bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term prognosis of patients with Perugini Grade 1 cardiac scintigraphy score
Authors: Itzhaki Ben Zadok O , Rhurman Shahar N , Vaturi M , Kandinov I , Kornowski R , Hamdan A 
Published: October 2022

Abstract

Background
A Perugini Grade 1 myocardial uptake on amyloid cardiac scintigraphy does not establish the diagnosis of amyloid transthyretin cardiomyopathy (ATTR-CA), and according to current position papers mandates an endomyocardial biopsy to rule in or rule out ATTR-CA. We aimed to investigate whether Perugini Grade 1 reflects an early stage of ATTR-CA or a false positive result thus obliviating the need for further evaluation.

Methods
Study population was comprised of consecutive ≥70 years old patients who underwent a baseline cardiac scintigraphy scan for the presumed diagnosis of ATTR-CA at our institution between the years 2017–2020 and had a Perugini Grade 1 score. Patients with Perugini Grade 2 or 3 comprised our control group. At the beginning of 2022, Perugini Grade 1 patients prospectively underwent a repeat follow-up evaluation which included clinical examination, echocardiography with strain parameters, cardiac biomarkers measurement and cardiac scintigraphy. Cardiac magnetic resonance (CMR) and genetic testing for ATTR-CA mutations were analyzed as well.

Preliminary results
Fifty patients were included in the baseline study cohort, of whom 44% (n=22) were females. A carpal tunnel syndrome history was present in 10 patients (20%). Baseline troponin T and NT pro-BNP levels were 23 (IQR 14,39) and 1557 (IQR 237, 5746) ng/L, respectively. Wall thickness by echocardiography was 12 (11, 15) mm and 8 patients (16%) had severe mitral annulus calcification. Left ventricular ejection fraction (LVEF) was 60 (IQR 50, 60)%. At a median follow-up of 31 (20, 35) months, 7 patients (14%) were diagnosed with plasma-cell dyscrasias and 6 patients (12%) were hospitalized for heart failure exacerbations. Follow-up troponin T and NT pro-BNP levels were 27 (IQR 21,46) pg/ml and 1158 (IQR 434, 7249) ng/L, respectively (p=NS compared to baseline). Wall thickness by echocardiography was 12 (12, 15) mm and LVEF was 60 (IQR 50, 60)% (p=NS compared to baseline). Follow-up cardiac scintigraphy demonstrated Perugini Grade 1 in all re-tested patients. Two patients and 14 patients (32% total) underwent an endomyocardial biopsy or CMR, respectively, for a definitive diagnosis. All 16 tests were incompatible with amyloid cardiomyopathy. Genetic data results will be added. All-cause survival was similar between patients with Perugini Grade 1 versus Grades 2 and 3 (log rank p=0.103).

Conclusion
At long-term follow-up, Perugini Grade 1 patients do not demonstrate progression of laboratory or imaging amyloid characteristics. This suggests that Perugini grade 1 reflects a false positive result for ATTR-CA rather than an early stage in the disease. Larger-scale data should further question the need for an endomyocardial biopsy in these patients.

Funding Acknowledgement
Type of funding sources: None.
Genetic and clinical characteristics of transthyretin cardiac amyloidosis in Koreans
Authors: Jeon K , Kim D , Choi J O , Kim K H , Park M S , Jeon E S 
Published: October 2022

Abstract

Background/Introduction
Transthyretin amyloidosis with mutations (aTTRv amyloidosis) have over 100 recognized pathogenic mutations of the TTR gene and its clinical manifestations are very heterogenous. Through the global THAOS (Transthyretin Amyloidosis Outcomes Survey) patient registry, different and several types of mutants and clinical differences have been identified. Awareness of aTTRv amyloidosis is now becoming somewhat significant amongst physicians all over the world. This is a detailed look at such efforts in Korea.

Purpose
We aimed to seek the geologic significance of aTTRv amyloidosis in South Korea.

Methods
This was an analysis of 638 Korean amyloidosis patients in a single center over a period of 16 years from 1995 to October 2021. 95 individuals were found with aTTR mutations.

Results
aTTRv amyloidosis constituted 14.8% (n=95) of amyloidosis patients, and the most commonly involved organ being the heart (61.7%, n=58). Unlike the rest of the world, the mixed phenotype was most common (51.0%, n=48) in Korea and the most universal mutation in Koreans were Asp38Ala, which only constitutes about 1.0% in the THAOS registry. Val30Met mutation, which comprises 76% of the mutation in the THAOS registry, was mostly associated the neurologic phenotypes. However, the same mutations in Korea mixed phenotypes with cardiac (38.4%) and neurologic (37%) symptoms.

