bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of pathological features and inflammatory cells in patients with giant cell myocarditis
Authors: Liu S , Hu Z , Yao Y 
Published: November 2020

Abstract

Background
Giant-cell myocarditis (GCM) is a rare disease with a poor prognosis, the etiology and pathophysiology of GCM remain largely unclear.

Purpose
Describe the distribution of GCM lesions, classify inflammatory cells, and explore the potential relationships of these features with clinical manifestations by examining the histopathological features of GCM in 8 patients who underwent heart transplantation.

Methods
Eight patients with pathological diagnoses with GCM underwent heart transplantation at our center. Hematoxylin- eosin (H-E) and Masson's tri-chrome staining were performed on biopsies of the free walls of the right and left ventricles and interventricular septa of the original hearts to determine the characteristic distribution of cardiac lesions and the composition of infiltrating immune cells. A multiplex immunohistochemistry and multispectral imaging analysis were applied to further classify the specific types of inflammatory immune cells.

Results
Inflammation found in a descending frequency gradually from the epicardium to the endocardium in the free wall of the left ventricle, but concentrated on the surface of right ventricular septum. Typical inflammatory infiltration and pathological changes were observed in the right-sided ventricular septum samples from all 8 patients. Numerous inflammatory immune cells, particularly CD4+ T cells, were detected in the lesion, which surrounded the emerging multinucleated giant cells. CD8+ T cells and a small number of regulatory T cells were scattered in the periphery.

Conclusions
In GCM, cardiac lesions appear to concentrate particularly beneath the epicardium of the left ventricular free wall and the right side of the ventricular septum. These findings provide a rationale for the diagnostic use of conventional endocardial biopsy. The findings further suggest that myocardial injury is mediated by a variety of lymphocytes, especially CD4+ T cells.
Distribution of lesions in GCM

Funding Acknowledgement
Type of funding source: None
The prolactine hypothesis for peripartum cardiomyopathy: has it found its feet for good?
Authors: Sousa J.P , Puga L , Lopes J , Saleiro C , Gomes R , Lourenco C , Goncalves L 
Published: November 2020

Abstract

Background
Peripartum cardiomyopathy (PPCM) is a rare but serious condition that affects childbearing women. Dopamine agonists (DAs) may represent a specific therapy, potentially facilitating left ventricular recovery, through inhibition of prolactin secretion. However, their therapeutic value in this setting has not been fully demonstrated.

Purpose
To perform a meta-analysis aimed at evaluating the extent to which DAs are able to interfere with the natural history of PPCM.

Methods
We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library, Google Scholar, Scopus and DARE for both randomized controlled trials (RCTs) and observational studies addressing the impact of DAs on main outcomes of PPCM patients, published up until February 1, 2020. Endpoints were those of mortality, recovery from heart failure and, likewise, the degree to which left ventricular ejection fraction (LVEF) was restored. All analyses were conducted under a DA plus optimized medical therapy (OMT) vs. OMT alone design, while results were pooled using traditional meta-analytic techniques, under a random-effects model. Odds ratios (ORs) were computed for the first two outcomes, whereas mean difference (MD) was calculated to quantify LVEF restoration.

Results
2 RCTs, 2 prospective cohort, 1 prospective case-control and 2 retrospective cohort studies, encompassing 452 patients, were regarded as eligible for quantitative evaluation. 180 patients were allocated to the DA arm, which was mostly represented by bromocriptine; in fact, only 1 study, including 24 patients, specified cabergolin utilization. Overall, 5 papers including 295 patients reported 42 deaths, whereas 5 papers comprising 305 patients detailed 220 heart failure recoveries, thus unveiling that LVEF restoration was the norm. The addition of a DA to OMT provided no signal of a survival benefit (OR 0.71, 95% CI 0.27–1.87, p=0.49, i2=27%). On the other hand, the incorporation of a DA into the therapeutic regimen narrowly missed significance for the heart failure recovery endpoint (OR 2.68, 95% CI 0.98–7.31, p=0.05, i2=56%). Furthermore, DAs were demonstrated to incrementally improve LVEF by 15% (MD 15.00, 95% CI 10.24–19.76, p&lt;0.00001, i2=77%). Adverse events, including thromboembolic ones, were rare, though adjunct anticoagulation was broadly reported.

Conclusion
In PPCM patients, the addition of a DA to OMT seems to be both effective at incrementally improving LVEF and safe, even though not reaching survival benefit status. These findings appear to corroborate the so-called prolactin hypothesis for PPCM pathophysiology.

