bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged ventricular activation time as a novel biomarker identifying burn-out phase of hypertrophic cardiomyopathy
Authors: Fragkiadakis K , Anastasiou I , Zervakis S , Savva E , Malikidis O , Zacharis E , Xatzinikolaou K , Kassotakis S , Marakes-Sideras E , Parthenakis F , Kochiadakis G , Marketou M 
Published: October 2024

Abstract

Background
Patients with hypertrophic cardiomyopathy (HCM) classically have preserved systolic function and decreased left ventricular end-diastolic volume. However, in a small sub-population, patients paradoxically develop systolic dysfunction, left ventricular dilatation, and ventricular wall thinning, which is known as end-stage hypertrophic cardiomyopathy or "burned-out cardiomyopathy’. Although an electrocardiogram (ECG) is a pivotal tool in HCM, its role in the detection of burned-out HCM has not been investigated.

Purpose
We assessed the ventricular activation time (VAT), an ECG marker of the duration of ventricular depolarization, as a predictive tool in the detection of the HCM burn-out phase.

Methods
We prospectively studied consecutive patients diagnosed with HCM via echocardiography at our medical center between 2017 and 2022. The ECG, along with echocardiography, was performed on the same day as the diagnosis. VAT was measured in milliseconds between the onset of the QRS complex to the peak or R wave on the V5 and V6 precordial ECG lead. HCM burn-out phase was supported when the left ventricular ejection fraction (LVEF) was below 50%, measured with echocardiography. Statistical analysis was performed using the SPSS software.

Results
Forty-five patients with HCM were studied, and their mean age was 51, while 78% (35/45) were male. Echocardiography data upon diagnosis revealed a mean maximum wall thickness of 19 (±3mm) and a mean left ventricular ejection fraction of 65% (±5%). Left ventricular outflow obstruction was present in 31% (14/45). During the study, 24% (11/45) presented atrial fibrillation, 44% (20/45) had an ICD implantation, and 22% (10/45) progressed to the burn-out phase of HCM. HCM patients who presented atrial fibrillation (63±31 vs. 46±14msec, p=0.018) or burn-out phase (65±32 vs. 46±13msec, p=0,009) had a significantly higher VAT than those subsets without. Notably, there was a significant positive relationship between VAT a burn-out phenotype (r=0,385, p=0.009). HCM patients with greater VAT also had a significantly higher risk of presenting a larger left atrial diameter (r=0,295, p=0.048), an increased left ventricular end-diastolic diameter (r=0.306, p=0.041), and a trend of presenting a lower LVEF (r=-0,262, p=0.082). Finally, we revealed a positive relationship between VAT and atrial fibrillation incidence (r=0,352, p=0.018).

Conclusion
Prolongation of VAT predicts the incidence of burn-out stage in patients with HCM and atrial fibrillation. Therefore, it seems to be a promising, inexpensive ECG marker for HCM progression and severity. Our findings emphasize the pivotal role of the ECG as a useful and inexpensive tool in the diagnostic follow-up of HCM.
Changes in peak oxygen consumption on excercise and cardiomyopathy disease stage in Fabry disease
Authors: Roy A , Thompson S , Hodson J , Van Vliet J , Condon N , Alvior A M , Nightingale T , Clift P , Geberhiwot T , Steeds R P 
Published: October 2024

Abstract

Background
Fabry disease (FD) is an X-linked lysosomal storage disorder manifesting as deficiency in the enzyme α-Galactosidase A (1) resulting in multi-organ accumulation of globotriaosylceramide (Gb3) (2) This causes predominantly cardiac, renal and cerebrovascular manifestations. Shortness of breath and exercise intolerance are common and can be related to multiple underlying mechanisms. Cardiopulmonary exercise testing (CPEX) quantifies aerobic fitness, functional capacity, chronotropic and haemodynamic response to exercise, and attributes effort intolerance to different aetiologies, including impaired cardiac and respiratory function.

Purpose
We hypothesise that there is progressive effort intolerance that reflects continual cardiac Gb3 accumulation, becoming common during myocardial hypertrophy and disabling in the fibrosis and inflammation stage. The aims of this study were to ascertain frequency and severity of exercise intolerance in FD by investigating the relationship between peak maximal oxygen uptake (VO2 max) and cardiac disease stage, quantified based on a four-point scale, as proposed in published literature (3).

