bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison between coronary calcium score and segment involvement score when used in clinical routine
Authors: Lofmark H , Muhrbeck J M , Shahgaldi K S , Ostenfeldt E O , Jernberg T J
Published: October 2024

Data from a nationwide registry on coronary computer tomography angiography.

Background

The Coronary Artery Calcium Score (CACS) and segment involvement score (SIS) are crucial factors in assessing the severity of coronary artery disease (CAD) and determining the likelihood of future cardiovascular events. However, there are few large multicenter studies comparing the predictive value of CACS and SIS when used in the clinical routine.

Objectives

To compare CACS and SIS ability to predict cardiovascular outcomes when used in the clinical routine.

Methods

This retrospective cohort study included patients who underwent Coronary Computed Tomography Angiography (CCTA) for CAD evaluation between 2006-2022 in 29 different centers in Sweden. CACS was calculated using the Agatston method, and SIS was determined based on the number of coronary segments exhibiting plaque. For SIS, patients were categorized into SIS=0, SIS=1, SIS=2, SIS=3, SIS³4, for CACS patients were categorized into CACS=0, CACS=1-9, CACS=10-99, CACS=100-299, CACS³300. Patients were followed regarding the primary outcome of death or myocardial infarction. Multivariable Cox proportional hazards models were used for adjusting for potential confounders.

Results

A total of 23034 patients underwent CCTA and were followed for up to ten years. Median age (IQR) was 58 (49–67) years, 50% were women, 9% had diabetes mellitus, 42% had hypertension, 25% had hyperlipidemia, 5% had previously known CAD. There were 955 patients (4.1%) with myocardial infarction (MI) and 409 patients (2.2%) died during follow up. There was an increase in cardiovascular events with increasing SIS. When comparing SIS and presence of obstructive stenosis, SIS was a better predictor of outcome (Figure 1). There was also an increase cardiovascular events with increasing CACS (Figure 2). When adjusted for age, sex, risk factors, previous cardiovascular disease and intervention, both SIS and CACS were independently associated with outcome. When SIS and CACS were compared in a receiver operating characteristic curve, CACS had significantly larger AUC than SIS, (0.70[0.67-0.73] vs 0.62[0.60-0.63]).

Conclusion

Our findings show that both CACS and SIS are important and independent predictors of cardiovascular outcomes thereby offering a valuable tool for personalized risk stratification and management in clinical settings. When used in the clinical routine, CACS appears to be more strongly associated with outcome than SIS.Figure1 Survival SISFigure 2 Survival CACS
Patient characteristics and incidence of cardiac amyloidosis: an observational study in the UK clinical setting using electronic health records
Authors: Guha K , Baruah R , Mamza J B , Das S , Habash M , Laws E , Ramalingam T , Coats C , Anderson L
Published: October 2024

Background

Cardiac amyloidosis (CA) is associated with a high mortality rate due to sudden or progressive heart failure. It is often misdiagnosed due to non-specific symptoms, and its true incidence and prevalence in the United Kingdom (UK) remain uncertain.

Purpose

To describe patient characteristics and incidence of CA in the UK clinical setting using electronic health records.

Methods

In this retrospective observational study, anonymised, linked primary and secondary care data (Clinical Practice Research Datalink, CPRD and Hospital Episode Statistics, HES) were used to describe individuals diagnosed with CA. The CPRD database contains de-identified patient data sourced from a sample of general practitioner (GP) practices in the UK. Patients aged 18 years and older with a recorded Read or SNOMED-CT diagnosis code for CA or record of treatment with tafamidis (a licensed but not reimbursed treatment for transthyretin amyloid cardiomyopathy, ATTR-CM in the UK) in the period between January 2004 to December 2021 were included. The index date was defined as the earliest recorded date of CA diagnosis or tafamidis treatment. Demographic and clinical data were summarised using descriptive statistics. Incidence rates were reported per 100,000 person-years (PY).

