bluuebunny/crossref_metadata_2025_split huggingface dataset:
The added value of advanced echocardiography in dilated cardiomyopathy: looking at the right heart
Authors: Hadareanu D R , Hadareanu C D , Stoiculescu F M , Florescu C , Donoiu I 
Published: October 2024

Abstract

Introduction and aims
Right ventricular (RV) dilation and dysfunction significantly impact the prognosis of dilated cardiomyopathy (DCM) patients, and early detection of subclinical changes is mandatory. Furthermore, right atrial (RA) size and function are still often neglected in DCM patients. Accordingly, our aims were to evaluate (i) right heart chambers and tricuspid annulus (TA) subclinical remodeling, and (ii) the prognostic value of RA compared to left atrial (LA) size and function in patients with DCM without clinical RV involvement, RV pressure/volume overload or sustained atrial tachyarrhythmias by advanced echocardiography techniques.

Materials and methods
Sixty-eight patients out of a cohort of 106 patients with DCM (mean age 60 years, 35 men) were evaluated by comprehensive transthoracic two- (2DE) and three-dimensional (3DE) and speckle-tracking (2DSTE) echocardiography, were compared to 62 age- and sex-matched healthy controls (mean age 61 years, 32 men), and were followed-up for 37 ± 16.6 months.

Results
DCM patients have RV and RA global longitudinal dysfunction by 2DSTE, and higher RA minimum volumes (Vmin) and TA areas despite having normal RV volumes and ejection fraction (EF) and RA maximum volumes (Vmax) by 3DE compared to controls (Table). RA and RV strain correlate with each other (r=0.360, p=0.013 for RA reservoir and r=0.347, p=0.017 for conduit strain). TA area correlates with RA contractile strain (r=-.293, p=0.046) and RV free-wall strain (r=0.373, p=0.008), RA Vmax (r=0.513, p&lt;0.001), RV (r=0.404, p=0.004 for end-diastolic and r=0.444, p=0.001 for end-systolic) and left ventricular (LV) volumes (r=0.394, p=0.016) and LV EF (r=-.361, p=0.028). RA reservoir strain (AUC=0.769) has higher value for outcome prediction compared to LA strain (p=0.02 between them).

Conclusion
Patients with DCM have RV longitudinal dysfunction and decreased RA function, in the absence of clinical RV involvement or atrial arrhythmias, and decreased RA strain is associated with an increased risk of hospitalization and cardiac death.Comparison of right heart parametersPrognostic value of atrial function
Myocardial DNA damage is responsible for the relationship between genotype and treatment response in patients with dilated cardiomyopathy
Authors: Dai Z , Ko T , Nomura S , Inoue S , Fujita K , Onoue K , Kuramoto Y , Asano Y , Amiya E , Hatano M , Takeda N F , Morita H , Saito Y , Takeda N H , Komuro I 
Published: October 2024

Abstract

Background
Dilated cardiomyopathy (DCM) is one of the leading causes of heart transplantation. Our group and others have previously reported that DNA damage accumulation in myocardial tissue and certain genetic variants such as those in LMNA are associated with treatment response and prognosis (ref 1-5). However, the potential association between myocardial DNA damage and genotype, and their contribution when combined to predicting treatment response, remains unclear.

Methods
We identified the deleterious variants in cardiomyopathy-related genes by analyzing the whole exome sequencing data from 89 patients with DCM who were recruited from two participating facilities. Immunostaining of γ-H2A.X, a DNA damage marker, was performed on endomyocardial biopsy specimens from the same patients, from which the percentage of nuclei positive for γ-H2A.X signals (%γ-H2A.X) was calculated. Left ventricular reverse remodeling (LVRR) was assessed by transthoracic echocardiography at 1 year after biopsy. We examined the associations among genotype, myocardial DNA damage, and the achievement of LVRR.

Results
Among the 89 patients with DCM, 11 (12.4%) carried pathogenic or likely pathogenic (P/LP) variants in sarcomere genes such as TTN, and 21 (23.6%) carried P/LP variants in non-sarcomere genes such as LMNA, while the rest had no P/LP variants in cardiomyopathy-related genes (Figure A). Patients with P/LP variants in sarcomere genes had a lower %γ-H2A.X [21.2 (10.7–29.0)% vs. 7.0 (4.3–12.4)%, P = 0.002] (Figure B), and a higher probability to achieve LVRR at 1-year (81.8% vs. 23.8%, P = 0.003) (Figure C) when compared to those with P/LP variants in non-sarcomere genes. The odds ratio for carriers of P/LP variants in sarcomere genes to achieve LVRR was 14.40 (95%CI 2.31–89.94) compared to that for carriers of P/LP variants in non-sarcomere genes. However, this effect was markedly attenuated after adjusting for the proportion of γ-H2A.X-positive nuclei [adjusted odds ratio 6.05 (95%CI 0.86–42.53)] (Table).

