bluuebunny/crossref_metadata_2025 huggingface dataset:
Infective endocarditis in patients with solid organ transplantation. A nationwide study
Authors: Martinez-Selles M , Valerio M , Farinas M.C , Rodriguez-Abella H , Navarro M.L , De Alarcon A , Gutierrez E , Cobo M , Goenaga M.A , Moreno A , Dominguez F , Garcia L , Dominguez L , Munoz P
Published: November 2020

Background

An increase in nosocomial and health care-related infective endocarditis (IE) has been described. Solid organ transplantation (SOT) implies immunosuppression and frequent health care contact. Our aim was to compare characteristics of patients with IE and SOT against those without SOT.

Methods

We used data from the Spanish Collaboration on Endocarditis obtained during the period 2008–2018.

Results

We identified 4794 cases of IE, 85 (1.8%) in SOT (56 kidney, 18 liver, 8 heart, 3 lung). Thirteen patients had other types of transplantation (bone marrow, hematopoietic precursors, and cornea) and were excluded from the analysis. Compared with patients without SOT, patients with SOT had a higher median age (69 vs. 61 years, p<0.001), more comorbidities (mean age-adjusted Charlson index 5.7±2.9 vs. 4.9±2.9, p=0.004), a lower prevalence of native valvular heart disease (29.4 vs. 45.4%, p=0.003), more in-hospital and healthcare-related IE (70.5% vs. 36.3%, p<0.001) and Staphylococcus etiology (57.7% vs. 39.7%, p=0.001). Regarding evolution, patients with SOT had more frequent kidney function worsening (47.1% vs. 34.6%, p=0.02), septic shock (25.9% vs. 12.1%, p<0.001), sepsis (27.1% vs. 17.2%, p=0.02). Surgery indication (54.1% vs 66.3%, p=0.02) and surgery (32.9% vs. 46.3%, p=0.01) were less frequent in patients with SOT. We were unable to find significant differences in mortality: inhospital (30.6% vs. 25.6%, p=0.31), 1-year (38.8% vs. 31.9%, p=0.18).

Conclusion

IE in SOT patients has specific characteristics. Most of the cases are nosocomial and over 70% are hospital-or health care-related. Half have previously normal heart valves and almost 60% are due to Staphylococcus infections.

Figure 1. Kaplan Meier survival curves for patients with and without solid organ transplantation (SOT). SOT: 56 kidney, 18 liver (2 combined with kidney), 8 heart, 3 lung.

Funding Acknowledgement

Type of funding source: None
18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-PET/CT) for the diagnosis of native valve infective endocarditis (NVIE): a prospective study
Authors: Philip M , Delcourt S , Cammilleri S , Gourriet F , Tessonnier L , Casalta J.P , Gardenat A , Gerard H , Riberi A , Hubert S , Habib G
Published: November 2020

Background and objectives

18F-FDG PET/CT has recently been added as a major criterion in the ESC 2015 infective endocarditis (IE) guidelines. We and others have demonstrated that18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) was useful in patients with suspected prosthetic valve and cardiac device IE. However, the sensitivity and specificity of ESC classification is unknown in patients with native valve endocarditis (NVE) as well as the clinical impact of PET findings.

Purposes

1. Primary objective: To assess the value of the new ESC criteria including 18F-FDG PET/CT in native valve infective endocarditis (NVIE).

2. Secondary objectives:

– to determine the usefulness of PET/CT concerning embolic or neoplastic detection.

– to describe a new PET/CT feature, i.e. the diffuse splenic uptake.

Methods

Between 2012 and 2017, 75 patients with suspected NVIE were prospectively included, after exclusion of patients with uninterpretable or not feasible PET/CT. Using the expert consensus of the Endocarditis Team after a 3-month follow-up as gold standard, 63 IE were confirmed and 12 were rejected. Patients follow-up was scheduled at one and three months after hospitalization.

Results

Significant cardiac uptake by PET/CT (major criterion) was observed in 11 among 63 patients with definite NVIE and no patients with rejected IE (sensitivity 18%, specificity 100%). Among the 63 patients with a final diagnosis of NVE, a peripheral embolism or mycotic aneurysm was observed in 20 cases (32%). Considering this, the ESC 2015 classification increased the sensitivity of Duke criteria from 64 to 70% (p<0.001) without no change on specificity (p<0.001). Twenty-four patients (38%) were diagnosed with secondary infectious sites or infectious portal of entry. A diffuse splenic uptake was observed in 39 (52%) patients, including 37 (59%) of patients with a final diagnosis of NVE (specificity 83%).

Conclusion

1. The value of 18F-FDG PET/CT in NVE diagnosis is poor (18% sensitivity)

2. Usefulness of PET/CT remains high when concerning embolic or neoplastic detection.

3. Our study describes for the first time in NVE a new potential endocarditis criterion, i.e. the presence of a diffuse splenic uptake on 18F-FDG PET/CT

Diffuse splenic uptake

Funding Acknowledgement

Type of funding source: None
Cardiovascular phenotyping of the first mouse model of Sarcoidosis
Authors: Bueno Beti C , Lim C , Protonotarios A , Kiss A , Sheppard M.N , Szabo P.L , Behr E , Hamza O , Podesser B , Weichhart T , Asimaki A
Published: November 2020

Introduction

Sarcoidosis is a potentially life-threatening, inflammatory, granulomatous disease that affects multiple organs including the heart. Heretofore, its unknown etiology had hindered the creation of experimental models and the understanding of the molecular mechanisms of pathogenesis behind it.

Purpose

To extensively phenotype the heart of the first mouse model of sarcoidosis created through deletion of the tuberous sclerosis 2 (Tsc2) gene in the CD11c-positive macrophage population.

