bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eosinophilic granulomatosis with polyangiitis, a new recurrent feature in an extremely rare disease
Authors: Zampieri M , Beltrami M , Fumagalli C , Dei L , Urban L , Emmi G , Marchi A , Carrassa G , Chiriatti C , Tomberli A , Baldini K , Olivotto I 
Published: November 2020

Abstract

Introduction
Eosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare necrotizing vasculitis affecting small- and medium-sized vessels. EGPA may affect the heart leading to myocardial inflammation and necrosis. Although, only a few cardiological based studies have been conducted.

Purpose
This study aimed to investigate the prevalence and clinical impact of cardiac-specific involvement (CSI+) and to give an update on EGPA cardiological manifestations.

Methods
This is a single-centre study. Cardiological evaluation included ECG, blood test, echocardiography, global longitudinal strain (GLS), cardiac magnetic resonance (CMR).

Results
We prospectively enrolled 52 consecutive EGPA patients, between October 2018 and October 2019, mean age 59±3 years, 30 (57%) female. We identified 13 (25%) CSI+ patients: 6 myocarditis, 2 pericarditis, 1 coronaritis, 1 Prinzmetal angina, 2 LV apical thrombosis, 1 unexplained wall motions abnormalities (WMA) in the absence of coronary artery disease.
Twelve-leads ECG revealed abnormalities in 11 (85%) CSI+ vs 9 (23%) CSI−, p=0.0001; ECG abnormalities identified CSI+ with 85% sensitivity, 77% specificity, 94% negative predictive value.
Median troponin level in CSI+ 9 ng/L (IQR 6–11) vs CSI− 11 ng/L (IQR 6–25), p=0.2548; NT-pro-BNP value in CSI+ 210 pg/L (IQR 175–484) vs CSI− 159 ng/L (IQR 66–299), p=0.0576.
Echocardiographic left ventricular end diastolic volume in CSI+ 62±4 ml/m2 vs CSI− 52±1 ml/m2, p=0.0116; LV ejection fraction in CSI+ 57%±2 vs CSI− 66%±1, p=0.0002. In CSI+ patients GLS was −15±1 vs CSI− GLS −21±0.4, p&lt;0.0001. Echocardiography identified WMA in 8 (61%) CSI+ vs 1 (3%) CSI−. In 7 (54%) CSI+ patients, apical segments showed WMA and among them 5 demonstrated the presence of apical aneurysm.
Twelve patients underwent CMR, it showed non ischaemic late gadolinium enhancement in 7 patients; in 5 patients we identified akinetic or dyskinetic segments without associated LGE. Two patients showed LV apical thrombus.

Conclusions
EGPA showed a high prevalence of CSI. We repeatedly found a tropism for apical involvement in WMA that often manifested themselves as apical aneurysm. These may be a new clinical feature, previously not described, in such a rare condition.
Cardiac involvement EGPA

Funding Acknowledgement
Type of funding source: None
Long term outcomes in left ventricular non-compaction
Authors: Casas G , Oristrell G , Limeres J , Gutierrez Garcia-Moreno L , Barriales R , Garcia-Pavia P , Zorio E , Gimeno J.R , Villacorta E , Jimenez-Jaimez J , Ripoll T , Bayes A , Diez C , Ferreira I , Rodriguez-Palomares J.F 
Published: November 2020

Abstract

Background
Left ventricular non-compaction (LVNC) is a highly heterogeneous entity with a wide phenotypic expression. Risk factors have not been well established and prognostic stratification remains challenging.

Objectives
Describe long term outcomes of LVNC patients and determine predictors of cardiovascular events.

Methods
Prospective multicentric study of consecutive patients fulfilling imaging criteria for LVNC. Demographic, ECG, imaging and genetic variables were collected. End points were heart failure (HF), ventricular arrhythmias (VA), systemic embolisms (SE) and all-cause death. Major adverse cardiovascular event (MACE) was described as the combination of the four previous end points.