Conclusions
Among patients with DCM, carriers of P/LP variants in sarcomere genes showed less DNA damage and a favorable treatment response, when compared with carriers of P/LP variants in non-sarcomere genes. Our results suggest that myocardial DNA damage was partially responsible for the relationship between genotype and treatment response in patients with DCM.Figure, panels A-C
Cardiac sympathetic innervation, assessed with 123I-MIBG SPECT, predicts left ventricular function improvement in patients with newly diagnosed dilated cardiomyopathy
Authors: Dziewiecka E , Holcman K , Kostkiewicz M , Wisniowska-Smialek S , Szot W , Winiarczyk M , Stepien A , Graczyk K , Przytula N , Kyslyi V , Gasiorek J , Plazak M , Kapczynski N , Rubis P 
Published: October 2024

Abstract

Introduction
Beta-blockers (BB) are commonly prescribed medications for heart failure (HF) due to their ability to counteract the increased sympathetic nervous system (SNS) activity seen in HF, resulting in downregulation and desensitization of β-receptors. In patients with dilated cardiomyopathy (DCM), the introduction of BB therapy can lead to left ventricular ejection fraction (LVEF) improvement in 30-50% of cases. Single-photon emission computed tomography (SPECT) with 123I-meta-iodobenzylguanidine (MIBG) is a useful tool for assessing cardiac SNS activity. Healthy individuals typically exhibit high SPECT-MIBG uptake and low washout rate (WR) due to normal β-receptor levels and low norepinephrine (NE) levels, respectively (Fig 1A). While better SPECT-MIBG results have been associated with LVEF improvement in the general HF population, less data is available for DCM patients.

Purpose
This study aimed to evaluate the predictive value of MIBG-SPECT for LVEF improvement in newly diagnosed DCM patients.

Methods
Twenty-one DCM patients (mean age 47 ± 10 years, 90% male, baseline LVEF 29.5 ± 8.7%, left ventricular end-diastolic volume (LVEDV) 114 ± 36 ml/m2) with stable HF symptoms (NYHA class 1.8 ± 0.6) and newly diagnosed DCM underwent baseline MIBG-SPECT and echocardiography. HF therapy was initiated and up-titrated, and echocardiography was repeated at 6 months. Semi-quantitative parameters from MIBG-SPECT, including the MIBG uptake ratio from the heart and mediastinum (H/M) at 15 minutes (-15) and 4 hours (-4), as well as the WR [WR = (H/M-15 - H/M-4) / H/M-15], were evaluated. Patients were stratified based on median WR - 8.79 (IQR 5.17-12.90).

Results
After 6-months of HF therapy up-titration, 18 patients improved LVEF, and the mean LVEF increase was 7.7 ± 10.4%. Although, patients with WR &gt; median did not differ in terms of baseline LVEF (30.2 ± 7.0 vs. 27.7 ± 9.6, p=0.52), they had worse LVEF at 6 months (32.0 ± 11.0 vs. 40.6 ± 9.2%, p=0.04). Moreover, WR at baseline strongly correlated with 6-month LVEF (R=-0.51, p=0.01) and was a significant predictor of 6-month LVEF (β=-0.55 ± 0.19, p=0.009). Moreover, WR could successfully predict LVEF improvement ≥ 10% (OR 1.27 [95%CI 1.01-1.61], p=0.03; AUC 0.82 [95%CI 0.63-0.99], p&lt;0.001) with a cut-off point of 8.0 (sensitivity 88%, specificity 77%) (Fig 1B).

Conclusion
Most DCM patients demonstrated LVEF improvement during 6 months of HF therapy up-titration. Baseline WR from MIBG-SPECT was found to be a reliable predictor of significant LVEF improvement in this patient population.Fig1.A-SPECT-MIBG results. B-ROC curve.
A systematic review and meta-analysis to determine the biological sex ratio in monogenic genetic and non-genetic dilated cardiomyopathy
Authors: Bergan N , Prachee I , Prasad S , Gregson J , Ware J , Tayal U 
Published: October 2024

Abstract

Background
Dilated cardiomyopathy (DCM) is characterised by left ventricular or biventricular systolic dysfunction and dilatation, in the absence of abnormal loading conditions or coronary artery disease (1). Up to 30% of cases have an identified monogenic cause, usually with autosomal dominant (AD) inheritance (2). The disease appears to be twice as common in males, suggesting either a sex specific penetrance or a potential difference in expressivity. This sex ratio has not been systematically evaluated for genetic forms of DCM.

