bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac sympathetic denervation in wild-type transthyretin amyloidosis
Authors: Aimo A , Gimelli A , Vergaro G , Genovesi D , Kusch A , Emdin M , Marzullo P 
Published: November 2020

Abstract

Background
Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt.

Methods
Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years, no one with prior myocardial infarction) underwent Cadmium Zinc Telluride tomographic imaging for amyloid burden (99mTc-hydroxymethylene diphosphonate - 99mTc-HMDP), innervation (123I-metaiodobenzylguanidine – 123I-MIBG), and perfusion (99mTc-tetrofosmin).

Results
Median summed 99mTc-HMDP score was 60 (58–62), denoting a severe and diffuse amyloid burden. Planar 123I-MIBG examination showed decreased early and late H/M ratios (late H/M ratio: 1.5 [1.3–1.6], range 1.2–1.9, reference value ≥2.0). Summed 123I-MIBG score was 12 (6–22), with the most prominent denervation in the infero-septal, inferior, and infero-lateral regions; summed rest score was 7 (5–11), with lowest degrees of myocardial perfusion in the inferior and infero-septal regions. The correlation between amyloid burden (as relative 99mTc-HMDP uptake) and innervation (as relative 123I-MIBG uptake) did not achieve statistical significance at both segmental (p=0.252) and regional level (p=0.251). Nevertheless, denervation tended to worsen in parallel with the amyloid burden, and 123I-MIBG scores increased with 99mTc-HMDP scores. Segments and regions with more prominent hypoperfusion were those showing the more intense denervation (r=0.500 and 0.591, respectively; both p&lt;0.001).

Conclusions
Patients with ATTRwt cardiomyopathy display cardiac sympathetic denervation, particularly in the inferior and septal myocardial wall. Myocardial hypoperfusion has a similar regional pattern, while the amyloid burden is more extensive.

Funding Acknowledgement
Type of funding source: None
Comparing machine learning approaches to identify myocardial scar from the ECG
Authors: Tung J , Rogers A.J , Ravi N , Bhatia N.K , Shah R.L , Purewal S.K , Baykaner T , Rappel W.J , Viswanathan M.N , Brodt C.R , Wang P.J , Clifford G , Tereshchenko L , Narayan S.M 
Published: November 2020

Abstract

Background
Detection of myocardial infarction (MI) traditionally requires ECG Q waves, which have poor sensitivity, or imaging, which is time consuming. We hypothesized that machine learning (ML) of the ECG could identify prior MI, but its accuracy may depend highly upon the architecture and parameters chosen.

Purpose
To compare ML architectures that predict prior MI from the ECG.

Methods
We curated ECGs in 608 patients seen in cardiology clinics at 2 centers. We transformed 12-lead ECGs to median beats in Frank (X, Y, Z) planes (fig. A). We tested 3 architectures: a 1D deep neural network (DNN), a 3D neural network, and a support vector machine (SVM). The 1D DNN used only temporal convolutions (fig B) while the 3D DNN uses a spatial convolution (fig C) prior to the fully-connected layer (fig. C). Predictive accuracy for history of MI was compared for all architectures (fig. D).

Results
Patients (61.4±14.5 years, 31.2% female) had a 28.7% (175/608) prevalence of prior MI. Optimized SVM of 6 features provided accuracy of 66.1% for identifying prior MI, similar to ECG Q wave analysis. 1D DDN had accuracy of 63.6% with an area under curve (AUC) of 0.625. 3D DNN outperformed 1D DNN and SVM, providing an accuracy of 71±5% (using k=5-fold cross validation), with an AUC of 0.730.

Conclusion
ECG machine learning can identify prior MI better than Q wave analysis, but is sensitive to technical parameters and specific computational architecture. It is important to develop a framework to enable robust comparisons of different ML studies and future refinements.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health - United States
Immunosuppression and outcomes of myocarditis patients presenting with ventricular arrhythmias
Authors: Peretto G , Sala S , De Luca G , Marcolongo R , Campochiaro C , Tresoldi M , Foppoli L , Palmisano A , Esposito A , De Cobelli F , Rizzo S , Thiene G , Basso C , Caforio A.L.P , Della Bella P 
Published: November 2020

Abstract

Background
Effects of immunosuppressive therapy (IST) on ventricular arrhythmias (VA) have not been reported in immune-mediated biopsy-proven myocarditis patients. Furthermore, myocarditis arrhythmic risk is still unpredictable. The aim of our study was to evaluate effectiveness of IST on VA in myocarditis patients, and stratify their arrhythmic risk, using clinical and diagnostic features, including serum organ-specific anti-heart (AHA) and antiintercalated-disk autoantibodies (AIDA).