Conclusion
aTTRv amyloidosis in Korea is different from other patients worldwide. The mixed phenotype was most common, emphasizing the need for heart failure management in the Korean population. Genotype wise, Koreans held a less common mutation of Asp38Ala. The most common mutation of Val30Met was more likely to be associated cardiac symptoms, which concurs with other studies that suggesting that geological features are more important than mutations itself.

Funding Acknowledgement
Type of funding sources: None.
Incidence and factors associated with de novo atrial fibrillation in patients with wild-type transthyretin cardiac amyloidosis
Authors: Fumagalli C , Zampieri M , Argiro' A , Musumeci B , Tini G , Di Bella G , Cipriani A , Porcari A , Canepa M , Merlo M , Sinagra G , Rapezzi C , Perfetto F , Cappelli F 
Published: October 2022

Abstract

Purpose
We described the incidence and ECG factors associated with de novo atrial fibrillation (AF) in patients diagnosed with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) to drive tailored arrhythmia screening.

Background
Data on the incidence rate and factors associated with de novo AF in patients with ATTRwt-CA is limited.

Methods
Multicenter, retrospective, observational cohort study performed in six referral centers for CA. All consecutive patients diagnosed with ATTRwt-CA between 2004 and 2020 with &gt;1-year follow up (FU) were enrolled in the study and were divided into three groups according to presence of AF: (1) patients with “known AF”; (2) patients in “sinus rhythm” and (3) patients developing “de novo AF” during FU. Incidence and factors associated with AF in patients with ATTRwt were the primary outcomes.

Results
Overall, 266 patients were followed for a median of 469 days: 148 (56%) with known AF, 84 (31.6%) with sinus rhythm, and 34 (12.8%) with de novo AF. Age and gender were similarly distributed. At multivariable analysis, PR (Hazard Ratio [HR]: 1.008; 95% CI: 1.001–1.016), QRS (HR: 1.022; 95% CI: 1.002–1.043) and left atrial dilatation &gt;50mm (HR: 3.429, 95% CI: 1.565–7.329) were associated with de novo AF at FU. Patients presenting with at least two risk factors (PR &gt;200ms, QRS &gt;120ms or LAD &gt;50mm) had a higher risk of developing de novo AF compared to patients with no risk factors (HR 14.918; 95% CI: 3.242–31.646).

Conclusions
Incidence of de novo AF in patients with ATTRwt is 20.7%/year. Longer PR and QRS duration and left atrial dilation are associated with arrhythmia onset.

Funding Acknowledgement
Type of funding sources: None.
Cardiac amyloidosis is not a single disease: a multiparametric comparison between the light chain and transthyretin forms
Authors: Neculae G , Adam R , Jercan A , Badelita S , Draghici M , Stan C , Rosca M , Beladan C , Coriu D , Popescu B A , Jurcut R 
Published: October 2022

Abstract

Background
Systemic amyloidoses represent a heterogeneous group of diseases resulting from the deposition of misfolded proteins as amyloid fibrils into the extracellular matrix of different organs. Based on this precursor protein, cardiac amyloidosis (CA) can be most frequently classified as: light chain (AL) and transthyretin (ATTR) amyloidosis, with different management and prognosis.

Purpose
The purpose of this study is to establish a differential diagnosis algorithm targeted towards these two most frequent subtypes of CA. Although confirmation through invasive or non-invasive diagnostic algorithms is still mandatory for a final diagnosis, a series of clinical, paraclinical and imaging differences could possibly guide the choice for more complex diagnostic steps.

Methods
We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in our center. All patients had a complete clinical, paraclinical and imaging evaluation including myocardial deformation study, and confirmation of the final diagnosis, according to the current international recommendations.