Results
592 patients from 13 referral centres were included from 2000 to 2018. Mean age at diagnosis was 45 years, 252 (43%) were female and mean LVEF was 48% (Table 1). During a median follow-up of 55 months (IQR 24–90), 144 (25%) patients presented HF, 101 (18%) VA, 27 (5%) SE and 33 (6%) died. MACE occurred in 223 (39%) patients.
In multivariate analysis, independent predictors of HF were LVEF (OR 0.9), PSAP (OR 1.17) and late gadolinium enhancement (LGE) (OR 1.3). VA were independently associated with LVEF (OR 0.97) and LGE (OR 2.51). Independent predictors of SE were LVEF (OR 0.96) and LA diameter (OR 1.07). No independent predictors of all-cause death could be described. MACE were independently associated with LVEF (OR 1.04) and PSAP (OR 1.08) (Table 1).
Among patients who underwent genetic testing (340, 57%), genotype was associated with outcomes: MYH7 and ACTC1 variants were protective while multiple mutations, TTN and MYBPC3 variants exhibited worse prognosis.

Conclusions
In a large prospective multicentric cohort of LVNC patients, there was a moderate long term incidence of cardiovascular events. LVEF and fibrosis were the main predictors and genotype was a modifier of outcomes. These factors might be used to risk stratify LVNC patients.

Funding Acknowledgement
Type of funding source: None
Clinical characteristics and natural history of PRKAG2 syndrome
Authors: Dominguez F , Lopez-Sainz A , Rocha-Lopes L , Barriales-Villa R , Climent V , Tiron C , Marques N , Rasmussen T.B , Espinosa M.A , Quarta G , Arad M , Asselbergs F , Olivotto I , Elliott P , Garcia-Pavia P 
Published: November 2020

Abstract

Purpose
Mutations in the PRKAG2 gene cause a syndrome characterized by hypertrophic cardiomyopathy, conduction disease and ventricular preexcitation. Only a small number of cases have been reported, and the natural history of the disease is poorly understood. The aim of this study is to describe phenotype and natural history of PRKAG2 mutation in a large multicenter international cohort.

Methods
We retrospectively studied clinical, electrocardiographic and echocardiographic data from 90 individuals with PRKAG2 mutations (53% males, 33±21 years) from 27 centers.

Results
At baseline evaluation, 93% of patients were in NYHA functional class I-II. Maximum left ventricular (LV) wall thickness was 18±8 mm and LV hypertrophy (LVH) was present in 60 (67%) subjects at baseline. LV ejection fraction was 61±12%. Seventeen pactients (19%) had a pacemaker (mean age at implantation 37±15and 16 (18%) had atrial fibrillation (AF) (mean age 41±23 years) and 33% had ventricular preexcitation or had undergone an accessory pathway ablation. After a median follow-up of 6 years (IQR:2.3–13.9), 71% of individuals had LVH, 29% had AF, 21% a de novo pacemaker (mean age at implantation 38±18 years), 14% required admission for heart failure (HF), 8% experienced sudden cardiac death or equivalent, 4% required a heart transplant and 13% died.

Conclusions
PRKAG2 syndrome is a severe, progressive cardiomyopathy characterized by high rates of AF, conduction disease, advanced HF and life-threatening arrhythmias. Outcome is not clearly related to the classical features of preexcitation and severe LVH, which are not always present.
Natural history of PRKAG2 syndrome

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III (ISCIII)
Gender variability in the clinical phenotype of hypertrophic cardiomyopathy
Authors: Wasserstrum Y , Larranaga-Moreira J.M , Lotan D , Fernandez-Fernandez X , Klempfner R , Sabbag A , Freimark D , Monserrat L , Arad M , Barriales-Villa R 
Published: November 2020

Abstract

Introduction
Hypertrophic cardiomyopathy (HCM) is a structural heart disease defined by an increase in left-ventricular (LV) wall thickness, that may be complicated with a clinical syndrome of heart failure, arrhythmia and death.