Methods
From a cohort of 498 consecutive patients, we enrolled 255 cases with biopsy-proven virus-negative myocarditis and evidence of VA (VF, VT, NSVT, and Lown's grade ≥2 PVC) at index hospitalization. Serum AHA and AIDA were detected by a standardised indirect immunofluorescence technique. Whenever accepted and non-contraindicated, IST was started. Controls (IST-) were chosen after 1:1 matching to IST+ cases by age, gender, ethnicity, left ventricular ejection fraction, VA type, and treatment. Prospective follow-up (FU), occurred at defined timepoints.

Results
58 matched patient couples (42±13 y, 67% males, 50% IST+) were analyzed in the main study cohort. Overall, 28 (24%) had VT, and 62 (53%) were discharged with ICD. IST duration was 12±1 months. No patients died and no serious complications from IST occurred. By 24-month FU, major VA occurred in 6 IST+ vs. 10 IST- patients (p=0.420), with no cases of VT following IST termination. As compared to IST- ones, IST+ patients showed a significant reduction in NSVT and PVC burden, as well as an improvement in clinical, laboratory and imaging findings (all p&lt;0.05). Major VA onset and positive AIDA status were independently associated with major VA at FU (HR 14.2, 95% CI 2.9–68.7, and 8.0, 95% CI 2.6–25.2, respectively, both p&lt;0.001). Furthermore, in the whole study population (N=255), IST played as an independent protective factor from major VA (HR 0.3, 95% CI 0.2–0.7, p=0.005) at 38±21 months FU.

Conclusions
In immune-mediated virus-negative myocarditis patients presenting with VA, IST is feasible and effective on NSVT and PVC burden, as well as on structural, laboratory and imaging endpoints. Short-term effects are limited on major VA, which were independently associated with major arrhythmic onset and positive AIDA, in keeping with the proposed etiopathogenetic involvement of autoimmunity in virus-negative myocarditis.

Funding Acknowledgement
Type of funding source: None
Predictors of atrial fibrillation occurrence in patients with hypertrophic cardiomyopathy
Authors: Castelo A , Rosa S , Fiarresga A , Marques H , Portugal G , Cunha P , Ferreira V , Bras P , Goncalves A , Oliveira M , Ferreira R 
Published: November 2020

Abstract

Introduction
Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of dysrhythmias, especially atrial fibrillation (AF).

Purpose
The aim of this study was to evaluate the incidence of AF in HCM patients (P) and to determine predictors of AF.

Methods
Retrospective analysis of HCM P at a single tertiary center. Baseline clinical, echocardiographic and cardiovascular magnetic resonance (CMR) characteristics were collected. On follow up AF was identified by electrocardiogram and/or 24 hours Holter monitoring.

Results
61P (59% male) were included, with a mean age of 58±2 years. 27.9% had angina (all of them CCS 2), 34.4% were in NYHA II and 14.8% in NYHA III, 8.2% had syncope and 39.3% had palpitations. A family history of sudden cardiac death (SCD) or cardiomyopathy was present in 40.4% of the cases. The mean HCM risk SCD score was 3.35±0.28%. On echocardiography left atrium (LA) diameter was 44.86±0.87mm, LA volume (LAvol) was 89.97±5.39mL (indexed LAvol 46.05±2.55mL/m2), interventricular septum (IVS) was 16.83±0.663mm, left ventricle (LV) mass was 290.94±13.897g and maximum wall thickness (MWT) was 20.59±0.596mm. 77% P had LA enlargement. 88.5%P had late gadolinium enhancement (LGE) in CMR with a median number of 5±7 segments involved. AF developed in 23P (37.7%), with a mean age of 58±3 years. Predictors of AF development were NYHA III (p=0.007), risk score (p=0.007), LA diameter (p=0.007), LAvol (p=0.005) and indexed LAvol (p=0.002), MWT (p=0.0015), LGE in more than 5 segments (p=0.029) and LGE in the inferior basal and inferior median IVS (p=0.033 and p=0.042). The only independent predictor was LAvol (p=0.0012), with an area under the curve of 0.755 and a cut off of 85.9mL being the best predictor (p=0.004). Combining LAvol &gt;85.9mL with LGE involving &gt;5 segments and LAvol &gt;85.9mL with LGE in inferior basal IVS (IBIVS) a statistically significant difference between groups was achieved (p=0.009 in the combined predictor LAvol + LGE &gt;5 segments and p=0.002 in the combined predictor LAvol + LGE in IBIVS) (figure 1 and figure 2). In a multivariable analysis including these 2 combined predictors and LAvol alone the only independent predictor was the combination of LAvol + IBIVS involvement.

