bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance and genetic basis of hypertrophic cardiomyopathy with apical phenotype: comparison of pure-apical form and distal-dominant form
Authors: Sugiura K , Kubo T , Yamada T , Inoue S , Nomura S , Ochi Y , Baba Y , Hirota T , Morita H , Yamasaki N , Doi Y , Komuro I , Kitaoka H 
Published: November 2023

Abstract

Background
Apical hypertrophic cardiomyopathy (apical HCM) is a variant of HCM first reported in Japan. The definition of apical HCM in the Japanese Circulation Society guideline is left ventricular hypertrophy limited to the level of the apex below the papillary muscle level. On the other hand, apical HCM in Western countries often includes hypertrophy that extends to the ventricular septum beyond the true LV apex. Although these variations may have different clinical characteristics and prognoses, they are often considered the same. Therefore, we previously proposed two phenotypes of apical HCM. Pure-apical form follows the definition of the JCS guideline. Distal-dominant form is defined as demonstrating apical hypertrophy extended to the ventricular septum without basal septal hypertrophy. However, the clinical significance and genetic basis of these phenotypes have not been reported. This study aimed to clarify clinical differences and yield of genetic testing in apical phenotype of HCM.

Methods
Regarding clinical presentation and prognosis, we retrospectively investigated 111 consecutive HCM patients with apical phenotype. HCM-related adverse events were defined as HCM-related death and nonfatal HCM-related events: heart failure admission, embolic stroke admission, and sustained ventricular tachycardia with hemodynamic instability or appropriate implantable cardioverter-defibrillator discharge. Furthermore, we performed a genetic analysis including 145 genes associated with cardiomyopathy in 69 unrelated patients within the cohort.

Results
In the cohort, 60 patients were pure-apical, and 51 were distal-dominant. The age at diagnosis was about 60 years, and the majority were male in both groups. The comorbidity rate of hypertension did not indicate a statistically significant difference. During the follow-up period of 10.3 ± 6.9 years, the occurrence of HCM-related adverse events was significantly higher in the distal-dominant group than in the pure-apical group (log-rank p=0.007). Detection rate of pathogenic or likely pathogenic variants in sarcomeric protein-encoding genes was significantly higher in the distal-dominant group than in the pure-apical group (21% vs. 3%; p=0.044).

Conclusions
Two phenotypes of apical HCM should be recognized and distinguished clinically because they have different prognoses and genetic features.
Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: validation of HCM Risk-Kids model and predictors of events
Authors: Boleti O , Norrish G , Field E , Tollit J , Zenker M , Wolf C , Kaski J P 
Published: November 2023

Abstract

RASopathies represent an important proportion of hypertrophic cardiomyopathy (HCM) cases presenting in childhood. Despite this, there are no published risk factors for sudden cardiac death (SCD) in this cohort of patients. Our primary aim was to validate the HCM Risk-Kids model in children with RASopathy-associated HCM and to investigate additional predictors of SCD in a cohort of 169 patients from 15 international paediatric cardiology centres (UK, Ireland and Germany). Eleven (6.5%) patients experienced a SCD equivalent event [5 (45.5%) an aborted cardiac arrest; 3 (27.3%) SCD; 2 (18.2%) sustained ventricular tachycardia (VT); and 1 (9.1%) appropriate implantable cardioverter-defibrillator (ICD) shock] at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD equivalent event incidence was 0.78 (95% CI 0.43 – 1.41) per 100 patient years. Six patients (54.54%) with a SCD equivalent event were in the low-risk category according to the HCM Risk-Kids model. Harrell’s C index was 0.5959 (95% CI 0.26-1.22) with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 90.99%; there was poor distinction between the different risk groups. Unexplained syncope (HR 102.63 (95% CI 14.94 – 704.99), p&lt;0.001) and non-sustained VT [NSVT (HR 5.67 (95% CI 1.30 – 24.70), p=0.021)] were independent predictors of SCD. The HCM Risk-Kids model should not be used for patients with RASopathy-associated HCM but NSVT and unexplained syncope appear to be predictors of SCD in this population. Larger multicentre collaborative studies are required to further investigate predictors of SCD in this group of patients.
Arrhythmic risk stratification in patients with left ventricular ring-like scar
Authors: Parisi V , Graziosi M , Lopes R L , Pasquale F , De Luca A , Targetti M , Tini G , Torlasco C , Ditaranto R , Chiti C , Crotti L , Olivotto I , Merlo M , Elliott P , Biagini E 
Published: November 2023

