiner Guido M
Published: January 2025

Inference for impulse responses estimated with local projections presents interesting challenges and opportunities. Analysts typically want to assess the precision of individual estimates, explore the dynamic evolution of the response over particular regions, and generally determine whether the impulse generates a response that is any different from the null of no effect. Each of these goals requires a different approach to inference. In this article, we provide an overview of results that have appeared in the literature in the past 20 years along with some new procedures that we introduce here.
Diagnostic yield of echocardiography in patients with palpitations: a retrospective analysis
Authors: Khalil A M , Al Badarin F A , Al Mahameed W , Khalil M E
Published: January 2025

Introduction

Transthoracic echocardiography (TTE) is a fundamental tool in evaluating patients with palpitations. However, diagnostic yield of TTE in this population, especially younger patients who are not previously known to have heart disease has not been adequately described. Therefore, we aimed to determine the prevalence of structural cardiac abnormalities among patients undergoing TTE for this indication.

Methods

Electronic database of all TTE studies performed at a single tertiary care center (November 2015 to December 2023) was used to identify consecutive patients undergoing TTE for the indication of palpitations alone. Studies performed for palpitations and other indications suggesting presence of structural heart disease were excluded. The primary outcome was the prevalence of any cardiac abnormality defined as any abnormality in chamber size, ventricular systolic or valvular function, or significant cardiac abnormality defined as presence of severe chamber dilation, severe valvular or systolic dysfunction. Binomial logistic regression was used to predict absence of structural abnormalities on TTE.

Results

Among 3,434 included patients, 348 (10.1%) had abnormal TTE, out of which 116 (3.4%) had significant abnormalities. Female sex, younger age, and lower BMI were independently associated with absence of all abnormalities on TTE (P<.001 for all). Prevalence of any or severe cardiac abnormalities in women was 7% and 2.3%, respectively, in patients <40 years was 4.1% and 0.9%, respectively, and in those with BMI<30 was 7.6% and 3.1%, respectively. In a subset of women younger than 40 with BMI<30 (n=887) the prevalence of any cardiac abnormality was 1.6% and of severe abnormalities was 0.9% (Figure).

Conclusion

Whereas TTE is frequently utilized for evaluation of patients with palpitations, its yield is relatively low, particularly in younger patients and those with lower BMI, especially women. A selective approach in utilizing TTE in this population is prudent, especially when guided by other clinical or electrocardiographic findings. Prospective studies may help refine the role of TTE in this context.
Using gamification tools to enhance self-organized echo-learning in a hospital setting
Authors: Trautmann N
Published: January 2025

Background

Gamification has been discussed in various settings of medical education, highlighting its potential to increase engagement and boost motivation. Tools like "points," "badges," or "leaderboards" are known to work well in any area of learning.

Purpose

In a mid-sized hospital, creating a structured echocardiography training curriculum for internal medicine residents can be challenging due to rotating teachers and students and a general lack of resources. A self-guided training curriculum using concepts from computer gaming seemed appropriate to engage and motivate trainees.

Methods

We set up a self-organized training program where residents without prior echocardiography skills could progress through a step-by-step curriculum to gain basic echocardiography expertise. After a brief introductory session and distribution of a paper curriculum, trainees were included in the daily echocardiography schedule. They could advance to higher "levels," each allowing them to use more advanced tools, such as spectral Doppler or the Simpson method ("weapons"). To complete each level, trainees had to answer theoretical questions, analyze echo loops stored on a network drive, and perform a short hands-on exam under the supervision of a senior cardiologist ("final boss"). We also published "highscores" regularly, highlighting residents with the most exams during a given interval. To enhance the skills of our senior cardiologists, we developed "challenges" introduced several times per year, covering techniques like lung ultrasound or pulmonary vein Doppler.

Results

The process was evaluated through an anonymous online questionnaire completed by about half of the residents. The training concept received positive feedback, but the results were overshadowed by the lack of time residents were able to allocate to perform echocardiographies at all. Additionally, the amount of in-depth personal supervision was criticized.

Conclusions

Although our echocardiography education concept did not fulfill all our expectations, developing a self-organized echocardiography training curriculum using gamification elements seems promising. Future refinements should include more supervision and regular training and briefing of all individuals involved in the process. Even more important seems to be a general allocation of resources to echocardiography training. Since medical education is vital for ensuring treatment quality and staff satisfaction, more research is necessary to test and compare different teaching approaches scientifically. In the future, an online or mobile-app based training platform could serve as a hub for echocardiography teaching, where institutions and learners register, access teaching resources, and track their progress, using gamification tools to motivate and engage trainees.

Training scheme

Challenge.jpg
The prevalence of indeterminate diastolic function in hypertensive women: 2024 BSE guidelines versus 2016 ASE/EACVI guidelines
Authors: Kolesnyk M , Sokolova M V
Published: January 2025

Background

There is a significant number of patients with indeterminate diastolic function (DF) using 2016 ASE/EACVI guidelines. The left atrial (LA) longitudinal strain could provide additional information in case of inconclusive results. Recently, a new 2024 BSE guidelines incorporated LA strain as routine measure of DF. However, there is still a grey-zone within a range of 18–29% for LA reservoir strain (LARs). The purpose of this study was to compare the prevalence of indeterminate DF based on the 2016 ASE/EACVI and 2024 BSE guidelines.

