bluuebunny/crossref_metadata_2025 huggingface dataset:
4118Cisplatin therapy as a risk factor for incident atrial fibrillation
Authors: Chalazan B , Samra H , Patel K , Ash D , Mehta A , Konda S , McCauley M , Dawood D
Published: October 2019

Background

Although aging is a major contributor to the rising epidemic of atrial fibrillation (AF), increased numbers of cancer survivors who suffer from chemotherapy and radiotherapy mediated cardiovascular disease also appear to be especially vulnerable to developing the arrhythmia. Currently, little is known about the long-term risk of AF in patients treated with these two treatment modalities for cancer.

Purpose

To define the incidence and prevalence of AF in a thoracic tumour cohort following radiotherapy and chemotherapy.

Methods

We conducted a retrospective study from the electronic health records (EHR) of patients who had a primary tumour of the breast and lung. Patients with AF, radiotherapy or chemotherapy prior to cancer diagnosis were excluded. All patients were followed for incident AF until last censoring or death using a validated AF algorithm (positive predictive value 96%). Radiation oncology treatment reports were reviewed and chemotherapy data was extracted from the EHR and manually reviewed for 43 chemotherapeutic agents.

Results

In the tumour registry, 17,402 patients were identified by histological and pathological reports. We examined 3,336 patients with a thoracic tumour diagnosis (breast and lung) with a mean age of 62.7±12.5 (SD) years. The AF incident rate for breast and lung cancer was 1.2 and 13.5 cases per every 100 persons with a cumulative rate of 2.49 and 0.67 respectively. We observed an overall AF prevalence of 3.4% and 7.4% in the breast and lung cohorts respectively. The average follow-up duration was 4.69 years (0.0–17.8 years) in breast cancer and 1.36 years (0.0–13.9 years) in lung cancer patients. A Cox regression model revealed no association between radiotherapy and AF in either cancer type (breast: P=0.18 and lung: P=0.16). However, patients who received cisplatin had 4-fold increased risk of developing AF after covariate adjustment (HR = 4.22, 95% CI: 0.10–17.85, P=0.05).

Conclusions

We show for the first time in a large thoracic tumour registry and using the EHR that patients treated with cisplatin were more likely to develop AF. Additional studies are needed to validate our findings and to further investigate the underlying mechanisms of these cardiotoxic effects.

Acknowledgement/Funding

This work was supported in part by grants from the AHA 17MCPRP33420153 (Brandon Chalazan) and NIH/NHLBI R01 HL092217 and HL138737 (Dawood Darbar).
4180Expression profile of microRNAs in cardiac tissue from pediatric patients with heart failure (HF) supported by Ventricular Assist Device and their involvement in pathophysiological mechanisms of HF
Authors: Ragusa R , Di Molfetta A , Rizzo M , Mercatanti A , Amodeo A , Trivella M G , Pitto L , Caselli C
Published: October 2019

Background

Ventricular Assist Device (VAD) has been increasingly used as bridge to transplantation for the treatment both of adult and pediatric patients with end-stage Heart Failure (HF). Several studies reported that VAD support could affect cardiac molecular mechanisms, including miRNA expression, in HF adult patients. However, little is known about the miRNA profile in pediatric HF patients supported by VAD.

Purpose

Aim of this study was to evaluate the effects of VAD support on expression profile of miRNAs in cardiac tissue from pediatric patients with HF, and to enrich the analysis by an in silico exploration of their potential functions and pathways.

Methods

Cardiac biopsies from HF children collected at the time of VAD implant [8 HF children; 57±33 (mean±SD) months; 2 males; 14.2±13.5 weight; 29±8 LVEF%] and at the time of heart transplantation after 155±33 days of VAD support [5 children; 90±46 months; 4 males; 30±15.8 weight; 38±3.9 LVEF%] were used for profiling miRNA expression by Next Generation Sequencing (NGS). Bioinformatic analyses were performed to identify the differentially expressed miRNAs in cardiac tissues after VAD support, to elucidate their potential functions (Gene Ontology), and to predict their target genes (miRWalk database).

Results

We identified two upregulated miRNAs (miR-29b-1-5p, miR-338-3p) and four downregulated miRNAs (miR-199a-5p, miR-199b-5p, miR-19a-3p, miR-1246) after VAD support. Gene enrichment analysis identified heart development/function, apoptosis and metabolism as main process modulated by the selected miRNAs (Fig A). Moreover, twenty genes were selected as putative miRNA targets involved in the pathophysiology of HF (Fig B).

Conclusion

In summary, the results of the present study suggest that modification of six miRNAs in cardiac tissue from HF children after VAD support may be involved in the regulation of several pathophysiological mechanisms underlying HF, thus providing novel perspectives for future researches.
4251Results from the Hungarian Cardiac Magnetic Resonance Registry of Structural Heart Disease and Aborted Sudden Cardiac Death in Athletes
Authors: Vago H , Szabo L , Czimbalmos C S , Dohy Z S , Csecs I , Toth A , Suhai I , Simor T , Becker D , Merkely B
Published: October 2019

Introduction

Sudden cardiac death (SCD) is the most common cause of death in athletes occurring usually during intensive training. Cardiac magnetic resonance (CMR) has a crucial role in the detection of structural myocardial abnormalities.

Aims

Our aim was to investigate the etiology of SCD and to estimate the prevalence of myocardial structural heart diseases among Hungarian athletes using CMR.

Methods

Between January 2011 and January 2019 we performed CMR scans on 228 athletes (199 males, age: 29.1±13.2) with suspected structural myocardial disease. Twelve athletes were investigated after aborted sudden cardiac death and normal coronary angiography.