Funding Acknowledgement
Type of funding source: None
High sensitivity troponin I in hypertrophic cardiomyopathy
Authors: Osmanska J , Connelly A , Nordin S , Vega A , Simpson J , Anusas J , Findlay I , Coats C 
Published: November 2020

Abstract

Background
ESC guidelines recommend measurement of troponin T in patients with hypertrophic cardiomyopathy (HCM) because high concentrations are associated with cardiovascular events, heart failure and death. The cardiac Troponin I subunit is not expressed in skeletal muscle making it a cardio-specific isoform. The use of troponin biomarkers in management of patients HCM is limited because concentrations only weakly correlate with clinical parameters. Most studies are small, and few have examined their relation with genotype and mortality.

Purpose
To assess the relationship between high-sensitive troponin I (hsTnI) and characteristics of adults with HCM.

Methods
Patients included were adults with an established diagnosis of HCM referred to a single centre for genetic testing. Demographic, clinical and imaging data were recorded at baseline. Echocardiography and cardiac magnetic resonance (CMR) were performed according to EACVI standards. Quantification of late gadolinium enhancement (LGE) was performed using the 5 SD quantitative threshold. Genotype was evaluated using a 16 gene panel in an accredited UK laboratory. Pathogenic and likely pathogenic variants were considered as a positive genotype. Serum hsTnI was measured by a two-site electrochemiluminescence immunoassay on a Roche E170 analyser. Normal values for the assay 0–34 ng/L for males and 0–16 ng/L for females.

Results
313 patients (n=200, 64% male) median age 57 (IQR 47–68) years were included. hsTnI concentration was abnormal in 69 (22%) patients. An abnormal hsTnI was more common in females (n=36, 32%) compared to males (n=33, 17%, c2 9.9, p&lt;0.05). A pathogenic variant in a sarcomere gene was identified in 95 (30%) individuals. An abnormal hsTnI concentration was associated with higher left ventricular (LV) wall thickness (20mm v 18mm, p&lt;0.05) and LV outflow tract (LVOT) gradient (34 v 22 mmHg) on echocardiography (n=313). Of the patients (n=204) who had a CMR, an abnormal hsTnI concentration was associated with higher LV mass (183 v 156g, p&lt;0.05) and greater % LGE (30 v 16%, p&lt;0.01, n=129). There was no difference in hsTnI between those with a positive or negative genotype. During follow-up, 18 patients died. Of the 9 patients that died with a normal hsTnI, two died suddenly.

Conclusions
In HCM, patients with abnormal hsTnI concentration have higher LV mass and LVOT gradient and more fibrosis. Whilst mortality is higher in those with abnormal hsTnI, sudden cardiac death may occur with a normal hsTnI. It may not be appropriate to extrapolate hsTnI sex-specific thresholds used in the diagnosis of myocardial infarction to HCM.

Funding Acknowledgement
Type of funding source: None
What happens &gt;10 years after percutaneous septal ablation for hypertrophic obstructive cardiomyopathy? Ultra long-term follow-up of 120 patients
Authors: Faber L , Scholtz S , Batzner A , Seggewiss H 
Published: November 2020

Abstract

Introduction and methods
Recent registry analyses including the European multicenter registry (Euro-ASA) documented a favourable long-term outcome of septal ablation (ASA/PTSMA) competitive to surgical myectomy. There is no information about the period beyond 10 years. We therefore analyzed the outcome in 120 HOCM patients (pts., mean age @ index intervention: 62±13 years) treated with ASA who survived &gt;10 years.

Results
Mean CK rise during the index intervention was 537±258 U/l (reference: &lt;80). A DDD-pacemaker (DDD-PM) had to be implanted in 26 pts. (22%) for procedure-related AV conduction problems. A re-intervention for residual or recurrent outflow obstruction (LVOTO) had to be performed in 12 pts. (10%; re-PTSMA: 10 pts.; myectomy: 2 pts). These cases included, at their last follow-up visit 107 pts. (89%) were in functional class I or II. During follow-up (159±33 [range: 122–264] months), 12 pts. (8%) died, of these 6 (4%) from non-cardiac, and 6 (4%) from cardiovascular causes including one sudden death. Furthermore, 4 (3%) ICDs were implanted (1 for secondary, 3 for primary prevention of sudden cardiac death). The most frequent clinical problem was atrial fibrillation which occurred in 27 pts. (23%), and which was refractory to rhythm control attempts in 21 pts. (18%).

