bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronary flow reserve by PET 13N-ammonia in patients with hereditary transthyretin amyloidosis with and without cardiac involvement
Authors: Alencar Neto A C , Cafezeiro C R F , Bueno B V K , Ribeiro De Souza F , Henrique Rissato J H S , Souza Borges T , Freitas Carvalhal S , Santos Lima M , Alberto Buchpiguel C , Azem Chalela W , Alvarez Ramires F J , Shcolnik Szor R , Kalil Filho R , Rochitte C E , Fernandes F 
Published: October 2022

Abstract

Background
Transthyretin Cardiac amyloidosis (ATTR) presents with diffuse deposition of amyloid fibrils in the heart. Biomarkers of cardiac involvement such as troponins are often elevated even in early disease stages, reflecting direct cardiomyocyte damage and coronary microvascular dysfunction by amyloid deposits.

Objectives
Evaluate global and segmental coronary flow reserve (CFR) by PET 13N-ammonia in patients with hereditary Transtirretina Amyloidosis with and without cardiac involvement.

Methodology
Thirty-eight ATTR mutation carrier patients (18 with cardiac amyloidosis and 20 without cardiac amyloidosis underwent CFR study by PET 13N-ammonia. Cardiac involvement was defined by means of echocardiography, with an end-diastolic interventricular septal wall thickness ≥12 mm or positive endomyocardial biopsy or grade II or III nuclear scintigraphy using bone avid radiotracers. The Mann-Whitney test was used to compare the values of coronary flow reserve between the groups. The effect size was calculated using the Wilcox method and 95% confidence intervals, obtained by bootstrapping. A multivariate linear regression model was applied to identify the main determinants of global coronary flow reserve.

Results
Compared with patients without cardiac involvement, patients with cardiac involvement were older (69±8 vs. 41±11 years old; p&lt;0,001), had worse NYHA functional classification, higher left ventricular mass index (198±51 g/m2 x 75±19 g/m2; p&lt;0,001), thicker interventricular septum (17,9±3,4 mm vs. 8,7 ± mm; p&lt;0,001]. Coronary flow reserve values were significantly lower in the cardiac amyloidosis group globally (1,8±0,4 vs. 2,9±0,7; p&lt;0,001) and in all analyzed segments (p&lt;0.01). The apical segments were also affected when comparing group with and without cardiac involvement (2,0±1 vs. 3,0±0,7; P=0,002), suggesting absence of microvascular apical preservation. In multivariable linear regression analyses, age and BNP were the main factors associated to coronary reserve flow. The reduction in global CRF was 0,25, 0,08 and 0,17 points, on average, for each decade of life, for each 100 mg/dl of serum BNP and for each 0,1 heart to contralateral lung ratio uptake in 3-hour caption on TcPYP scintigraphy respectively.

Conclusion
Patients with cardiac amyloidosis present lower coronary flow reserve both globally and segmental compared to mutation carrier without cardiac amyloidosis. The evaluation of Coronary flow reserve by PET 13N-ammonia may be a worthwhile tool in cardiac involvement in TTR patients.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer
Finding the gaps in managing Fabry disease in women: the Romanian experience
Authors: Mursa A , Militaru S , Neculae G , Adam R , Radoi V , Rusu E , Popescu B A , Jurcut R 
Published: October 2022

Abstract

Introduction
Fabry disease (FD) is an X-linked rare lysosomal storage disease caused by mutations in the GLA gene which lead to decrease in α Gal A enzyme activity and tissue accumulation of lysosomal globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). Due to X linked transmission, males are hemizygous, and females are heterozygous and were initially thought to be unaffected. However, women with FD can vary from asymptomatic, mildly symptomatic, to severely symptomatic as males. The aim of this study is to evaluate the particularities of FD presentation, cardiac imaging and management in females from the full Romanian FD cohort as compared to male patients.

Methods
This study included all consecutive patients diagnosed in or referred to our center with FD between 2014–2021. All patients had a complete clinical, biological and cardiac imaging workup.