Methods

The study enrolled 100 postmenopausal women (mean age 57 ± 4 years) with uncomplicated arterial hypertension and normal systolic function. The cohort was divided into 3 groups (normal DF, indeterminate DF, diastolic dysfunction). The DF was assessed with both 2016 ASE/EACVI and 2024 BSE algorithms. The initial assessment of DF included average E/e' ratio, left atrial volume index and tricuspid regurgitation velocity with BSE algorithm. LARs was analyzed, when only 2 criteria were available (1 positive and 1 negative). The LARs ≥ 30 % or pump strain ≥ 14 % were considered normal. The LARs < 18 % was abnormal. The range between 18-29 % was a grey-zone area.

Results

The prevalence of indeterminate DF was significantly lower with assessment by 2024 BSE versus 2016 EACVI/ASE algorithm (21 % vs 53 %). The proportion of patients with normal DF was significantly higher with BSE guidelines (72 % vs 40 %). Surprisingly, the presence of DD was the same (7 % using both algorithms) (Table). The tricuspid regurgitation was absent in 75 % of patients, leaving only 2 initial criteria for DF assessment with BSE guidelines. Among these patients 40 % had 2 negative criteria and 3 % had 2 positive criteria. 32 % had 1 positive and 1 negative criteria. Thus, a third of patients required additional evaluation with LA strain. 21 % of patients had LARs in a range between 18% and 29 % or pump strain < 14 % with indeterminate DF status. These patients need further evaluation.

Conclusions

Adding LA strain to the 2024 BSE DF assessment algorithm significantly reduced the number of indeterminate results. However, one fifth of hypertensive women had left atrial strain values in the gray zone area.

Diastolic function assessment
Overexpression of triadin in adipose tissue causes cardiac dysfunction
Authors: Singh S , Konja D , Velayutham Sampath K , Sun Q , Xu A , Wang Y
Published: January 2025

Introduction

As a member of the protein complex that regulates the ryanodine receptor (RyR) , triadin plays a critical role in intracellular calcium homeostasis. Our previous results demonstrate that the NAD-dependent deacetylase sirtuin-1 (SIRT1) downregulates the expression of triadin isoform Trisk 51 in adipose tissue. A transgenic mouse model with adipose tissue selective overexpression of Trisk 51 (Adipo-TRDN) was established.

Aim

The present study is designed to investigate the role of SIRT1-triadin signalling in the development of dilated cardiomyopathy/heart failure with reduced ejection fraction.

Methods

Wild type (WT) littermates, Adipo-TRDN without or with human SIRT1 overexpressed in adipose tissue (Adipo-TRDN/SIRT1) were used for this study. All mice were provided with standard chow diet, normal drinking water and kept in a 12/12 light-dark cycle. Echocardiography was performed in 30 weeks old male mice using Visual Sonics Vevo 2100 Imaging System to measure systolic and diastolic function using B-mode, M-mode, Color Doppler and Tissue Doppler parameters.

Results

Systolic cardiac impairment was present in the Adipo-TRDN mice compared with their littermate controls. Left ventricular internal diameter during systole (LVID, s) was increased in Adipo-TRDN compared with WT littermates (3.0031 vs. 2.1878 mm, p-value: 0.0059). Changes in the Left ventricular anterior wall thickness (LVAW) during systole and diastole were found to be non-significant (1.6180 vs. 1.3530 mm, 1.1443 vs. 1.0455mm). Although fractional shortening (FS %) differences were non-significant (27.64% vs. 34.83%), there was a significant reduction in ejection fraction (EF %) in Adipo-TRDN mice compared with their WT controls (49.41% vs. 64.73%, p-value: 0.0472). No differences were found in the Left ventricular mass (LV) (106.80 vs.84.10 mg). Left ventricular volume during systole (LV Vol; s) was also significantly enhanced in Adipo-TRDN compared with their WT controls (35.25 vs.16.30 μL, p-value: 0.0047). Overexpression of human SIRT1 lead to partial improvement in the pathogenesis of dilated cardiomyopathy in Adipo-TRDN mice. Ejection fraction and fractional shortening were both increased in the Adipo-TRDN/SIRT1 compared with Adipo-TRDN mice (70.70% vs. 49.41%, p-value: 0.0017, 39.60% vs. 27.64% p-value: 0.0151). LV mass and LV Vol;s were reduced in the Adipo-TRDN/SIRT1 compared with Adipo-TRDN mice (75.83 vs. 106.80 mg, p-value: 0.0543) (14.02 vs. 35.25 μL, p-value: 0.0005). LVID (s), LVAW (d) and LVAW (s) were also reduced in Adipo-TRDN/SIRT1 compared with Adipo- TRDN mice (2.1641 vs. 3.0031mm, p-value: 0.0041, 0.8728 vs. 1.1443, p-value: 0.0319, 1.2369 vs. 1.6180mm, p-value: 0.0018).

Conclusion

Development of dilated cardiomyopathy induced by adipocyte specific overexpression of Triadin is partially prevented by adipose SIRT1.
Subclinical abnormalities of systolic and diastolic function in longitudinal echocardiography after mild initial COVID illness
Authors: Shchendrygina A S , Ka M M , Rodriguez Bolanos C , Alsoufi S , Hoffmann J , Kumar P , Carerj M , Vanchin B , Holm N , Karyou A , Mijidsuren M G , Nagel E , Puntmann V
Published: January 2025

Background

Cardiac inflammatory involvement is an increasingly recognized sequelae of COVID-19 disease. The aim of this study was to evaluate the subclinical patterns and evolution of cardiac abnormalities using transthoracic echocardiography (TTE) in patients with mild initial COVID-19 illness.