Conclusions
The procedure-related DDD-PM rate in this septal ablation cohort including the early learning curve more than doubled the current one. Nevertheless, during ultra long-term follow up a durable clinical improvement was observed with mortality rates around 1%/year, nearly equivalent to that of 0.8% observed in normal populations. Atrial fibrillation is a frequent problem in this elderly, formerly obstructive HCM population.

Funding Acknowledgement
Type of funding source: None
The influence of age on the diagnostic yield of genetic testing in dilated cardiomyopathy
Authors: Cannie D.E , Protonotarios A , Lorenzini M , Akhtar M , Syrris P , Lopes L , Elliott P 
Published: November 2020

Abstract

Background
Dilated cardiomyopathy (DCM) has an estimated population prevalence of 1/250 and is the underlying diagnosis in a third of heart failure patients. A substantial proportion of patients have familial disease caused by dominant mutations in one of more than 50 genes, but clinical practice guidelines recommend genetic testing in young patients with idiopathic DCM. There is an absence of robust data on the influence of age on the diagnostic yield of genetic testing.

Methods
The study cohort comprised 825 consecutive and unrelated patients (524 male (63.5%)) with DCM who underwent genetic testing from 2015 to 2019. Genetic variants were classified using American College of Medical Genetics (ACMG) criteria. Analyses were stratified by age and sex.

Results
173 (20.1%) patients had a positive genetic test (“pathogenic” or “likely pathogenic” variant); 292 (34.4%) had a variant of unknown significance. Mean age at genetic testing was 49.9±14.4 years. Mean age of patients with a positive test was 47.6±13.6 years. 99 (18.9%) men and 67 (22.3%) women had a positive test (p=0.246).
Mutations in the TTN gene, encoding for titin, accounted for 46.1% of positive results. 13.8% of mutations were in DSP, 8.4% in RBM20, 6% in FLNC, 4.2% in LMNA, 3.6% in BAG3 and 3.6% in MYH7.
There was a trend to declining yield with age (likelihood ratio chi-square p value = 0.047). The yield was 17.2% in the 56–65 year age group and 11.5% above 66 years of age (figure 1).

Conclusions
Approximately 1 in 5 patients with DCM had a positive genetic test. The yield declined in patients over 66 years but remained above 11%, suggesting that genetic testing should not be confined to younger patients with DCM.
Figure 1. Yield of Genetic Testing by Age

Funding Acknowledgement
Type of funding source: None
Prognostic impact of suspected cardiac amyloidosis in aortic stenosis patients referred for transcatheter aortic valve implantation
Authors: Ferreira V , Aguiar Rosa S , Rodrigues I , Moura Branco L , Galrinho A , Rio P , Patricio L , Cacela D , Ramos R , Mendonca T , Castelo A , Garcia Bras P , Mano T , Viegas J , Cruz Ferreira R 
Published: November 2020

Abstract

Background
The prevalence of cardiac amyloidosis (CA) and aortic stenosis (AS) both increase with age. Transcatheter aortic valve implantation (TAVI) expands the number of patients (P) eligible for treatment of AS, emphasizing the need to understand the prevalence of CA in AS and its prognostic associations. Echocardiography with speckle tracking has emerged as a useful method to enhance the clinical suspicion and to provide prognostic information.

Purpose
To estimate the prevalence of CA in P with severe AS referred for TAVI and to evaluate the impact of concomitant CA in prognosis.

Methods
94 consecutive AS P who underwent TAVI with maximum left ventricular wall thickness (LVWT)&gt;12 mm were retrospectively identified. Clinical data, pre TAVI echocardiographic parameters and follow up (FU) data regarding all-cause mortality and MACE (including all-cause mortality, admission for heart failure, pacemaker implantation and stroke) were analysed. We registered apical sparing pattern in bull's eye plots (ASPB), calculated relative apical longitudinal strain formula (RALS) [average apical LS/(average basal LS + mid-LS)] and ejection fraction/global longitudinal strain (EF/GLS) ratio.

Results
Mean age was 82.2±5.8 years (Y), with 43 men (45.7%). 27.7% were in NYHA functional class II, 64.9% in functional class III and 7.4% in functional class IV. Median EF was 57±15% and 26.6% presented EF&lt;50%. Suspected CA evaluated by ASPB was found in 39 P (41.5%) and RALS &gt;1 was identified in 22 P (23.4%). An EF/GLS ratio &gt;4.1 was obtained in 53 P (56.4%). Over a median follow-up of 13.4±25.8 months, 28 deaths (29.8%) and 31 MACEs (33.0%) occurred.
The presence of ASPB was associated with increased all-cause mortality (33.3% vs. 5.6%, p=0.002) and MACE (48.7% vs 22.2%, p=0.01). RALS&gt;1 correlated also with all-cause mortality (31.8% vs. 12.5%, p=0.04) and with new bundle branch block and indication for pacemaker implantation (46.2% vs 37.0%, p=0.05). P with GLS&gt;−14.8% and ASPB had significantly worse prognosis regarding all-cause mortality (p=0.003) and MACE (p=0.007). Kaplan–Meier survival analysis showed that survival was significantly worse for P with ASPB (log-rank 0.002). With multivariate Cox regression analysis, ASPB was independently associated with all-cause mortality (HR=4.49, p=0.039).