Methods
This was a retrospective review of adults with FD and exercise intolerance attending a specialist clinic who had undergone either CPEX or six-minute walk testing (6MWT) in those less mobile. Biochemical, cardiac magnetic resonance (CMR) imaging and transthoracic echocardiographic (TTE) data were also collected.

Results
N=54 patients underwent CPEX and N=35 patient underwent 6MWT. Estimated peak VO2 max was calculated using 6MWD in those undergoing 6MWT. Median age was 54 (IQR 40-62) years and 53% were male. Patients were equally distributed across disease stage (1-4). There were significant trends in age (increasing) and gender (male predominance) from stage 1-4. Age/sex-normalised peak VO2 max values were calculated as per published literature due to the confounding effect of age and male gender. Mean normalised VO2 max was 35.5ml/kg/min for the cohort, an underperformance of 12.3 ± 8.0 ml/kg/min. The magnitude of underperformance began from stage 1 (no cardiomyopathy) and increased with each stage (Figure 1). Impairments in renal (creatinine and albumin: creatinine ratio) and cardiac biomarkers (troponin and N-terminal pro brain natriuretic peptide) was associated with reduced VO2 max (Table 1). Increased indexed left ventricular mass on CMR and impairments in atrial volume and function on TTE were also associated with a reduction in VO2 max (Table 1).

Conclusion
This study is the first of its kind to demonstrate impairments in peak aerobic capacity in adults with FD and no cardiomyopathy (stage 1) which impairs further with cardiac disease stage. Future work should focus on how disease-modifying therapy can target this using VO2 as an endpoint and marker of response.Normalised peak VO2 max + disease stageVO2 max and blood / imaging parameters
Relationship between six-minute walk distance and cardiopulmonary exercise testing in non-obstructive hypertrophic cardiomyopathy
Authors: Coats C J , Pavlou M , Watkinson O T , Bakalakos A , Protonotarios A , Moss L , Hyland R , Rantell K , Pantazis A , Tome M T , Mckenna W J , Frenneaux M P , Omar R , Elliott P M 
Published: October 2024

Abstract

Background
Recent studies have shown the promise of new approaches to the management of hypertrophic cardiomyopathy (HCM) symptoms. However, as HCM is a chronic disorder that evolves slowly over decades with low annual event rates, therapeutic trials in the disease rely on surrogate measures of disease severity and progression rather than hard endpoints such as mortality. Exercise capacity is one potential surrogate endpoint.

Purpose
To examine the relationship between peak oxygen uptake (VO2) and six-minute walk test distance (6MWD) in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) and describe the association with clinical parameters and quality of life.

Methods
We examined baseline data from patients with nHCM enrolled in a randomised placebo-controlled trial of trimetazidine therapy. The study was conducted in a single European centre. Cardiopulmonary exercise testing (CPET) was performed to assess peak oxygen consumption (pVO2), ventilatory anaerobic threshold (VAT) and ventilatory equivalent for carbon dioxide (minute ventilation to carbon dioxide production (VEVCO2). Health related quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ). ECG and echocardiography were performed on the same day and biomarkers (NT-proBNP and cardiac Troponin T, cTnT) were measured prior to exercise testing.

Results
In 51 patients (age 50 ± 13 years; 71% male) with nHCM, pVO2 ranged from 10 to 24.3 ml/kg/min and 6MWD from 188 to 650 metres. 6MWD correlated with peak VO2 (Pearson r=0.41, 95% CI 0.15 to 0.67, p=0.003) and anaerobic threshold (r=0.32, 95%CI 0.04 to 0.55, p=0.024). After adjusting for age and sex, NT-proBNP concentration correlated with peak VO2 (radi=-0.35, 95% CI -0.69 to -0.01, p=0.042) but not 6MWD (radj=-0.05, 95% CI -0.42 to 0.32, p=0.779). Health related quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) correlated moderately with 6MWD (radi=-0.54, 95% CI -0.79 to -0.29, p&lt;0.001) but weakly with peak VO2 (radi 0.28, 95% CI -0.55 to -0.01, p=0.042). I