Methods and results

343 infected individuals (163 males; age 44 (interquartile range, IQR 35-52) years) underwent serial TTE assessments at a median of 109 (interquartile range (IQR), 77–177) and 327 (276-379) days after infection. Compared to non-COVID infected controls (n=94, male n=49), baseline systolic (LVEF, TAPSE) and diastolic function (e’, a’, E/e’) were significantly different in infected participants (p<0.05 for all). Compared to baseline assessments, there was a reduction in global longitudinal strain (GLS), and an increase in E wave, E/A ratio and E/e’ at follow up. At baseline symptomatic participants had lower LVEF and TAPSE, increased IVRT, e’ and E/e’. At follow-up symptomatic patients had lower LV end-diastolic diameter (LVEDd). Symptoms were independently associated with E/e’ at baseline (OR (95%CI) 1.45 (1.12-1.87), p=0.005). At follow up symptoms were associated LVEDd (OR (95%CI): 0.91 (0.86-0.96), p<0.001), followed by the model that also included NTproBNP (OR (95%CI): 1.01 (1.00-1.01), p=0.047). There were significant associations for GLS and troponin, and E/e’ with CRP and NTproBNP at baseline.

Conclusion

In the present cohort of COVID-19 infected individuals with mild initial illness, echocardiographic measurements reveal significant yet subclinical differences in systolic and diastolic function compared to controls, as well as between individuals with cardiac symptoms and those without. All the measured differences were small in magnitude, thus unlikely detectable clinically on an individual level.
Artificial intelligence-enhanced electrocardiogram left ventricular diastolic function assessment for prognostic assessment in mitral annulus calcification
Authors: Tsaban G , Lee E , Wong Y W , Wopperer S B , Abbasi M A , Kane G C , Lopez-Jimenez F , Guerrero M , Eleid M , Nkomo V T , Deshmukh A J , Noseworthy P A , Friedman P A , Attia I , Oh J K
Published: January 2025

Background

Moderate-severe mitral annulus calcification (MAC) and left ventricular (LV) diastolic dysfunction are both linked to increased risks of heart failure and mortality. Assessing LV diastolic function (LVDF) in moderate-severe-MAC by echocardiography is frequently challenging and unreliable. We recently validated an AI-ECG model for LVDF. We aimed to determine if this tool can predict long-term mortality in patients with moderate-severe-MAC and whether it can help establish MAC-specific echocardiographic LVDF parameter cutoffs.

Methods

This retrospective study included all patients from the AI-ECG LVDF study test cohort who underwent comprehensive transthoracic echocardiography confirming moderate-severe-MAC and ECG within fourteen days of each other at Mayo Clinic between 09/2001 and 06/2022. AI-ECG LVDF was determined based on the index ECG. Patients were categorized based on AI-ECG into groups representing normal/grade-1 LVDF, grade-2 LVDF, or grade-3 LVDG (DF-1, DF-2, and DF-3, respectively).

Results

Of 2,506 patients with moderate-severe-MAC [mean age 77, 64.1% females], 709 (28.3%), 1,510 (60.3%), and 287 (11.5%) were classified as DF-1, DF-2, and DF-3, respectively. Worse LVDF grade was associated with older age, male sex, lower LV ejection fraction, and higher rates of noncardiovascular and cardiovascular comorbidities. Over a median follow-up of 2.8 years, 1,059 (42.3%) patients died. In multivariable survival analysis, DF-2 [adjusted hazard ratio (aHR) 1.43, 95% confidence interval (95%CI) 1.21-1.68] and DF-3 (aHR 1.54, 95%CI 1.22-1.93) were independently associated with a higher risk of death (figure). Findings were also consistent after adjusting to mitral inflow gradients. When comparing LVDF echocardiographic parameters in controls without MAC matched by age, sex, left ventricular ejection fraction, and AI-ECG DF grade, significant differences were observed. Patients with moderate to severe MAC generally exhibited lower e' velocities, higher TR velocities, elevated E/e' ratios, and increased LAVi. Interestingly, the E/A ratio between MAC patients and their matched controls across AI-ECG LVDF grades remained consistent.

Conclusion

AI-ECG LVDF predicts mortality risk in patients with moderate-severe-MAC, regardless of mitral inflow gradients. Utilizing AI-ECG LVDF might aid in the risk stratification of patients with significant MAC.
Myocardial work indices and global longitudinal strain: equivalent prognostic value in chronic HFrEF
Authors: Fortuni F , Biagioli P , Sforna S , Mengoni A , Zuchi C , Lauciello R , D'addario S , Bardelli G , Ambrosio G , Carluccio E
Published: January 2025

Background

Non-invasive myocardial work (MW) indices can be estimated from pressure-strain loops obtained by integrating left ventricular global longitudinal strain (LVGLS) with brachial systolic blood pressure (SBP) and cardiac event timings (opening and closure of the aortic and mitral valve). Compared to LV GLS, MW indices offer the possibility to correct myocardial performance for LV afterload and dyssynchrony.

Purpose

To assess whether MW indices could provide additional prognostic value in a contemporary cohort of stable outpatients with chronic heart failure with reduced ejection fraction (HFrEF) on optimal medical and device therapy, with controlled afterload and no dyssynchrony.