Results
During the inclusion interval, data from 66 consecutive Romanian FD patients (37 women and 29 men) from 29 unrelated families were collected. Diagnosing mode in FD women differs compared to men (p&lt;0.001): most women were diagnosed through family screening or by a cardiologist, while most men were diagnosed by nephrologists. Women had higher levels of α Gal A levels (1.3±0.8 μmol/L/h vs 0.5±0.7 μmol/L/h, normal cutoff &gt;1.2) (p&lt;0.001) and smaller levels of lyso-GB3 (5.8±2.6 ng/ml vs 110±35.6 ng/ml, normal cutoff&lt;3.8) (p&lt;0.001). More women are asymptomatic carriers than men (27% vs 3.4%), but when symptoms were present, they could be as severe as in men. Enrolled women were older (50.9±16.3 vs 41±14.9 years, p=0.014), diagnosed later (46.8±16.8 vs 32.7±14.3 years, p&lt;0.001) and had later symptom onset of the disease compared with men (38.1±14.4 vs 20.3±14.9 years, p&lt;0.001). Women had less angiokeratomas (p=0.001) and hypohydrosis (p=0.04), with no difference in cornea verticillata or ENT involvement. Both women and men developed cardiac symptoms starting from the fifth decade, with no differences in terms of angina, NYHA class, syncope between sexes. Women tend to have a lower prevalence of LVH compared to men (p=0.052), with no differences regarding ejection fraction or global longitudinal strain between genders. Regarding other organs involved, women were equally affected as men from acroparesthesia and stroke, with similar age at first cerebrovascular event. Women had milder kidney involvement (stages 1 and 2) when compared to men (56.8% vs 37.9%, p=0.004). Regardless of these findings, it appeared that women were less treated with pathogenic therapy comparing to men (48.6% vs 82.7%) (p=0.004).

Conclusions
Women with FD are not merely genetic carriers as they can be as affected as men. However, they benefit later from diagnosis and less of pathogenic therapy. Further studies with more female participations are needed to better understand the Fabry burden and needs in women.

Funding Acknowledgement
Type of funding sources: None.
Evaluation of non-breath-hold, ultra-fast, low-dose high-pitch (flash) CT scan as a practical alternative to standard spiral scan for pre-TAVI patients: a real-world single-center experience
Authors: Vitkon Barkay I , Dvir D , Elkan M , Pichkhadze O , Bogot N , Shaheen F , Chutko B , Glikson M , Wolak A 
Published: October 2022

Abstract

Introduction and aim
Aortic annulus dimensions change during the cardiac cycle. A retrospective ECG-gated (Spiral) scan is the default technique for pre TAVR evaluation since it includes systolic phases considered optimal for aortic annulus assessment. Ultra-fast, Low-Dose High-Pitch (FLASH) offers faster, potentially low radiation and low contrast dose scans. However, it lacks the ability to time data acquisition to the systole. Therefore, measurements derived from FLASH scan are considered suboptimal for reporting. The effect of this potential annular measurement difference on procedural success and safety was not evaluated. Therefore, we aimed to assess the feasibility and safety of FLASH vs. Spiral scan before TAVI.

Methods
We conducted a retrospective, single-center study. 409 patients underwent CT-TAVI scan with either FLASH or SPIRAL acquisition. Baseline characteristics, CT study, procedural and f/u data were acquired from the EMR. Outcomes defined by Valve Academic Research Consortium3 (VARC-2) endpoint definitions included in-hospital mortality, bleeding, vascular complications, acute kidney injury (AKI), conduction disorders, mechanical complications, and prosthetic aortic valve regurgitation. Composite endpoints such as device success were also examined.

Results
Of the 409 patients, 55.7% underwent FLASH scans. The median age was 80 years, and males accounted for 55%. The FLASH-protocol patients had higher rate of chronic kidney disease, their CT-measured aortic annulus area and diameter were smaller, and they were exposed to a smaller amount of contrast agent and radiation than the SPIRAL group. There was no statistically significant difference in primary clinical and safety endpoints between the two groups, including mechanical complications (such as annular rupture and valve malposition) and conduction disorders.

Conclusions
FLASH CT scan is a pragmatic and safe approach that potentially may replace spiral scan for the evaluation before TAVI procedure in the appropriate patients.

Funding Acknowledgement
Type of funding sources: None.
Prognostic role of low QRS voltages in patients with cardiac amyloidosis
Authors: Guerra F , Coretti F , Torselletti L , Coraducci F , Belleggia S , Manfredi R , Silenzi M , Falanga U , Principi S , Stronati G , Ciliberti G , Barbarossa A , Casella M , Dello Russo A 
Published: October 2022

Abstract

Introduction
Cardiac amyloidosis (CA) is an underdiagnosed and heterogeneous cardiac disease characterized by the extracellular deposition of misfolded proteins in the cardiac tissue. Clinical manifestations are heterogeneous leading to progressive heart failure, often complicated by arrhythmias and conduction system disease. Among several sign and symptoms that are suspicious for the disease, named “red flags”, disproportionally low QRS voltages on the ECG has been described.