Methods

Tsc2 fl/fl CD11c Cre+ (Tsc2-KO; n=7) and Tsc2 fl/fl CD11c Cre- (Tsc2-WT; n=7) mice were subjected to echocardiography at 25 weeks of age (woa) to assess myocardial dimensions and function. Hearts of 13 and 25woa animals were subjected to histological and immunological stains to assess tissue changes, subtype inflammatory infiltrates and examine the localization of key proteins shown to be re-distributed in patients.

Results

At 13 woa, Tsc2-KO animals show inflammatory infiltrates; subtyped mainly as macrophages as well as evidence of myocyte destruction. At 25 woa, the number of inflammatory cells is significantly higher and there is heavy fibrotic replacement primarily in the septum and trabeculae. Older animals also show giant cells and non-necrotizing granulomas. The hearts show heterogeneous gap junction remodeling known to constitute an arrhythmogenic substrate and lack of immunoreactive signal for the desmosomal protein plakoglobin from the cell-cell junctions just as described in patients. The left ventricular ejection fraction and LV morphology was not significantly different between the two groups (EF: 64±4% in Tsc2-KO vs 64±2% in Tsc2-WT; LV end-systolic diameter: 4.51±0.54 mm in Tsc2-KO vs 4.59±0.29 mm in Tsc2-WT). However, there was a strong trend towards increasing filling pressure (E/e'ratio; 14.24±4.01 vs 12.15±2.54) and mean pulmonary pressure (21±6 vs 18±3 mmHg) in Tsc2-KO mice compared to controls suggesting diastolic dysfunction.

Conclusion

Hearts of the Tsc2 fl/fl CD11c Cre+ animals show a phenotype highly reminiscent of cardiac sarcoidosis in patients. We anticipate that this model will be very useful in deciphering molecular mechanisms of pathogenesis as well as testing much-needed mechanism-based therapies.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): British Heart Foundation - PG/18/27/33616
High sensitive troponin T as gatekeeper for cardiac magnetic resonance imaging in patients with suspected acute myocarditis
Authors: Frick M , Bauermann K , Kirschfink A , Hamada S , Weber O , Marx N , Altiok E
Published: November 2020

Background

The diagnosis of acute (AM) is difficult because of the variable, unspecific clinical presentation. Cardiac magnetic resonance (CMR) is the noninvasive gold standard diagnostic tool, but limited availability and high costs make a quick and inexpensive test necessary to clarify the need for CMR. Quantification of high sensitive Troponin T (hsTNT) is a broadly available, specific blood test for cardiomyocyte damage.

Aim

The aim of this study was to evaluate hsTNT as a gatekeeper for CMR with a lower cut off-value for exclusion and an upper cut-off value for confirmation of acute myocarditis as defined by CMR.

Methods

This retrospective analysis included 244 patients (age 39±17 years, 71% male) who received CMR for clinically suspected AM and quantification of hsTNT within 28 days (Median: 2 days) of CMR. CMR (1.5 Tesla) consisted of cine-sequences, edema-sensitive T2 and late gadolinium enhancement (LGE) imaging. AM was diagnosed in presence of both, myocardial edema and LGE consistent with acute myocarditis.

Results

Of 244 patients, 78 (32%) were CMR-positive (CMR+) for AM. 166 (68%) were CMR negative (CMR−). Mean hsTNT was 206±454 pg/ml.

HsTNT was significantly higher in CMR+ than in CMR− (604±639 pg/ml vs 20±56 pg/ml, p<0.001, see figure A). 8 CMR+ patients (10%) had hsTNT in the normal range (<14 ng/ml).

HsTNT showed good discriminatory performance in the Receiver Operator Characteristic (ROC) analysis (AUC 0.91, see figure B).

A lower cut-off value of 4 pg/ml had a sensitivity of 98.7% for diagnosis of AM (hsTNT ≥4 pg/ml) and a negative predictive value of 98.2% for rule out of AM (hsTNT<4 pg/ml) as defined by CMR, leading to a reduction of 23.4% of CMR exams. An upper cut-off value of >343 pg/ml had a specificity of 99.4% and positive predictive value of 97.8% for diagnosis of AM, leading to a reduction of 18.4% of CMR exams (see table).

Conclusions

hsTNT showed good discriminatory capacity for acute myocarditis (AM) as defined by CMR. However, 10% of patients had hsTNT in the normal range (<14 pg/ml). A lower cut-off value of <4 pg/ml ruled out AM with very high negative predictive value, whereas an upper cut-off of >343 pg/ml had a very high positive predictive value for confirmation of AM as defined by CMR. Performing CMR only in patients with hsTNT between 4 and 343 pg/ml would have led to a reduction of 41.8% of CMR exams.

Funding Acknowledgement

Type of funding source: None
Regional disparities in the clinical profiles of patients with peripartum cardiomyopathy in Nigeria: results from the peripartum cardiomyopathy in Nigeria Registry
Authors: Karaye K , Sai'du H , Balarabe S.A , Ishaq N.A , Adamu U.G , Mohammed I.Y , Oboirien I , Umuerri E.M , Mankwe A.C , Shidali V.Y , Dodiyi-Manuel S , Olunuga T , Josephs V , Mbakwem A.C , Ogah O.S
Published: November 2020

Background

Peripartum cardiomyopathy (PPCM) seems to have varied epidemiology within and between countries. We recently reported that Kano (North-West Nigeria) has the highest known incidence of PPCM in the world, but the clinical profiles of the patients by regions have not been previously reported. In this study, we aimed to describe the regional differences (if any) in the clinical profiles of patients with PPCM in Nigeria.

Methods

We consecutively recruited 244 PPCM patients over 9 months from 3 hospitals in Kano (n=199; 81.6%) and from 11 hospitals spread across the North-Central, South-West, South-East and South-South zones (n=45; 18.4%) of Nigeria.

Results

The baseline characteristics of the patients are summarised in Table 1. 35 (17.6%) patients in Kano and 10 (23.2%) patients in other zones died (p=0.0523) after a median of 17 months.