Methods

We retrospectively analyzed 307 patients (mean age 65.6±12.7 years, 78% males) with reduced LV ejection fraction (LVEF<50%). Liner regressions were performed to assess the relationships between MW indices and LVGLS, SBP, and parameters of inter- (i.e. inter-ventricular mechanical delay>40 msec) and intra-ventricular (i.e. mechanical dispersion>100 msec) dyssynchrony. The study endpoint was a composite of all-cause death/HF-hospitalization. Multivariable models including each MW indices once at a time [global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE)] were compared with the model including LVGLS by C-statistics.

Results

Mean LVEF was 32±9%, mean LVGLS was -9±3, mean GWI was 800±378 mmHg% and median NT-proBNP was 1.800 pg/ml (IQR: 731–4110). The majority of patients (84%) had SBP< 130 mmHg (mean 117±16 mmHg), and had no inter- (71%) and (68%) intra-ventricular dyssynchrony. Over a median follow-up of 20 months (IQR: 11-34), 82 patients reached the study endpoint. After multivariable adjustment for MAGGIC score, natriuretic peptide levels, LV end-diastolic volume index, left atrial volume index, E/e’ ratio, and TAPSE/PASP ratio, both GWI and GCW were independently associated with adverse outcomes, with identical goodness of fit compared to the model including LVGLS (C-index 0.75 for all). On the contrary, both GWW and GWE were not independently associated with outcomes. While GWI and GCW were strongly correlated with LVGLS (B coefficient<-0.85; Figure), their association with SBP was modest and there was no significant association between them and parameters of intra- and inter-ventricular dyssynchrony.

Conclusions

In a cohort of stable chronic HFrEF patients on optimal medical and device therapy, with controlled afterload and without dyssynchrony, MW indices showed similar prognostic value to LVGLS.

Association between LVGLS and MW indices
Moderate aortic stenosis and preserved ejection fraction are not benign combination
Authors: Petrovic O , Jovanovic I , Paunovic I , Rakocevic I , Vidanovic S , Tesic M , Jankovic N , Vratonjic J , Ostojic M , Boricic-Kostic M , Trifunovic-Zamaklar D , Ivanovic B
Published: January 2025

Background

Degenerative aortic stenosis (AS) is the most common progressive valvular disease and it is followed by adaptive left ventricular (LV) hypertrophy. LV hypertrophy is a compensatory mechanism aimed at reducing wall stress it also alters myocardial perfusion and impairs function and is tightly associated with heart failure with perserved ejection fraction (HFpEF). The outcome in patients with AS depends on the condition of the left ventricle and the presence of symptoms as well as the degree of the stenosis. Current guidelines do not address whether aortic valve replacement should be recommended in patients with moderate aortic valve stenosis regardless of the presence of symptoms and LV dysfunction.

Purpose

This study aimed to evaluate the association between moderate AS, symptoms, and myocardial structure and function after adjustment for comorbidities.

Methods

We conducted a matched cohort analysis. 61 patients with moderate aortic stenosis (MAS), LV ejection fraction <50% and sinus rhytm were matched with 1 comparator by age, gender and presence of arterial hypertension, diabetes, coronary artery disease, chronic obstructive pulmonary disease and renal failure. Echocardiographic parameters and presence of any of three symptoms (dyspnoea, chest pain and syncope) were recorded at and compared between two groups.

Results

No significant difference was found between the two groups concerning the left ventricle (LV) and right ventricle (RV) size, LV ejection fraction RV systolic function, and, pulmonary artery pressure, although patients with MAS tend to have greater end systolic diameter (ESD) but not statistically significant (35.20±8.28mm vs 32.86±6.08; P=0.083), LV global longitudinal strain was less in the MAS patients (-14.29 ±5.37 % vs. -17.95±2.44 %; P = 0.003). The LV mass index (LVMi) was greater, (122.30±31.16g/m2 vs 103.81±27.07; P=0.001), The relative wall thickness (RWT) was greater in MAS patients but not statistically significant (0.43 ± 0.09 vs. 0.41 ± 0.07 cm; P = 0.079). Left atrial volume index (LAVi) was greater in MAS (44±15ml/m2 vs 39±15; P=0.047), E/E′ ratio was greater in MAS (14±6 vs 11±3; P<0.001). Symptoms occurred more frequently in patients with MAS (24.6 %; 15/61 patients) than in the control group (8.2%; 5/61 patients, P=0.013).

Conclusions

LVEF as a means of assessing systolic function is insufficient. Ventricular hypertrophy and dysfunction were more common in patients with MAS than in the matched control group as well as the presence of symptoms. Timing of valve intervention in patients with symptomatic moderate aortic stenosis should be optimized.
Correlation of right heart catheterization with simultaneous echocardiography for the assessment of pulmonary hypertension in patients with severe tricuspid regurgitation
Authors: Kim O , Kim J I H O O N , Choi K H , Yang J H , Park S U N G J , Son J I H E E
Published: January 2025

Background

In severe tricuspid regurgitation (TR), it is important to accurately measure pulmonary artery pressure because pulmonary hypertension is a poor prognostic factor in severe TR. Therefore, we sought to investigate the correlation between PASP using simultaneously measured echocardiography and right heart catheterization (RHC).

Method

In this observational prospective study, a total of 33 patients with severe TR were enrolled between September 2021 and May 2024. Data was obtained by simultaneously measuring echocardiography and RHC. The correlation between the PASP by echocardiography and RHC was analyzed using Pearson correlation and Bland-Altman analysis. To properly evaluate right atrial pressure (RAP), additional parameters, including systolic flow reversal of the hepatic vein and the V wave cut-off sign, were incorporated.