Results

There were a total of 3,788 patients with CA (mean age: 67 years; 61% males) of which only 277 were coded as having wild-type transthyretin (ATTRwt) CA in mostly older patients (mean age: 79 years). The low patient counts of ATTRwt amyloidosis could be attributed to the lack of specificity in CA types and the low utilisation of ATTR amyloidosis codes. Heart Failure, essential hypertension and dyspnoea were the most common clinical presentations recorded in the 12 months to first diagnosis code or tafamidis prescription for CA (Table). The incidence of CA varied from 0.75 in 2004 to a peak of 1.96 in 2021, per 100,000 PY; a 2.9-fold increase in newly coded diagnoses in CA. There was a slight decline in the rates in 2020 and 2021 (Figure). Incidence rates in males and females increased over the 17-year period, with males consistently having higher rates than females. The incidence rate in females started from a lower base at 0.62/100,000 PY in 2004, increased by a factor of 1.9 to 1.1/100,000 PY, whereas in males it started at 0.88/100,000 PY and rose by a factor of 2.9 to 2.5 /100,000 PY. Incidence rates in subgroup populations have also been analysed.

Conclusions

In the UK clinical setting, the incidence rate of newly coded CA increased overall between 2004 and 2021, as well as in both male and female subgroups. The data suggest CA is becoming more common, or that awareness has improved, and there is now an urgent need for enhanced methods of detection, characterisation, and the need for thorough data capture to shape future pathway advancements.
Effect of left atrial function on cardiovascular outcome in non-dilated left ventricular cardiomyopathy
Authors: Kang J M , Song S
Published: October 2024

Background

This study aimed to determine whether atrial function and strains can provide the greatest or joint incremental prognostic value in patients with non-dilated left ventricular cardiomyopathy (NDLVC) over a long follow-up period.

Methods

One hundred sixty-four NDLVC patients were included retrospectively. Comprehensive clinical evaluation and echocardiographic investigations were obtained, including measurements of strain derived left atrial (LA) reservoir, conduit, booster strain. All patients were followed up for adverse cardiac events (MACE) including all-cause mortality, hospitalization due to heart failure aggravation. The predictors of MACE were examined with univariable and multivariable Cox regression analysis. Subsequently, nested Cox regression models were built to evaluate the incremental prognostic value of strain parameters. Patient survival was illustrated by Kaplan–Meier curves and differences were evaluated by log-rank test.

Results

During a median follow-up of 3.8 years, MACEs were identified in 34 (21%) patients. Cox regression models showed that the predictive value of LA conduit strain was independent from and incremental to LAVi and baseline variables. Age, E/e', RASP and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.05). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, age, RASP remained associated in the multivariable model (LA conduit strain HR: 2.14 [95% CI: 1.37-3.87; P < 0.007]; age HR: 1.05 [95% CI: 1.01-1.10; P = 0.020]; and RASP HR: 1.07 [95% CI: 1.01-1.14; P = 0.021]), whereas LVEF, LAVi were not. Adding LA conduit strain to other independent predictors (age and LAVi) improved the prediction of MACEs. (p < 0.05). Also, when a Kaplan Meier graph was obtained for the occurrence of MACE based on LA conduit strain 17%, a significant difference was shown between the two groups.

Conclusion

LA conduit strain provided the good prognostic value and added incremental value to conventional clinical predictors for patients with NDLVC.Incremental value of LA strainKM according to LA strain 17%
Effect of extracellular vesicles derived from inflammatory H9C2 cardiomyocytes on the polarization of macrophages and its mechanism
Authors: Han B , Jiang Y J , You Y N , Zhang L
Published: October 2024

Objective

The aim of this study was to investigate the effect of Extracellular vesicles (EVs) derived from inflammatory cardiomyocytes on the polarization of macrophages and its related mechanism.