Conclusions
Suspected CA appears prevalent among patients with AS and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation.

Funding Acknowledgement
Type of funding source: None
Iatrogenic transthyretin cardiac amyloidosis after sequential liver transplantation
Authors: Costa R , Rodrigues P , Felix R , Oliveira M , Frias A , Campinas A , Santos M , Reis H , Torres S 
Published: November 2020

Abstract

Introduction
Sequential liver transplantation (SLT) uses livers excised from patients with hereditary transthyretin-related amyloidosis during liver transplantation as grafts to other patients with severe hepatic pathologies and a reserved prognosis. We intended to investigate the development of cardiac manifestations consistent with iatrogenic transthyretin amyloidosis (iATTR).

Methods
We retrospectively analyzed the medical records of 72 consecutive patients submitted to SLT between 2007 and 2010, who received livers with V30M mutation.

Results
Our sample had 79% male patients and a mean age at transplantation of 55±6 years. Median follow-up time was 80 months, were 44% of the patients died. One-year mortality rate after SLT was 7%. Clinical manifestations of iATTR occurred in 29% of individuals, on average 6 years after SLT, and amyloid was seen in 76% of those who underwent a biopsy. Left ventricular hypertrophy (LVH) was identified in 42 (58%) patients at baseline. Considering 39 patients that had an echocardiography at baseline and during follow-up, 22 (61%) presented de novo LVH or basal LVH worsening during follow-up, with a significant increase of wall thickness (11±1 to 13±3 mm; p&lt;0.001). They had similar age at presentation (55±5 vs 58±5, p=0.249) and incidence of hypertension (52% vs 64%, p=0.365) but higher incidence of chronic kidney disease (CKD; 68% vs 29%, p=0.023). Mortality during follow-up was higher in patients with de novo LVH or worsening LVH but not significantly, probably due to the sample size (23% vs 7%, p=0.221, log rank test p=0.262). Considering the global sample, significant conduction changes were rarely seen (1 patient); however, there was a trend towards an increase in PR interval and atrial fibrillation was reported in 8% of cases.

Conclusions
In our sample, probable iATTR was often seen within a decade after SLT. Further investigation of LVH needs to be made in these patients, as it can represent amyloid cardiomyopathy, but other contributing factors such as hypertension, CKD and age need to be taken into consideration. In our sample, development of a possible infiltrative pattern was relatively more common and conduction disorders were rarer than one would extrapolate from hereditary early onset ATTR V30M patients. Further studies may help us clarify if indeed these patients behave like late onset ATTR V30M. Our data suggests that these patients should probably undergo periodic cardiac imaging during follow-up.

Funding Acknowledgement
Type of funding source: None
Sarcoid heart disease: rates of arrhythmias, implantable cardiac devices and endomyocardial biopsy
Authors: Gonuguntla K , Patil S.P , Rojulpote C , Borja Z.E , Bravo P.E 
Published: November 2020

Abstract

Introduction/Background
Sarcoidosis is a granulomatous disease with various cardiac manifestations such as arrhythmias, heart block, heart failure and sudden cardiac death.

Objective
We sought to determine and compare the rates of arrhythmias, implantable cardiac devices in patient with sarcoid heart disease (SHD) after excluding those with a history of coronary artery disease

Methods
The United States Nationwide Inpatient Sample was queried from 2010 to 2014 using ICD-9 diagnosis code (135) for sarcoidosis among patients &gt;18 years. We combined it with code (425.8) for cardiomyopathy in others disease including sarcoid and sarcoid heart muscle disease. We excluded patients with a history of prior myocardial infarction, percutaneous coronary intervention and coronary artery bypass graft.