Purpose
The aim of this prospective observational study is to evaluate potential prognostic features of QRS amplitude in AL e ATTR CA patients.

Methods
All consecutive patients admitted to the Cardiomyopathy Clinic of our institution have been enrolled after receiving CA diagnosis, according to the current guidelines. We included all patients ≥18 years with a diagnosis of CA and written informed consent. A complete assessment including a standard 12-lead electrocardiogram (ECG) and echocardiogram was performed at enrollment. Low QRS voltages (LQRSV) was defined as a QRS total amplitude of ≤5 mm in every limb leads and ≤10 mm in every precordial lead. LQRSV was tested as an independent predictor of death from all causes (primary endpoint), hospitalization from cardiovascular causes, ventricular and supraventricular arrhythmias.

Results
Sixty patients (46 males, 77±12 years old) were enrolled, of which 18 (30%) met the criteria for LQRSV. Patients with LQRSV presented more frequently with an history of ventricular arrhythmia (27.8% vs. 6.7%, p=0.04), a lower left ventricular diastolic volume (31±7 vs. 44±18 ml/m2; p=0.04), and higher retinol-binding-protein 4 (9.3±2.2 vs 3.2±1.5 mg/dl; p=0.02). No differences were seen in the primary outcome (46% vs. 50%; p=NS; Figure 1) or in the secondary ones (cardiovascular hospitalization 25% vs. 21%; ventricular arrhythmias 12% vs 4%; supraventricular arrhythmias 29% vs 19%; all p=NS) between the two groups during a median follow up of 1.1 year.

Conclusions
In the present cohort of CA patients LQRSV did not emerge as independent predictor of all-cause mortality at 1 year. Although LQRSV is a recognized diagnostic “red-flag” in the work-up of CA, its role as prognostic marker remains unclear. Further studies with a longer follow-up are needed to better define the prognostic role of LQRSV among CA patients.

Funding Acknowledgement
Type of funding sources: None.
Fabry disease and hypertrophic cardiomyopathy: similar albeit different
Authors: Allam C , Saouma M 
Published: October 2022

Abstract

Background
Fabry disease (FD) is a lysosomal storage disease that affects one or multiple organ systems and can cause left ventricular hypertrophy (LVH). FD can mimic hypertrophic cardiomyopathy (HCM), and clinicians occasionally miss the diagnosis of FD for HCM. The factors associated with FD-HCM misdiagnosis remain unclear.

Purpose
We sought to determine the prevalence of FD among patients with LVH and uncover the factors associated with FD-HCM misdiagnosis.

Methods
We searched online databases for all studies that performed a screening for FD in patients with LVH with reporting of a prevalence. We constructed a list of patients with LVH diagnosed with FD and collected their clinical, echocardiographic, and electrocardiographic characteristics and GLA gene mutation. We classified LVH as symmetric or asymmetric and GLA gene mutations as missense or non-missense. We calculated the prevalence of FD among patients with LVH adjusted for the founder effect. We later divided all FD patients into two groups depending on whether they were misdiagnosed for HCM (Group 1) or not misdiagnosed (Group 2). We used the chi-square and Student's t-test, respectively, to compare the quantitative and qualitative variables of Group 1 and Group 2.

Results
Thirty-one studies (n=11434 patients) met the inclusion criteria. There were 148 patients with LVH diagnosed with FD, and after adjusting for the founder effect, the prevalence of patients with LVH diagnosed with FD (n=117) was 1%. The number of FD patients misdiagnosed (Group 1) and not misdiagnosed (Group 2) for HCM was respectively 109 (73.6%) and 39 (26.4%). Patients in Group 1 were more likely to have an asymmetrical LVH, χ2(1, N=148)=18.6, p&lt;0.001, a missense mutation, χ2(1, N=112)=7.8, p=0.0053 after adjusting for the founder effect, and a normal renal function, χ2(1, N=148)=16.2, p&lt;0.001. The genetic results of five patients were missing. The maximal left ventricular wall thickness (LVWT) of Group 1 (M=19.84, SD=0.95) compared to Group 2 (M=17.58, SD=1.684) was significantly higher, t(109)=2.44, p=0.0165, and data were missing in 37 subjects. We did not find a significant difference in the following factors: age, nonclassic FD, angiokeratoma, acroparesthesia, stroke history, left ventricular outflow tract obstruction, history of syncope, atrioventricular block, history of tachyarrythmias, and history of pacemaker or defibrillator implantation.