Purpose
To assess the sex ratio in patients with all-cause DCM compared to genetic (monogenic) and gene-elusive subtypes, defined by the presence or absence of a pathogenic variant in DCM-associated genes.

Methods
A literature search was conducted to identify cohorts of DCM patients with identifiable sex ratios. Exclusion criteria were patients with syndromic, X-linked, mitochondrial, or autosomal recessive (AR) DCM. Studies with a small cohort size (n&lt;100), a paediatric population, unidentifiable sex ratio, or ischaemic and peripartum DCM were excluded. 98 studies with a total of 36,662 participants were included in this study. A random-effects meta-analysis generated a pooled proportion of female participants with a 95% confidence interval (95% CI) for an overall DCM cohort as well as for the subtypes – all genetic DCM, individual gene level for 10 key DCM genes (including titin, TTN, and lamin, LMNA), and gene elusive DCM.

Results
The overall DCM cohort had a 0.30 female proportion (95% CI: 0.28-0.32; Figure 1). This corresponds to a male:female (M:F) ratio of 2.38:1. This ratio did not significantly change in patients with an identified causative DCM variant (0.31 [95% CI 0.26-0.36]; M:F ratio of 2.22:1; p=0.563). There was also no significant difference when compared to patients who had been genetically tested with no identified variant (0.30 [95% CI 0.24-0.37]; M:F ratio of 2.29:1; p=0.814). Furthermore, the ratio within participants with AD gene variants was not significantly different for the specific genes of TTN (0.28 [95% CI 0.22-0.36]; M:F ratio of 2.51:1) and LMNA (0.35 [95% CI 0.27-0.44]; M:F ratio of 1.84:1). Overall, the sex ratio amongst patients with these AD gene variants was similar to the all-cause group (0.34 [95% CI 0.28-0.40]; M:F ratio of 1.98:1; p=0.18); Figure 2.

Conclusions
This meta-analysis suggests that DCM is twice as prevalent in males than females, even in pooled monogenic genetic subtypes with an equally prevalent genetic risk factor, indicating a difference in penetrance between the sexes. Further studies are required to determine the drivers of this sex specific penetrance.Forest plots: overall DCM cohortForest plots: gene-specific DCM cohort
Clinical and laboratorial profile of patients with ATTR cardiomyopathy: comparison between wild type and p.Val142Ile forms in the Brazilian population
Authors: Simoes M , Jadan G , Correia E B , Carvalho A A S , Macedo A V S , Schwartzmann P V , Scheinberg P , Antunes M O , Coelho-Filho O R , Mangini S , Coneglian F S , Valicelli F H , Garibaldi P M M , Marques-Junior W , Fernandes F 
Published: October 2024

Abstract

Background
In Brazil, besides the wild type (wt) form, transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly caused by hereditary form with Val142Ile mutation. Considering that both forms occur in elderly people, the clinical presentation may be similar. We sought to compare the clinical presentation of patients with wt and Val142Ile mutation in a Brazilian cohort of ATTR-CM patients.

Methods
Among the 642 patients enrolled in REACT/SP, 283 presented ATTR-CM, being 85 wt and 90 Val142Ile patients. We compared the main clinical characteristics between groups.

Results
The wt in comparison to Val142Ile patients, respectively, presented: older age (78.4+/-8.5 vs 74.2+/-8.1 y.o., p = 0.0009); similar proportion of males (82% vs 81%, p=0.85); lower proportion of blacks (11% vs 39%, p=0.0001); similar prevalence of heart failure (HF) symptoms (85% vs 79%, p=0.33); higher prevalence of syncope (13% vs 2%, p=0.008) and Pacemakers (PM) implantation (8% vs 1%, p=0.027); similar prevalence of neuropathy manifestations (38% vs 51%, p=0.17); lower creatinine (1.5+/-0.8 vs 2.1+/-2.1 mg/dL, p=0.02) and NT-ProBNP levels (2860.0+/-2843.3 vs. 5488.3+/-5455.6 pg/ml, p=0.0001); reduced interventricular septal thickness (15.6+/-3.3 vs 17.0+/-3.3 mm, p= 0.006), posterior left ventricular (LV) posterior wall thickness (14.2+/-2.4 vs 16.2+/-4.4 mm, p=0.0003), higher LV ejection fraction (52.0+/-10.1 vs 48.2+/-13.6%, p=0.038), higher global LV longitudinal strain (8.6+/-8.7 vs 3.4+/-9.8, p=0.0003), smaller LV diastolic diameter (45.9+/-6.1 vs 43.0+/-7.3 mm, p=0.005) at 2D-Echocardiogram.