Conclusions
There is a modest correlation between peak VO2 and 6MWD in nHCM. The pVO2 correlates more strongly with NT-proBNP whereas 6MWD better reflects quality of life. These data suggest pVO2 and 6MWD provide complementary information about health status in nHCM.Relationship between 6MWD and CPETCharacteristics of study cohort
Artificial intelligence (AI)-enhanced electrocardiography: a machine-learning model for differential diagnosis between hypertrophic cardiomyopathy, cardiac amyloidosis and Anderson-Fabry disease
Authors: Ruotolo I , Saglietto A , Saturi G , Sena G , Ponziani A , Parisi V , Ditaranto R , Zaccaro A , Casale M , Schiavo M A , Longhi S , Galie' N , Raineri C , De Ferrari G M , Biagini E 
Published: October 2024

Abstract

Background
The differential diagnosis between Hypertrophic Cardiomyopathy (HCM) and phenocopies is challenging and relies on a comprehensive approach, which includes clinical and instrumental data, as well as laboratory exams and genetic testing. In this setting, 12-lead electrocardiogram (ECG) represents a valuable tool, but although typical patterns have been described, their diagnostic ability to discriminate between different etiologies is limited and requires considerable clinical experience. However, a correct diagnosis is of pivotal importance, allowing the prompt initiation of phenotype-specific therapies and consequently improving patient survival.

Purpose
Aim of this study was to develop a machine-learning model based on human-based ECG features to support the differential diagnosis between HCM, Cardiac Amyloidosis (CA) and Anderson-Fabry Disease (AFD).

Methods
We retrospectively examined ECGs of 200 patients, 50 affected by HCM, 100 affected by CA (50 AL CA and 50 transthyretin CA) and 50 with a diagnosis of AFD cardiomyopathy. The patients were then divided in sinus rhythm (SR) subgroup (158 patients) and atrial fibrillation (AF) subgroup (42 patients). For each subgroup, patients were randomly split into a training (80%) and a testing cohort (20%), and a random forest (RF) model was trained on the training cohort, with hyperparameter tuning via 10-fold cross validation. The resulting model was then tested on the testing cohort to assess its predictive accuracy.

Results
Both RF models (SR and AF) showed good discriminative performance in this multiclass classification task on the testing cohort [SR: accuracy 67%; multiclass area under the curve (AUC) 0.797, 95% confidence interval (CI) 0.472 -0.827; AF: accuracy 75%; multiclass AUC 0.792, 95% CI 0.349 – 0.968]. Figure 1 and figure 2 report for each model the rank of the most important variables for class prediction.

Conclusions
An AI-based ECG interpretation based on human-derived ECG features can predict the etiology underlying an hypertrophic phenotype, helping to perform a correct diagnosis and consequently to set a specific therapeutic process.
Prognostic impact of SGLT2-inhibitor therapy on survival in patients with transthyretin amyloid cardiomyopathy
Authors: Toferer C , Schwegel N , Santner V , Zach D K , Hoeller V , Wallner M , Gollmer J , Aziz F , Von Lewinski D , Kolesnik E , Ablasser K , Zirlik A , Sourij H , Verheyen N 
Published: October 2024

Abstract

Background
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) significantly improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction. Recently published data indicates the safety and tolerability of SGLT2i therapy in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, there is a lack of evidence regarding the impact of SGLT2i therapy on clinical outcomes in those patients.

Purpose
This study aims to investigate the association between SGLT2i therapy and clinical outcomes in patients with ATTR-CM.

Methods
This is an analysis of a prospective registry conducted at an expert center for hypertrophic cardiomyopathies. We included all participants with a confirmed diagnosis of ATTR-CM, who were enrolled until December 2022. Prior and concomitant SGLT2i treatment was systemically assessed according to the patient interview and medical records. Patients’ outcomes were retrieved from local medical and health insurance records.

Results
We enrolled 116 patients, of whom 7 patients (6%) were treated with SGLT2i at inclusion and 44 patients (38%) were started on SGLT2i therapy during the observational period while 65 patients (56%) were SGLT2i-naïve. There were no significant differences in baseline characteristics between groups, as shown in the table. Median (interquartile range) age was 80 (76-82) years with 15% females. Median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 2844 (1519-5033) pg/ml, median estimated glomerular filtration rate (eGFR) 58 (46-69) ml/min/1,73m2, and median troponin T 56 (34-83) pg/ml.
During a median follow-up of 2.6 (1.8-3.7) years, 28 patients (24%) died, of whom 6 patients (5%) were in the treatment group and 22 patients (19%) in the control group. In univariate Cox-regression analysis, SGLT2i treatment was significantly associated with a lower mortality (HR 0.325, 95%CI 0.132-0.802, p=0.015). This association persisted after adjusting for age and sex (HR 0.347, 95%CI 0.139-0.867, p=0.023). However, when treatment initiation time was considered, the benefit did not remain statistically significant. No significant associations between SGLT2i treatment and worsening heart failure hospitalizations or cardiovascular death were observed.