Conclusion
FD is common among patients with LVH with a prevalence of 1%. Asymmetrical LVH and severe LVH are incorrectly thought to be uncommon in FD and tend to mislead clinicians in their diagnostic approach. FD patients with LVH and misdiagnosed HCM are more likely to have a missense mutation. FD patients with LVH and CKD are less likely to be misdiagnosed for HCM, and the most probable cause is that clinicians misdiagnosed some of these patients for CKD-related LVH. To conclude, we must increase awareness among clinicians on the red flags of FD.

Funding Acknowledgement
Type of funding sources: None.
Outcomes of heart failure with preserved ejection fraction (HFpEF) in patients with and without cardiac amyloidosis: analysis from 2016–2019 national inpatient sample
Authors: Kambalapalli S , Baral N , Seri A , Bhakta S 
Published: October 2022

Abstract

Background
Cardiac amyloidosis (CA), a restrictive cardiomyopathy that leads to heart failure, is often under-diagnosed in its early-stages, leading to patients being diagnosed with it in advanced stages. Most patients presenting with heart failure are presumed as non-amyloid heart failure due to a lack of awareness. A high degree of clinical suspicion is of paramount importance for early diagnosis and management of CA because the extent of cardiac involvement determines overall prognosis.

Purpose
Our study highlights the outcomes of HFpEF in patients with and without CA.

Methods
This is a retrospective cohort study involving principal hospitalizations for HFpEF between January 1, 2016 and December 31, 2019 from the National Inpatient Sample (NIS), the largest all-payer public database of hospital care data in the United States. Our study sample included discharged adult patients (≥18 years) hospitalised for HFpEF using ICD-10 codes validated in previous studies. Confounders were adjusted using multivariable regression analysis.

Results
During the study period, there were 87,219 index hospitalizations for HFpEF. Among them, 38.3% (n=33405) were males, 61.7% (n=53814) were females, and 0.24% (n=209) had CA. Racial distribution is as follows: 76% Whites, 13.4% Blacks, 6.4% Hispanics, and 4.2% other races. Mean patient age was 74.6±13.2 years, and 68.1% were on Medicare. A total of 59,135 (67.8%) hospitalizations had a Charlson Comorbidity Index (CCI) of &gt;3, with an in-hospital mortality of 2.5%. Compared to the non-CA cohort, the CA cohort had lower prevalence of diabetes mellitus (8.5% vs 27%, p&lt;0.0001) and COPD (23.5% vs 46.8%, p&lt;0.001) but a higher prevalence of renal disease (51.6% vs 41.9%, p=0.004), cancer (25.4% vs 4.2%, p&lt;0.001) and greater incidence of cardiogenic shock (5.2% vs 0.5%, p&lt;0.001).
Compared to the non-CA cohort, patients with CA were less likely to be female (38% vs 61.7%, p&lt;0.001), were of similar age (mean age 74.7 vs 74.6 yrs, p=0.907), had longer length of hospital stay (LOS, 6.7 vs 5.1 days, p&lt;0.001), higher in-hospital mortality (5.2% vs 2.5%, p=0.023), and a higher likelihood of having a CCI &gt;3 (74.2% vs 67.8%, p=0.017). Multivariate regression analysis showed that subjects in the CA cohort had significantly increased adjusted odds of in-hospital mortality (aOR=2.2; 95% CI: 1.2–4.4; p=0.017) and cardiogenic shock (aOR=9.5; 95% CI: 5–17.9; p&lt;0.001) than those in the non-CA cohort after adjusting for age, sex, race, and CCI.

Conclusions
Our study illustrates that patients with a history of CA admitted for HFpEF had greater incidence of cardiogenic shock, higher prevalence of renal diseases and cancer with a longer LOS, and higher in-hospital mortality.

Funding Acknowledgement
Type of funding sources: None.
Predictive value of novel circulating biomarkers in Chagas disease: The Brazilian Chagas disease cohort
Authors: Raguindin P , Rocha M O , Mattoso Barbosa A M , Muka T , Glisic M , Suosa G 
Published: October 2022

Abstract

Introduction
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the leading causes of non-ischemic heart failure and premature cardiac deaths in Latin America. Identifying predictive biomarkers of morbidity and progression of Chagas cardiomyopathy (CCC) is important to deciphering novel pathways and aid in early identification of patients at highest risk for future adverse cardiovascular (CV) outcomes.