Methods

EVs derived from the inflammatory and normal cardiomyocyte cell line H9C2 were extracted by differential centrifugation respectively. The extracted EVs were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot analysis (WB). The RAW264.7 macrophages in the inflammatory environment were treated with EVs, the proliferative activities were detected by CCK8, the expression of inflammatory factors were detected by qRT-PCR, and the differentiation of RAW264.7 macrophages into M1 and M2 was analyzed by flow cytometry. In vivo experiments, the animal model of viral myocarditis was established in Balb/c mice with intraperitoneal injection of CVB3. EVs derived from inflammatory H9C2 cardiomyocytes and medium were injected into mice by tail vein injection, respectively. The mice myocardium was stained by immunohistochemistry, and the total RNA of myocardial tissue was extracted for the detection of inflammatory factors by RT-PCR. In terms of mechanism research, mRNA expression profiles of RAW264.7 cells after EVs treatment were analyzed by RNA sequencing for functional annotation and mechanism study. At the same time, the extracted EVs derived from H9C2 normal group and the inflammatory group were subjected to 4D-Lable Free technology for quantitative proteomic analysis, and the results were analyzed bioinformatics, and then by WB analysis.Results We found that EVs derived from inflammatory H9C2 cardiomyocytes decreased the proliferative activity of RAW264.7 macrophages, the expression of pro-inflammatory cytokines IL-6, IL-1β, TNF-ɑ, and the proportion of M1 macrophages in the inflammatory state, while the proportion of M2 macrophages, which mainly inhibit inflammation, increased, and the expression levels of anti-inflammatory cytokines IL-10 and CD-206 increased. Results of immunohistochemical staining and RT-PCR showed that the EVs of inflammatory H9C2 regulated the heterogeneity of infiltrating macrophages and the expression of several inflammatory cytokines in mouse myocardium inflammatory tissue. Meanwhile, in vitro studies have found that the regulatory effect of EVs derived from inflammatory H9C2 cardiomyocytes on macrophage heterogeneity is mediated by MAPK signaling pathway.

Conclusion

EVs derived from inflammatory H9C2 cardiomyocytes can regulate the polarization of macrophages, change the expression of inflammatory factors, and regulate the myocardial inflammatory microenvironment, which may be achieved by mediating the p38 MAPK pathway through the delivery of PP2A.
Acute myocarditis presentation and intra-hospital prognosis: results of the multicenter prospective MYOCARDITIRM study
Authors: Bouleti C , Bejan-Angoulvant T , Lairez O , Genet T , Tea V , Alos B , Bonnet G , Jacquier A , Latucca B , Mousseaux E , Huttin O , Lim P , Redheuil A , Angoulvant D , Ou P
Published: October 2024

Background

Acute myocarditis (AM) usually presents as chest pain with rising troponin and normal coronary arteries. Despite frequent favorable evolution at the acute phase, it is associated with heart failure and ventricular rhythm disorders and is considered the leading cause of sudden cardiac death in young apparently healthy adults. There is no recommendation for AM, only expert consensus, given the lack of important databases for a strong level of confidence.

Methods

We performed a multicenter prospective observational study of patients admitted for AM acknowledged by cardiac MRI to describe baseline characteristics, management, in-hospital and long-term outcomes of AM patients in France. Secondary objectives were to investigate determinants of prognosis, modalities of treatment and follow-up, and to identify gaps between expert consensus and real-life management.

Results

We enrolled 805 consecutive patients hospitalized for AM in 49 participating centers between May 2016 and February 2019. Median age was 31 (IQR 23-41) with 19% of female. Chest pain was the most frequent symptom (93%) and 112 (14%) had severity criteria upon admission (LVEF<50% or severe ventricular arrythmia or high-grade AV block or cardiogenic shock). ST elevation was observed in 49% of patients. One 26-years old patient died during initial hospital stay. Overall, 62 patients (8%) experienced intra-hospital complication of their AM, defined as a combined endpoint of death, LVEF<40% (MRI), sustained ventricular or supraventricular arrythmia, acute renal failure, cardiogenic shock, need for ventricular assistance device, need for inotropic drugs, temporary cardiac pacing, pace-maker or cardiac defibrillator implantation. Patients with initial severity criteria were 10 times more likely to present intra-hospital complication (33% vs 3.6%, p<0.001).

Conclusion

This prospective cohort represents the largest database on AM worldwide. Here we report baseline characteristics and in hospital events. Most patients had typical presentation with favorable outcomes but as much as 8% of patients did exhibit intra-hospital complication. The prospective follow up will provide valuable data to better identify subset of patients with poor prognosis that may be of interest to develop new therapeutic strategies.Acute myocarditis on cardiac MRI
Adherence to sports counselling in middle-aged individuals with myocarditis
Authors: Schuetze J , Bernhard B , Stark A W , Boscolo M , Pavlicek M , Graeni C
Published: October 2024

Introduction

Although current guidelines recommend abstaining from sports for a duration of a minimum of three months in patients with myocarditis, the implementation of this recommendation and its adherence to it are unknown.

