bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nexilin-related cardiomyopathy (NEXN-CMP) - an island's perspective
Authors: Abela M , Cassar M , Mifsud J , Scerri J , Debattista J , Gialanze' Y , Farrugia Wismayer M , Scerri C , Felice T 
Published: October 2024

Abstract

Introduction
The phenotypic features of Nexilin related cardiomyopathies (NEXN-CMP) are poorly understood and under-reported. A better understanding of the genotype-phenotype association is paramount.

Objectives
The main objective of this study was to investigate the causative role and phenotypic expression of the NEXN gene in the Maltese Islands.

Methodology
Probands and relatives referred for a cardiac gene panel were evaluated. Subjects harbouring NEXN variants were identified. Those finally classified as having NEXN-CMP were evaluated for the purpose of this study.

Results
Out of 444 probands (confirmed or suspected cardiomyopathy), 12 probands were labelled with NEXN-CMP. This equates to a prevalence of 2.7% in the local cardiomyopathy pool, substantially higher to what has been previously reported.
Genetic testing identified 19 individuals (probands [n=15] and relatives [n=4]) all harbouring the same novel frameshift variant: NEXN c.1589_1590del p.(Arg530LysfsTer3), classified as likely pathogenic according to ACMG criteria.
Three (15.8%) harboured a second pathogenic variant (n=2 MYH7, n=1 TTN). Another 3 were not clinically affected (n=1 FH of SCD, n=2 first degree relatives of NEXN-CMP probands). These individuals were excluded from further analysis.
The NEXN-CMP cohort (n=13) consisted of a dominant male (68.8%) population (54±22 years at presentation, 7.7% athletes, 12 families). Most were probands (n=12/13). DCM was the dominant phenotype (n=8, 61.5%) followed by HNDLVC (n=3, 23.1%) and HCM (n=2, 15.4%). One infantile DCM was homozygous for the NEXN variant.
Symptoms were the most frequent method of presentation (n=6, 46.2%), followed by a FH of SCD and/or cardiomyopathy (n=3, 23.1%), abnormal echocardiogram (n=2 15.4%), OHCA (n=1, 7.7%) and inutero diagnosis (n=1, 7.7%). A FH of SCD was present in a third (n=4/12, 33.3%).
The ECG was abnormal in the majority (n=10/11, 90.9%). Most patients had a LBBB (6/11, 54.5%) followed by inferolateral TWI (n=3, 27.3%), ventricular arrhythmias/high-grade AVB (n=1, 9.1% each).
NEXN-CMP appears to be a left dominant cardiomyopathy. LV dilation and reduced LVEF were present in 84.6%. Non-ischaemic scar was present in 3/8 cases (37.5%), 2 had a ring-like pattern. RV morphology and function was normal in all cases.
Tachyarrhythmias were frequently observed (n=4/6, 66.7%) during holter monitoring or exercise testing (n=2 NSVTs, n=1 VEs, n=1 SVEs). A fourth (n=3/11, 27.3%) were implanted with an electrophysiological device. No significant predictors for device implantation were identified at univariate analysis. One patient is on the transplant list (infantile DCM).

Conclusion
The prevalence of NEXN-CMP in Malta appears higher than previously reported (2.7%), possibly because of a founder mutation. DCM and HCM are the dominant presenting phenotypes, frequently associated with symptoms, an abnormal ECG, a FH of SCD and LV dilatation/dysfunction.
Novel risk scoring model to assess the need for venoarterial-extracorporeal membrane oxygenation in patients with acute myocarditis
Authors: Hong D , Yang J H 
Published: October 2024

Abstract

Background
Some patients with acute myocarditis unpredictably deteriorate into a fulminant form and their prognosis is poor. However, it is uncertain which acute myocarditis patients are likely to exacerbate and even require venoarterial-extracorporeal membrane oxygenation (VA-ECMO).

Objectives
This study aimed to identify the risk factors associated with the need for VA-ECMO in patients with acute myocarditis and to develop a predictive model.

Methods
This retrospective study included 841 patients from seven hospitals in Korea with biopsy-proven or clinically suspected acute myocarditis. Logistic regression was performed to identify clinical characteristics of patients who required VA-ECMO and to construct a scoring system that can predict the need for VA-ECMO.