Abstract

Background
Myocardial fibrosis assessment with late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has recently emerged as an independent predictor of major adverse events in patients with non-ischemic cardiomyopathy. Several studies have examined different locations and extension degrees of LGE, and the so called "ring-like pattern" has been related with an increased incidence of ventricular arrhythmias, in patients with dilated cardiomyopathy (DCM), but also in patients with preserved systolic function.

Purpose
To describe clinical, electrocardiographic, echocardiographic, CMR and genetic features of the left ventricular (LV) ring-like scar phenotype and to evaluate which characteristics may be associated with the risk of sudden cardiac death (SCD).

Methods
Patients diagnosed with LV ring-like scar were identified at 6 referral Centres. Diagnosis was based on: 1) ring-like LGE LV pattern, defined as at least 3 contiguous segments with subepicardial/midwall LGE in the same slice with or without fatty infiltration; or 2) pathology examination of explanted hearts/autoptic cases suffering from sudden cardiac death (SCD). Moreover, patients must have an additional inclusion criterion: a positive genetic test, or ≥1 patient in the same family with an ascertained cardiomyopathy. Major adverse arrhythmic cardiac events (MAACE), defined as a composite of SCD, aborted SCD, and sustained ventricular tachycardia (SVT), were the primary study endpoint.

Results
The final cohort comprised 129 patients (male 59.7%, median age at diagnosis 44 years). During a median follow-up of 3.4 years (IQR 1.2 – 64.), MAACE occurred in 31 patients (24%). Nearly 70% of the patients had a likely pathogenic/pathogenic mutation, mostly in desmoplakin (DSP) and filamin-C (FLNC) genes (65% and 19%, respectively). Sex, QRS width, and LGE in LV anterior wall and/or apex, were the only independent predictors of the outcome events (HR: 0.329, 95% CI: 0.119-0.916, P = 0.033; HR: 1.036, 95% CI 1.019-1.053, P &lt; 0.001; HR 4.270, 95% CI 1.337-13.630, P = 0.014, respectively). A significant interaction between sex and LGE in anterior wall/apex was observed, being this regions associated with MAACE only in male patients (p for interaction = 0.033). Although related to the arrhythmic endpoint at the Kaplan-Meier survival curves, neither DCM echocardiographic phenotype, nor LV ejection fraction ≤35% remained statistically associated to MAACE at the multivariate analysis. Age, genetic mutations, right ventricular involvement, proband status, LV-LGE extension (number of segments) were not statistically related to the study endpoint.

Conclusions
In this selected cohort of patients with LV ring-like scar and either a genetic test or family history, malignant arrhythmic events were predicted by male sex, QRS width and LGE in anterior wall and/or apex.Graphical Abstract
Genotype influences end-stage heart failure occurrence in dilated cardiomyopathy
Authors: Cannie D , Bakalakos A , Protonotarios A , Syrris P , Lorenzini M , Guttmann O , O'mahony C , Savvatis K , Lopes L , Sekhri N , Mohiddin S , Elliott P 
Published: November 2023

Abstract

Introduction
A monogenic cause of a dilated cardiomyopathy (DCM) phenotype is found in upto 37% of patients [1].

Purpose
Evaluate the influence of genotype on end-stage heart failure (ESHF) outcomes in DCM.

Methods
Consecutive patients carrying variants from the 3 most prevalent DCM genotypes in a database from a cardiomyopathy unit (TTN, DSP and LMNA) and with features of DCM at baseline were retrospectively recruited. Consecutive DCM patients returning a negative result from a next generation DCM panel were recruited for comparison. ESHF was defined as left ventricular assist device implantation, heart transplantation or heart-failure related death. The incidence of ESHF was compared between genotypes during follow-up.