Conclusion

PPCM patients in Kano were younger, had lower socio-economic status, presented to hospitals later, were less symptomatic, had larger sizes of cardiac chambers, worse right ventricular systolic function, higher pulmonary artery systolic pressure and were receiving less treatment at enrolment, than those in other zones in Nigeria. This information will be used for advocacy and interactions with healthcare providers.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Dantata Group of Companies (Nigeria). Ammasco International Ltd. (Nigeria). Fortune Oil Mills Nigeria Ltd.
Penetrance of hypertrophic cardiomyopathy and outcome in sarcomeric mutation carriers
Authors: Lorenzini M , Norrish G , Field E , Ochoa J.P , Cicerchia M , Akhtar M.M , Syrris P , Lopes L.R , Kaski J.P , Elliott P.M
Published: November 2020

Background

Predictive genetic screening of the first degree relatives of patients with hypertrophic cardiomyopathy (HCM) caused by sarcomere protein (SP) gene mutations is current standard of care, but there are few data on long-term outcomes in mutation carriers without HCM.

Purpose

To establish the role of sex and genotype in HCM penetrance as well as the rate of major adverse clinical events in SP mutation carriers and following the diagnosis of HCM.

Methods

Retrospective analysis of consecutive adult and paediatric SP mutation carriers identified during family screening and who did not fulfill diagnostic criteria for HCM at first evaluation.

Results

321 individuals from 170 families [median age first evaluation 15.2 years (IQR 7.3–32.6); 153 (47.7%) males] were evaluated. Causal SP genes were: MYBPC3 (n=133 (41.4%)), MYH7 (n=77 (24.0%)), TNNI3 (n=51 (15.9%)), TNNT2 (n=40 (12.5%)), TPM1 (n=9 (2.8%)), MYL2 (n=6 (1.9%)), and ACTC1 (n=1 (0.3%)); 4 (1.3%) carried multiple mutations.

After a median follow up of 7.4 years (IQR 2.5–12.7), 89 (27.7%) patients developed HCM. Disease penetrance at the age of 50 years was 47% (95% CI 38%-56%). One hundred and fifty three (47.7%) individuals underwent cardiac magnetic resonance (CMR) imaging; among those diagnosed with HCM, 22/89 (24.7%) fulfilled criteria on CMR but not echocardiography.

In a multivariable model adjusted for genotype, follow up duration and evaluation with CMR, independent predictors of HCM development were male sex (HR 3.11; CI 1.82–5.32) and abnormal ECG (HR 7.87; CI 4.43–13.97). Patients with MYH7 and multiple mutations were more likely to develop HCM than those with MYBPC3 mutations (HR 2.03; CI 1.04–3.96 and HR 10.13; CI 1.40–72.92, respectively). Disease penetrance was lowest in carriers of TNNI3 mutations (HR 0.13; CI 0.03–0.48).

There were no major adverse events in individuals without HCM. Following the diagnosis of HCM, the combined rate of all-cause death, appropriate defibrillator shock or resuscitated cardiac arrest was 1.1%/year [median follow up 4.0 years (IQR 2.1–8.9)].

Conclusions

Approximately 50% of SP mutation carriers develop HCM by the age of 50 and become prone to disease complications during long-term follow-up. Sex, MYH7 mutations and the presence of an abnormal ECG are associated with a higher risk of disease development. CMR should be employed systematically in long-term screening.

HCM penetrance by sex

Funding Acknowledgement

Type of funding source: None
Prognostic impact of atrial fibrillation in patients with hypertrophic cardiomyopathy in a community-based Japanese cohort: results from Kochi RYOMA study
Authors: Kubo T , Sugiura K , Ochi Y , Takahashi A , Baba Y , Hirota T , Yamasaki N , Doi Y.L , Kitaoka H
Published: November 2020

Background

The prognostic impact of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) is not fully elucidated.

Purpose

The aim of this study was to examine the prevalence and prognostic impact of AF in a prospectively assembled community-based HCM patient cohort in an aged Japanese community.

Methods

In 2004, we established a cardiomyopathy registration network in Kochi Prefecture, Japan, consisting of 9 hospitals, and finally 293 patients with HCM were followed.

Results

The ages at registration and at diagnosis were 63±14 and 56±16 years, respectively, and 197 patients (67%) were men. 86 patients (29%) showed AF. During follow-up period of 6.1±3.2 years, 44 patients died. In those patients, HCM-related deaths occurred in 23 patients with an annual mortality rate of 1.3%. Regarding HCM-related adverse events including HCM-related deaths, appropriate ICD discharge, heart failure admission and hospitalization for embolic events, a total of 77 cardiovascular events in 70 patients occurred. Multivariate analysis revealed that presence of AF, left ventricular (LV) outflow obstruction, NYHA functional class III, and lower LV fractional shortening at registration were significant predictors of these adverse events. During the follow-up period, additional 31 patients (11%) developed new-onset AF. Importantly, the incidence of HCM-related adverse events was significantly higher in patients with new AF observed from its onset compared with those with AF at registration (log-rank p=0.029) (Figure 1).

Conclusions

In an unselected HCM registry in an aged Japanese community, presence of AF, particularly new-onset AF, was associated with unfavorable clinical outcomes. AF is not just a marker of the disease stage but an important trigger of HCM-related adverse events.

Figure 1

Funding Acknowledgement

Type of funding source: None
Matrix metalloproteainase-3 polymorphism association with hypertrophic cardiomyopathy
Authors: Fourti N , Benhlima M , Guizani I , Aloui S , Zaroui A , Zidi W , Mechmeche R , Mourali M.S , Feki M , Allal Elasmi M
Published: November 2020

Background

Matrix metalloproteinase-3 (MMP-3) level disequilibrium in hypertrophic cardiomyopathy (HCM) may be due to a specific genetic variation. The MMP-3 gene promoter contains an insertion/deletion polymorphism characterized by an array of 5 or 6 adenosine residues (5A/6A) at –1612 positions.