Objective

Investigate counselling and adherence to sports behaviour in patients with myocarditis.

Methods

A cohort of patients diagnosed with myocarditis, based on the ESC criteria, received questionnaires three months post-diagnosis to assess their activity levels before and after the diagnosis as well as the adherence to sports counselling.

Results

In our study, 46 myocarditis patients (11; 25% women) with a mean age of 52±14.5years were analysed. At the time of diagnosis, 39 patients (84%) reported physical activity, with 7 (15%) engaging in competitive sports. Following myocarditis diagnosis, 27 (60%) were recommended to abstain from sports or reduce physical activity, with 92% adherence. Of those 11 (23%) were physically active without receiving recommendations continued physical activity (p< 0.001). After three months, less patients were physically active (i.e. 25; 54% patients) compared to 39 (84%) patients at baseline (p = 0.038), 13 of those being physically active but with reduced exercise intensity according to recommendations. Of those who continued exercise without changes (n=13, 28%), only 2 (4%) reported having received recommendations. All competitive athletes (7, 15%) received counselling, whereas significantly fewer recreational athletes 19 (41%) did (p = 0.039). Women received numerical non-significant fewer counselling (4, 36% of all women, compared to 23, 67% of all men; p = 0.186).

Conclusion

Middle-aged individuals with suspected myocarditis exhibit excellent adherence to recommendations regarding physical activity. However, a notable proportion did not recall receiving counselling on exercise and physical activity. This highlights the need for clinicians to provide comprehensive counselling to all patients with suspected myocarditis consistently.Illustrating the sports behaviourcomparing activity at 0 and 3 months
The relationship between serum lumican levels and myocardial fibrosis in patients with hypertrophic cardiomyopathy
Authors: Hancioglu E , Ozcan S , Donmez E , Okuyan E , Sahin İ
Published: October 2024

Background

Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death in young individuals and an important cause of heart failure at any given age. Lumican, is an indicator of fibrosis and has been studied in various cardiac conditions. In this study, we aimed to evaluate the relation between serum Lumican levels and presence and extent of myocardial fibrosis in HCM.

Methods

The patients diagnosed with HCM between June 2022 and March 2023 were enrolled consecutively in this prospective study. Age and gender-matched healthy individuals formed control group. Additionally, HCM patients divided into two groups according to extent of late gadolinium enhancement (LGE).

Results

A total of 114 patients (62.3% male, 54.5±9.4 mean age) were enrolled in this prospective study. 64 patients formed HCM (+) and 50 patients formed HCM (-) group. The HCM (+) group is divided into two groups as LGE (+) and LGE (-) according to LGE involvement. Serum Lumican [p=0.018, β: 1.561, OR (95% CI): 1.080-2.257], NT-proBNP [p=0.043, β: 1.209, OR (95% CI): 1.079-2.527] and maximum wall thickness (MWT) [p=0.033, β: 1.322, OR (95% CI): 1.023-1.707] were revealed as independent risk factors associated with LGE by multivariate logistic regression analysis (Figure 1). ROC curve analysis was performed to identify the optimal cut-off value and calculate area under the curve (AUC) for Lumican, troponin (Tn) and NT-proBNP in order to predict the presence and extent of LGE in patients with HCM. A cut off value of 9.06 for Lumican was associated with 67.8% sensitivity and 65.5% specificity in prediction of LGE. A cut-off value of 932.4 for NT-proBNP was associated with 60% sensitivity, 60% specificity in prediction of LGE.

Conclusion

Myocardial fibrosis is one of the important mechanisms in HCM pathophysiology. Although LGE on cardiac magnetic resonance imaging(CMR) allows comprehensive evaluation of myocardial fibrosis, the support of diagnosis with a biomarker would be beneficial in clinical practice.Our study revealed that serum Lumican level is an independent predictor of severe LGE in HCM patients. Lumican can be used in addition to CMR for evaluating extence of myocardial fibrosis in HCM patients and may help clinicians in guiding follow-up and treatment.
Anderson-Fabry disease patients with anatomical heart hypertrophy express a higher degree of electrocardiographic hypertrophy compared to hypertrophic cardiomyopathy patients
Authors: Di Nicola F , Barile L , Schiavo M A , Sena G , Ruotolo I , Catalano C , Parisi V , Fanciullo N , Barlocco F , Lillo R , Re F , Graziani F , Galie' N , Olivotto I , Biagini E
Published: October 2024

Background

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disease that has progressively gained attention due to the availability of specific therapeutic options. Heart involvement is of critical prognostic significance and differential diagnosis with Hypertrophic Cardiomyopathy (HCM) is as challenging as it is crucial to provide the patient with the appropiate treatment.