Purpose
To characterize the clinically significant factors for female HCM patients and bring forward the awareness to gender-based differences in HCM.

Methods
We reviewed the patient records of 1297 patients age ≥18 years, diagnosed with HCM, from two tertiary medical centers in Spain and Israel, and analyzed 748 male and female patients matched for age ≥60 years at admission, BMI, hypertension, diabetes and obstructive HCM.

Results
Female patients were older at original diagnosis [median 54 years (38–66) vs. 50 years (35–60), p=0.007], and had higher rates of family history of both HCM (46% vs. 37%, p=0.01) and sudden cardiac death (23% vs. 15%, p=0.02). Female patients had lower rates of active smoking (11% vs. 25%, p&lt;0.001) and coronary disease (3% vs. 8%, p=0.007). In echocardiographic studies, females had a smaller LV cavity both during diastole [median 42mm (39–46) vs. 46 (42–50), p&lt;0.001] and during systole [median 24 (21–29) vs. 27 (23–31), p&lt;0.001]. Female patients had higher rates of significant mitral insufficiency (37% vs. 19%, p&lt;0.001), and despite no significant differences in the rates of obstructive HCM, diastolic dysfunction, left-atrial enlargement, atrial fibrillation, ventricular tachyarrhythmia or pulmonary disease, they also had more significant pulmonary hypertension (≥45mmHg, 29% vs. 14%, p&lt;0.001). Women had a lower functional capacity (p&lt;0.001 for differences in NYHA, see fig.), and lower exercise capacity [median 7.0 METs (5–10) vs. 10.0 (7–12), p&lt;0.001) and more abnormal blood pressure response to exercise (35% vs. 26%, p=0.03). Electrocardiographic features were similar across genders, except for a non-clinically significant shorter QRS duration in females. No significant differences were seen in 5-year mortality follow-up, which was ∼3% in the entire cohort.

Conclusions
Female patients suffering from HCM have a clinical phenotype defined by slightly later presentation (and shorter time until admission to a tertiary-center cardiomyopathy clinic), smaller LV cavity size, higher severity of mitral insufficiency and pulmonary hypertension and worse functional and exercise capacities. Genders did not differ in 5-year mortality, which was relatively low.
Functional and exercise capacity

Funding Acknowledgement
Type of funding source: None
Ruling in or out the presence of cardiac amyloidosis based on cut-off values using T1-mapping – caution is required regarding the control group
Authors: Korthals D , Chatzantonis G , Bietenbeck M , Meier C , Florian A , Yilmaz A 
Published: November 2020

Abstract

Background
Cardiac amyloidosis (CA) is an infiltrative disease that is characterized by accumulation of amyloid deposits in the interstitium of the myocardium. In contrast, hypertrophic cardiomyopathy (HCM) is caused by a disorganized arrangement of myocyte hypertrophy as well as expanded extracellular matrix, composed of interstitial and replacement fibrosis.

Purpose
A diagnostic algorithm based on (native) T1-mapping using cardiovascular magnetic resonance (CMR) was suggested in a recent study for the diagnosis of CA: A native T1 &lt;1,036ms was mentioned to have a 98% negative predictive value (NPV) for ruling out CA whereas a native T1 &gt;1,164ms showed a 98% positive predictive value (PPV) for the presence of CA. In the present study, we critically addressed the calculation of such cut-off values considering possible differences in the composition of the control group.

Methods
N=30 patients with CA, N=20 patients with HCM and N=15 healthy controls without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised standard sequences for cine-imaging, native and post-contrast MOLLI-based T1-mapping and late-gadolinium-enhancement (LGE). ECV measurements were based on pre- and post-contrast T1-mapping images.