Results
493 patients from 445 families (311 (63.1%) males, presenting at a median [IQR] age of 50.8 years [37.3 – 59.8]) with a median follow-up of 46.5 [28.1 – 88.2] months were recruited (Table 1). 26/493 (5.3%) of patients had ESHF by last evaluation. The highest incidence of ESHF was seen in LMNA variant-carriers and the lowest in genotype-negative patients (Figure 1). In a multivariable Cox model including age at presentation, sex and proband status, LMNA variant-carriage was associated with an increased risk of ESHF (HR 9.7 [4.6 – 20.6], p &lt; 0.001) and genotype-negative status was associated with a reduced risk of ESHF (HR 0.08 [0.02 – 0.41], p = 0.002)

Conclusions
Genotype impacts the incidence of ESHF in patients with DCM. Close monitoring with early initiation of heart failure therapies is essential to mitigate this risk, particularly in LMNA variant-carriers.Table 1Figure 1
Myocardial Stiffness evaluation by shear wave elastography in transthyretin amyloidosis with and without cardiac involvement
Authors: Comte de Alencar Neto A C , Caio Reboucas Fonseca Cafezeiro C R F C , Bruno Vaz Kerges Bueno B V K B , Joao Henrique Rissato J H R , Viviane Tiemi Hotta V T H , Aristoteles Comte De Alencar Filho A C A F , Fernando Linhares Pereira F L P , Katia Couceiro K C , Carlos Eduardo Rochitte C E R , Joao Marcos Bemfica Barbosa J M B B , Jose Soares Junior J S J , Felix Jose Alvarez Ramires F J A R , Roberto Kalil Filho R K F , Wilson Mathias Junior W M J , Fabio Fernandes F F 
Published: November 2023

Abstract

Introduction
Cardiac involvement (CI) in hereditary transthyretin amyloidosis (ATTRh) occurs by deposition of amyloid fibrils in the heart, resulting in stiffening and diastolic dysfunction. Shear wave elastography, non-invasively and without the emission of ionizing radiation, quantitatively assesses tissue stiffness, a passive component of diastole, complementing the complex echocardiographic assessment.

Objective
To evaluate myocardial stiffness, through diastolic myocardial elasticity (DME), in ATTRh patients with and without CI and a healthy control group (CG).

Methodology
Prospective, cross-sectional study, 60 patients divided into 3 groups: ATTRh with CI (n:20), ATTRh without CI (n:20) and GC (n:20). DME was evaluated in the septal wall of the left ventricle (LV) (basal, middle, and apical segments) and in the free wall of the right ventricle (RV). They were also submitted to 2D-ECO, EKG, troponin, BNP, 6-minutes-walking test and pyrophosphate-labeled scintigraphy (Tc-99m-PYP). Data were analyzed using a one-way ANOVA, verifying myocardial stiffness, measured by DME, among the 3 groups. Then, pairwise comparisons were adjusted using Tukey's technique.

Results
DME was a significant factor for distinguishing between groups when analyzed in the parasternal long axis (PLAX) basal septum (p=0.013), parasternal short axis (PSAX) basal septum (p=0.03) and in the PLAX RV free wall (p=0.004). Was observed in the apical septum segment similar stiffness between groups, suggesting a pattern of apical preservation. In the post hoc evaluation, DME in the basal septum region was significantly higher among the ATTRh with CI group than in the control group, but without significant difference between ATTRh with CI and ATTRh without CI, suggesting that the latter group has intermediate values between the sick patient and the healthy patient. Also, right ventricle DME in ATTRh with CI was greater than in the other two groups (Table 1 and Figure 1). In a regression model, the results indicate that 17.2% of the DME variance can be attributed to 3-hour scan uptake on the Tc-99m-PYP (R2=0.172, F (1-36) =7.2, p&lt; 0.011), estimated by the equation: 3-hour scan uptake = 0.91 +0.078 x DME.