Results
Among the study population, 217 (25.8%) patients underwent VA-ECMO. The study population was divided into training (N=621) and testing (N=220) cohorts according to participating center. The final predictive model of VA-ECMO insertion derived from the training cohort included the following: initial mean blood pressure &lt;65mmHg, cardiac arrest, Glasgow Coma Scale ≤12, platelet &lt;100×103/mL, pulmonary congestion on chest X-ray, QRS interval ≥120ms, left or right bundle branch block, and left ventricular ejection fraction &lt;40%. Using this predictive model, a β-coefficient-weighted Korean Acute Myocarditis (KAM) score was developed. The VA-ECMO insertion rate increased with increasing KAM score (odds ratio 1.683, 95% confidence interval 1.529-1.853, P&lt;0.001). External validation of the predictive model and KAM score using the testing cohort showed excellent discriminant ability (areas under the curve of 0.945 and 0.921, respectively). Furthermore, at a KAM score of 8 or higher, which was the cut-off KAM score to predict the need for VA-ECMO, patients without VA-ECMO tended to have higher in-hospital mortality than patients who needed VA-ECMO.

Conclusions
A risk scoring system based on simple clinical and laboratory parameters at initial presentation could predict the need for VA-ECMO and clinical course in patients with acute myocarditis.Graphic Abstract
Is unsatisfactory outcome of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy predictable?
Authors: Lawin D , Stellbrink C , Poudel M R , Marx K , Lawrenz T 
Published: October 2024

Abstract

Background
Alcohol septal ablation (ASA) has been introduced for left ventricular outflow tract gradient (LVOTG) reduction in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, some patients may not profit from ASA. Thus, we identified characteristics of patients with unsatisfactory outcome of ASA in a large single-center cohort.

Methods
Consecutive ASAs between 1997 and 2023, performed at our institution, were retrospectively enrolled. Those ASAs performed in patients with missing follow-up (FU), previous septal reduction therapy (SRT), and atypical HOCM were excluded. Patients with unsatisfactory outcome (PUO) were defined as continuing to meet the guideline criteria for SRT (NYHA ≥III or NYHA ≥II with exertional syncope and resting/exercise-induced LVOTG ≥50mmHg). PUO were compared to patients with good outcome (PGO). Results are expressed in % or median and interquartile range (IQR). Pre-procedural predictors of poor hemodynamic outcome were identified using logistic regression analysis.

Results
65 of 1003 patients were PUO (6.5%). Those were younger (48.0 years [40.5-61.8] vs. 57.0 years [IQR 47.0-67.0] in PGO; p=0.0030), more often reported syncope at baseline (35.4% vs. 22.2% in PGO; p=0.0214), and had lower body-mass-index (26.4kg/m2 [23.8-29.2] vs. 27.7kg/m2 [25.2-23.1] in PGO; p=0.0160). In PUO, resting LVOTG was higher at baseline (53.0mmHg [24.5-82.0]) than in PGO (40.0mmHg [22.0-75.0]; p=0.0292; Table 1). Differences in sex, family history of sudden cardiac death, dyspnoea, medication, and interventricular septum diameter (IVSD) were not observed at baseline (all p&gt;0.05; Table 1).
Age (OR 1.023; CI: 1.005-1.042; p=0.0129), syncope at baseline (OR 1.890; CI: 1.049-3.324; p=0.0296), and BMI (OR 1.072; CI: 1.007-1.145; p=0.0355) were found to independently influence poor hemodynamic response to ASA using multiple logistic regression controlling for confounders. However, sex, baseline IVSD, and LVOTG were not found to influence poor hemodynamic outcome (p&gt;0.05).
There were no differences with regard to the number of embolized branches (1 in both groups), the size of the balloon used to cover the septal branch (1.5mm in both groups), the volume of ethanol (PUO: 1.4ml [1.0-2.0]; PGO: 1.5ml [1.2-2.0]), or creatine kinase release (PUO: 879.0U/l [375.0-1187.0]; PGO: 842.0U/l [501.5 - 1234]) (all p&gt;0.05).
At 6-months-FU, PUO had significantly higher IVSD (18.0mm [13.5-22.0] vs. 16.0mm [12.0-19.0] in PGO; p=0.008), higher resting LVOTG (31.0mmHg [20.0-55.5] vs. 14.0mmHg [10.0-22.0] in PGO; p&lt;0.0001) and higher exercise-induced LVOTG (105.0mmHg [84.5-143.0] vs. 35.0mmHg [22.0-64.0] in PGO; p&lt;0.0001).

Conclusion
ASA was overall effective with only few patients experiencing unsatisfactory outcome. Syncope, age, and BMI were found predicting poor hemodynamic outcome.Baseline characteristics
Characterizing disease burden and health care resource utilization in patients with hypertrophic cardiomyopathy: a nationwide real-world study in Finland
Authors: Laine M , Holsa O , Simin J , Laatikainen O , Vilen S , Kuusisto J 
Published: October 2024

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease with an estimated prevalence of 1:500 in the general population.