Results
Native T1 and ECV were significantly increased in CA compared to HCM and receiver operating characteristic (ROC) analyses revealed an area-under-the-curve (AUC) = 0.984 for native T1 (p&lt;0.001) and AUC = 0.985 for ECV (p&lt;0.001) regarding the diagnosis of CA). When CA patients were compared to HCM patients (excluding healthy controls), a native T1 &lt;1,036ms or an ECV &lt;33% were associated with a 99% NPV for ruling out CA whereas a native T1 ≥1,082ms or an ECV ≥41% were associated with a 99% PPV for diagnosis of CA. However, when CA patients were compared to healthy controls (excluding HCM patients), a native T1 &lt;1,025ms or an ECV &lt;34% were associated with a 99% NPV for ruling out CA whereas a native T1 ≥1,025ms or an ECV ≥34% were associated with a 99% PPV for diagnosis of CA since there was no overlap in native T1 and ECV values between CA patients and healthy controls.

Conclusion
Cut-off values for native T1 or ECV derived from ROC analyses (in a specific group of study patients) for ruling in or out the presence of CA are – amongst others - determined by the native T1 and ECV values of the respective “control group”. A different composition of the control group (e.g. HCM patients vs. healthy volunteers) will result in different cut-off values. Hence, previously suggested cut-off values obtained in single center studies need to be considered carefully – with a special attention to the control group of the underlying study – and should not be transferred to other centers carelessly.

Funding Acknowledgement
Type of funding source: None
Long-term integrated safety of patisiran in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy
Authors: Gillmore J , Berk J , Dispenzieri A , Polydefkis M , Gonzalez-Duarte A , Sekijima Y , Sweetser M.T , Arum S , Wang J.J , White M.T , Maurer M 
Published: November 2020

Abstract

Background/Introduction
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, life-threatening disease; the majority of patients develop a mixed phenotype of polyneuropathy and cardiomyopathy. Patisiran halted or reversed polyneuropathy and improved quality of life in the Phase 3 (APOLLO) study. In a prespecified cardiac subpopulation of APOLLO, patisiran also improved cardiac structure and function versus placebo.

Purpose
To describe the long-term comprehensive, integrated safety data from the patisiran clinical development program in patients with hATTR amyloidosis with polyneuropathy.

Methods
Safety data as of October 7, 2019 from the Phase 2 Open-Label Extension (OLE) (NCT01961921), Phase 3 APOLLO (NCT01960348), and ongoing Global OLE (NCT02510261) studies were analysed.

Results
Across the three studies, 224 patients received patisiran for a mean (range) of 43.6 (0.7–71.7) months, with a cumulative 813.9 patient-years of exposure; 105 (46.9%) patients received patisiran for ≥4 years and 35 (15.6%) patients received patisiran for ≥5 years. In this cohort, 149 (66.5%) had medical histories of cardiac disorders per MedDRA System Organ Class (SOC), which may be reflective of a mixed phenotype in some patients. A total of 222 (99.1%) patients experienced at least one adverse event (AE) and 132 (58.9%) patients experienced at least one serious AE. AEs considered to be related to patisiran and occurring in &gt;5% of patients included infusion-related reactions (IRRs) (25.9%) and diarrhoea (6.3%). Cardiac AEs occurring in &gt;5% of patients included atrial fibrillation (10.7%) and cardiac failure (7.6%). Amongst all patients, the exposure-adjusted mortality rate was 4.3 deaths per 100 patient-years.

Conclusions
Patients with hATTR amyloidosis with polyneuropathy in the patisiran clinical development program represent those with the longest treatment with an RNAi therapeutic, including more than 15% of patients receiving patisiran for ≥5 years. Patisiran continues to demonstrate a positive benefit:risk profile in patients with hATTR amyloidosis with polyneuropathy.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Alnylam Pharmaceuticals
Family screening in patients with isolated bicuspid aortic valve in a general hospital, yield and subgroup analysis
Authors: Cozijnsen L , Braam R.L , Bakker-De Boo M , Otten A.M , Post J.G , Schermer T , Bouma B.J , Mulder B.J.M 
Published: November 2020

Abstract

Background
Bicuspid aortic valve (BAV) may frequently lead to aortic dilatation with risk of aortic dissection. In patients with BAV both familial clustering and aortic dilatation in first-degree relatives (FDR) without BAV has been demonstrated. Based on these findings the ESC Aortic Guidelines recommend to consider screening of FDR, while the ACC/AHA Guidelines on Valvular Heart Diseases consider screening of FDR only if the index patient has associated aortopathy. Currently, no data about the effectiveness of screening is available.