Results
The study population included 81 patients divided into 2 groups: ATTR (group 1, n=32: 30 variant and 2 wild type) and AL (group 2, n=49).
ATTR patients were younger (50.7±13.9 vs. 60.2±7.3 years, p=0.0001), had predominantly more neurological symptoms, milder cardiac symptoms and lower values of cardiac biomarkers than AL: NT-proBNP (3095±4433 vs. 10382±9008 ng/ml, p=0.001) and high sensitive troponin I (0.0129±0.01 vs 0.177±0.2 ng/ml, p=0.0002), with better renal function (mean GFR 84.74±26.9 vs. 64.5±29.45 mL/min, p=0.003). We found no significant differences in terms of ECG changes.
Moreover, at similar left ventricular (LV) wall thickness and ejection fraction, ATTR group had less pericardial effusions (53.6 vs. 86.8%, p=0.0027), better LV global longitudinal strain (−12.0±3.7 vs. −9.7±4.6%, p=0.03), RV strain (RVFW strain −19.7±6.2 vs. −14.5±11.0%, p=0.03) and also better reservoir and contractile function of the LA (LASr 17.2±12.3 vs. 11.2±7.4%, p=0.02).
Based on this multiparametric comparison we proposed a prediction algorithm to differentiate between the 2 forms of CA. A score of equal or more than 4 from a maximum of 9 points, has been able to differentiate between AL and ATTR with a sensitivity and specificity of 78 and 80%, respectively; AUC= 0.82.

Conclusions
CA is a complex entity and requires extensive testing through serum biomarkers, imaging, and invasive confirmation of amyloid infiltration in some cases. This study highlighted a series of non-invasive checkpoints, which can be useful in guiding the decision making process towards a more accurate and rapid differential diagnosis, in cases where a final diagnosis is crucial to be immediately established.

Funding Acknowledgement
Type of funding sources: None.
Sustained vasodilation after cold pressor test is an independent predictor of poor survival in primary AL amyloidosis
Authors: Patras R , Georgiopoulos G , Petropoulos I , Theodorakakou F , Delialis D , Angelidakis L , Gavriatopoulou M , Dimopoulou M A , Sianis A , Maneta E , Neofytou O , Terpos E , Dimopoulos M A , Kastritis E , Stamatelopoulos K 
Published: October 2022

Abstract

Background
Primary AL amyloidosis is a rare yet lethal systemic disorder. Dysfunction of the autonomous nervous system due to disease-related nerve infiltration is a common manifestation of AL amyloidosis. Previously published own work indicated that AL patients present sustained paradoxical vasodilation in response to sympathetic stimulus, as assessed by cold pressor test (CPT). The clinical relevance of this finding is unknown.

Purpose
We sought to investigate the relationship between CPT-induced vascular response and mortality in AL amyloidosis.

Methods
We consecutively recruited 97 newly diagnosed patients with AL amyloidosis. CPT of the brachial artery was performed before treatment initiation. All measurements were assessed using high resolution ultrasonography (14.0Mhz multifrequency linear array probe, Vivid 7 Pro; General Electric Healthcare, Milwaukee, Wisconsin, USA). The maximum vasodilation of the brachial artery was measured during the sympathetic stimulus and 3 minutes after withdrawal (sustained response). All-cause mortality was defined as the primary end-point of the study.

Results
Mean age was 66 years with prevalence of male gender. Sustained vasodilation (but not vasodilation during CPT) was associated with heart failure, NYHA stage, BNP and peripheral vascular involvement (p&lt;0.05 for all). Sustained vasodilation after withdrawal of the sympathetic stimulus was significantly associated with mortality as assessed by Cox regression analysis (HR: 1.149, 95% CI 1.042–1.269, p=0.005). This association remained significant after adjustment for age, sex, systolic blood pressure (SBP), nerve involvement and Mayo stage (HR: 1.123, 95% CI 1.014–1.243, p=0.026). A sustained vasodilation ≥3.35% from pre-stimulus diameter was associated with shorter survival (log-rank test, p=0.022, Figure 1). No association between vasodilation during sympathetic stress and mortality was observed.

Conclusions
In AL amyloidosis, sustained paradoxical vasodilation in response to sympathetic stimulus was associated with poor survival. The clinical utility of this index of vascular autonomic dysfunction as a potential prognostic and therapeutic biomarker in AL amyloidosis merits further investigation.

Funding Acknowledgement
Type of funding sources: None.
Detection of arrhythmias in patients with cardiac amyloidosis using implantable ECG recorders
Authors: Taborsky M , Aiglova R , Fedorco M , Bradac P , Flasik J , Danek J , Schee A 
Published: October 2022

Abstract

Introduction
Cardiac Amyloidosis frequently results in congestive cardiac failure and arrhythmias, from a disruption in cardiac substrate with subsequent electro-mechanical remodeling. Arrhythmias are vary based on the amyloidosis type. Conduction defects and atrial arrhythmias are more prevalent in transthyretin amyloidosis compared with light chain amyloidosis, and this difference might be a reflection of the longer survival time in the former.