Conclusion
In a prospective registry-based cohort of patients with ATTR-CM, SGLT2i therapy was associated with significantly better survival, with a potential treatment initiation time bias. These results suggest that SGLT2i may exert beneficial effects in patients with ATTR-CM and warrant a randomized controlled trial.
Feasibility of ultra-low volume contrast pulmonary arterial injection protocol for CTA in TAVI candidates with severe renal failure
Authors: Babbaro M , Perillo N , Bedogni F , Spagnolo P 
Published: October 2024

Abstract

Introduction
Computer tomography angiography (CTA) has an important role in patient screening before TAVI. The high volumes of iodinated contrast media (CM) injected during the examination represents the main limitation of CTA with a dose-dependent association with contrast-induced nephropathy.

Purpose
Show the feasibility of an ultra-low-dose CM pulmonary arterial injection protocol for CTA in TAVI candidates in high risk patients with severe renal failure.

Methods
In our retrospective study seventy-seven (77) patients with CKD on stage 3b or worse (eGFR ≤ 45/min/1.73 m2) underwent pre-procedural CTA for TAVI-planning with a pulmonary arterial administration of CM.
All CTA examinations were performed using a Dual Source 256-slice CT system. All enhanced CT acquisitions were performed using our dedicated biphasic injection protocol composed of two connected phases of contrast medium injection using different amount of CM (8, 10, 15 and 20 ml) according to BMI (&lt;22 kg/m2; 22-24 kg/m2; 24-28 kg/m2; &gt;28 kg/m2). The CM was administered directly into the pulmonary artery in all patients. For each examination was measured Intraluminal attenuation at thoraco-abdominal aorta and along the ilio-femoral vessels using the ROI (mean SD in HU) as objective image parameters (Picture 1). Serum creatinine and the eGFR were recorded pre-TAVI CT scan and after the procedures as reference of CM to renal function.

Results
CTA was successfully performed in all patients. Mean creatinine was 2.25 ± 0,76 mg/dL and mean GFR was 26.5± 8.1 mL/min/m2. Mean vessel attenuation was 352±164 HU at the aortic annulus, 238.1 ± 141,3 HU in the aortic arch and 266±168 in the iliac arteries (Picture 2).
The mean image noise was 28.2 ± 7 HU in the aortic annulus, 24.4 ± 10,9 in the right external iliac artery, and 25. ± 12,8 HU in the left external iliac artery. After CTA examination, a total of 74 patients (96%) underwent TAVI. Mean CM dose administered during TAVI procedure was 150,6 ± 85,8. Three patients (3.9%) were abolished for TAVI.
Postprocedural settings complications were recorded. A total of 31 patients (41%) had grade 1 paravalvular regurgitation, 10 patients (14%) grade 2. No cases of valve embolization or anulus rupture occured. No major vascular complications occured. No significant differences between creatine and eGFR pre and post procedures (p&lt;0,001).

Conclusions
The use of an ultra-low-dose CM pulmonary arterial injection protocol for CTA in TAVI candidates does not affect the renal function and procedural success rate is high and the clinical outcomes after TAVI is satisfactory according to the litterature.
Genotype predicts heart failure independent of left ventricular ejection fraction and NT-proBNP levels in hypertrophic cardiomyopathy
Authors: Bakalakos A , Protonotarios A , Coats C J , Monda E , Cannie D E , O' Mahony C , Syrris P , Lorenzini M , Elliott P M 
Published: October 2024

Abstract

Background/Introduction
Hypertrophic cardiomyopathy (HCM) is a myocardial disease associated with progression to heart failure. In around 40% of cases, the disease is caused by variants in genes encoding sarcomere proteins.

Purpose
To evaluate the role of genotype in predicting heart failure (HF) outcomes.

Methods
In this observational single-centre cohort study, consecutive patients with HCM were assessed for heart failure clinically stratified by genetic status into genotype-elusive which included those with no significant variants (G-) or variants of unknown significance (VUS) and genotype-positive (G+) with pathogenic/likely pathogenic (LP/P) variants. Heart failure endpoint was defined as left ventricular assist device implantation, heart transplantation or heart-failure-related death. The incidence of HF endpoint was compared between genotypes during follow-up using a time-to-event analysis.