Purpose

The aim was to analyze whether the MMP-3 5A/6A gene promoter polymorphism is related to its level in HCM patients.

Methods/Results

In this study, we recruited 33 HCM patients and 35 non-HCM. The ELISA sandwich assay measured MMP-3 plasmatic level. The MMP-3 –1612 5A/6A polymorphism was genotyped by RFLP-PCR. The studied population was consistentin Hardy-Weinberg equilibrium. There were 17% 5A/5A homozygotes, 65% 6A/6A homozygotes, and 17% 5A/6A heterozygotes. The HCM was related to the existence of the –1612 5A/6A polymorphism (p<0.05). Patients carrying the 5A allele had a higher MMP-3 level than those with the 6A allele (16.03±9.43 vs 8.68±5.89 ng/ml, respectively; p=0.01).

Conclusion

Our data shows that the –1612 5A/6A MMP-3 gene polymorphism is associated to the hypertrophic cardiomyopathy and do influence the MMP-3 plasmatic circulating level.

Funding Acknowledgement

Type of funding source: None
Discovery and analyses of pathogenic variants in explanted hearts from primary cardiomyopathy patients
Authors: Gunnarsdottir O , Kim Y , Reichart D , Nguyen Q , Zhang H , Nikhanj A , Pereira A.C , Gorham J , Depalma S.R , Seidman J.G , Oudit G , Seidman C.E
Published: November 2020

Background

Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are disorders of the myocardium that affect the structure and function of the heart.

Purpose

The primary aim of this study was to discover damaging genetic variants in myocardial tissue from patients with DCM or HCM, who underwent heart transplantation.

Methods

Whole exome sequencing was performed on myocardial tissue from 103 explanted hearts with diagnosis of cardiomyopathy; 80 DCM and 13 HCM. Sanger sequencing was performed to confirm the loss-of-function variants in genes known to be linked to cardiomyopathy. RNA sequencing was conducted to confirm copy number variation deletions detected in the cohort. Burden analysis was performed by comparing the frequency of variants found in the study cohort to the frequency in the population database gnomAD.

Results

Rare (minor allele frequency <1.0E-04) loss-of-function variants, deleterious missense variants, or copy number variation deletions, collectively described as damaging variants, were identified in cardiomyopathy genes in 42 of all 93 samples (45.2%). Damaging variants were identified in 37 of 80 DCM samples (46.3%) and 5 of 13 HCM samples (38.4%). The mean read depth for normal and variant allele were comparable. All the 28 loss-of-function variants in cardiomyopathy genes found in the cardiomyopathy cases were confirmed by Sanger sequencing. Two copy number variation deletions both in titin (TTN) were also detected and confirmed. Burden analyses showed that the genes TTN and lamin A/C (LMNA) had a higher frequency of loss-of function variants in the DCM cohort (17.5% and 3.75%, respectively) compared to the reference population with genome-wide significance (p=3.45E-22 and 4.34E-07, respectively). Furthermore, our analysis showed that deleterious missense variants in osteoclast-stimulating factor 1 (OSTF1), which previously has not been associated with cardiomyopathy, was highly enriched in the DCM cohort compared to the reference population (p=2.10E-06).

Conclusions

The frequency of damaging variants that are likely pathogenic (46.3%) is higher in DCM cases in this cohort compared to previous studies. These data indicate that patients with end-stage DCM are more likely to have a genetic cause for their disease. As read depth of variant and normal alleles were, these are likely germline and not mosaic variants, and can enable cascade testing in family members. Moreover, our study demonstrates that CNVs in TTN that alter the reading frame can cause DCM.

Funding Acknowledgement

Type of funding source: None
First-in-world assessment of outcomes of catheter ablation for atrial arrhythmias in arrhythmogenic right ventricular cardiomyopathy
Authors: Gasperetti A , James C.A , Chen L , Compagnucci P , Casella M , Dello Russo A , Tondo C , Platonov P , Jensen H.K , Schenker N , Shibu M , Kany S , Calkins H , Duru F , Saguner A.M
Published: November 2020

Introduction

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically inherited disease characterized by fibro-fatty infiltrations (FFI). FFI in ARVC patients usually originates in the ventricles, but recent imaging studies showed FFI at the atrial level as well. Effectiveness of catheter ablation (CA) for atrial arrhythmias (AA) in this subset of patients is currently unknown.

Purpose

Aim of our study is to describe acute and long-term effectiveness of CA for AA in ARVC patients.

Methods

Nine ARVC registries from Europe, US, and China were retrospectively searched for ARVC patients undergoing CA for AA (namely: atrial fibrillation (AF), atrial tachycardia (AT), and cavo-tricuspid dependent atrial flutter (CTI-FL)). Baseline, procedural, and long-term outcome data were collected.

Results

Thirty-five pts (86% male, median CHA2DS2-VASc 1 [1–2], HAS-BLED 1 [0–2], and EHRA scores 2 [2–3]) were enrolled, in which a total of 45 CA procedures for AA were performed (left atrial CA: n=19 AF, n=10 AT; right atrial CA: n=16 CTI). Mean age at AA CA was 48.2±14.8 y.o. At baseline, 63% of pts were on oral anticoagulants (OAC) (n=9 warfarin; n=13 NOAC). Catheter ablation was successful and sinus rhythm obtained at the end of the procedure in all patients, with 2 (6%) AF patients requiring electrical cardioversion. Over a median follow-up of 36 [14–74] months, 12 (27%) pts experienced arrhythmia recurrence (left atrial group: n=6 AF recurrences, n=3 AT recurrences; CTI-FL group: n=1 CTI-FL recurrence; n=1 new AF with previous CTI-dependent flutter ablation), with a 1-year follow-up resulting comparable to what has been reported in the literature for the general population. [Figure 1 and 2]. 61% pts were on OAC at last follow-up.