Purpose
This study aimed to investigate healthcare resource utilization (HCRU) and associated costs in patients diagnosed with HCM (and the associated subtypes: obstructive or non-obstructive) in a nationwide cohort in Finland.

Methods
This retrospective, registry-based cohort study included all Finnish patients diagnosed with HCM between 2000 and 2021, who were 12+ years old at the time of diagnosis, as identified from the national care registers for healthcare. HCRU data were collected between 2014 and 2021 from the Finnish national care registers for health care and the social insurance institution. Data pertaining to New York Heart Association (NYHA) classification were collected from three Finnish university hospitals.

Results
The study cohort comprised 5,834 patients with an HCM diagnosis; obstructive HCM accounted for 34% of cases. Mean per patient-year costs were €6638, 95% confidence interval (CI) €6472-€7415, and €6112, 95% CI €5957-€6560 for those with obstructive and non-obstructive HCM respectively. All-cause hospitalizations at specialized care were the most prominent cost associated with patients with obstructive and non-obstructive HCM equating to 46.3% and 46.1% of the total cost respectively (Fig 1.). Comorbidity burden, as measured by Charlson comorbidity index (CCI) score, was greater in patients with the obstructive than non-obstructive phenotype of the disease (CCI ≥4: 2.2 and 1.8, p&lt;0.01, respectively). The highest utilization of invasive procedures was found for patients with NYHA class III-IV.

Conclusion
This population-based study, utilizing real-world data, provides novel insights into HCRU and related costs among Finnish patients with HCM (and associated subtypes). HCRU appears to be primarily driven by hospitalizations at specialized care. Furthermore, the data indicate that patients with obstructive HCM are likely to have a more severe disease, with higher comorbidity burden and requiring more invasive procedures than patients with the non-obstructive form of the disease. However, there were no statistically significant differences in health care costs between those with obstructive and non-obstructive HCM.
Effectiveness of contemporary risk stratification in patients with hypertrophic cardiomyopathy: a pilot study
Authors: Bonaventura J , Jensovsky M , Puchnerova V , Gleta E , Hansvenclova E , Ostadal P 
Published: October 2024

Abstract

Introduction
Risk stratification and primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is a challenging discipline. When using current stratification systems, there is always a compromise between sensitivity and specificity.

Objective
In our pilot study, we sought to determine the incidence of SCD and the effectiveness of stratification systems, i.e., the ESC HCM Risk-SCD score and the system of individual major risk factors (RF) according to ACC/AHA in patients followed in an expert center.

Methods
Patients with HCM were risk-stratified and followed for 10 ± 8 years at the referral HCM center.

Results
Five hundred and five patients were stratified, and 71 (14%) were implanted with a cardioverter-defibrillator (ICD) based on risk stratification. ICD patients were stratified at age 39 ± 17 years, of which 26 (35%) were women, maximal left ventricular wall thickness (MLWT) was 23 ± 7 mm, and left atrial dimension (LA) 46 ± 7 mm. During follow-up, 12 (17%) patients had ≥ 1 appropriate ICD therapy at age 46 ± 19 years. Patients with ≥ 1 appropriate ICD therapy had an average 5-year ESC score of 1.8 ± 0.4% and an average ACC/AHA major RF of 1.4 ± 0.8, MLWT 25 ± 6 mm, LA 47 ± 7 mm. None of the ICD patients died of SCD. Five (7%) patients suffered from ICD complications, including 4 (6%) inappropriate shock, and one patient experienced infective endocarditis requiring system extraction.
During follow-up, 118 (23%) patients died, of which 28 (6%) from HCM-related causes, 12 (2%) from stroke, 11 (2%) from advanced heart failure, one perioperatively (myectomy) and 4 (1%) patients died suddenly (SCD). The mean age of SCD patients at the time of stratification was 59 ± 14 years; all were male, MLWT 18 ± 5 mm, LA 49 ± 2 mm, mean ESC score 2.0 ± 0.9%, and three (75%) had no RF present according to ACC/AHA. The ESC HCM Risk-SCD score was markedly less sensitive (sensitivity 56%; 95% CI 21-86) but more specific (specificity 98%; 95% CI 96-99) than the ACC/AHA approach (sensitivity 77%; 95% CI 46-95; and specificity 71%; 95% CI 67-75) (Figure).