Purpose
To investigate the yield of screening FDR of patients with isolated BAV and to explore subgroups with FDR of patients who had needed surgery or of patients with aortic dilatation. We hypothesized that aortic dilatation (&gt;40mm) in the index patient is not a risk factor for BAV in FDR.

Methods
From 2012, patients with BAV visiting the outpatient clinic of a teaching hospital, received information advising cardiac screening of FDR. FDR of patients with isolated BAV who were referred, were included. From the 10 index patients from other hospitals, information was retrieved. [Fig.1]

Results
Referred were FDR from 118 index patients (mean age 60 years, standard deviation [SD] 14, range 15–90 years, 82 males [70%]). Of all index patients 63 (53%) had undergone aortic valve replacement, including concomitant ascending aorta replacement in 25 (21%). In the non-operated index patients, 31 (26%) had dilatation (&gt;40mm) of sinus of Valsalva and/or tubular ascending aorta.
Screened were 257 FDR (median 2 per index patient) comprising 20 parents (8%), 103 siblings (40%) and 134 offspring (52%). Mean age of FDR was 48 years (SD16, range 4–83 years) and 89 subjects (42%) were male. The diagnostic imaging modality was echocardiography in 240 cases (93%) and MRI in 17 cases. Ten FDR had an already known BAV and were not included in the screening.
Among the 257 FDR, we diagnosed 12 new BAV (4.7%, 95% confidence interval [CI]2.9–8.0%) (mean age 44 years, 50% male). Additionally, we diagnosed 23 new isolated aorta dilatations (8.9%; 95% CI 6.0–13%) at level of sinus of Valsalva and/or tubular ascending aorta (mean age 57 years, 18 [78%] were male) [Fig. 1]. Among them, 11 had hypertension.
FDR (n=147) of index patients with BAV and previous aortic valve surgery (n=63), had a risk ratio (RR) of 2.25 (95% CI 0.62–8.10) of having a BAV. FDR (n=126) of index patients with BAV and repaired or unrepaired aortic dilatation (n=56) had RR 0.35 (95% CI 0.10–1.25) of having a BAV.

Conclusions
Screening FDR of patients with isolated BAV resulted in a reasonable yield of 14% new cases with BAV or isolated aortic dilatation. The RR of the subgroup with aorta dilatation did not justify the limitation of the FDR as suggested in the ACC/AHA Guidelines.
Figure 1. Flowchart of screening and result

Funding Acknowledgement
Type of funding source: None
Risk of infective endocarditis among patients with tetralogy of fallot
Authors: Havers-Borgersen E , Butt J.H , Groening M , Smerup M , Gislason G.H , Torp-Pedersen C , Soendergaard L , Koeber L , Fosboel E.L 
Published: November 2020

Abstract

Introduction
Patients with tetralogy of Fallot (ToF) are considered at high risk of infective endocarditis (IE) as a result of altered hemodynamics and multiple surgical and interventional procedures including pulmonary valve replacement (PVR). The overall survival of patients with ToF has increased in recent years. However, data on the risk of adverse outcomes including IE are sparse.

Purpose
To investigate the risk of IE in patients with ToF compared with controls from the background population.

Methods
In this nationwide observational cohort study, all patients with ToF born in 1977–2017 were identified using Danish nationwide registries and followed from date of birth until occurrence of an outcome of interest (i.e. first-time IE), death, or end of study (July 31, 2017). The comparative risk of IE among ToF patients versus age- and sex-matched controls from the background population was assessed.