Conclusion

Age at the time of CA for AA is about 10 years younger in patients with ARVC as compared to the general population. CA for AA in ARVC pts is safe and effective; surprisingly, long-term CA outcomes for AF and left AT result comparable to those reported in the general population, whereas recurrence rates of CTI-dependent flutter seem to be higher.

Funding Acknowledgement

Type of funding source: None
Long time clinical course of cardiac sarcoidosis with corticosteroid therapy -from Japanese nationwide questionnaire survey-
Authors: Kamada H , Ishibashi K , Nakajima K , Ueda N , Kamakura T , Wada M , Yamagata K , Inoue Y , Miyamoto K , Nagase S , Noda T , Aiba T , Isobe M , Terasaki F , Kusano K
Published: November 2020

Background

Sarcoidosis is a systemic inflammatory syndrome of unknown etiology and cardiac involvement has been reported to be an important prognostic factor in this disease. An autopsy study has reported that the frequency of this cardiac involvement (cardiac sarcoidosis: CS) varies in the different countries and races and very frequent in Japanese patients. We therefore performed the nationwide questionnaire survey and try to clarify the clinical characteristics and corticosteroid effect in CS, especially focused on arrhythmic events in this disease.

Methods

Total of 757 Japanese patients from 57 hospitals who diagnosed CS were examined. Patients who unsatisfied the criteria of the Japanese new guidelines, or who underwent cardiac transplantations were excluded, and 420 patients (287 females, median follow-up periods 1864 days [interquartile range: 845–3159 days]) were analyzed. The clinical outcome and corticosteroid effect were evaluated.

Results

Clinical characteristics at diagnosis was as follows: female dominant (68%), mean age of 60±13 years old, mean left ventricular ejection fraction was 49±16%. Arrhythmic events were very frequently observed as an initial cardiac manifestation in 263 patients (62%) of CS, of which atrioventricular block (AVB) in 174 (41%), ventricular tachycardia (VT) in 73 (17%) and AVB with VT in 17 (4%) (Figure 1A). Pacemaker was implanted in 166 patients (40%) and defibrillators was 137 patients (33%). Corticosteroid was prescribed in 144 (83%) of 174 patients with AVB and in 62 (85%) of 73 patients with VT. Initial dose was mean 47.9 mg and maintenance dose of mean 7.3 mg. Corticosteroid improved VT as good as AVB (27% vs. 29%). However, corticosteroid sometimes worsened VT events compared with AVB (10% vs. 2%) (Figure 1B). During the course of follow-up, 32 patients were needed to increase corticosteroid in 23 of AVB and 10 of VT cases. However, there were no difference in mortality between the groups, whether or not to increase corticosteroid. All survival rate was 92% (5-year mortality), 83% (10-year mortality) and free from all cause death and defibrillator charge was 81% (5 year), 71% (10 year).

Conclusion

Fatal arrhythmia is commonly observed in CS as a primary symptom. Corticosteroid sometimes worsen ventricular arrhythmia and appropriate defibrillator discharge was common. Thus, careful attention for activating ventricular arrhythmia would be needed during the follow-up period even after corticosteroid therapy.

Funding Acknowledgement

Type of funding source: None
Quantitative and functional evaluation of endothelial progenitor cells in patients with cardiac amyloidosis
Authors: Itzhaki Ben Zadok O , Leshem-Lev D , Ben-Gal T , Hamdan A , Schamroth-Pravda N , Steinmetz T , Kandinov I , Kornowski R , Eisen A
Published: November 2020

Background

Endothelial microvascular dysfunction is a known mechanism of injury in cardiac amyloidosis (CA), but evidence regarding the level and function of endothelial progenitor cells (EPCs) in patients with CA is lacking.

Methods

Study population included patients with light-chain or transthyretin (ATTR) CA. Patients with diagnosed heart failure and preserved ejection fraction (HFpEF) without monoclonal gammopathy and a 99mTc-DPD scan incompatible with TTR were used as controls. Blood circulating EPCs were assessed quantitatively by the expression of VEGFR-2(+), CD34(+) and CD133(+) using flow cytometry, and functionally by the formation of colony forming units (CFUs). MTT assay was used to demonstrate cell viability. Tests were repeated 3 months following the initiation of amyloid-suppressive therapies (either ATTR-stabilizer or targeted chemotherapy) in CA patients.

Results

Our preliminary cohort included 14 CA patients (median age 74 years, 62% ATTR CA).

Patients with CA vs. patients with HFpEF (n=8) demonstrated lower expression of CD34(+)/VEGFR-2(+) cells [0.51% (IQR 0.4, 0.7) vs. 1.03% (IQR 0.6, 1.4), P=0.043] and CD133(+)/VEGFR-2(+) cells [0.35% (IQR 0.23, 0.52) to 1.07% (IQR 0.6, 1.5), P=0.003]. Functionally, no differences were noted between groups. Following the initiation of amyloid-suppressive therapies in CA patients, we observed the up-regulation of CD34(+)/VEGFR-2(+) cells [2.47% (IQR 2.1, 2.7), P<0.001] and CD133(+)/VEGFR-2(+) cells [1.38% (IQR 1.1, 1.7), P=0.003]. Moreover, functionally, active EPCs were evident microscopically by their ability to form colonies (from 0.5 CFUs [IQR 0, 1.5) to 2 CFUs (IQR 1, 3.5), P=0.023]. EPCs' viability was demonstrated by an MTT assay [0.12 (IQR 0.04, 0.12) to 0.24 (IQR 0.16, 0.3), p=0.014].