Conclusions
In the Brazilian population wt and Val142Ile patients had similar clinical presentation regarding HF and neuropathy symptoms, but higher prevalence of syncope and PM in wt patients. Conversely, Val142Ile patients presented more severe amyloid cardiac infiltration.
DPD quantification correlates with ECV and disease severity in patients with ATTR-CM
Authors: Rettl R , Calabretta R , Duca F , Kronberger C , Binder C , Willixhofer R , Dona C , Beitzke D , Loewe C , Nitsche C , Hengstenberg C , Badr Eslam R , Bergler-Klein J , Hacker M , Kammerlander A 
Published: October 2024

Abstract

Background
The pathophysiological hallmark of transthyretin amyloid cardiomyopathy (ATTR-CM) is the deposition of amyloid within the myocardium. However, the association between myocardial amyloid load and quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) uptake is barely investigated.

Purpose
We aimed to investigate the relationship between quantitative cardiac 99mTc-DPD uptake and myocardial amyloid load, assessed by extracellular volume (ECV) on cardiac magnetic resonance (CMR) imaging, along with cardiac function in patients with ATTR-CM.

Methods
Forty ATTR-CM patients underwent 99mTc-DPD single-photon emission computed tomography/computed tomography (SPECT/CT) and CMR imaging.

Results
We observed significant correlations (r, Spearman's correlation coefficient) between the standardized uptake value (SUV) retention index and myocardial amyloid load (ECV: r=0.677, p&lt;0.001; native T1 time: r=0.430, p=0.006), longitudinal cardiac function [right ventricular longitudinal strain (RV-LS): r=0.472, p=0.002], cardiac biomarkers (NT-proBNP: r=0.543, p&lt;0.001; troponin T: r=0.401, p=0.011), exercise capacity [6-min walking distance (6MWD): r=-0.410, p=0.010] and disease stage [National Amyloidosis Centre (NAC) ATTR stage: r=0.479, p=0.002]. ATTR-CM patients were divided into two cohorts based on the median of the SUV retention index (low cardiac uptake: &lt;5.19 mg/dL, n=20; high cardiac uptake: ≥5.19 mg/dL, n=20). We observed significant between-cohort differences in terms of ECV (p&lt;0.001), native T1 time (p=0.011), RV-LS (p=0.007), NT-proBNP (p&lt;0.001), troponin T (p=0.030), 6MWD (p=0.002) and NAC ATTR stage (I: p&lt;0.001, II: p=0.030, III: p=0.021).

Conclusions
In ATTR-CM, quantitative cardiac 99mTc-DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage. DPD quantification may provide a valuable tool for quantifying and monitoring cardiac disease burden in affected individuals.Table.Baseline Characteristics.Figure.Correlations.
RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy
Authors: Schwarting S , Poledniczek M , Metodiev Y , Stolz L , Hofmann E , Hegenbart U , Schoenland S , Kaeaeb S , Massberg S , Frey N , Aus Dem Siepen F 
Published: October 2024

Abstract

Background
Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM.

Methods
In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio.

Results
Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p&lt;0.001) within 3 years of follow up than those with RV-PAc ratio &gt; 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p &lt;0.001).

Conclusion
Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves
Health-related quality of life disparity in cardiac sarcoidosis versus other myocardial diseases
Authors: Raak-Tarkiainen J , Lehtonen J 
Published: October 2024

Abstract

Background
Sarcoidosis, a systemic inflammatory disorder, can manifest as progressive inflammatory heart disease, termed cardiac sarcoidosis (CS). Despite advances in treatment, the impact of CS on health-related quality of life (HRQoL) remains incompletely understood. This study aimed to compare HRQoL between patients with CS and those with non-inflammatory cardiomyopathies, namely dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM).

Purpose
To assess and compare HRQoL across patients with cardiac sarcoidosis and non-inflammatory cardiomyopathies.