Results
A total of 1,156 patients with ToF were identified and matched with 4,624 controls from the background population. Among patients with ToF, 266 (23.0%) underwent PVR during follow-up. During a median follow-up time of 20.4 years, 38 (3.3%) patients and 1 (0.03%) control were admitted with IE. The median time from date of birth to IE was 10.8 years (25th-75th percentile 2.8–20.9 years). The incidence rates of IE per 1,000 person-years were 2.2 (95% confidence interval (CI) 1.6–3.0) and 0.01 (95% CI 0.0001–0.1) among patients and controls, respectively. In multivariable Cox regression models, in which age, sex, pulmonary valve replacement, and relevant comorbidities (i.e. chronic renal failure, diabetes mellitus, presence of cardiac implantable electronic devices, other valve surgeries), were included as time-varying coefficients, the risk of IE was significantly higher among patients compared with controls (HR 171.5, 95% CI 23.2–1266.7). Moreover, PVR was associated with an increased risk of IE (HR 3.4, 95% CI 1.4–8.2).

Conclusions
Patients with ToF have a substantial risk of IE and the risk is significantly higher compared with the background population. In particular, PVR was associated with an increased risk of IE. With an increasing life-expectancy of these patients, intensified awareness, preventive measures, and surveillance of this patient group are advisable.
Figure 1. Cumulative incidence of IE

Funding Acknowledgement
Type of funding source: None
Right ventricle function longitudinal evaluation after norwood procedure: comparison between right ventricle-pulmonary artery shunt and blalock-taussing shunt
Authors: Borrelli N , Sabatino J , Avesani M , Josen M , Fraisse A , Guccione P , Michielon G , Di Salvo G 
Published: November 2020

Abstract

Background
Norwood procedure represents the first of three surgical steps toward Hypoplastic left heart syndrome (HLHS) complete palliation. Two are the main surgical techniques allowing the reconstruction of Norwood circulation: the right ventricle-pulmonary artery shunt (RVPAS) and the modified Blalock-Taussing shunt (mBTS). However, still little is known about the impact on right ventricle (RV) function of the required ventriculotomy for the RVPAS.

Purpose
The aim of the study was to investigate the changes in RV function in HLHS patients after RVPAS vs mBTS.

Methods
The cohort included 27 consecutive HLHS patients (10 in the modified Blalock-Taussig shunt group and 17 in the RVPAS group) who successfully underwent Norwood procedure in a single tertiary paediatric cardiology centre. Longitudinal strain (LS) and strain rate (LSR), tricuspid annulus peak systolic excursion (TAPSE) and fractional area change (FAC) were evaluated in all patients before Norwood and in three different breakpoints in the steady state after Norwood procedure (30 days after Norwood, 90 days after Norwood, 140 days after Norwood).

Results
Ventricular loading conditions (diuretic treatment, blood pressure and tricuspid regurgitation) were similar in both groups. No significant differences were found at different time points between RVPAS and mBTS group in terms of LS, LSR, TAPSE and FAC. However, when we compared RV function before and after Norwood procedure, 90 days after the procedure, patients who did not undergo RV ventriculotomy (mBTS group) showed significant improvement in LS compared to pre-surgical assessment (mBTS: +27.35±43.47% vs RVPAS: −8,20±25.25%, p=0,03). This finding was consistent but no longer statistically significant at 140 days after Norwood (mBTS: +13.81±21.99% vs RVPAS: −4.90±27.97%, p=0,12).

Conclusion
After Norwood procedure mBTS patients showed a significant increase in LS when compared with patients who underwent RVPAS. This finding was consistent but no longer significant at 140 days after Norwood probably because the number of patients was too small to reach a significant level. These data support the use of LS in HLHS patient's evaluation and may be of value to find a patient-tailored timing for the second surgical stage.
TAPSE, FAC, LS and LSR trends

Funding Acknowledgement
Type of funding source: None