Methods
112 transthyretin amyloidosis (TTR) patients with completed underlying diagnosis including 99mTc-DPD scan, genetic testing and endomyocardioal biopsy (27%) without documented arrhythmias were randomized to standard clinical follow-up including arrhythmias or implantation of an ECG loop recorder (ILR). The classic FU took place in a heart failure clinic, and the group of patients with ILR was monitored by remote control with automatic daily report of the occurrence of arrhythmias by an independent organization. If an arrhythmia was detected, the patient was contacted immediately. The mean follow-up time for both groups was 17±7 months.

Results
The results are summarized in Table 1.

Conclusions
Currently, there is no consensus on the absolute benefit that ICDs in patients with cardiac amyloidosis. When non-sustained VT and syncope are captured and documented, ICD implantation for prevention of SCD in CA is most likely a reasonable approach. However, intensive monitoring of arrhythmias in patients with CA using ILR can lead to accurate and early detection of ventricular arrhythmias in particular and early initiation of ICD treatment as a prevention of SCD. Documentation of ventricular arrhythmias in CA patients was significantly higher by ILR (p&lt;0.005) and was a clear predictor of patient survival (HR 2.51).

Funding Acknowledgement
Type of funding sources: None.
Transthyretin cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: a single center experience
Authors: Scudeler L , Gallone G , Bongiovanni C , Bruno F , Landra F , Andreis A , Fava A , Pidello S , Raineri C , Giorgi M , D'Ascenzo F , Conrotto F , Alunni G , Rinaldi M , De Ferrari G M 
Published: October 2022

Abstract

Background
Even if prevalent among patients with severe aortic stenosis (AS), the clinical suspicion for transthyretin cardiac amyloidosis (ATTR-CA) remains difficult in this subset.

Methods
Consecutive severe AS patients undergoing transcatheter aortic valve replacement (TAVR) evaluation at a single center were prospectively included. Those with suspected ATTR-CA based on clinical assessment underwent 99mTc-DPD cardiac scintigraphy. The RAISE score, a novel screening tool with high sensitivity for ATTR-CA in AS, was retrospectively calculated to rule-out ATTR-CA in the remaining patients. Patients were categorized as follow: “ATTR-CA+”: patients with confirmed ATTR-CA at 99mTc-DPD cardiac scintigraphy; “ATTR-CA−”: patients with negative 99mTc-DPD cardiac scintigraphy or a negative RAISE score; c) “ATTR-CA indeterminate”: patients not undergoing ATTR-CA assessment with a positive RAISE score. The characteristics of ATTR-CA+ and ATTR-CA− patients were compared.

Results
Of 107 included patients, ATTR-CA suspicion was posed in 13 patients and confirmed in 6. Patients were categorized as follow: 6 (5.6%) ATTR-CA+, 79 (73.8%) ATTR-CA−, 22 (20.6%) ATTR-CA indeterminate. Excluding ATTR-CA indeterminate patients, the prevalence of ATTR-CA was 7.1%. As compared to ATTR-CA− patients, ATTR-CA+ patients were older, had higher procedural risk and more extensive myocardial and renal damage. They had higher left ventricle mass index and lower ECG voltages, translating into a lower voltage to mass ratio. Moreover, bifascicular block was more common. No difference in procedural outcomes and 1-year mortality was observed between groups.

Conclusions
Among severe AS patients, ATTR-CA is prevalent and presents with phenotypic features that may aid to differentiate it from lone AS. A clinical approach based on routine search of amyloidosis features may effectively lead to selective 99mTc-DPD cardiac scintigraphy with a satisfactory positive predictive value.

Funding Acknowledgement
Type of funding sources: None.
Right ventricular mechanics and its association with symptoms in transcatheter aortic valve replacement candidates: a three-dimensional echocardiography study
Authors: Ladanyi Z , Lakatos B K , Ruppert M , Fabian A , Ujvari A , Molnar B , Turschl T , Fejer C , Apor A , Nagy A I , Molnar L , Kovacs A , Merkely B 
Published: October 2022