Results
From 2010 to 2014, we identified 9,063 patients with SHD (Mage = 53.11±11.28 years; men 51.8% and black 52.5%). The overall in-hospital mortality rate was 227 (2.5%). Average Length of stay (LOS) (M ± SD) was 6.15±8.964. Various arrhythmias include atrial fibrillation 1,659 (18.4%), ventricular fibrillation 223 (2.5%), ventricular tachycardia 2,248 (24.7%), complete heart block 506 (1.5%) and second degree Mobitz type II 45 (0.5%). Rates of implantable cardiac devices included implantable cardioverter-defibrillator (ICD) 881 (9.7%), Cardiac Resynchronization Therapy Defibrillator (CRT-D) 83 (3.6%), PPM 172 (1.9%). Rates of Endomyocardial biopsy were 257 (2.8%). Overall rates of sudden cardiac arrest was 161 (1.8%). On comparing the two groups, sarcoidosis without cardiac involvement and sarcoid heart disease the rates of arrhythmias, implantable cardiac devices, in-hospital mortality and sudden cardiac arrest were as follows: atrial fibrillation (9.4 vs 18.3; p&lt;0.001), ventricular fibrillation (0.1 vs 2.5; p&lt;0.001), ventricular tachycardia (1.3 vs 24.8; p&lt;0.001), complete heart block were (0.3 vs 5.6; p&lt;0.001), and second degree Mobitz type II (0.1 vs 0.5; p&lt;0.001), Pacemaker (0.4 vs 1.9; p&lt;0.001), ICD (0.2 vs 9.7; p&lt;0.001), CRT-D (0.1 vs 3.6; p&lt;0.001), in-hospital mortality (2.5 vs 2.5; p=0.8), Sudden cardiac arrest (0.6 vs 1.8; p&lt;0.001).

Conclusions
Based on the results of our study, we conclude that SHD is associated with a variety of cardiac arrhythmias and conduction defects. Sarcoidosis with cardiac involvement is associated with increased rates of atrial fibrillation, ventricular fibrillation, ventricular tachycardia, complete heart block, and second degree Mobitz type II. They also had a higher rate of pacemaker implantation, ICD, CRT-D and had a overall higher rate of sudden cardiac arrest. Based on the results of our study we conclude that sarcoidosis with cardiac involvement has worse outcomes and hence, early diagnosis and prompt treatment can prevent the progression of the disease.

Funding Acknowledgement
Type of funding source: None
Utility of updated diagnositc criteria to detect isolated cardiac sarcoidosis
Authors: Sato K , Yamamoto M , Ishizu T , Ieda M 
Published: November 2020

Abstract

Background
Prior study reported around one-third of cardiac sarcoidosis (CS) are considered as isolated CS. Detection of CS is challenging due to the limited sensitivity of endomyocardial biopsy and applicability of guidelines, especially in patients without extra-cardiac involvement. Existing diagnostic criteria by Japanese Ministry of health and Welfare (JMHW) or Heart Rhythm Society (HRS) require the presence of extra-cardiac sarcoidosis for clinical diagnosis, isolated CS is not diagnosable in the absence of a positive histological finding. Recently, Japanese Society of Cardiology (JCS) updated diagnostic criteria for CS, which provides the pathway to diagnose isolated CS.

Purpose
We aimed to assess the reliability of the updated CS guideline in diagnosing CS compared to the prior guidelines.

Methods
We retrospectively identified 162 consecutive patients who underwent FDG-PET for suspected CS from 2012 through 2019. According to the updated JCS diagnostic criteria, patients were classified as histologic diagnosis of CS, clinical diagnosis of CS, or isolated CS (Figure A). We compared the association between diagnostic criteria and response with anti-inflammatory therapy.

Results
The JCS criteria classified 24 patients (15%) as having clinical CS, 4 (3%) as histological diagnosis of CS, and 21 (13%) as isolated CS. The JMHW criteria defined 22 patients (14%) as having CS (clinical 11%, histological 3%) and HRS criteria classified 11 patients (7%) as having CS (clinical 4%, histological 3%). Extra-cardiac involvement was detected in 36 patients (22%) with 8% of histological confirmation. Among the 126 patients without extra-cardiac involvement, prevalence of cardiac involvement was higher in isolated CS (P&lt;0.05 for all). Compared with clinical diagnosis group, patients with isolated CS showed higher incident of regional wall motion abnormality (WMA) or left ventricular (LV) dysfunction (p=0.023). In the subgroup of 45 patients with serial FDG-PET evaluation, only updated CS criteria was associate with improvement in myocardial inflammation by FDG-PET (p&lt;0.001).

Conclusions
Updated JCS diagnostic criteria detects CS patients with active myocardial inflammation which require anti-inflammatory therapy regardless of extra-cardiac involvement better than the prior guidelines.
Diagnostic criteria for CS

Funding Acknowledgement
Type of funding source: None