Conclusions

These preliminary results demonstrate reduced EPCs levels in CA patients indicating significant microvascular impairment. Amyloid-targeted therapies induce the activation of EPCs, thus possibly promoting endothelial regeneration. These findings may represent a novel mechanism of action of amyloid-suppressive therapies

EPCs in CA patients and during therapy

Funding Acknowledgement

Type of funding source: None
Long-term follow up ventricular tachycardia patients with preserved cardiac function -from Japanese cardiac sarcoidosis nationwide questionnaire survey-
Authors: Kamada H , Ishibashi K , Nakajima K , Ueda N , Kamakura T , Wada M , Yamagata K , Inoue Y , Miyamoto K , Nagase S , Noda T , Aiba T , Isobe M , Terasaki F , Kusano K
Published: November 2020

Background

Prior ventricular tachycardia (VT) and low left ventricular ejection fraction (LVEF) are the most important prognostic factors in cardiac sarcoidosis (CS). Recently diagnosis of CS was renewed according to Japanese new guidelines. Patients with preserved cardiac function often have VT events, thus new guidelines recommends to assess the implantable cardioverter defibrillator (ICD) implantation for CS patients with preserved LVEF (35%≤LVEF<50%). However, the long-term prognosis of CS patients with preserved LVEF is unclear.

Objective

In CS patients with preserved LVEF, we evaluated the prognosis between VT manifestation and non-VT manifestation groups at CS diagnosis from Japanese nationwide questionnaire survey.

Methods

Total of 757 Japanese patients from 57 hospitals who diagnosed CS were examined. Patients who unsatisfied the criteria of the Japanese new guidelines, who had LVEF≤35%, LVEF>50%, or who underwent cardiac transplantations were excluded. 104 patients with LVEF 35–50% (67 females, mean age 60±15 years old, median follow-up periods 2134 days [interquartile range: 758–2935 days]) were analyzed. The prognosis between VT manifestation and non-VT manifestation groups at CS diagnosis were evaluated.

Results

30 patients had VT manifestation at CS diagnosis and 24 patients (80%) received ICDs. 74 patients had no VT manifestation at CS diagnosis and 19 patients (44%) received ICDs during follow up period. All-cause mortality was not different between two groups (Figure). Appropriate ICD therapy of non-VT manifestation group was significantly lower compared with that of VT manifestation group (log-rank p=0.001), however considerable number (n=7, 15%) of non-VT manifestation group had appropriate ICD therapy event during follow-up period. Cox hazard analysis revealed that concomitant non-sustained VT (NSVT) with atrioventricular block (AVB) was a predictor of appropriate ICD therapy in non-VT manifestation group.

Conclusion

This nationwide survey showed that considerable number of CS patients with preserved LVEF had VT events, independent of VT manifestation. Concomitant NSVT with AVB was a predictor of VT events, and ICD implantation should be assessed.

Funding Acknowledgement

Type of funding source: None
Cardiac function at diagnosis is important prognostic factor in patients with cardiac sarcoidosis -from Japanese nationwide questionnaire survey-
Authors: Kamada H , Ishibashi K , Nakajima K , Ueda N , Kamakura T , Wada M , Yamagata K , Inoue Y , Miyamoto K , Nagase S , Noda T , Aiba T , Isobe M , Terasaki F , Kusano K
Published: November 2020

Background

Sarcoidosis is a systemic non-caseating granulomatous disease of unknown etiology. Cardiac involvement (cardiac sarcoidosis, CS) has been reported to be an important prognostic factor in this disease because of heart failure and/or ventricular arrhythmia, and corticosteroid therapy is usually prescribed to prevent cardiac events. However, little is known about the relationship of cardiac function and concomitant corticosteroid therapy on later cardiac events in CS.

Objective

We evaluated the relationship between prognosis and left ventricular ejection fraction (LVEF) at the time of diagnosis in CS patients from the Japanese nationwide questionnaire survey.

Methods

Total of 757 Japanese patients from 57 hospitals who diagnosed CS were examined. Patients who unsatisfied the criteria of the Japanese new guidelines, or who underwent cardiac transplantations were excluded, and 420 patients (287 females, mean age 60±13 years old, median follow-up periods 1864 days [interquartile range: 845–3159 days]) were analyzed. The relationship of adverse events (all-cause death, cardiovascular death, and appropriate ICD [Implantable Cardioverter Defibrillator] discharge) and LVEF (with corticosteroid 84%) (low LVEF: LVEF≤35% n=98 [with corticosteroid in 78%], moderate LVEF: LVEF 35–50% n=104 [with corticosteroid in 93%], normal LVEF: 50≤LVEF n=218 [with corticosteroid in 83%]) were evaluated respectively.

Results

89 CS patients developed all-cause death (n=50), cardiovascular death (n=30) or appropriate ICD discharge (n=48). The frequency of corticosteroid therapy was not different in the each LVEF group, but Kaplan-Meier analysis revealed that all-cause death, cardiovascular death, and all cardiovascular adverse events were more observed in lower LVEF group (log-rank p<0.0001). Furthermore, multivariate Cox hazard analysis revealed that LVEF was a most important independent prognostic factor in CS.

Conclusion

This Japanese nationwide questionnaire survey data showed that initial LVEF was an independent and strong prognostic predictor in CS, therefore primary prevention would be needed even after starting corticosteroid in patients with decreased cardiac function.

Funding Acknowledgement

Type of funding source: None
Recurrences of disease activity in patients with cardiac sarcoidosis under corticosteroid therapy: prevalence, clinical background and prognosis
Authors: Kaneta K , Takahama H , Tateishi E , Moriuchi K , Amano M , Okada A , Amaki M , Hasegawa T , Ohta Y , Kiso K , Kanzaki H , Kusano K , Yasuda S , Izumi C
Published: November 2020

Background

Corticosteroid therapy (CTx) has been widely accepted as first-line therapy for cardiac sarcoidosis (CS), but there are very limited data regarding recurrence of disease activity of CS. We retrospectively investigated the prevalence, patient characteristics and prognostic significance in patients with recurrences of CS.