Results

CMR confirmed the diagnosis of structural myocardial disease in 62 athletes (26.2%) (28.8±9.1 years, 59 male): hypertrophic cardiomyopathy (HCM) in 14 cases (22.6%), arrhythmogenic right ventricular cardiomyopathy (ARVC) in 9 cases (14.5%), noncompaction (NCCMP) in 6 cases (9.7%) and dilated cardiomyopathy (DCM) in 5 cases (8.1%). Subendocardial late gadolinium enhancement (LGE), reflecting myocardial scar, was typical of previous myocardial infarction (post MI) in 3 cases (5.5%). Acute myocarditis was found in 2 cases (3.6%). Nonischaemic LGE pattern was found in 20 cases (32.2%): patchy subepi-midmyocardial LGE suggesting previous myocarditis in 8 athletes, and with aspecific pattern in 12 athletes. Athletes with nonischaemic LGE had normal clinical and laboratory parameters without wall motion abnormalities, in their cases further investigations ruled out systemic disease. One athlete was diagnosed with Fabry-disease, one with coronary artery abnormality (anomalous origin of the left main coronary artery from the right sinus of Valsalva), one athlete showed pheochromocytoma-related Tako-Tsubo cardiomyopathy (each 1.6%). Five athletes with confirmed structural heart disease were investigated after sustained ventricular tachycardia, seven athletes after aborted SCD: ARVC (n=6), aspecific LGE pattern (n=4), HCM (n=1) and pheochromocytoma-related Tako-Tsubo cardiomyopathy (n=1) were diagnosed.

RVOT movie of an ARVC pts

Conclusion

In our national CMR registry the most common structural alteration was nonischaemic fibrosis, the most common cardiomyopathy was HCM, and the leading cause of SCD in Hungarian competitive athletes was ARVC. The national registers are highly important for a better understanding the etiology and the geographical differences of SCD in athletes.

Acknowledgement/Funding

Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary
4290Results of transcatheter mitral valve repair for severe mitral regurgitation from a real-world patient cohort according to COAPT and MITRA-FR trial inclusion criteria and echocardiographic parameter
Authors: Orban M , Stolz L , Orban M , Braun D , Stocker T , Stark K , Nabauer M , Massberg S , Hausleiter J
Published: October 2019

Background

Two randomized trials (MITRA-FR and COAPT) of transcatheter mitral valve repair (TMVR) for functional MR have shown symptomatic improvement but discordant results for heart failure hospitalizations compared to optimal medical therapy. Differences between real-world patients similar to the trial population in terms of symptomatic outcome and mortality have not been shown yet.

Purpose

Our study compared patients similar to both studies in terms of NYHA development and mortality at 1-year follow-up (FU).

Methods

In our center, 447 patients were treated with TMVR for MR grade 3 and 4 between 2012 and 2018. For the comparative analysis with MITRA-FR and COAPT, we applied filters to our database patients according to the published echocardiographic inclusion criteria and baseline data (COAPT: effective regurgitant orifice area [ERO]) 0.41±0.15cm2; left ventricular ejection fraction [LV-EF] 31.3±9.1%, left ventricular end-diastolic volume [LVEDV] 194.4±69.2ml; MITRA-FR: ERO 0.31±0.1 cm2; LV-EF 33.3±6.5, indexed LVEDV 136.2±37.4 ml).

Results

Out of our database, 91 patients were categorized as COAPT-like and 92 as MITRA-FR-like. COAPT-like patients had an ERO of 0.40±0.16cm2, LV-EF of 32.7±4.8%, LVEDV of 195±53.7ml and indexed LVEDV of 103.6±26.0ml/cm2 (Figure A). MITRA-FR-like patients had an ERO of 0.31±0.07 cm2, LV-EF of 31.7±5.0%, LVEDV of 221.7±60.8ml and indexed LVEDV of 117.9±29.1 ml/cm2. The difference of ERO and LVEDV between both groups was statistically significant. The majority of patients in both groups were in NYHA class III or IV at baseline (97% COAPT-like group, 98% MITRA-FR-like group, p=0.44).

MR reduction was equally effective in both groups, with 85 (93%) COAPT-like patients and 88 (96%) MITRA-FR-like patients having MR grade 1 or 2 at discharge. Clinical FU was available in 62 (68%) and 67 (73%) COAPT-like and MITRA-FR-like patients, respectively. The majority of patients improved symptomatically after TMVR. Before TMVR, 1 (98%) COAPT-like patient and 2 (97%) MITRA-FR-like patients were in NYHA class I or II compared to 36 (58%, p<0.01) COAPT-like patients and 38 (57%, p<0.01) MITRA-FR-like patients at FU (p=1.0 for intergroup comparison). Overall, 40 (65%) COAPT-like patients and 43 (64%) MITRA-FR-like improved at least one NYHA class (p=1.0 for intergroup comparison; Figure B). There were no differences in overall survival between groups with 68.9% of COAPT-like patients and 74.5% of MITRA-FR-like patients alive at 1-year FU (p=0.53, Figure C).

Figure 1

Conclusion

Our real-world data shows that TMVR leads to symptomatic improvement in both MITRA-FR-like and COAPT-like patients to a similar extent, despite substantial echocardiographic differences. Both patient groups have a similar survival rate.
4291Six-month outcomes from the multicenter, prospective study with the novel PASCAL transcatheter valve repair system for patients with mitral regurgitation in the CLASP study
Authors: Kar S , Lim S , Spargias K , Kipperman R , O Neill W , Ng M , Fam N , Raffel C , Webb J , Smith R , Rinaldi M , Latib A , Cohen G , Schaefer U , Feldman T
Published: October 2019

Background

Severe mitral regurgitation may lead to an impaired prognosis if left untreated. Transcatheter treatment options have emerged as an alternative to surgery and an adjunct to medical therapy. We report the six-month results of the PASCAL transcatheter valve repair system in treating patients with mitral regurgitation enrolled in the multicenter, prospective, single arm CLASP study.