Result

PASP by RHC was strongly correlated with PASP by simultaneous measured echocardiography, with a correlation coefficient (r) of 0.87. The bias was 1.5 mmHg, and the limits of agreement (LoA) ranged from -12.5 to 15.5 mmHg. Recategorizations with systolic flow reversal on hepatic vein Doppler and V wave cut-off sign as well as the size and respiratory collapsibility of inferior vena cava provide a more accurate estimate of RAP (eRAP) by echocardiography (p = 0.004). Using this approach for eRAP, a correlation between PASP by RHC and PASP by echocardiography was more prominent (r = 0.91, LoA -9.9 ~ 13.0 mmHg).

Conclusion

PASP simultaneously measured by echocardiography with systolic flow reversal on hepatic vein Doppler and V wave cut-off sign was highly correlated with PASP by RHC in patients with severe TR.
Reverse remodeling according to the aetiology after mitral TEER
Authors: Marut B , Lee Frost C , Istratoaie S , Leurent G , L'official G , Auffret V , Oger E , Donal E
Published: January 2025

Introduction

Mitral transcatheter edge-to-edge repair (M-TEER) is increasingly used. Reverse remodeling is expected to impact prognosis, yet pre-operative prediction of the beneficial impact of MR treatment remains limited.

Objective

We aimed to describe the impact of M-TEER on heart remodeling according to etiology and to define pre-intervention parameters that might predict this beneficial heart remodeling after M-TEER.

Methods

Consecutive isolated M-TEER patients recruited between 2019 and 2022 were considered. Patients who died or required re-operation within 30 days were excluded (n=9). Preoperative and follow-up echocardiograms were all recorded in the same tertiary center. A core lab analysis was conducted. Patients without follow up at the TEER-center were not included in the final analysis. Transthoracic echocardiography (TTE), including speckle tracking imaging for LV, RV and LA, was analyzed alongside clinical characteristics. Cardiovascular events and other occurrences were recorded up to a 24-month follow-up. The relative variation in left ventricular end-diastolic indexed volume compared to baseline and according to the etiology group was the primary outcome.

Results

Eighty-six (out of 146) patients were included in the final analysis (55% men, 55% functional MR, median LVEF 56%, IQR [45-64]), no major difference in the final analysis population compared to the whole cohort. The decrease in left ventricular end-diastolic volume indexed (LVEDVi) was greater in primary MR (-16.4% vs -7.06%, p-value=0.04). No reverse remodeling was found for LA. Baseline global longitudinal strain (GLS) (p=0.03) but also RV free wall strain (RV FWS) (p=0.02) were independent parameters to predict change in LVEDVi (Fig.1). In secondary MR, NYHA functional class improvement after TEER was also associated with relative change in GLS between baseline and follow-up.

Conclusion

Mitral TEER has a greater impact on LVEDVi in primary MR. LV and RV Speckle tracking parameters are the most reliable parameters to predict the amount of reverse remodeling expected after M-TEER. RV function should be assessed precisely before M-TEER. LA remodeling was non-significant after M-TEER in an elderly population with high prevalence of AF.

Baseline GLS and LV reverse remodeling
Prevalence and significance of late gadolinium enhancement in patients with severe aortic stenosis based on myocardial damage stages in the PARTNER trial
Authors: Hirata K , Kuwabara K , Matsuo Y , Yokoi Y
Published: January 2025

Background

Late Gadolinium Enhancement (LGE) in cardiac MRI marks myocardial fibrosis and irreversible damage. In aortic stenosis (AS), LGE helps assess myocardial damage, crucial for risk stratification and treatment planning. The Placement of Aortic Transcatheter Valves (PARTNER) trial's staging system, based on echocardiographic parameters, stratifies patients from stages 0 to 4. While this staging indicates prognosis, the extent of myocardial fibrosis remains unclear.

Objectives

To clarify the frequency of LGE positivity across different stages of myocardial damage based on echocardiographic assessment in patients with severe aortic stenosis.

Methods

We analyzed MRI data from 58 severe AS patients undergoing transcatheter aortic valve implantation. Patients were categorized into myocardial damage stages using the PARTNER trial's echocardiographic criteria: Stage 0: No cardiac damage, Stage 1: Left ventricular damage, Stage 2: Left atrial or mitral damage, Stage 3: Pulmonary vasculature or tricuspid damage, Stage 4: Right ventricular damage. The frequency of LGE positivity was assessed for each stage. Chi-square tests determined statistical significance across stages.

Results

Among 58 patients, LGE was present in 16 (27.6%). LGE positivity increased with advancing stages: 0% in Stage 0, 20% in Stage 1, 67% in Stage 2, and 100% in both Stage 3 and Stage 4. Chi-square analysis showed significant differences in LGE positivity across stages (χ² = 46.159, df = 4, p < 0.0001).

Conclusions

LGE positivity increases with myocardial damage severity in severe AS patients. This echocardiographic-based staging system reflects the extent of myocardial fibrosis, as even in Stage 1, 20% of patients show fibrosis, and in Stage 2, two-thirds have irreversible damage.
Natural history of tricuspid regurgitation, a single center cohort analysis
Authors: Michelinakis N , Xamodraka E , Blazakis G , Fragkoulis I , Sfantou D , Kiki I , Pervana A M , Koutsogiannaki E , Siama A , Tsoukas A , Poulimenos L
Published: January 2025

Background-Purpose

High severity of tricuspid valve regurgitation (TR) is associated with poor clinical outcomes. However, the natural history of progression from less severe to more severe TR has not been well characterised.