Conclusion
Myocardial stiffness is increased in ATTRh with CI, showing a decreasing pattern of stiffness in the apex direction, suggesting a pattern of apical preservation. Cardiac elastography has the potential to be an important tool in the assessment of cardiac involvement in systemic amyloidosis.
A biopsy-based pilot clinical study: monitoring the effectiveness of tafamidis treatment of patients with transthyretin amyloid cardiomyopathy
Authors: Elsanhoury A , Diekmann S , Kuehl U , Klein O , Willner M , Kelle S , Klingel K , Tschoepe C 
Published: November 2023

Abstract

Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare and progressive disease associated with high mortality. It is caused by the accumulation of TTR amyloid protein in various tissues, including the myocardium. Tafamidis is currently the only approved therapy for ATTR-CM. The results of the phase III ATTR-ACT trial showed lower rates of mortality and hospitalization, besides lower rate of decline for both quality of life (QoL), and 6-minute walk test (6mwt) distance [1]. Whether the reported clinical outcomes represent a change in myocardial ATTR-accumulation and remodeling remains unclear. Here we monitor the clinical outcome and the corresponding myocardial histological changes of tafamidis-treated patients using endomyocardial biopsy (EMB).

Methods
Eleven patients with EMB-proven ATTR-CM, 10 wild type, 1 hereditary, 9 males, 2 females age= 77±9 years, were prescribed with 61 mg tafamidis once daily indefinitely. The course of the disease was evaluated via EMB, 99mTc-DPD scintigraphy, cardiac magnetic resonance imaging (cMRI), echocardiography, 6mwt, Minnesota QoL questionnaire and serum N-terminal pro brain natriuretic peptide (NT-proBNP) analysis, at baseline and after 321±72 days of treatment (ethics application number EA2/140/16). EMBs were examined via immunohistochemistry and Imaging mass spectrometry. All patients received standard heart failure medications. Paired clinical measurements were compared via paired t test for parametric data or Wilcoxon rank test for non-parametric data.

Results
Following the course of treatment, EMB ATTR-positive area measured via immunohistochemistry increased by 7.7±9.5% (p&lt;0.05). Myocardial CD3+ and CD68+ cell counts remained within normal limits. The EMB peak intensities of ATTR, collagen and macrophage migration inhibitory factor, measured via imaging mass spectrometry were increased by 23% (AUC= 0.677, p&lt;0.001), 25% (AUC= 0.620, p&lt;0.001) and 18% (AUC= 0.609, p&lt;0.001), respectively. Echocardiography measured left ventricular (LV) ejection fraction and LV end-diastolic diameter, as well as 6mwt distance, QoL and serum NT-proBNP showed no significant changes. cMRI did not show any significant changes in fibrosis/amyloidosis markers (N=9). 99mTc-DPD scintigraphy-derived Perugini score (N=10) improved by one-point in two patients and remained stable in the rest. The New York Heart Association (NYHA) functional class improved in one patient and remained stable in 10/11 patients.

Conclusion
Our findings demonstrate, for the first time, the persistence of myocardial ATTR-accumulation and remodeling despite a clinically stable disease course. Whether this finding is relevant in terms of disease-progression or indicate a need for more intensive treatment warrants further investigation.
Prognostic value of different echocardiographic and cardiac magnetic resonance parameters in patients with AL amyloidosis
Authors: Hernandez Martos A , Eiros Bachiller R , Gonzalez Calle V , Alejo Alonso E , Puig Moron N , Gallego Delgado M , Perez Sanchez P , Hernandez Hidalgo M , Mateos Manteca M V , Sanchez Fernandez P L , Villacorta Arguelles E 
Published: November 2023

Abstract

Introduction
Light chain amyloidosis (AL) is a systemic disease, highlighting its infiltration at the myocardium. Recent advances in imaging have increased the suspicion of cardiac involvement. Current risk stratification models are based exclusively on serum biomarkers.
We studied the prognostic value of echocardiographic and cardiac magnetic resonance (cMRI) parameters in a cohort of patients with a confirmed diagnosis of AL amyloidosis.

Methods
Retrospective observational study of consecutive patients diagnosed with AL amyloidosis by the Hematology Department in our center between 1999-2022. All had to have quantification of biomarkers (free light chains -dFLC-, NTpro-BNP and troponin T -TnT-) and transthoracic echocardiography (TTE) at diagnosis, collecting clinical and epidemiological characteristics and complementary tests.