Conclusion
With current risk stratification, albeit imperfect, SCD is rare in HCM patients managed at an expert center.
Effect of alcohol septal ablation on exercise hemodynamics, symptoms and quality of life in patients with obstructive hypertrophic cardiomyopathy
Authors: Dybro A M , Rasmussen T B , Ladefoged B T , Pedersen A L , Andersen M J , Nielsen B R , Terkelsen C J , Jensen M K , Poulsen S H 
Published: October 2024

Abstract

Background
The comprehensive impact of septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy (HCM), including exercise hemodynamics and quality of life (QoL), remains poorly understood.

Purpose
The aim of this study was to evaluate the effect of alcohol septal ablation (ASA) in mitigating left ventricular outflow tract (LVOT) obstruction, reducing filling pressures during exercise, and the effect on QoL in patients with obstructive HCM.

Methods
This prospective study enrolled 24 patients with obstructive HCM referred for ASA. Evaluations included right-heart catheterization and echocardiography performed at rest and during exercise, before and approximately six months post-ASA. The primary outcome was the difference in filling pressures assessed by pulmonary capillary wedge pressure (PCWP) at 75 Watt (W). Secondary outcome assessed LVOT gradients, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and exercise capacity.

Results
ASA significantly reduced PCWP at 75 W (24 ± 10 mmHg vs 33 ± 9 mmHg; P = 0.0001) (Figure 1), decreased LVOT gradients at rest (49 mmHg (24-90) vs 17 mmHg (14-27); P=0.002), at peak exercise (45 mmHg (29-90) vs 32 mmHg (21-61); P = 0.02), and post-exercise (96 mmHg (34-161) vs 28 mmHg (21-62); P=0.004). The KCCQ-OSS score was also significantly reduced (75.6 ± 18.8 vs 64.7 ± 16; P = 0.006), without affecting peak oxygen consumption (19.9 ± 4.8 ml/kg/min vs 18.7 ± 3.6 ml/kg/min; P = 0.26). The improvement in the KCCQ score was confirmed by changes in NYHA functional class. Before ASA treatment, 54% of patients were in NYHA functional class III compared to 13% after ASA (P &lt; 0.0005).

Conclusion
ASA substantially reduces exercise-induced filling pressures, reduces LVOT obstruction, and improves symptoms and QoL in obstructive HCM, without impacting maximal exercise capacity.
Real-life experience with rilonacept for the treatment of recurrent pericarditis
Authors: Thomas G , Mbualungu J , Golino M , Abbate A 
Published: October 2024

Abstract

Background
Rilonacept, a soluble Interleukin-1 (IL-1) receptor fusion protein that neutralizes IL-1α and IL-1β, has shown efficacy in symptom resolution, weaning of standard-of-care therapies, and reducing the frequency of recurrent pericarditis (RP) episodes in clinical trials.

Purpose
We aimed to review the efficacy, safety, and duration of treatment with Rilonacept reliance in managing RP in our practice.

Methods
We analyzed 22 patients with RP treated with Rilonacept, 55 [43-69] years, 11 (50%) females. We reviewed clinical characteristics and outcomes, including the time since initial diagnosis of pericarditis, the presence of pericardial effusion/thickening, the duration of Rilonacept treatment, the ability to wean off steroids, and the recurrence of pericarditis symptoms attempting discontinuation.

Results
The length of time from the initial diagnosis of pericarditis to Rilonacept initiation was 9 [4-32] months. Fifteen patients out of 22 (68%) had pericardial effusion, 3 (20%) with tamponade requiring pericardiocentesis. Median length of treatment with Rilonacept was 14 [6-23] months, with 17/22 (77%) of patients being treated for ≥ 6 months. All patients who were on steroids (14/22, 64%) were able to discontinue their usage 1 [1-9] months after starting Rilonacept. Of the seventeen who were treated for 6 months or more, 12 (70%) remained on Rilonacept 160 mg weekly at the most recent assessment, 3 (18%) continued treatment with Rilonacept 160 mg every 2 or 4 weeks, and 2 (12%) discontinued Rilonacept treatment after 6 and 50 months. Of the 12 patients who remained on weekly treatment after a period of 6 months, 8 (67%) required Rilonacept for symptom control, 1 (8%) had recurrent symptoms after treatment every 2 weeks, and the remaining 3 (25%) preferred to continue despite a lack of symptoms (Figure 1).