Methods

The PASCAL Transcatheter Valve Repair System is a leaflet repair therapy that uses clasps and paddles to place a woven Nitinol spacer between the native valve leaflets to fill the regurgitant orifice via a transseptal approach. Eligible patients had clinically significant MR despite optimal medical therapy and were deemed candidates for transcatheter mitral repair by the local Heart Team. Safety, performance, and clinical outcomes were prospectively assessed at baseline, discharge, 30 days, and 6 months post-procedure. All major adverse events (MAE) were adjudicated by an independent clinical events committee and echocardiographic images were assessed by a core lab. The MAE rate was the primary safety endpoint, defined as the composite of cardiovascular mortality, stroke, MI, new need for renal replacement therapy, severe bleeding, and re-intervention for study device-related complications.

Results

Between June 2017 and September 2018, 62 patients were enrolled at 14 sites worldwide for transcatheter mitral valve reconstruction using the PASCAL system. The mean age was 76.5 years (62.9% male). All patients had MR grade ≥3+, with 59% functional, 34% degenerative, and 7% mixed etiology, and 51.6% of patients were in NYHA Class III/IV. Successful implantation of the PASCAL device was achieved in 95% of patients. At discharge, 95% of patients had MR grade ≤2+ with 81% grade ≤1+. There was one cardiovascular mortality and the MAE rate was 4.8%. At 30-day follow-up, paired analyses shows that 98% of patients had MR grade ≤2+ with 81% grade ≤1+ and 88% were in NYHA Class I/II (p<0.0001). The 6MWD improved by 38.9 m (p=0.0015) and was accompanied by average improvements in KCCQ and EQ5D scores by 14.1 points (p<0.0001) and 8.3 points (p=0.0028), respectively. The six-month data will be available for presentation.

Conclusions

In this early device experience, the PASCAL transcatheter valve repair system showed an acceptable safety profile and performed as intended in treating patients with mitral regurgitation. The PASCAL device resulted in significant MR grade reduction, which was associated with clinically and statistically significant improvements in functional status, exercise capacity, and quality of life. Continued follow-up is warranted to validate these initial promising results.

Acknowledgement/Funding

Edwards Lifesciences
4311Decreased CD177 expression and its association with intravenous immunoglobulin resistance in Kawasaki disease
Authors: Huang Y
Published: October 2019

Kawasaki disease (KD) is the most common acute coronary vasculitis disease occurring in children. Its occurrence has been attributed to the combined effects of infection, genetics, and immunity. While the etiopathogenesis of KD remains unknown, we have performed a survey of global genetic DNA methylation status and transcripts expression in KD patients to address how they contribute to the pathogenesis of KD.

Methods

We recruited 148 participants for this study. The chip studies consisted of 18 KD patients that were analyzed prior to administering intravenous immunoglobulin (IVIG) treatment and at least 3 weeks afterward, as well as 36 non-KD control subjects. We performed a separate cohort of 94 subjects to validate real-time quantitative PCR.

Results

According to the microarray study, CD177, a neutrophil surface molecule, appeared to be most significantly upregulated in KD patients compared to controls with epigenetic hypomethylation. After patients received IVIG treatment, CD177 mRNA levels decreased significantly. PCR validation indicated that the expression of CD177 is consistent with the Transcriptome Array 2.0 results. Furthermore, the area under the curve values of CD177 between KD patients and controls is 0.937. We also observed significantly higher CD177 levels in typical KD than incomplete presentation, which was associated with IVIG resistance in KD patients.

Conclusion

The present study is the first to highlight the epigenetic hypomethylation of an increased CD177 transcript during the acute stage of KD. Furthermore, the higher expression of CD177 in a typical presentation of KD patients and was related to IVIG resistance.
4327Results of the DERIVATE study in non-ischemic dilated cardiomyopathy (NICM)
Authors: Guaricci A I , Masci P G , Lorenzoni V , Schwitter J , Pontone G
Published: October 2019

Background

Standard of care (SOC) suggests implanted cardioverter defibrillator (ICD) therapy based on the left ventricular ejection fraction (LVEF) cut-off value as detected by transthoracic echocardiography (TTE-LVEF)

Purpose

The aim of this study was to evaluate the additional prognostic value of a cardiac magnetic resonance (CMR) based score over SOC in a large cohort of non-ischemic cardiomyopathy (NICM) patients evaluated for primary ICD therapy

Methods

DERIVATE is an international, multicenter, prospective, observational registry including consecutive patients with chronic heart failure (HF) who undergo clinical evaluation. We included 1000 patients (derivation cohort) and 509 patients (validation cohort) with chronic heart failure (HF) with LVEF<50% affected by NICM enrolled in the period between January 2007 and October 2017. All-cause mortality and arrhythmic major adverse cardiac events (MACE) were the primary and the secondary endpoint, respectively.

Results

During a median follow-up of 959 days, all-cause mortality and combined MACE occurred in 72 (7%) and 93 (9%) patients respectively. Regarding to primary endpoint, age and number of myocardial segments with late gadolinium enhancement (LGE) midwall>3 were the only independent predictors of mortality (HR: 1.037, 95% CI: 1.018–1.057, p<0.001 and HR: 1.78, 95% CI: 1.062–3.005, p=0.029, respectively). Regarding to the secondary endpoint, gender, left ventricle end-diastolic volume indexed as detected by CMR (CMR-LVEDVi)>120.5 ml/m2, and number of myocardial segments with LGE midwall>2 were independent predictors of MACE (HR: 2.13, 95% CI: 1.231–3.690, p=0.007; HR: 3.16, 95% CI: 1.750–5.709, p<0.001 and HR: 1.69, 95% CI: 1.084–2.644, p<0.02 respectively). Accordingly, a weighted CMR score, including these three variables with a maximum of 7 points was calculated and when added to the model based on SOC provided a net reclassification improvement (NRI) of 63.7% (p<0.001). Finally, when the CMR-score was applied to validation cohort showed a NRI of 31.3% (p: 0.022) with a good prognostic stratification (p: 0.001) as compared to the SOC.