Results
Of a total of 71 diagnoses of AL amyloidosis, 39 patients who met the inclusion criteria were selected, most diagnosed in the last 5 years. The mean age was 65.2 ± 12.9 years old, 56.4% male. The sample was divided according to the Mayo Clinic risk stratification model, into low (I-II, 33%) and high (III-IV, 67%) risk stages. Cardiac imaging variables were analyzed using Bootstrap statistics increasing the database to 150 patients (Table 1). Among echocardiographic variables, patients in the high-risk groups had greater systolic dysfunction of both ventricles, diastolic dysfunction, myocardial thickness, and pericardial effusion was observed more frequently. Among patients with cMRI (53.8%), we highlight the presence of an interventricular septal thickness ≥12 mm (47.6%) and a late gadolinium enhancement (LGE) in the left ventricle (66.6%, LV), most with a diffuse subendocardial pattern. In our cohort, the presence of LGE, greater maximum LV thickness, and increased LV extracellular volume (ECV) were significantly associated with the Mayo Clinic high-risk stages groups.
Finally, a global longitudinal strain &gt; -11.5% by TTE, and a T1 mapping &gt; 1042 ms or ECV &gt; 49% by cMRI, were significantly associated with a reduction in overall survival (Figure 1).

Conclusions
There are cardiac imaging variables that have prognostic implications and could have a role in risk stratification of patients with AL amyloidosis. Its inclusion in new risk stratification models along with serum biomarkers should be considered.Table 1Figure 1
Echo-derived hemodynamic categorization for risk stratification in transthyretin cardiac amyloidosis
Authors: Cantone A , Dal Passo B , Sanguettoli F , Fabbri G , Maio D , Arzenton M , Vitali M , Tolomeo P , Pavasini R , Campo G , Serenelli M 
Published: November 2023

Abstract

Background
Transthyretin cardiac amyloidosis (TTR-CA) is a rare disease characterized by the deposition of abnormal proteins in the heart, which can lead to heart failure (HF) and death. Echocardiography provides valuable diagnostic and prognostic information in CA, but indices of left ventricular performance alone cannot thoroughly characterise patients with restrictive cardiomyopathy. Evaluating the hemodynamic profile by studying the forward flow and left ventricular filling pressure (LVFP) already proved its value in stratifying disease severity in patients with heart failure (HF).

Purpose
This study evaluated the prognostic relevance of a non-invasive hemodynamic categorization of TTR-CA patients based on the estimation of stroke volume index (SVi) and systolic pulmonary artery pressure (PAPs).

Methods
Baseline clinical, transthoracic echocardiogram and laboratory data were collected prospectively in patients with diagnosed TTR-CA. Patients were classified into four groups based on forward flow (SVi &lt; or ≥30 ml/m2) and systolic pulmonary artery pressure (PAPs ≥ or &lt;40 mmHg). The four profiles obtained were Profile-A, normal-flow, normal-pressure; Profile-B, low-flow, normal-pressure; Profile-C, normal-flow, high-pressure; Profile-D, low-flow, high-pressure. We assessed the incidence of the composite endpoint of cardiovascular death and HF hospitalization accordingly to the hemodynamic profile. We performed univariate and multivariate Cox regression using profile A as a reference for HR estimation (profile A corresponding to HR=1).

Results
Fifty-nine patients were enrolled in the analysis (Table). Over a mean follow-up of 35.9 months (IQR 11.7 - 51.2 months) 23 patients met the composite endpoint (10%, 23%, 43%, 60% for Profile A, B, C and D respectively). Compared to Profile A, Profile D showed the greatest risk of CV mortality and HF hospitalization (HR 10.17), followed by Profile C (HR 6.77) and B (HR 3.45), with P-value=0.015. The C-statistic for the model was 0.72. Kaplan-Meier curves confirmed that patients with PAPs &gt;40 mmHg and SVi&lt; 30 ml/m2 presented the highest risk of the composite endpoint (Log-rank P = 0.010) (Figure). Hemodynamic profiling remained an independent predictor of outcome even after adjusting for the NAC stage (Profile B, HR 2.26; Profile C, HR 6.96; Profile D, HR 17.13; P-value=0.0012).

Conclusions
The proposed echocardiographically-derived hemodynamic classification based on forward-flow and LVFP estimation is useful for TTR-CA patients risk stratification. Patients with low SVi and high PAPs have the greatest risk of CV death and HF hospitalization, even after adjustment for NAC stage. These findings highlight the importance of early detection and monitoring of hemodynamic changes in TTR-CA patients for tailored management and to improve outcomes.Table.Figure.