Conclusions
The efficacy of Rilonacept in treating patients with RP and the ability to stop steroid therapy in the real world is in line with the efficacy data from clinical trials.Figure 1
Prognostic factors and etiological insights in constrictive pericarditis
Authors: Admella Severiano L , Sonora S , Rodenas E , Oristrell G , Soriano T , Ferreira I , Rello P 
Published: October 2024

Abstract

Constrictive pericarditis (CP) is an infrequent disease that poses a diagnostic and therapeutic challenge, with mortality often linked to underlying etiological factors. Our unicentric retrospective research aims to elucidate prognostic indicators and unravel the diverse etiological spectrum of this condition. The study is accepted by the Ethical Committee of our Center. Between January 2010 and December 2023, we have identified a total of 112 patients diagnosed with CP, with an average follow-up time of 6.42 years (IQR 1.98 - 11.45). We present the baseline variables of the patients, etiology and prescribed treatments in the table 1, comparing patients who survive with those who do not survive. 66.1% of patients were males and median age was 60.8 years old.
We present two Kaplan-Meier curves (Figures 1 and 2) comparing the survival rates between CP etiologies. In Figure 1, all causes are represented separately. In Figure 2, CP related to cardiac surgery, radiotherapy, purulent pericarditis, tuberculous pericarditis, mixed and other causes are combined. Our results suggest a better prognosis in patients with idiopathic CP and worse prognosis in patients with oncological related CP.
The significant predictors in the univariate Cox analysis were age, cachexia, ascites, oncology etiology, hemoglobin, sodium, Euroscore II and surgical pericardiectomy. The best predictive model (selected with a lower AIC) to predict mortality throughout follow-up, with a Harrell's C of 0.835, included the variables age, cachexia, oncological cause and hyponatremia as risk factors for mortality and surgical treatment by pericardiectomy as a protective factor (Figure 3).
In conclusion, our study suggests that CP etiology has an impact on survival with oncological cause having the worst prognosis. Furthermore, other factors as hyponatremia, cachexia, shock and age at diagnosis have also resulted in indicators of poor outcome.Figure 1.Kaplan meierFigure 3.Predictive model
Arrhythmia burden in patients with congenital heart disease
Authors: Eckerstrom F , Dellborg M , Kok W G , Eriksson P , Mandalenakis Z 
Published: October 2024

Abstract

Background
The prevalence of congenital heart defects (CHD) is rising. Many patients experience arrhythmias either due to the defect itself or necessary intervention. Sudden onset of arrhythmia poses grave risks such as heart failure, stroke, or cardiac death. Research gaps exist regarding high-risk defects, age susceptibility, and prognostic implications of arrhythmia.

Purpose
Delineate the burden of arrhythmias in patients with CHD.

Methods
Patients born in the period 1970-2017 and diagnosed with CHD were identified in Swedish nationwide medical registries. Each patient was matched by birthyear and sex with ten controls from the general population. Cox proportional hazard regression model and Fine-Gray regression model with death as competing risk were used to compute risk (hazard ratio [HR]) and cumulative incidence of arrhythmias (supraventricular and ventricular arrhythmias). Estimates were compared with the matched controls. Follow-up started at time of birth.

Results
We included 63,559 patients and 583,205 matched controls with median follow-up of 12.8 years. Almost two-thirds of the total CHD population were born after year 2000 and 89% (n=56,564) had a simple lesion (defined as atrial or ventricular septal defect, coarctation of the aorta or malformation of the heart valves). During follow-up, 1,632 events of arrhythmia (90% of supraventricular origin) were registered in the population of patients with CHD, yielding an incidence rate of 16.4 per 10,000 person-years (versus 1.6 in the control population). The cumulative incidence of arrhythmias in the total CHD population was slightly increased during childhood compared with the control population, but rose significantly hereafter, illustrated in Figure 1, yielding an overall risk of 10.5 (CI 95%: 9.8-11.2). Stratified by lesion severity, the risk for arrhythmias was 8.7 (CI 95%: 7.6-8.7) and 30.4 (CI 95%: 26.2-35.2) in patients with simple and complex lesions, respectively. Patients with simple CHD lesions displayed a risk of 7.7 (95% CI: 7.1-8.4) for supraventricular arrhythmias and 11.5 (95% CI: 9.2-14.5) for ventricular arrhythmias. Correspondingly, patients with complex CHD lesions displayed risks of 66.7 (95% CI: 42.7-104.2) and 28.9 (95% CI: 24.8-33.6).

Conclusion
Arrhythmias, irrespective of origin, are common in patients with CHD and correlate with lesion severity. The overall burden of arrhythmias increased significantly after childhood. Meticulous follow-up is vital in order to prevent, detect and treat arrhythmias as it might trigger clinical deterioration and even sudden cardiac death in patients with CHD.