Methods

We identified 102 consecutive patients who were clinically diagnosed CS (admission: 2012 and 2019) and whose disease activity was diminished clinically at least once. Recurrence of CS was defined as detection of increased uptake of 18F-fluoro-2-deoxyglucose or gallium-67 in the follow-up examination. Composite adverse events (events) were defined as all-cause of death or hospitalization for heart failure. Echocardiographic and laboratory data before initiation of CTx were obtained.

Results

During the follow-up term (median: 4.9 years), the recurrences of CS occurred in 28 patients at 30 months (median) after the initiation of CTx. In patients with recurrence, left ventricular (LV) ejection fraction before initiation of CTx was lower than in those without recurrences (median: 31% vs. 39%, p<0.05). After the detection of CS recurrences, 17 patients were treated with only increases of PSL and remaining 11 patients were treated with adding other immunosuppressive therapies to CTx. The univariate analysis demonstrated that there were no parameters in echocardiographic and laboratory examinations to predict the recurrences of CS. The results of univariate analysis for event occurrences (n=12) are shown in the Table. Additionally, the Kaplan-Meier analysis showed that there were no differences in event free survival rate in the patients with and without CS recurrences (Figure).

Conclusion

This study showed that the recurrences of disease activity were observed in a substantial number of patients with CS even under the CTx. All patients received intensification of CTx or additional immunosuppressive therapy, and LV systolic function, rather than the recurrence itself, was associated with clinical outcomes in this study.

Kaplan-Meier analysis for events

Funding Acknowledgement

Type of funding source: None
Long-term monitoring of arrhythmias in cardiac sarcoidosis
Authors: Bakker A , Mathijssen H , Balt J , Van Dijk V.F , Veltkamp M , Swaans M , Akdim F , Grutters J.C , Post M.C
Published: November 2020

Introduction

Screening for cardiac sarcoidosis (CS) is recommended since it can manifest with ventricular arrhythmias (VA), atrioventricular conduction block (AVB) and sudden cardiac death (SCD). However, risk stratification for SCD is challenging, in particular in patients without overt cardiac symptoms.

Purpose

This study reports the practice-based risk stratification for SCD and the incidence of arrhythmias and mortality in CS patients by long-term monitoring of arrhythmias.

Methods

A retrospective, single center cohort study was performed in 537 patients with sarcoidosis screened for cardiac involvement with cardiac MRI and fluorodeoxyglucose PET in an hospital, a Dutch tertiary referral center. CS was diagnosed in 115 of 537 patients (21%), complete follow up was available in 108 patients (94%). After risk assessment for SCD (figure 1) an ICD was implanted in 16 high-risk patients. Within the92 low-risk patients, 80 had an internal loop recorder (ILR) implanted and 12 patients received no device. Chart review was performed to assess the occurrence of VA, AVB, death, ICD therapy and device related complications.

Results

During a mean follow-up of 31±15 months, 9 out of 80 ILR patients (11.3%) received an ICD of whom 7 (8.8%) based on recorded arrhythmias (VA in 5 and AVB in 2 patients).

Five out of the total 25 ICD patients (20%) experienced sustained VA successfully treated with anti-tachycardia pacing in 2 (8%) and terminated spontaneously in all other patients. Two ICD patients experienced a mild pocket infection, treated with antibiotics. Two deaths occurred in the low-risk patients: 1 non-cardiac death and 1 SCD due to asystole.

Conclusion

The practice-based risk stratification supported an ICD implantation in up to 5% of sarcoidosis patients screened for CS. Sustained VA occurred in 20% of ICD patients.Early detection of important arrhythmias with an ILR can optimize risk assessment for SCD in CS.

Practise-based risk stratification

Funding Acknowledgement

Type of funding source: None
Prominent involvement of basal left ventricular longitudinal strain in patients with monoclonal gammopathy of undetermined significance
Authors: Canonico M.E , Fiorillo L , Santoro C , Lembo M , Esposito L , Capone V , Casciano O , Esposito R , Galderisi M
Published: November 2020

Background

In cardiac amyloidosis the application of Speckle Tracking Echocardiography allows to identify a specific left ventricular (LV) longitudinal strain (LS) pattern characterized by “apical sparing”, with a prominent involvement of basal and middle segments and normal LS of apical cap. The pattern of regional LS has been never investigated in monoclonal gammopathy of undetermined significance (MGUS), a condition which can predispose to cardiac amyloidosis.

Purpose

To compare LV regional LS patterns and LS base-to-apex behaviour of patients affected by MGUS in comparison with healthy subjects.

Methods

We enrolled 40 patients affected by MGUS (M/F=20/20; age 62.6±13.8 years), asymptomatic for cardiac symptoms, and a control group of 40 healthy subjects, matched for sex and age. Nineteen (47%) MGUS patients showed prevalent free K light chain and 21 (53%) had prevalent free λ light chain. Participants underwent standard echo-Doppler exam, including Speckle Tracking of the three apical views. Global longitudinal strain (GLS), the average LS of six basal (BLS), six middle (MLS), and six apical (ALS) segments (considered in absolute values) and relative regional strain ratio RRSR [=ALS/(BLS+MLS)] were computed. Exclusion criteria were overt heart failure, LV ejection fraction <53%, coronary artery and congenital heart disease, moderate to severe valvular disease, primary cardiomyopathies, atrial fibrillation and inadequate echo imaging.

Results

The two groups were comparable for body mass index, blood pressure and heart rate. LV mass index, relative wall thickness, left atrial volume index and Doppler-derived LV diastolic parameters did not differ significantly between the two groups. LV ejection fraction was also similar in MGUS and healthy controls. GLS resulted significantly lower in MGUS group than in controls (20.5±3.0 vs. 22.4±2.0%, p<0.02). BLS (17.1±3.7 vs. 19.2±2.2%, p=0.004), MLS (24.9±3.8 vs. 27.1±3.6%, p<0.01) and ALS (25.1±3.8 vs. 27.1±3.5%, p<0.01) were significantly lower in MGUS than in controls. The intergroup difference of RRSR (0.60±0.05 vs. 0.58±0.04) did not achieve the statistical significance (p=0.26) and none of the MGUS patients had RRSR>1. The figure depicts a LS bull'eye of a MGUS patient showing the prominent involvement of LV basal segments.