Purpose

To describe ECG features in AFD patients according to the presence of anatomical hypertrophy and compare them with matched HCM patients.

Methods

One-hundred-sixty-two AFD patients were recruited in the present multicentre study cohort and divided into 2 groups according to the presence (Group A, n=111) or the absence (Group B, n=51) of anatomical hypertrophy. Group A patients were then compared with a matched cohort of HCM patients (n=111) with the use of Propensity Score Martching relatively to sex, age and maximal wall thickness.

Results

AFD patients with cardiac hypertrophy, compared with matched HCM patients with the same indexed cardiac mass at echocardiography [151 (124-211) vs 145 (123-182) g/m2; p=0.1675], showed on the surface electrocardiogram a higher degree of electrical hypertrophy expressed as increased total QRS score [204 (158-271) vs 177 (138-221) mm; p=0.0004] and R wave amplitude in aVL ≥ 11 mm [51 (45.9%) vs 25 (22.5%); p<0.0001], whereas they did not differ with respect to Sokolow-Lyon index [31 (18-44) vs 32 (22-40) mm; p=0.518] and Cornell index [19 (12-25) vs 17 (12-24) mm; p=0.5].

Furthermore, AFD patients featured wider QRS complexes [110 (100-134) vs 100 (90-106) ms; p<0.0001] and a higher prevalence of Right Bundle Branch Block (RBBB), both complete [25 (22.5%) vs 3 (2.7%); p<0.0001] and incomplete [17 (15.4%) vs 2 (1.8); p<0.0001], as well as non specific intraventricular block [14 (12.6%) vs 4 (3.6%); p<0.0001].

Conclusions

Our cohort of Anderson-Fabry patients, compared with HCM patients with the same indexed cardiac mass at echocardiography matched by age, sex and wall thickness, featured a higher degree of electrocardiographic hypertrophy expressed as increased total QRS score and R wave amplitude in aVL, whereas it did not differ with respect to Sokolow-Lyon and Cornell indexes. These findings may prove beneficial in achieving earlier the diagnosis of AFD, enabling clinicians to initiate swiftly and without delay the specific disease modifying therapies available.Electrocardiographic differencesTotal QRS Score AFD vs HCM
Sex differences in paediatric onset hypertrophic cardiomyopathy
Authors: Norrish G , Hall K , Field E , Boleti O , Cervi E , Kaski J K
Published: October 2024

Background

Hypertrophic Cardiomyopathy (HCM) is a heterogeneous disease characterised by age related incomplete penetrance and variable long term outcomes. Sex differences have been described in both the clinical phenotype and natural history of adults with the disease, which have been attributed to both biological (eg sex hormone effect) and non-biological (eg societal and cultural effects) factors. It is unknown if similar sex differences exist in childhood-onset HCM.

Purpose

This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM.

Methods

Retrospective cohort study from an international registry of patients diagnosed under the age of 18 years with HCM. Patients with syndromic disease (RASopathy syndromes, inborn errors of metabolism, neuromuscular disease) were excluded. Sex differences in baseline characteristics and clinical outcomes were described. Primary outcomes were all-cause mortality or cardiac transplantation, Major Arrhythmic Cardiac Event (MACE) and heart failure event (defined as heart failure death or cardiac transplantation)