Conclusions

CMR provides additional prognostic stratification as compared to the SOC, which may have direct impact on the indication of ICD implantation. Further, prospective randomized trial should be addressed to test the cost-effectiveness of a CMR strategy as compared to SOC in patients undergoing ICD implantation.

Acknowledgement/Funding

funded by the Italian Ministry of Health, Rome, Italy (RC 2017 R659/17-CCM698
4331Safety and efficacy of sacubitril/valsartan by dose level in patients hospitalized with acute heart failure: Observations from PIONEER-HF
Authors: Morrow D A , Velazquez E J , Devore A D , Duffy C I , Gurmu Y , McCague K , Rocha R , Braunwald E
Published: October 2019

Background

In hemodynamically stabilized patients with acute decompensated heart failure (ADHF) enrolled in the PIONEER-HF trial, compared with enalapril, sacubitril/valsartan started in-hospital and continued for 8 weeks was well tolerated, achieved a greater reduction in NT-proBNP, and reduced cardiovascular death or rehospitalization for HF. Nearly 1/2 of patients achieved the target dose of blinded study drug. We performed an exploratory analysis of the safety and efficacy of sacubitril/valsartan according to the dose level dispensed at 4 weeks in PIONEER-HF

Methods

PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan vs. enalapril in 881 hospitalized ADHF pts following hemodynamic stabilization. Blinded study medication was administered for 8-weeks, with initial dosing selected based on the systolic blood pressure (SBP) at randomization (starting dose 24/26 or 49/51 mg twice daily vs 2.5 or 5 mg twice daily) and titrated toward a target of sacubitril/valsartan 97 mg/103 mg twice daily, or enalapril 10 mg twice daily with an algorithm using SBP along w/ the investigator's assessment of tolerability.

Results

At the week 4 visit, 199 patients (45.2%) in the sacubitril/valsartan group and 210 (47.6%) in the enalapril group were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. The prespecified adverse events of special interest were similar between sacubitril/valsartan and enalapril irrespective of dose level (Table) with no significant heterogeneity. In addition, there was no heterogeneity across dose levels in the favorable effect of sacubitril/valsartan on the change in NTproBNP by week 8 (Table, p-interaction=0.54) or the serious composite endpoint (p-interaction=0.71).

Efficacy and Safety by Dose-Tier

Conclusion

In hemodynamically stabilized patients with ADHF, the safety and efficacy of sacubitril/valsartan appears generally consistent among patients at various dose levels.

Acknowledgement/Funding

Novartis Pharmaceuticals
P3096The cardioprotective effect of FFR-significant multivessel disease detected by cardiac magnetic resonance imaging in patients following ST-segment elevation myocardial infarction. Results from DANAMI3
Authors: Ekstroem K , Nielsen J V W , Nepper-Christensen L , Ahtarovski K A , Kyhl K , Goeransson C , Bertelsen L , Ghotbi A A , Kelbaek H , Hoefsten D E , Koeber L , Schoos M M , Vejlstrup N , Loenborg J , Engstroem T
Published: October 2019

Background

In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), reperfusion injury accounts for a significant part of the final infarct size, which is directly related to patient prognosis. In animal studies brief periods of ischemia in non-infarct related coronary arteries protects the myocardium via remote ischemic perconditioning. Fractional flow reserve (FFR) measures functional significant coronary stenosis which may offer remote ischemic perconditioning of the myocardium. It has not previously been investigated if FFR-significant stenosis in non-culprit myocardium offers cardioprotection following STEMI.

Purpose

To investigate cardioprotective effect of FFR-significant multivessel disease (MVD) on final infarct size and myocardial salvage in a large contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI).

Methods and results

We included 509 patients with STEMI from the DANAMI-3 trial, divided into three groups: 388 (76%) patients had single vessel disease (SVD), 34 (7%) had non-FFR-significant MVD and 192 (17%) had FFR-significant MVD. CMR was performed at baseline and three months after primary PCI. There was no difference in final infarct size; mean infarct size (% left ventricular mass) SVD 9±3%; non-FFR-significant MVD 9±3%; and FFR-significant MVD 9±3%, p=0.95, or in myocardial salvage index (MSI) between groups, calculated as (area-at-risk – infarct size)/area-at-risk; mean index (%) SVD 67±23%; non-FFR-significant MVD 68±19%; and FFR-significant MVD 67±21%, p=0,99. In multivariable regression analyses FFR-significant MVD was not associated med larger MSI (p=0.84) or lower infarct size (p=0.60).

Figure 1. A. Late gadolinium (LGE) cardiac magnetic resonance (CMR) image of a mid-ventricular short-axis slice. Hyperintense signals (arrow) shows contrast enhancement in the anterior-septal segments, indicating myocardial infarction (MI). B. Same patient. T2-weighted image of the same mid-ventricular short-axis slice. Hyperintense signals (arrows) shows edema in the anterior-septal segments.

Conclusions

FFR-significant functional MVD of non-culprit myocardium does not offer cardioprotection in patients following STEMI.
P3103Cardiac rehabilitation referral after ACS, are women deprived?
Authors: Klein J , Farkash R , Bayya F , Taha L , Abeles N , Kischner A , Yaacobi E , Glikson M
Published: October 2019

Background

Referral and participation rates to Cardiac Rehabilitation (CR) after acute coronary syndrome (ASC) are low despite a Class I recommendation in the present guidelines. Our aim was to examine the role of gender on referral, participation and outcomes of CR.