Results
474 patients (50.9 ±14.5 years, 67.3 males) with HCM (25% with left ventricular (LV) outflow obstruction) were followed for 10.9 years (IQR 5.1-13.5). G+ LP/P patients (201/474 (42.4%)) were younger (45.8. ±14.0 years) compared to G- (225/474 (47.5%), 55.2 ±13.4 years) and VUS (48/474 (10.1%), 52.0 ± 15 years); 29/474 (6.1%) reached the heart failure endpoint. The incidence of heart failure endpoints was 12.4% (25/201) in the G+ LP/P group compared to 1.5% (4/273) in the gene elusive group. A multivariate Cox proportional hazards model including NT-proBNP and LV ejection fraction (LVEF) and genetic status showed that G+ LP/P was associated with increased risk of heart failure outcomes (HR: 5.11, 95% CI: 1.43–18.25, p=0.012). Every 100-unit rise in NT-proBNP was associated with a 41% increase in risk (HR: 1.41, 95% CI: 1.20–1.66, p&lt;0.0001). A one-unit (1%) reduction in LVEF correlated with a 10% increase in heart failure risk (HR: -0.90, 95% CI: 0.87–0.93, p&lt;0.0001).

Conclusion(s)
Genetic status is a predictor of heart failure outcomes independent of LVEF and NT-proBNP levels in HCM. This underscores the importance of genetic testing in the clinical management of HCM.
Trans-femoral transcatheter intramyocardial septal radiofrequency ablation: a novel therapeutic approach for obstructive hypertrophic cardiomyopathy
Authors: Huang Y , Fang Z , Zhou S 
Published: October 2024

Abstract

Background
Septal reduction techniques play a pivotal role in mitigating morbidity and mortality among patients with obstructive hypertrophic cardiomyopathy (oHCM). While trans-apical intramyocardial septal radiofrequency ablation (PIMSRA or LIWEN procedure) has shown promise in reducing left ventricular outflow tract (LVOT) gradients and improving symptoms in oHCM patients, it is associated with complications such as cardiac tamponade and atrioventricular block.

Objective
This study introduces a novel approach for transcatheter radiofrequency ablation of hypertrophic septum via femoral access, utilizing the DragonFire Transcatheter Myocardial Puncture and Radiofrequency Ablation System. We aim to evaluate its safety and medium-term outcomes in patients with oHCM.

Methods
A prospective, single-center, single-arm study of tf-PIMSRA was conducted in patients with drug-refractory oHCM. Ten patients were enrolled and underwent the procedure under the guidance of transesophageal echocardiography. The primary outcome was 30-day major adverse clinical events, with secondary outcomes including 90-day improvements in outflow obstruction and quality of life.

Results
All patients, with an average age of 57±10 years, including 4 males, underwent the procedure successfully without any complications, including major adverse clinical events or conduction abnormalities. The average duration of the procedure was 125.2±34.6 minutes, with an average ablation time of 38.69±18.29 minutes and ablation energy of 3.60±1.49KJ. At 90-day follow-up, significant reductions were observed in peak LVOT gradients (resting gradient: from 82.00 [56.00] mmHg to 14.00 [6.25] mmHg; p &lt; 0.001; provoked gradient: from 102.00 [76.25] mmHg to 33.00 [16.50] mmHg; p = 0.002), and interventricular septum thickness (from 22.00 [19.00] mm to 17.00 [15.00] mm; p = 0.002). These improvements were associated with enhancements in NYHA functional classification (from 3.00 [2.75] to 1.00 [1.00]; p &lt; 0.0001), Kansas City Cardiomyopathy Questionnaire scores (from 59.00 [44.50] to 80.00 [77.25]; p &lt; 0.02), 6-minute walk distance (from 441 [400] m to 480 [465] m; p &lt; 0.01), and pro B-type natriuretic peptide levels (from 1738.00 [1113.25] pg/ml to 252.00 [200.00] pg/ml; p = 0.002). All patients achieved New York Heart Association functional class I or II at follow-up.

Conclusions
Transfemoral PIMSRA appears to be a safe and effective procedure for relieving LVOT obstruction and symptoms in patients with drug-refractory oHCM. These findings support further investigation through randomized clinical trials comparing it with established septal reduction therapies.Patient-Level Outcomes for the trans-fem