Results

Of 1262 patients, 851 (67.4%) were male (median age 11 yrs (IQR 7.4, 14.4) vs 11.1 (IQR 6.9, 14.0) in females, p=0.0312). Female patients were more likely to have a sarcomeric variant identified (n=208, 85.6% vs 388 (79.4%), p=0.041) despite equivalent genetic testing utilisation between sexes. Female patients were more likely to have severe heart failure symptoms (NYHA 3 or 4) (n=19, 6.1% vs n=20, 2.5% p value 0.030) but there was no difference in the proportion on medical therapy (male n=328, 39.7%, female n=167, 41.8, p value 0.476). The clinical phenotype in terms of degree of hypertrophy, left atrial size and left ventricular outflow tract gradient did not differ by sex. Over a median follow up of 5.2 years (IQR 2.4, 9.9) all-cause mortality or cardiac transplantation did not vary by sex but females were more likely to experience a heart failure event (females 0.6/100,000 pt years (95% CI 0.39-0.92) vs males 0.32/100,000 pt years (95% CI 0.21 – 0.50), hazard ratio 1.89, p value 0.0467). The incidence of MACE did not differ by sex but there was a trend towards higher implantable cardioverter defibrillator implantation in females (n=123, 30.7% vs n=210, 25.4%, p value 0.051).

Conclusions

For the first time, this study has shown sex differences in paediatric-onset hypertrophic cardiomyopathy. Despite no difference in baseline clinical phenotype, young female patients are more likely to experience heart failure symptoms and heart failure events over follow up. Further studies are required to explore the underlying mechanisms for these observed differences.Table summarising outcomes by sexSurvival free from heart failure
Improved quantification of coronary stenosis in patients with high calcium scores using spectral reconstructions in coronary CT angiography
Authors: Monteagudo Ruiz J M , Martinez Vives P , Garcia Sebastian C , Carrion Sanchez I , Garcia Linacero L M , Arteagoitia Bolumburu A , Garcia Martin A , Hinojar Baydes R , Casas Rojo E , Jimenez Nacher J J , Fernandez Mendez M A , Arribas Marcos A , Zamorano Gomez J L , Fernandez-Golfin Loban C
Published: October 2024

Background

Coronary CT angiography has demonstrated reduced accuracy in patients with high calcium scores due to blooming artifacts, often resulting in overestimated stenosis.

Purpose

This study aimed to assess the impact of spectral reconstructions on coronary stenosis quantification in patients with high calcium scores (>500), utilizing invasive coronary angiography as the gold standard.

Methods

Twenty consecutive patients referred for coronary artery disease assessment underwent both coronary CT angiography and invasivecoronary angiography. Conventional 120 kV images, 100 keV virtual monoenergetic images, and iodine-no-water images were reconstructed. Two blinded operators independently reviewed the images. Lesions were qualitatively classified in both CCTA and invasive angiography as stenosis of 1-24%, 25-49%, 50-70%, and >70%.

Results

A total of 87 plaques were evaluated. Mean age was 72 years (SD=7.7) and 79% were male. Pre-test probability were low, medium and high in 15.8, 26.3% and 57.9% of patients respectively. Mean calcium score was 1662, with an average dose of 7.5 mSv (67.9% retrospective studies). Nitrates were administered in 89.5% of patients, and 47.4% received intravenous beta-blockers. Sensitivity, specificity, positive predictive value, and negative predictive value to detect lesions > 50% improved from 94%, 57%, 38%, 97% with conventional images to 94%, 82%, 59%, 98% with 100 keV virtual monoenergetic images.

Conclusion

Spectral reconstructions significantly enhance diagnostic accuracy in coronary CT angiography of severely calcified coronary arteries.
Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients
Authors: Seuthe K , Feidakis A , Nies R , Bruewer M , Pennig L , Mons U , Baldus S , Pfister R
Published: October 2024

Background

Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking.

Methods

In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events.

Results

A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication.

The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide.

As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p<0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks.

Regarding adverse events, there was one case of ejection fraction dropping to <50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions.

Conclusion

In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.
Functional capacity by cardiopulmonary exercise testing is not related to health status in obstructive hypertrophic cardiomyopathy
Authors: Bjerregaard L , Maron M S , Maron B J , Myrte E , Jensen M S K , Rowin E J
Published: October 2024

Background

In obstructive hypertrophic cardiomyopathy (HCM), the primary goal of therapy is to improve patient quality of life by decreasing symptom burden. Increasingly, cardiopulmonary exercise testing (CPET), with peak oxygen consumption (pVO2) and ventilator efficacy (VE/VCO2), is used to assess efficacy of novel therapies in clinical studies and selectively in clinical practice to determine treatments. However, the relationship of CPET variables to symptom burden in HCM is not well established. Therefore, we examined the relationship between CPET variables and health status measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional classification in a cohort of obstructive HCM patients.