Conclusions

In presence of a normal LV ejection fraction, MGUS patients show a subclinical LV longitudinal systolic dysfunction. This is testified by a reduction of GLS and of regional LS which involves mainly LV basal segments, without substantial changes of relative regional strain ratio. LV regional longitudinal dysfunction could be useful to monitor LV myocardial mechanics during follow-up of MGUS patients.

LS bull's eye in a MGUS patient

Funding Acknowledgement

Type of funding source: None
Randall-type monoclonal immunoglobulin deposition disease: description of cardiac involvement
Authors: Ramonatxo A , Garcia R , Joly F , Degand B , Bidegain N , Bouleti C , Christiaens L , Levesque S , Desport E , Bridoux F
Published: November 2020

Background

Randall-type monoclonal immunoglobulin disease (MIDD) is a rare complication of a monoclonal plasma cell clone. MIDD differs from AL amyloidosis by the presence of Congo red negative non-organized immunoglobulin (Ig) deposits, most commonly light chains (LCDD) along basement membranes and sometimes heavy chains (HCDD) or light and heavy chains (LHCDD). As AL amyloidosis MIDD is a multi-systemic disease, and affects the heart. To date no study has focused on the clinical characteristics of heart disease in MIDD.

Purpose

The aim of this study was to describe the cardiologic features of patients with biopsy-proven MIDD and suspected cardiac involvement.

Methods

This multi-center, nation-wide retrospective study extracted from the database of the French reference center for AL amyloidosis and other Ig deposition diseases between 2012 to 2019. Diagnosis of cardiac involvement was assessed according to the International Society of Amyloidosis criteria for amyloid heart disease, as follows: left ventricular hypertrophy with a diastolic septum thickness ≥12mm, NTproBNP serum level ≥332 ng / L, histological evidence on cardiac or extra cardiac biopsy of typical linear non-organized Ig deposits along basement membranes. Severity was defined according to the Mayo Clinic classification for AL amyloidosis.

Results

Among 20 patients included (mean age was 70±9 years), 11 (55%) were males; 13 (65%) were LCDD, 3 (15%) HCDD and 4 (20%) LHCDD. At diagnosis, 19 (95%) had a history of hypertension, 3 (16%) had atrial fibrillation, 3 (15%) had NYHA grade 3 or 4 dyspnea. Mayo Clinic score was stage 3a in 4 patients (20%) and stage 3b in 6 patients (30%). The most frequent ECG changes were microvoltage (40%) and pseudo Q wave (40%); 64% of patients had altered sinus variability on 24-hour Holter monitoring, one patient had a high-grade conduction disorder and another had ventricular tachycardia. On echocardiography, all showed diastolic dysfunction; mean diastolic septum thickness was 13.5mm; only one patient had LVEF impairment but 38% had global longitudinal strain impairment. 10 patients had cardiac MRI, none showed contrast enhancement after gadolinium injection.

After median follow-up of 28 months, 4 patients were hospitalized for heart failure, including 2 with cardiogenic shock. Seven (35%) patients died within a median of 10 months from diagnosis. Among patients with Mayo clinic stage 3 (a or b), 67% died within a median of 8 months from the diagnosis.

Conclusions

To our knowledge, we present the first case series dedicated to the description of cardiac parameters in MIDD patients with cardiac involvement. Except for MRI appearance of cardiac infiltration, these patients showed features close to that of AL amyloid heart disease. Overall prognosis appears seemingly poor in MIDD patients with Mayo Clinic stage 3 cardiac disease.

Funding Acknowledgement

Type of funding source: None
The right heart in cardiac amyloidosis: a comparison between subtypes and with other genetic and non-genetic causes of left ventricular hypertrophy
Authors: Palmiero G , Rubino M , Monda E , Caiazza M , Trinchillo M.G , Ascione L , Caso P , Limongelli G
Published: November 2020

Background

Right chambers involvement is common in cardiac amyloidosis (CA) but has been ever compared to control groups.

Purpose

Aim of this study is to compare right heart involvement between CA subgroups (AL vs. ATTR amyloidosis) and between CA and other forms of genetic and non-genetic left ventricular hypertrophy.

Methods

We enrolled 25 patients with CA (10 pts with AL and 15 pts with wild type ATTR amyloidosis) and 75 patients with LVH (25 HCM pts; 25 HypCMP pts; 25 AS pts). Beside routine echocardiographic measurements, we analysed right chambers dimensions and classical and novel parameters for right ventricular (RV) function [TAPSE (Tricuspid Anulus Plane Systolic Excursion), St (S' wave at RV TDI), global and free-wall strain].

Results

ATTR group showed higher right dimensions compared to AL, without differences in RV systolic parameters (see table). CA patients, compared to LVH group, showed no differences in right dimensions. RV systolic parameters were significantly reduced while diastolic Doppler parameters were higher (E/E' 21.7±9.0 vs. 11.2±5.0; p<0.0001). At ROC curve analysis TAPSE showed the best ability in discriminating CA among other forms of LVH (AUC 0.936; 95% CI: 0.879–0.993; p<0.0001), with a sensibility of 94.7% and specificity of 87.3% for a cut-off value of 19.5 mm. At Kaplan-Meier estimation CA patients showed a significantly higher cardiovascular mortality compared to LVH group (9/25 deaths vs. none). At multivariate analysis TAPSE was the only independent prognostic factor (β 1.324; 95% IC: 1.086–1.614; p<0.006).

Discussion

CA group showed a significantly impaired RV systolic function with higher pulmonary pressures compared to LVH group. TAPSE proved to be the only able to discriminate CA among genetic and non-genetic forms of LVH and also to have prognostic significance.

Funding Acknowledgement

Type of funding source: None