Methods

A retrospective cohort analysis was performed on patients who underwent TTE from 2008-2024 on a single center. Patients with congenital heart disease or prior tricuspid valve intervention were excluded.

Results

Of initial 28715 patients, 4807 (mean age 71 years) had serial TTE evaluation and were included for analysis. Median follow-up was 917 days (Interquartile range 326-1934 days). Patients were categorised by TR severity on initial TTE: 2051 (42.6%) had none/trace, 2092 (43,5%) were mild, 480 (9,9%) were moderate, and 184 (3,8%) were severe. At median follow up, progression to severe TR was seen in 0.1%, 1.5% and 12.0% of the none/trace, mild, and moderate groups, respectively (Log rank p<0.001). At 3600 days, progression to severe TR was seen in 17.95% of the moderate group. Patients with depressed LV function (LVEF<50%) were associated with greater risk of progression to severe TR compared to preserved LVEF (EF≥50%) (Relative Risk 2.8, 95% CI 2.01-3.7, Log rank p<0.001).

Conclusion

Moderate TR is associated with significant risk of progression to severe TR within 10 years. Patients presenting with moderate TR and LVEF< 50% were associated with increased risk of progression to severe TR. Further studies are required to determine if earlier identification and intervention on patients in this greater risk cohort can result in improved patient outcomes.
Evidence for prognostic yield of dynamic arterial compliance in asymptomatic severe aortic stenosis
Authors: Armenis I , Leontiadis E , Leontiadis E , Tsiapras D , Tsiapras D , Kyrzopoulos S , Kyrzopoulos S , Iakovou I , Iakovou I , Athanassopoulos G D , Athanassopoulos G D
Published: January 2025

Introduction

Degenerative aortic stenosis (AS) is a part of a continuum that may also include a reduction in systemic arterial compliance (Ac). Lower Ac affects cardiovascular prognosis but there are scarce data concerning AS and especially during exercise.

Purpose

Aim of the study was to assess the prognostic role of calculated Ac at rest (R) and during supine ergometry (Ex) in the outcome of asymptomatic severe AS.

Methods

Forty eight AS patients, followed-up on valve clinic in a tertiary center (age 66±12 years), were referred for Ex. AS-related cardiac events (independent decision for surgery, occurrence of AS-related symptoms) during a follow-up of 33±21 months occurred in 19 patients (EV group).

The following parameters were estimated noninvasively both at R/Ex: LV ejection fraction (EF:%), strain (SR:%), transmitral E/e ratio, peak transtricuspid systolic pressure (TRPG: mmHg), AV mean gradient (meanGR: mmHg), valvuloarterial impedance (Za: mm Hg·ml-1m2), peripheral vascular resistance (PVR: Wood units) and arterial compliance (Doppler stoke volume/pulse pressure=Ac: ml/mmHg).

Results

Event (EV) and non-event (nEV) groups had similar % target heart rate at Ex, (96±17 vs 100±12%), age (66±12 vs 66±12 years), women/men ratio (9/19 vs 14/29), EF-R (55±8 vs 56±7%), ST-R (15.0±4.0 vs 14.5±3.5%), TRPG R/Ex (35±14 vs 30±8 and 60±15 vs 54±11mmHg), SR-Ex (16.0±5.0 vs 17.0±4.0%) but lower EF-Ex (59±9 vs 64±6%, p=0.03).

EV group had greater meanGR at R (45±16 vs 37±12mmHg, p=0.03), but similar Za both at R/Ex (2.3±1.0 vs 2.0±0.8 and 2.7±0.8 vs 2.7±1.0mm Hg·ml-1m2 ).

PVR at R/Ex was similar (29.3±12.0 vs 32.0±13.0 and 20.5±6.0 vs 22±9.0 Wood).

Ac was similar between the 2 groups at R but it showed a greater reduction during Ex in EV group (R: 0.85±0.44 vs 0.92±0.60 and Ex: 0.70±0.60 vs 0.84±0.40, p=0.05).

Binary logistic regression analysis for events, including the different parameters between groups (meanGR, Ac-Ex, EF-Ex), selected only EF-Ex [exp(b)=1.15 (1-1.3 p=0.02] as independent predictor.

ROC analysis for event provided a cut off for Ac-Ex of 0.56 (area 0.65, sens=0.72, spec=0.60). ROC classification for events was better for age>70 years (cut off 0.52, area 0.82, sens=0.88, spec=0.77-figure 1).

Kaplan Meier event analysis for a greater Ac-Ex than 0.56 provided an increased hazard ratio (log rank =8, p=0.003 figure 2).

Conclusion

Arterial compliance provides prognostic yield for the outcome of asymptomatic severe AS especially in the aged population. The additive value becomes evident when this parameter is calculated during supine ergometry.
Alfieri mitral valve repair for the zone of apposition in adult patients with significant mitral regurgitation
Authors: Park Y , Lee S H , Kim G Y , Je H G
Published: January 2025

Objectives

Although it is recommended to close the zone of apposition (ZoA) as part of repair of atrioventricular septal defect (AVSD), it had often been left untouched or significant mitral regurgitation (MR) ensued. Adult patients with previously incompletely closed or left open ZoA have more retracted and thickened edges due to long standing MR. Combined with mitral annular dilatation, these factors aggravate MR and consequently complicate surgical repair eventually leading to mitral valve replacement (MVR). In an effort to overcome this problem, we have recently added Alfieri type repair to conventional suture of ZoA.