Methods

Consecutive patients with HCM and resting left ventricular outflow tract (LVOT) obstruction (≥50 mmHg) underwent CPET between October 2022 to January 2024. Patients with a peak RER <1.0 were excluded (n=4). To investigate distribution of patient reported health status (KCCQ) and NYHA functional classification, patients were stratified into groups for pVO2 (<14, 14-20, and >20 mL/kg/min) to reflect moderate to severe, mild to moderate, and little to no functional limitation, respectively.

Results

Of 58 patients, clinical evaluation was at 59 ± 13 years of age, 55% male, with LVOT gradient of 83 ± 28 mmHg at rest with 84% NYHA class II or III and 76% with KCCQ overall summary (OS) <75. Both pVO2 and VE/VCO2 had significant but weak correlation with NYHA class and KCCQ scores (Table 1), with the strongest correlation observed with pVO2 and KCCQ-OS (R2= 0.13, p=0.004). In contrast, % predicted pVO2 was not significantly correlated with NYHA or KCCQ. Notably, despite 14 patients being classified as having little to no limitations by pVO2, 29% of these patients had mild to moderate disability and 29% had moderate to severe disability by KCCQ-OS (Figure 1).

Conclusion

In patients with symptomatic obstructive HCM, objective measures of exercise performance, including pVO2 and VE/VCO2, correlate poorly with measurements of health status. These data suggest that CPET results should not be considered a surrogate marker of heart failure symptom burden in obstructive HCM.
Epidemiology and prognosis of obstructive and non-obstructive hypertrophic cardiomyopathy in Finland: a nationwide cohort study
Authors: Laine M , Holsa O , Simin J , Laatikainen O , Vilen S , Kuusisto J
Published: October 2024

Background

Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease. The Finnish population has a specific genetic background, which may influence and even predispose people to various hereditary diseases. Whilst advances in genetic testing and imaging techniques may have influenced the detection of HCM and associated subtypes, contemporary data on incidence and prevalence remain limited.

Purpose

This study aimed to evaluate the current trends in the incidence, prevalence, and prognosis of obstructive and non-obstructive HCM in a nationwide cohort in Finland.

Methods

A population-based registry study was conducted using data from Finnish nationwide healthcare registries (HILMO/avoHILMO) including individuals aged at least 12 years with recorded HCM diagnosis between 2000 and 2021. The incidence was calculated by dividing the number of newly diagnosed HCM patients by the Finnish background population. Furthermore, the mean incidence per age-group was calculated by dividing the sum of age-group specific incidences by the number of age groups. The date and cause of death were obtained from national registries (Statistics Finland). Mortality was computed by dividing the number of deaths by follow-up length. Patients were followed from 2014 to 2021, and incident cases were defined as new diagnoses after 2014. HCM cases were stratified into obstructive HCM and non-obstructive HCM based on ICD-10 codes I42.1 and I42.2, respectively.

Results

Among 5,834 documented patients with HCM, the overall mean incidence by age-group was 2.64/100,000, with incidence increasing with age, peaking in those aged ≥85 years (6.22/100,000 patient-years [PY]). Annual incidence of obstructive HCM decreased from 2.2 to 1.4/100,000 PY, while non-obstructive HCM increased from 4.6 to 5.4/100,000 PY between 2014 and 2021 (Fig 1). Prevalence of non-obstructive HCM rose from 40 to 56/100,000 PY, while obstructive HCM prevalence remained stable (23-24/100,000 PY). All-cause mortality was 5.5/100 PY, with obstructive and non-obstructive HCM mortality at 5.7 and 4.6/100 PY, respectively. HCM-specific deaths accounted for 16% and 12% of all deaths in patients with non-obstructive and obstructive HCM, respectively.

Conclusions

This nationwide study in Finland revealed an increasing incidence and prevalence of non-obstructive HCM over time, contrasting with stable rates among patients with obstructive HCM. Incidence and prevalence were strongly age dependent. Non-HCM-related deaths were predominant in both HCM subtypes.
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

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

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

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<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

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.