Conclusion
AF is frequent in patients with HCM and develops in younger ages than in general population. NYHA III, risk score, LA diameter, LAvol, MWT, LGE &gt;5 segments and LGE in IBIVS and in IMIVS were predictors of AF, with LAvol being the independent predictor. The combination of LAvol with LGE &gt;5 segments and LAvol with LGE in IBIVS presented stronger predictor value comparing with these characteristics alone.

Funding Acknowledgement
Type of funding source: None
Prevalence of device-detected atrial fibrillation and stroke in patients with hypertrophic cardiomyopathy
Authors: Fumagalli C , Ruggieri R , De Filippo V , Cappelli F , Beltrami M , Bertini A , Carrassa G , Marchi A , Tomberli A , Baldini K , Olivotto I 
Published: November 2020

Abstract

Introduction
Atrial fibrillation (AF) is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and is associated with adverse outcome, impaired quality of life, loss of productivity, and the risk for embolic stroke. However, still today, the real burden of AF is unresolved due to the unknown frequency of silent asymptomatic episodes.

Purpose
To assess the prevalence of device-detected AF and stroke in patients with HCM implanted with cardiac implantable electronic devices (CIEDs) at our institution, a long-standing high flow referral center for cardiomyopathies.

Methods
Clinical and instrumental data of HCM patients implanted with CIEDs (either pacemakers [PM] or implantable cardioverter defibrillator [ICD]) from 1998 to 2019 were retrospectively reviewed. Inclusion criteria were site-designated diagnosis of HCM, age at diagnosis &gt;18 years, &gt;1 follow up visit, follow up &gt;1 year. HCM phenocopies (e.g. Fabry disease) were carefully excluded.
Patients were divided into three categories according to presence of AF (“AF prior to CIED implantation” vs “AF after CIED implantation” vs “no arrhythmia detected”). Outcome was measured against prevalence of thromboembolic events (stroke or transient ischemic attack [TIA]) at follow up. All-cause and cardiovascular (CV) mortality were also assessed.

Results
A total of 255 patients received a CIED (57% men, mean age at implantation 54±17 years). Men were younger at implantation (52±17 vs 56±18 years, p=0.022). At baseline, AF was present in 90 (35.3%) patients.
During 5.0±4.1 years, de novo AF was detected in 30 (11.8%) individuals, resulting in an annual incidence rate of 6.1%/year. Overall, 135 (52.9%) of patients remained is sinus rhythm.
Stroke/TIAs were reported in 30 (11.8%) patients: 16 (53.3%) occurred in patients with prior history of AF, 3 (10%) in patients with de novo AF (with men being at higher risk, OR 3.73, 95% CI 1.88–6.09, p=0.041), and 11 (36.7%) in patients with no history of arrhythmias.
Long term, 45 (17.6%) patients died (CV mortality N=38, 14.9%). At multivariable analysis, history of stroke was directly related to all-cause mortality irrespective of AF in men (OR 4.15, 95% CI 1.35–12.77, p=0.018) but not in women (OR 0.891, 95% CI 0.17–4.64, p=0.801).

Conclusions
In a large cohort of consecutive high risk HCM patients referred to CIED implantation, the incidence of de-novo AF was high. Thromboembolic events were associated to worse outcome only in men, likely due to competing heart failure related causes in women. Strategies promoting early identification of AF and anticoagulation may play an important role in management and prevention of disease-related complications.
Prevalence of AF and Stroke

Funding Acknowledgement
Type of funding source: None
Phenotype and clinical outcomes of dystrophin associated dilated cardiomyopathy
Authors: Restrepo Cordoba M.A , Wahbi K , Florian A , Mogensen J , Jimenez-Jaimez J , Climent-Paya V , Politano L , Garcia-Alvarez A , Arad M , Barriales-Villa R , Kubanek M , Lopes L.R , Jurcut R , Hazebroek M.R , Garcia-Pavia P 
Published: November 2020

Abstract

Background
Mutations in dystrophin gene (DMD) can cause skeletal myopathy and dilated cardiomyopathy (DCM) independently or in combination. Natural history of DMD mutation carriers and dystrophin-associated DCM is poorly understood.