Methods

Data of ACS patients hospitalized during 2007–2016 in our cardiology department were extracted and compared between referred to CR to those who were not. Multivariable models were used to assess the impact of gender on referral to CR and survival.

Results

Of the 6175 ACS patients, 1455 (23.6%) were female. Overall referral rate to CR was 66.5%, 51.3% among female and 70.0% in male; p<0.0001.

Female were more likely to have characteristics associated with lower referral rate; they were older, had lower rates of STEMI and higher rates of cardiac risk factors. Multivariable model, adjusted for those characteristics revealed that female gender is independently associated with lower referral rate to CR: OR = 0.77 95% CI [0.66–0.89]; p<0.0001. (Table 1)

Multivariable COX analysis showed that patients referred to CR had lower mortality hazard – HR = 0.427 95% CI [0.35–0.53]; p<0.0001, with no gender difference – HR=1.04 95% CI [1.04–1.06]; p=0.640.

Participation rate within referred patients, program duration as well as number of meetings were similar in female and male p=NS for all.

Independent predictors for CR referral OR 95% CI p-value Cath 6.5 5.3–8.0 <0.001 STEMI** 3.9 3.3–4.6 <0.001 NSTEMI** 2.1 1.8–2.4 <0.001 Smoker 1.9 1.6–2.1 <0.001 Age* 0.9 0.9–1.0 <0.001 Hypertension 0.8 0.7–0.9 0.023 Prior MI 0.8 0.7–0.9 0.032 Female gender 0.8 0.7–0.9 0.001 Prior CABG 0.7 0.6–0.9 0.003 CVA 0.7 0.6–0.9 0.010 PVD 0.7 0.52–0.9 0.033 CHF 0.7 0.6–0.9 0.001 *Age: continuous; **UA as reference group.

Conclusions

Referral of ACS patients to CR significantly lowers mortality rate. Referral rate of women to CR is significantly lower than men. Once referred to CR, no gender difference was found in CR participation rate and program compliance.

Acknowledgement/Funding

None
P3115Effect of calcitriol attenuates doxorubicin-induced cardiac dysfunction in mice model: focus on endothelial-to-mesenchymal transition
Authors: Tsai T H , Chen W Y
Published: October 2019

Objective

Doxorubicin (DOX) is an effective anti-neoplasm drug, but the early and late cardiac toxicity limits its clinical use. The Endothelial-to-mesenchymal transition (EndMT) has been found to involve in the process of heart failure. It's unclear whether EndMT plays a role in DOX-induced cardiomyopathy (DoIC). Calcitriol is an active form Vitamin D3, which blocks the growth of cancer cells via inhibiting Smad pathway. This study investigated the cardiac protective effect of calcitriol via inhibiting of EndMT in DoIC.

Methods/Findings

C57BL/6 mice and endothelial-specific labeled mice were administered Dox twice weekly for 4 weeks [intraperitoneally (i.p.), 32 mg/kg cumulative dose]and were subsequently treated with/without calcitriol for 12 weeks. The cardiac echography revealed diastolic dysfunction at 13 weeks following the first DOX treatment and was accompanied by increased of myocardial fibrosis and up-regulated pro-fibrotic proteins.(Figure A-C) Calcitriol attenuated DOX-induced myocardial fibrosis, down-regulated pro-fibrotic proteinsand diastolic function. Endothelial fate tracing revealed that endothelium-derived cells contributed DOX-induced cardiac remodelling through EndMT and Calcitriol attenuated this process without attenuating Dox-induced cardiac myocyte and endothelial cell damage.(Figure D) In vitro, we examined if calcitriol would inhibit EndMT and fibroblast-to-myofibroblast transition (FMT) through the Smad pathway. Human umbilical vein endothelial cells (HUVECs) and mouse cardiac fibroblasts were treated with TGF-beta with or without calcitriol. Morphological, immunofluorescence staining, and western blot analyses were carried out to evaluate EndMT and FMT. Calcitriol attenuated EndMT and FMT by inhibiting the Smad2 pathway. Taken together, calcitriol didn't reduced Doxorubicin induced damage of cardiomocyte and endothelial cells. But calcitriol inhibit doxorubicin induced heart failure by attenuating cardiac fibrosis through inhibiting Smad pathway.

Conclusion

Calcitriol attenuated DOX-induced cardiomyopathy partial through inhibiting EndMT process.

Acknowledgement/Funding

CMRPG8E0661-3
P3122Complete versus culprit-vessel only revascularization for patients with acute coronary syndromes and multivessel disease
Authors: Ferreira J , Monteiro S , Baptista R , Goncalves F , Monteiro P , Goncalves L
Published: October 2019

Background

Recent randomized clinical trials have suggested that complete revascularization (CR) instead of culprit-vessel only revascularization (CVO) strategies may take a stand in the optimal management of patients admitted for acute myocardial infarction (AMI) with multivessel (MV) disease undergoing primary percutaneous coronary intervention (P-PCI). However, despite the 2017 ST-elevation acute coronary syndrome (STEMI) guidelines update with a new class of recommendation for CR, it remains controversial whether this strategy leads to better outcomes.

Purpose

To compare CR versus CV strategies during hospitalization in patients presenting with AMI with multivessel disease at P-PCI.

Methods

We analyzed data from all patients admitted with non-ST acute myocardial infarction (NSTEMI) and STEMI in a portuguese coronary care unit (CCU), between 2007 and 2016. We then evaluated potential differences of CR versus CVO with PCI during hospitalization in AMI patients with multivessel disease, defined by at least 2 different diseased main coronary vessels, saphenous vein or mammary artery conduits. We used 1:1 ratio propensity score matching to study the impact of CR on patient mortality and adjusted data for relevant risk factors at admission time.