Abstract

Aortic valve stenosis is one of the most prevalent valvular disease with significant clinical burden. While it is initially a disorder of the left ventricle (LV), long-term effects of the disease also affect the right ventricle (RV) as well. Nevertheless, data are scarce regarding the changes of RV mechanics and their association with symptomatic status of the patients. 3D echocardiography allows a more detailed assessment of the RV, which may unveil distinct changes of its morphology and function in this clinical setting.
Accordingly, our aim was to examine LV and RV mechanics in TAVR candidate patients with severe aortic stenosis using three-dimensional (3D) echocardiography.
Seventy patients (51% male, age: 80±6 years) were enrolled. Detailed medical history and symptomatic status were obtained. Beyond conventional transthoracic echocardiographic protocol, 3D loops were also acquired. We measured 3D LV and RV end-diastolic volume indexed to body surface area (EDVi), ejection fraction (EF) and global longitudinal (GLS) using dedicated software. Furthermore, we have determined 3D RV global longitudinal (RV GLS) and circumferential strain (RV GCS) using the ReVISION method.
LV EF (r=0.28, p&lt;0.05) and LV GLS (r=−0.26, p&lt;0.05) significantly correlated with age, while RV EF (r=0.21, p=0.11), RV GLS (r=−0.17, p=0.19) and RV GCS (r=−0.07, p=0.61) did not show association with it. 41% (n=29) of the patient population mentioned angina or had syncope. Patients with these symptoms had comparable LV EDVi (73±23 vs. 69±25 mL/m2, p=0.47), LV EF (47±15 vs. 51±10%, p=0.14) and LV GLS (−13.6±4.8 vs. −14.8±2.6%, p=0.25) to those who did not mention these complaints. On the other hand, patients with angina or syncope in their medical history had significantly lower RV EDVi (58±13 vs. 70±23 mL/m2, p&lt;0.05), while having significantly higher RV EF (46±10 vs. 52±7%, p&lt;0.05). Moreover, symptomatic patients had significantly lower RV GCS (−15.7±5.6 vs. −19.6±5.3%, p&lt;0.01), while RV GLS did not differ (−15.8±4.8 vs. −17.4±4.1%, p=0.17).
Patients with severe aortic stenosis have marked changes in not only the LV, but the RV mechanics as well. While the symptomatic status does not seem to be associated with LV morphology and function, patients with angina or syncope had distinct changes in RV size and the contraction pattern of the chamber.

Funding Acknowledgement
Type of funding sources: None.
Safety of heart radiotherapy for malignant cardiac tumors: a short and long term study
Authors: Lestuzzi C , Cosei I , Navarria F , Viel E , Ravasel A , Fumagalli A , Miolo G M , Popescu B , Buonadonna A 
Published: October 2022

Abstract

Background
Radiotherapy (RT) may be used as a complementary or palliative treatment for selected cases of malignant cardiac tumors, and improves the overall and relapse-free survival in cardiac sarcomas (1–3). Its use is limited by the risk of radiation injury on the cardiac structures (4). Only few data about the safety of cardiac RT are available.

Purpose
This study aimed to assess the short and long term adverse cardiac effects in a cohort of patients with cardiac malignancies treated with RT directly on the heart.

Methods
We reviewed the clinical and echocardiographic data of 25 patients (pts) treated with cardiac RT from 2002 to 2021, using Intensity Modulated RT or Tomotherapy at doses of 25–59 Gy over 5–25 fractions for primary or metastatic tumors (21 sarcomas). The patients had ECG and echocardiogram (ECHO) before RT and weekly during the treatment. After RT, the cardiac surveillance included a visit with ECG and ECHO every 3 months for the first 2 years, every 6 months for 3 years, and yearly thereafter. We compared the left ventricular ejection fraction (LVEF) before RT and at the last available follow-up for all patients; for 12 pts whose radiation field included the right chambers, we analyzed also the right ventricular shortening fraction (RVSF) at the last available follow-up.

Results
The pts were 14 males, 11 females, aged 22 to 75 (median 54) when treated. The intent was adiuvant after R1 surgery in 12 pts, preoperative in 3, palliative or curative for metastatic or unresectable tumors or in patients refusing redo surgery or chemotherapy (10 pts). Anthracyclines chemotherapy was used in 19 pts. The radiation field included the left atrium and/or ventricle in 11 pts, the right heart in 9, both left and right structures in 3. Two pts were lost to follow-up after 36 and 50 months; 17 died, 3 to 175 months after RT (median 12), all for non-cardiac causes; 6 are alive (with complete local remission) 15 to 126 months (median 79) after completing RT. Acute toxicities were: atrial fibrillation in 2 pts, pericarditis in 2 (both reverted in one week with medical therapy) and temporary worsening of ventricular arrhythmias in one pt with myocardial metastases. At last follow-up no significant valvular or pericardial disease was evident; the LVEF was &gt;50% in all pts (5–10% decreased -compared to baseline- in 2 pts, improved in 3, stable in the others) and the RVSF was &gt;35%.

Conclusions
In our experience, RT may be used in the treatment of cardiac malignancies with little adverse effects both on short term and at a median follow-up of 13 months (and lasting up to &gt;10 years).

Funding Acknowledgement
Type of funding sources: None.