Methods
A total of 240 CS patients (86% response rate), 96 DCM patients (55% response rate), and 81 HCM patients (65% response rate) completed the RAND-36 general health-related questionnaire, comprising eight dimensions. Patients listed for transplantation were excluded. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry for CS patients and from medical records in hospitals for HCM and DCM patients.

Results
Median age ranged from 56 to 59 years across the groups. Unlike DCM, which typically presents with heart failure symptoms, a substantial proportion (82%) of CS patients presented with advanced atrioventricular block or ventricular arrhythmias, while HCM cases were often incidentally detected or identified through family screening. Most CS patients (94%) had implanted pacemakers or ICDs, compared to a lower proportion in HCM (26%) and DCM (63%). DCM patients exhibited a higher prevalence of impaired LVEF (&lt;50%) compared to CS and HCM patients. Functional impairment, as measured by NYHA class, was most pronounced in DCM patients. CS patients experienced more adverse events between diagnosis and the study entry, particularly sustained ventricular tachycardia/ventricular fibrillation. However, heart failure hospitalizations did not significantly differ between groups.
Table 1 presents a comparative analysis of patient-reported outcomes across four functional and mental dimensions to assess the relative burden of disease among patients with CS, HCM, and DCM. While the functional dimensions in CS exhibited disparities from both HCM and DCM, no significant differences were observed in the mental dimensions between CS and HCM. CS patients reported lower scores in the domains of role physical, and general health compared to either HCM or DCM counterparts.

Conclusion
Patients with CS demonstrated significantly poorer HRQoL compared to those with non-inflammatory cardiomyopathies. This underscores the substantial burden of disease associated with CS and highlights the importance of comprehensive management strategies to address both clinical and quality of life aspects in affected individuals.
Improving early mortality risk detection in light-chain cardiac amyloidosis patients with routine echocardiographic indicators and mayo staging
Authors: Li J , Qiu L , Guo F , Sun K , Xu X , Tian Z , Zhang S 
Published: October 2024

Abstract

Background
Light-chain cardiac amyloidosis (AL-CA) is a fatal cardiomyopathy caused by the deposition of monoclonal immunoglobulin light-chain in the cardiac fibers, conduction system, valves, and other parts of the heart. The Mayo 2004 staging system is widely used to assess the prognosis of AL-CA. Those in the highest-risk categories, Mayo 2004 stage IIIb, exhibit extremely poor responses to conventional treatment regimens, resulting in high early mortality rates. However, within the same stage, prognostic outcomes among patients can still vary significantly. Hence, a more detailed stratification of high-risk patients is crucial for pinpointing those at extreme risk.

Objective
To investigate whether conventional echocardiographic measurements can enhance the identification of high-risk patients with early mortality in AL-CA on the basis of existing risk stratification.

Methods
Continuous enrollment of patients diagnosed with AL-CA at our center from May 2020 to December 2022. Clinical data, echocardiography, and follow-up results of the patients were collected. Logistic regression analyses were used to identify risk factors for early mortality, with risk factor thresholds calculated using Receiver Operating Characteristic (ROC) curves. Kaplan-Meier survival analysis was employed to assess endpoint events. The diagnostic efficacy of the model was evaluated using the area under the ROC curve and the Integrated Discrimination Improvement (IDI).

Results
A total of 76 patients were included with an average age of 59±10 years. Among them, 51 were male (67.1%). The median follow-up duration was 10 months (ranging from 5 to 20 months). Early mortality, defined as death within 6 months, occurred in 20 patients (26.3%). Twenty-three patients were categorized under the Mayo 2004 stage IIIb (30.3%). The 6-month mortality rate for patients in the Mayo 2004 stage IIIb was 56.5%. The sensitivity of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity ratio divided left ventricular ejection fraction [(E/e’) /LVEF] in predicting early mortality in patients with AL-CA is 63%, and the specificity is 92%.When compared to the Mayo 2004 stage IIIb alone, (E/e')/LVEF≥0.5 combined with the Mayo 2004 stage IIIb had an area under the curve of 0.731 and 0.824, respectively, in the ROC curve. The IDI was 0.113 (95% CI: 0.013-0.213, P=0.026), representing an 11.3% enhancement in the predictive value of early mortality in AL-CA patients.

Conclusion
Routine echocardiography derived E/e' to LVEF ratio offered added prognostic value for early mortality beyond Mayo staging.Kaplan-Meier survival curve