Results

A total of 4758 patients were admitted for AMI, 2690 NSTEMI (56.5%) and 2068 STEMI (43.5%). Access to PCI records was possible in 3162 (66.5%) patients, of which 1707 (54%) underwent CR versus 1455 (46%) who underwent CVO. CVO patients were older (67.9±11.8 vs. 63.5±13.1 years, p<0.001), more diabetic (56.5% vs. 47.1%, p<0.001), hypertensive (78.4% vs. 72.2%, p<0.001), dyslipidemic (82.1% vs. 75%, p<0.001), had greater GRACE score at admission (mean score 143.4±37.2 vs. 131.2±131.2, p<0.001), had more severe coronary disease (mean number of diseased vessels – 2.56±0.6 vs. 2.18±0.4, p<0.004), reached higher Killip class (mean – 1.42±0.9 vs. 1.26±0.7, p<0.001) and had lower left ventricular ejection fraction (48.07±11.6 vs. 51.25±10.5, p<0.001). No significant differences were found in peak troponin-I release between CR and CV (44.7±69 vs. 46.9±76, respectively, p=0.468). After propensity matching, we obtained 130 CR and 133 CVO patients. In this cohort all-cause mortality was lower in CR group at 6-month (RR 0.262, CI 95% 0.071–0.962, p=0.031) and 1-year (RR 0.340, CI 95% 0.119–0.973, p=0.036) follow-up. When comparing STEMI versus NSTEMI all-cause mortality was nonsignificantly lower in CR (RR 0.394 vs. 0.226, p=0.12 vs. p=0.16).

Conclusions

In patients presenting with AMI and MV disease, CR strategy during hospitalization leads to greater 6-month and 1-year survival when compared with CVO strategy. Despite not having found significant differences when STEMI was directly compared to NSTEMI, we believe this was due to the great loss of patient numbers after propensity matching, requiring larger trials to prove the effect.
P3140Burden and the clinical significance of the retained cardiac implantable electronic device components after heart transplantation
Authors: Simsek E , Tamnik F , Demir E , Nalbantgil S
Published: October 2019

Background

Cardiovascular implantable electronic devices (CIEDs) are common in patients undergoing heart transplantation (HT), and complete removal is not always possible at the time of transplantation. Frequency and clinical significance of retained CIED components after HT is not well studied.

Methods

Adult heart failure patients whom had heart transplantation in our institution from date June 2000 to December 2018 were retrospectively evaluated. Pre-post operative chest x-rays and recorded fluoroscopy images of the previous coronary angiograms or endomyocardial biopsies were reviewed by a single observer for retained CIED components. All patients clinical records were also reviewed for adverse outcomes of retained components such as deep venous thrombosis of upper extremity, infection and mortality.

Results

A total of 226 patients had bicaval orthotopic heart transplantation during study time. 73 (32%) of the patients had CIED before transplantation and 24 (32.8%) of the patients had retained lead components after HT. (Table 1) All of the components were part of a superior vena cava coil of the right ventricular ICD lead. Mean follow up time was 46.6±49.8 months and only 1 (1.3%) adverse event (right subclavian DVT) occurred in a patient with retained lead. There were not any statistical significance for mortality and infection between patients with and without lead fragments. Patients were also compared for history of any cardiac surgery before HT, especially ventricular assist device procedures and no differences were observed between groups.

For history of any cardiac surgery p=0.748, for assist device surgery, p=0.269). Patient's medical records reviewed for a history of magnetic resonance imaging (MRI). Two patients with retained lead fragments had non-thorocic (abdominal and cranial) MRI and any clinical pathology did not observed after MRI.

Table 1 All Patients With Retained CIED comp. Without Retained CIED comp. p (n=226) (n=24) (n=49) Age ± sd 42.91±12.2 44.88±12.6 41.59±13 0.290 Ischemic etiology 65 (28.8%) 8 (33.3%) 13 (26.5%) 0.546 CIED type   CRT-D 5 (20.8%) 5 (%10.2) 0.215   DR-ICD 5 (20.8%) 8 (16.3%) 0.636   VR-ICD 14 (58.3%) 35 (71.4%) 0.263 Dual coil ICD lead 24 (100%) 48 (97%) 1 Mortality (%) 96 (42.5) 7 (37%) 20 (40.8%) 0.463

Conclusion

Retained CIED components were seen 32.8% of the HT patients with CIED prior to transplantation. According to our data retained leads are not associated with severe adverse clinical outcomes. Also non cardiac MRI could be safe in patients with retained lead fragments.
P3348Prevention of stroke in intracerebral haemorrhage survivors with atrial fibrillation (PRESTIGE-AF): a retrospective cohort study
Authors: Nielsen P B , Soegaard M S , Skjoeth F S , Andersen S D , Larsen T B L , Lip G Y H L
Published: October 2019

Background

Atrial fibrillation (AF) patients surviving an intracerebral haemorrhage (ICH) present a clinical challenge. The PRESTIGE-AF trial is an ongoing trial designed to investigate the optimal stroke prevention strategy in AF patients who have suffered an ICH.

Purpose

To describe baseline clinical characteristics of a study population similar to the expected PRESTIGE-AF trial.

Methods

The patient population was identified from the Danish Stroke Registry, linked with additional registries to obtain information on comorbidities and medication. Specific incl/excl criteria from the PRESTIGE-AF trial were applied, including indication for OAC treatment due to AF and the ICH was not related to trauma.