Methods

We retrospectively reviewed ten adult patients with moderate to severe MR due to ZoA including those with postoperative residual MR after previous repair from 1 January 2009 to 31 December 2021. All patients either had AVSD at presentation or had it closed through prior surgery. We describe the outcome of five patients in whom Alfieri type repair was performed and other five patients who underwent different surgeries.

Results

Mean follow-up was 0.9 years (range 0.1-2 years) in those subjected to Alfieri group. Of these five patients, trivial to mild MR was seen in four patients and one patient who had prior repair showed moderate mitral stenosis (MS) at last follow-up after Alfieri type repair (Figure 1, 2). Of five patients who underwent other surgical corrections, two patients had ZoA repaired previously. Three patients eventually undergone MVR due to severe fibrosis and poor mobility of ZoA and posterior mitral valve. Pericardial leaflet augmentation was performed on one patient and showed mild MR with no MS at one-year follow-up. Another patient had conventional repair but eventually MVR was done due to severe postoperative MS.

Conclusions

For adult patients with significant MR owing to ZoA associated with AVSD, Alfieri type repair in addition to conventional suture of ZoA may be considered to avoid failure of conventional repair or the need for MVR. However, it may cause significant MS when performed long after prior repair.

Figure 1. Result of Afieri stitch

Figure 2. Echocardiography
Progression of truncal valve regurgitation during fetal life: a retrospective multicenter study
Authors: Borzillo I , Masci M , Gosnell K , Peyvandi S , Brook M , Annoni G , Toscano A , Cresalia N
Published: January 2025

Background

Truncus arteriosus is a rare congenital heart defect characterized by a single vessel arising from both ventricles. Truncal valve regurgitation is known to impact the patients’ outcomes; however, it is less known whether the regurgitation progresses during the fetal life. We aim to describe how the truncal valve regurgitation evolves during pregnancy.

Materials and Methods

It is a retrospective multicenter study between January 2003 and April 2024. We compared the two fetal echocardiograms (the first and the second trimester echocardiograms) and the first postnatally echocardiogram. The first endpoint was describing how truncal valve insufficiency progresses during the fetal life and to establishing whether it is related to an abnormal number of cusps, to the Type of Truncus and to the genetic abnormalities.

Results

A total of forty-two fetal echoes were valuated. Compared with the third trimester echocardiograms, twenty echocardiograms were performed, the regurgitation of the TV progressed from absent/mild to moderate in two cases (8%). Comparing with the second trimester echocardiograms, twenty-one echocardiograms were performed and the regurgitation of the TV progressed from absent/mild to moderate in four cases (19%). Bicuspid and quadricuspid valves are more likely to progress to moderate regurgitation (p=0.049) but there is no association with the genetic abnormalities and with the type of truncus.

Conclusion

The truncal valve regurgitation rarely progresses during the fetal life, the insufficiency is more likely related to quadricuspid and bicuspid valve.
External validation of a dual-task deep learning model for the assessment of biventricular systolic function in adults with congenital heart disease
Authors: Constantine A , Tokodi M , Szijarto A , Szeier A , Szavai L , Fabian A , Lakatos B K , Merkely B , Bagyura Z , Alviento M , Austria-Manlapig A , Takeuchi M , Kovacs A , Surkova E
Published: January 2025

Background/Introduction

Accurate assessment of left ventricular (LV) and right ventricular (RV) systolic function is crucial in managing people with congenital heart disease (CHD), but can be challenging given the vast anatomic heterogeneity and varied surgical history in this population. While 3D echocardiography (3DE) is the most reproducible and best-validated echocardiographic technique for assessing biventricular systolic function, it requires special equipment and expertise and is not feasible in patients with poor acoustic windows. EF2Net, a dual-task deep learning model, has shown promise in predicting 3DE-derived LV and RV ejection fraction (EF) from standard 2D echocardiographic (2DE) 4-chamber views (1). The model has been previously tested in patients with acquired heart disease, healthy volunteers, and a low-risk community-based cohort but has not been validated in adults with CHD yet.

Purpose

We sought to validate the performance of the EF2Net model in predicting LV and RV EF in adults with CHD.

Methods

Ninety-six consecutive adults with CHD who had undergone echocardiography as part of their routine clinical follow-up were screened. Patients with univentricular physiology and systemic RV were excluded, as were those with insufficient image quality to obtain 3DE full-volume datasets for both ventricles. The final cohort comprised 90 patients (177 apical 4-chamber views). The EF2Net deep learning model was applied and its predictions of LV and RV EF were compared to the actual 3DE measurements (Figure).

Results

The median age of the cohort was 28.0[IQR 23.0-34.5] years and 48.9% were female. The most common CHD diagnosis was a shunt lesion in 37.8% (of which 64.7% included a post-tricuspid component), followed by LV outflow tract disease in 28.8%, and RV outflow tract disease in 24.4%. Most patients (90%) were in NYHA functional class I. The mean 3DE LV EF was 60.9±6.8% and the mean 3DE RV EF was 51.5±6.8%. EF2Net predicted 3DE-derived LV EF and RV EF with a mean absolute error (MAE) of 5.0 and 6.4 percentage points, respectively.