Objectives
This study sought to describe phenotype and prognosis of DMD mutations in a large multicenter cohort of Non-Duchenne DMD mutations carriers.

Methods
The study cohort comprised 223 individuals with a DMD mutation (83% males, 33±15 years at first evaluation) followed at 26 European centers. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, heart transplant, LVAD implantation, aborted SCD or appropriate ICD shock.

Results
At initial evaluation, 85 patients (38%) had DCM (52 in combination with muscular disease) and 92 (41%) had isolated muscular disease. After a median follow-up of 96 months, 112 individuals (53%) had DCM and 20% of the individuals who had normal cardiac function at baseline developed DCM. DCM penetrance by age 30 was 56%. DCM onset was associated with male sex and was independent of the type of mutation, the presence of skeletal myopathy or serum creatine kinase levels. MACE occurred in 11% and 22% individuals from the entire cohort and with DCM respectively, and were more frequent in DCM patients without muscular disease than in those with skeletal myopathy (35.5% vs 17.7%; p=0.04). Among patients with DCM, 18% developed end-stage heart failure and 9% a major arrhythmic event (SCD/aborted SCD/ICD shock/VT). There were not differences in survival between patients with isolated DCM and those with DCM and muscular phenotype. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Atrial fibrillation and neurological events were also frequent. Prognosis of individuals who did not develop DCM was good with 96% survival during follow-up.

Conclusions
DCM caused by mutations in DMD is characterized by moderate penetrance but a high risk of MACE, progression to end-stage heart failure and ventricular arrythmias. DCM onset is the major determinant of prognosis in DMD mutation carriers with similar survival irrespectively of the presence of concomitant muscular disease.
Survival free of MACE analysis

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III. Contratos i-PFIS: Doctorados IIS-empresa en Ciencias y Tecnologías de la Salud
A clinical and instrumental study of heart failure in amyloidotic cardiomyopathy
Authors: Caponetti A.G , Longhi S , Saturi G , Ponziani A , Sguazzotti M , Massa P , Milandri A , Salvi F , Biagini E , Rapezzi C , Galie' N , Gagliardi C 
Published: November 2020

Abstract

Background
Heart failure (HF) is one of the main features of amyloidotic cardiomyopathy (AC) and it is supposed to carry important prognostic implications. Despite the intrinsic etiologic heterogeneity of AC, HF has been mainly attributed to diastolic dysfunction, but the role played by the different amyloid subtypes of AC and by the clinical and hemodynamic factors in the pathophysiology of HF remains unclear.

Objectives
We aimed to assess the hemodynamic profile and outcome of patients with or without advanced HF (defined as NYHA class III-IV) at the time of first evaluation in light-chain (AL), hereditary transthyretin-related (h-ATTR) and non-mutant transthyretin-related (wt-ATTR) AC.

Methods
Among the 411 patients diagnosed with AC (156 AL, 131 h-ATTR, 124 wt-ATTR) at our Centre between 1990–2019, we analyzed central hemodynamic data, echocardiographic, clinical, ECG details and survival of the whole cohort. Cox regression analysis was used to stratify prognosis.

Results
112 (27%) patients presented advanced HF at first evaluation and frequently showed severe symmetric left ventricle wall thickening (higher values in h-ATTR), non-dilated left ventricle, preserved ejection fraction and pathological global longitudinal strain and/or myocardial contraction fraction.
At ECG, a significantly lower QRS voltage was present in advanced HF patients. Hemodynamically, elevated filing pressures on both cardiac sides were present in patients in NYHA III-IV class of the three etiologies. Overall survival at 2 years was 35% for AL, 83% for h-ATTR, 65% for wt-TTR. H-ATTR and wt-TTR were favorable predictors of survival, while reduced cardiac index and elevated filling pressures were indepedently associated with higher mortality.