Results

From 2003–2015 a total of 1405 patients with AF and ICH were included, mean age of 79.4 years [Table]. 40% had suffered a “mild” index ICH, and approximately 25% had a “moderate” or a “severe” index event based on the SSS score. Hypertension (75%) and prior thromboembolic events (33%) were common comorbidities. In the year before the index ICH, 27% recieved antiplatelet therapy, 34% OAC, and 22% receiving both treatments.

Table 1 Demographics and clinical characteristics Percent (number) Number of patients 1,405 Females 695 (49.5) Age, mean (SD) 79.4 (8.8) Scandinavian Stroke Scale*, median (IQR) 40.0 (22.0–50.0) “Mild” intracerebral haemorrhage (43–58) 563 (40.1) “Moderate” intracerebral haemorrhage (26–42) 377 (26.8) “Severe” intracerebral haemorrhage (<26) 361 (25.7) Hypertension 1067 (75.9) Prior thromboembolism 460 (32.7) CHA2 DS2 -VASc score, mean (SD) 4.2 (1.3) Antiplatelet therapy (mono) 377 (26.8) VKA treatment 436 (31.0) NOAC treatment 40 (2.9) OAC and antiplatelet treatment 311 (22.1) *Scale from 0–58; lower score indicates more severe stroke; 7% missing information.

Conclusion

The identified study population using the criteria for the PRESTIGE-AF trial were generally elderly and had a high prevalence of hypertension and prior stroke. The PRESTIGE-AF trial is required to determine optimal stroke prevention treatment in a population of AF patients presenting with ICH.

Acknowledgement/Funding

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 754517
P3359Myocardial flow reserve using 13N ammonia PET for detection of cardiac allograft vasculopathy in heart transplant patients
Authors: Kikuchi N , Yamamoto E , Nagao M , Momose M , Hattori H , Suzuki A , Shiga T , Niinami H , Hagiwara N , Nunoda S
Published: October 2019

Purpose

Risk stratification and early detection of cardiac allograft vasculopathy (CAV) are essential in heart transplantation patients. CAV is associated with poor outcome in the chronic phase after heart transplantation. CAV presents a diffuse vascular involvement and has been difficult to noninvasively diagnose by the lack of a sensitive method to detect developing vascular pathology in the allograft. The present study investigates the ability of 13N-ammonia PET for detection of CAV in heart transplant patients.

Methods

Data of adenosine-stress 13N-ammonia PET imaging for thirty-one patients (mean age, 39 years-old) after 11 + 7 years from transplant was analyzed. Five patients had undergone percutaneous coronary intervention (PCI), and the remaining 26 patients had no history of definite myocardial ischemia. Myocardial flow was generated from the time activity curve of left ventricle input and myocardial uptake using 3-compartment model and the first 2 minutes' dataset of list-mode acquisition. Global - myocardial flow reserve (MFR) was calculated by stress to rest flow ratio. Patient with global-MFR <2.0 was defined as significant decrease. Summed difference score (SDS) was used as an estimate for the extent of ischemia, and the patient showing SDS >2 was identified as those having significant ischemia.

Results

The mean Global-MFR of our subjects were 2.3 (1.2 to 3.9). MFR using 13N-ammonia PET significantly decreases in one third of heart transplant patients in chronic stage. Eleven patients with Global-MFR <2.0 (35%) were observed, and eight of them had no history of clinical myocardial ischemia. The proportion of patients with a history of PCI is 18% in patients with Global-MFR <2.0 (vs 5%, p=0.210). Moreover, there were eight patients with SDS >2 (26%) including three patients having a history of PCI. The proportion of patients with a history of PCI tends to be high with SDS >2 (38% vs 9%, p=0.056).

Conclusion

This modality using 13N ammonia PET is useful for easily detection of CAV before manifestation of symptomatic myocardial ischemia in heart transplant patients.
P3361Pathophysiology measured with positron emission tomography is equally impaired in hypertrophic and non-hypertrophic regions in hypertrophic cardiomyopathy
Authors: Nordstrom J , Magnusson P , Harms H , Lubberink M , Morner S , Sorensen J
Published: October 2019

Background

Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease with regard to clinical manifestations. It is characterized by an asymmetric pattern of hypertrophy of the left ventricle. However, less is known about pathophysiological distribution of the abnormalities. Positron emission tomography (PET) provides quantitative assessment of myocardial blood flow (MBF), oxidative metabolism, and sympathetic innervation using the following tracers: 15O-water, 11C-acetate, and 11C-HED.

Purpose

The purpose of the present study was to investigate if physiological parameters measured with PET are more impaired in hypertrophic regions compared to non-hypertrophic regions.

Methods

We examined 25 HCM patients using a Discovery MI PET/CT with 15O-water, 11C-acetate, and 11C-HED. Wall thickness (WT) was calculated from the 11C-acetate scan for basal and mid segments (n=12) in the 17-segment model and hypertrophic regions were defined as segments >15 mm. 15O-water PET was performed during rest and adenosine induced stress. Quantification of MBF, oxygen consumption (MVO2) and retention index of 11C-HED (RIHED) was done in aQuant software. Comparison of parameters in hypertrophic regions to non-hypertrophic regions was done using Mann-Whitney U- test and Bland-Altman analysis with repeatability coefficient defined as 2 times the standard-deviation of differences.

Results

One patient had all segments >15mm and one patient had all segments <15mm and were therefore excluded from analysis. WT was 18.2±1.9 mm in hypertrophic regions and 12.2±1.5 mm in non-hypertrophic regions. None of the PET-parameters showed a significant difference between hypertrophic and non-hypertrophic regions, see table 1.