Objectives
To determine the association of novel circulating biomarkers with CCC and disease survival.

Methods
Serum levels of 184 unique cardiometabolic and inflammation proteins were measured using proximity extension immunoassay using age- and sex- matched patients without history of any other cardiovascular or infectious diseases as well as diabetes mellitus, who were identified and selected at the referral outpatient center for Chagas Disease at a clinical hospital in Brazil. Univariable linear regression using standardized protein levels were compared between patients with and without CCC. All p-values were adjusted for multiple testing and in findings with p value&lt;0.0002 were considered statistically significant. Proteins that reached significance level were further compared between disease mortalities and survival. We also performed network analysis using STRING-DB on overexpressed proteins to determine its interaction.

Results
We used data from 44 with CCC and 44 with asymptomatic T. cruzi-positive patients (indeterminate). Among individuals with CCC, 22 patients had a fatal cardiovascular event during follow-up period of 4.1 (SD ±1.4) years. In linear regression analyses, we identified 45 candidate biomarkers associated with chronic CC (all p values &lt;0.0002). Among these, only three proteins (IL33, CD40, REG1A) were significantly different between individuals with CCC who died vs survived over a period of 4.1 years. We used 38 overexpressed proteins in network analysis. THBS4, marker of cardiac remodeling, was overexpressed in CCC. CXCL11 were seen co-expressed with CXCL9 and CXCL10, all are known activators of CD4+ Th1 cells in CCC.

Conclusion
We identified 45 novel cardiometabolic and inflammatory markers that are associated with chronic Chagas cardiomyopathy.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Leading House of Latin America of the Swiss State Secretariat for Education, Research and Innovation (SERI)
Pattern of pericardial calcification determines the mid-term postoperative outcome after pericardiectomy in chronic constrictive pericarditis
Authors: Lee Y H , Kim S M , Kim E K , Park S J , Lee S C , Park S W , Jeong D S , Chang S A 
Published: October 2022

Abstract

Background/Introduction
Although pericardiectomy is an effective treatment of constrictive pericarditis (CP), clinical outcome is not always successful. Pericardial calcification is a unique finding in CP. However, the amount and localization of calcification vary. Computer tomography (CT) can visualize the pericardial calcification with high sensitivity and provide the anatomical assessment.

Purpose
We investigated that how the pattern and amount of pericardial calcification affect the mid-term postoperative outcome after pericardiectomy in CP.

Methods
All of the patients who underwent total pericardiectomy in our hospital from 2010 to 2020 were derived from electrical medical records (n=105). Among them, preoperative CT scans (non-gated non-contrast) of 98 patients were available and, thus, 98 consecutive patients were finally analyzed. Medical records were reviewed in a retrospective manner. Cardiovascular event is defined as cardiovascular death or hospitalization associated with a heart failure symptom and all cause event is defined as all events that require admission. CT scan was analyzed by Aquarius Workstation, and the volume and localization pattern of pericalcification were derived. Pericardium calcium score was given as an Agatston score.

Results
Of 98 patients, 25 (25.5%) patients were hospitalized with heart failure symptom after pericardiectomy. Median follow up duration of patients is 172 weeks. A group with cardiovascular event had higher NYHA grade (P&lt;0.001), lower calcium volume (P=0.004), and lower calcium score (P=0.01). Multivariate cox proportional analysis showed that high ln(calcium score) before pericardiectomy was dependent predictor of cardiovascular event (hazard ratio, 0.90; P=0.04) and all cause event (hazard ratio, 0.91, P=0.04) after pericardiectomy. When we set the cut off value at 7.22, based on ROC curve, there was a significant difference in cardiovascular event between the groups divided by this cutoff value in Kaplan-Meier curve (P=0.002) and multivariate cox proportional analysis (P=0.04). In the subgroup analysis, myocardium invasion and circumferential calcification were more common in the high calcium score group. Idiopathic & tuberculosis pericarditis were more associated with high calcium score group and post-operative pericarditis, other reasons (infection, radiation, etc) were more associated with low calcium group.

Conclusion
Low burden of pericardial calcification was associated high rate of mid-term clinical event after pericardiectomy CP. Preoperative evaluation of pericardial calcification pattern can be used as predictor of postoperative outcomes.

Funding Acknowledgement
Type of funding sources: None.