Conclusions
The characterization of hemodynamic profile plays a central role in predicting the natural history of AC, since reduced stroke volume and elevated filling pressures are the best predictors of mortality, reflecting a physiopathological restrictive model of the disease. Conversely, left ventricular ejection fraction is rarely abnormal and it is not a reliable marker of poor prognosis, especially in the early stages of the disease. AL amyloidosis shows the worst outcome probably due to a combination of the underlying illness and light chains cardiotoxicity.
LVEF and cardiac index in HF

Funding Acknowledgement
Type of funding source: None
Interleukin-1 blockade in patients with pericardial constriction
Authors: Andreis A , Imazio M , Brucato A , De Ferrari G.M , Rinaldi M , Adler Y 
Published: November 2020

Abstract

Background
Recurrent pericarditis is very difficult to treat, especially when symptoms become refractory to conventional treatments (nonsteroidal anti-inflammatory drugs,colchicine,corticosteroids). Interleukin-1 (IL-1) blockade with anakinra has been proved to be useful in this setting. Indeed, persistent inflammation of the pericardium may lead to pericardial constriction, worsening prognosis.

Purpose
This study was aimed to assess the incidence and clinical course of pericardial constriction in patients with corticosteroid-dependent, colchicine-resistant recurrent pericarditis (CCRP) undergoing anti IL-1 treatment.

Methods
We selected patients included in the IRAP (International Registry of Anakinra for Pericarditis). A subgroup of 39 CCRP patients enrolled at the coordinating center underwent echocardiographic and clinical assessment for pericardial constriction.

Results
Thirty-nine patients were assessed, aged 42±12 years old, 67% females, 74% idiopathic etiology, with a median disease duration of 12 months (IQR 9–20) and a recurrence rate of 2.79 flares-patient/year before starting anakinra. Echocardiographic signs of pericardial constriction were demonstrated in 8 patients (21%). After starting anakinra, in 5/8 patients (63%) a complete resolution of pericardial constriction was observed within a median of 1.2 months,IQR 1–4. In other 3/8 patients (37%) pericardial constriction persisted and became chronic, requiring pericardiectomy within a median of 2.8 months, IQR 2–5.
Compared with others, the 8 patients with pericardial constriction hadn't had a greater burden of pericardial flares before anakinra (3.87 flares-patient/year vs. 2.62/patient-year, p=0.07) and after anakinra (0.71 flares-patient/year vs. 0.72/patient-year, p=0.99). However, among 11 patients (28%) with incessant symptoms, an higher incidence of pericardial constriction was observed, compared with patients with recurrent symptoms (respectively 64% vs. 3.6%, RR=47, 95% CI 4.5–492, p&lt;0.01).

Conclusions
In CCRP patients, pericardial constriction may be reversed by anti IL-1 agents. The risk of pericardial constriction is associated with incessant symptoms rather than simple recurrent course.

Funding Acknowledgement
Type of funding source: None
Outcomes in patients with cardiac masses: the underestimated burden of pseudotumours
Authors: Paolisso P , Foa' A , D'Angelo E.C , Saturi G , Bergamaschi L , Toniolo S , Magnani I , Bartoli L , Angeli F , Donati F , Stefanizzi A , Rinaldi A , Pacini D , Pizzi C , Galie' N 
Published: November 2020

Abstract

Background
Cardiac masses (CMs) include benign and malignant formations. So far, clinical presentation and prognosis have been reported only in small series without discriminating between subtypes. We investigated the clinical presentation and long-term prognosis of patients with cardiac masses stratifying our results according to the lesions' nature.

Methods
We enrolled all consecutive patients admitted to our Institution between 1999 and 2018 with imaging evidence of CMs. Definitive diagnosis was achieved by histologic examination or by radiological evidence of thrombotic resolution after anticoagulant treatment. The study population was classified as benign or malignant and subsequently into 4 subtypes: pseudo-tumours, primary benign tumours, primary malignant tumours and secondary tumours. Cardiovascular and non-cardiovascular mortality was described.

Results
We identified 172 patients with CMs, 125 benign and 47 malignant. Benign lesions were often incidentally diagnosed in the left heart chambers whereas malignancies were usually detected in the pericardium and right sections, resulting in more advanced symptoms. Over time – median follow-up of 48 months - survival of patients with benign formations was three-fold greater than patients with malignancies (p&lt;0.001) with no differences in cardiovascular mortality. Patients with pseudo-tumours showed a significantly lower survival than primary benign tumours (p=0.018) while no difference was found within the malignant stratum between primary and secondary neoplasms.

Conclusions
CMs are a heterogeneous entity where advanced symptoms and a pericardial involvement suggest malignant forms, which exhibit a poor outcome. Among patients with benign lesions, pseudo-tumours were associated with reduced survival, supposedly as a consequence of the different underlying conditions.

Funding Acknowledgement
Type of funding source: None