Conclusions

The EF2Net model accurately predicts biventricular EF in adults with CHD using routine 2DE 4-chamber views. This validation underscores the potential of EF2Net to enhance clinical practice by providing reliable, non-invasive assessments of ventricular function in patients with complex ventricular morphology, particularly in settings where 3DE is not readily available.
Simulator transesophageal echocardiography: the new horizon of training?
Authors: Bianchi L , Costa P , Gil Ad V , Masoero G , Rosa G M , Porto I , Bezante G P
Published: January 2025

Background

trans-esophageal echocardiography (TEE) plays a crucial role in the diagnosis of cardiovascular diseases. In recent years, the importance of theoretical-practical training based on advanced simulation systems in learning specific medical skills has emerged but evidence for the effectiveness for TEE are limited.

Purpose

evaluate the impact of a theoretical-practical course with simulator for TEE in the diagnostic interpretation of morpho-functional images and acquisition of projections according to standard protocol of the American Society of Echocardiography (ASE).

Methods

cardiologist specialists and resident cardiologists who participated in the TEE course at a center of simulation and advanced training center from 2018 to 2023, were retrospectively enrolled in the study.

Before the course, participants underwent a question multiple-choice based test, aimed at assessing theoretical knowledge and clinical interpretation of morpho-functional images and clips recorded during interventional procedures.

During the course, learners where divided into three groups: one utilizing the simulator to conduct exams with clinical cases and acquisition of clips according to ASE protocol, another one participating in interactive discussions of the first group's TEE hands-on activities, and the last one attending lectures with clinical cases. The activities were switched during the two days of the course.

Following the course, the same test was administered to evaluate changes in results.

Results

290 hospital cardiologists and resident cardiologists (95.2% and 4.8%, respectively) participated in the course. Among them, mean age was 45.2 ± 11 years old, 164 were male (57%). Before the course, the learners answered correctly the 77.6% of questions, while after the course this value increase to 89.5% (p value < 0.001).

This improved result was driven by the group above 54 years (p = 0.026) and by the one with an age between 45 and 54 years (p = 0.042), as shown in Figure 1.

205 learners (71.9%) improved their test results after the course, while 41 (14.4%) lowered the score and 39 (13.7%) achieved the same result.

In the learners that improved (205), 79% wronged ≥3 questions at the first evaluation and after the course this number decreased to 15% (p < 0.001); on the other hand, in the ones that not improved (80), 14% wronged ≥ 3 questions and this value grew to 45% after the course (p < 0.001), as shown in Figure 2.

Moreover, at the end of the training, all the learners were able to complete the sequence of 28 projections of the standard protocol of trans-esophageal echocardiographic recommended by international society of echocardiography.

Conclusions

In our cohort of cardiologist specialists and fellows, a two-day theoretical-practical course with a TEE-based simulator improved competencies in interpretation of TEE clips and images.

These findings should therefore encourage greater use of advanced training with simulation TEE training.
Atrial strain analysis predicts atrial arrhythmias recurrence following cavotricuspid isthmus ablation of typical atrial flutter
Authors: Iannaccone G , Scacciavillani R , Graziani F , Tusa F , Piccinni C , Gabrielli F A , Narducci M L , Perna F , Camilli M , Meucci M C , Montone R A , Bencardino G , Lanza G A , Pelargonio G , Lombardo A
Published: January 2025

Background

The evaluation of left atrial (LA) and right atrial (RA) function by two-dimensional speckle-tracking echocardiography has recently appeared as a valuable method to predict atrial arrhythmias (AA) recurrence after electrical cardioversion or transcatheter ablation. However, there are no similar studies performed in patients with typical atrial flutter (AFL).

Aims

The aim of our study is to assess the ability of RA and LA strain reservoir (RASr and LASr) to predict recurrence following cavotricuspid isthmus ablation (CTIA) for typical AFL.

Methods

Consecutive AFL patients who underwent CTIA at our hospital from January 2020 to May 2023 were retrospectively enrolled. Transthoracic echocardiography was performed within one month before CTIA and strain analysis was performed off-line. At follow-up, AA recurrence was recorded reviewing medical records.

Results

A total of 62 patients were analysed (mean age 64.8±13.2 years, 29% females). At a median follow up of 12.1 months (IQR: 7–18.4), AA recurrence occurred in 21 (33.8%).

The study endpoint occurred mainly among females (p=0.021), patients who developed atrial fibrillation (AF) during CTIA and patients with lower RASr and LASr values (both p<0.001). At multivariable Cox regression analysis, only RASr and LASr remained independent predictors of AA recurrence (OR 0.904, 95% CI [0.831–0.984], p=0.02 and OR 0.919, 95% CI [0.852–0.992], p= 0.03, respectively). At ROC curve analysis, RASr and LASr showed similar and satisfactory ability to predict AA recurrence with optimal cut-off values of 16.8% and 17.7%, respectively.

At survival analysis, RASr >16.8% and LASr >17.7% were associated with significantly higher freedom from AA (log rank p=0.001 and p=0.002, respectively).

Conclusion

In our study, lower values of both RASr and LASr resulted to be independent predictors of AA recurrence following CTIA for typical AFL. Therefore, pre-ablation atrial strain analysis may help in the detection of patients at higher risk of recurrence, which could benefit from closer follow up visits and prolonged antiarrhythmic therapy.