Table 1 MBFREST MBFSTRESS MVO2 RIHED Hypertrophic segments (mm) 0.70±0.20 1.74±0.92 0.092±0.026 0.12±0.037 Non-hypertrophic segments (mm) 0.68±0.18 1.71±0.87 0.094±0.025 0.12±0.036 p-value 0.767 0.851 0.956 0.684 Repeatability coefficient (%) 25.4 35.4 13.3 16.2 Mean ± standard deviation for PET-parameters in hypertrophic and non-hypertrophic segments. Relative repeatability coefficient (%) between regions and p-value for Mann-Whitney U-test.

Conclusion

Pathophysiology in terms of myocardial blood flow at rest and stress, oxygen consumption and sympathetic innervation are not significantly different in hypertrophic segments compared to non-hypertrophic segments in patients with HCM. Thus, the disease is not confined to hypertrophied areas but spread throughout the left ventricle.

Acknowledgement/Funding

Selanders stiftelse, Regionala forskningsrådet
P3375The parasternal long axis ultrasound view does not allow the maximum diameter of the aortic root to be measured in atypical BAV
Authors: Milleron O , Masi P , Paul J F , Arnoult F , Ould Ouali N , Tchitchinadze M , Lansac E , Jondeau G
Published: October 2019

Background

Following guidelines, maximal aortic root diameter have to be measured in parasternal long axis view (PLA TTE) in trans-thoracic echocardiography (TTE). However, asymmetry of the aortic root is common in BAV and the larger diameter might be missed when using PLA TTE, depending on the asymmetric root orientation.

Purpose

Assess whether the maximum aortic diameter measured with PLA TTE and CT differs according to the type of BAV.

Methods

86 patients with BAV without significant valvulopathy (aortic regurgitation <2 and no more than mild stenosis with mean gradient <10mmHg) referred for aortic aneurysm assessment and who had benefited from TTE and CT were studied.

Definition: Typical BAVs have a horizontal valve opening (type I L-R and type 0 anteroposterior) while atypical BAVs have a vertical valve opening (type I N-R and type 0 lateral). (Figure) We compared: – using CT, the orientation of the largest diameter of the aortic root in typical and atypical BAVs using the sagittal plane as a reference (Figure). – the difference of the maximal aortic root diameter measured with PLA TTE and CT in typical and atypical BAVs.

Results

Patients with typical and atypical BAVs were comparable for age, sex, weight, height, aortic root surface area and maximum diameter of the aoric root.

When comparing maximal aortic root diameter measured in PLA TTE and CT:

– in the whole cohort, PLA TTE underestimates the maximal aortic root diameter with a mean difference of 3 mm.

– in atypical BAVs, the difference between CT and PLA TTE is 6,0 mm significantly different from the 2,3 mm found in typical BAVs p=0.0008 (Figure)

The orientation of the maximal aortic diameter is correlated with the type of BAV: Using the sagittal plan as a reference, this angle is 64.3° for the typical BAV and 143,1° for the atypical BAV p<0.0001 (Figure).

The use of a blue arrow (figure) to show the ultrasound beam direction in PLA ETT helps to understand that, in typical BAVs, the maximal aortic root diameter has the same direction that ultrasound beam while in atypical BAVs, the ultrasound beam direction is perpendicular to the direction of the maximum aortic diameter.

Figure 1

Conclusion

The difference in maximal diameter of the aortic root measured with CT and PLA TTE is significantly greater in atypical BAVs than in typical BAVs (6.0 mm vs 2.3mm). This difference can be explained by the fact that in the atypical BAV, the orientation of the maximal diameter of the aortic root differs from the typical BAV: using the sagittal plane as a reference, in the atypical BAV, the mean angle is around 140° and this orientation is perpendicular to the direction of the ultrasonic beam, explaining the inability to measure the maximum aortic diameter in PLA TTE for the atypical BAVs.
P3377MDCT-derived left ventricular global longitudinal strain and left ventricular ejection fraction in patients with aortic stenosis: a comparative analysis with echocardiographic measurements
Authors: Gegenava T , Bijl P , Vollema M , Kley F , Weger A , Hautemann D , Reiber J , Ajmone-Marsan N , Bax J , Delgado V
Published: October 2019

Introduction

Known predictors of poor outcome in aortic valve stenosis patients include older age, significant valvular calcification, rapid hemodynamic progression and impaired left ventricular (LV) systolic function. LV global longitudinal strain (GLS) quantifies myocardial deformation and LV function and is associated with prognosis in patients with severe aortic stenosis (AS). Multi-detector row computed tomography (MDCT) data are key in the evaluation of patients undergoing transcatheter aortic valve implantation (TAVI) and when acquired throughout the entire cardiac cycle, LV systolic function can be assessed. Novel software can assess LV GLS from MDCT-data.

Purpose

The present study aimed at assessing the feasibility of determining novel MDCT-derived LV GLS as well as MDCT-derived LV ejection fraction (EF) and their agreement with echocardiographic LV GLS and LVEF in patients treated with TAVI.

Methods

LVEF and LV GLS were measured on echocardiography and dynamic MDCT using novel CT-software. Agreement between the measurements of two different modalities was assessed using Bland-Altman analysis.

Results

A total 214 patients (51% male, mean age: 80±7 years) were analysed retrospectively. Mean value of LV GLS on echocardiography was −14±4% whereas mean MDCT-derived GLS was −12.5±4%. Mean value of LVEF on echocardiography was 47±10% and mean MDCT-derived LVEF was 39±11%. On Bland-Altman analysis, MDCT-derived strain analysis underestimated LV GLS compared to echocardiography with a mean difference of 1.44% (95% limits of agreement −3.8 to 6.7%). LVEF was also underestimated on CT with a mean difference of 7.68% (95% limits of agreement −11.5% to −26%). Correlation of measurements between MDCT-derived LV GLS and echocardiographic LV GLS was significant (r=0.791, p<0.001), as well as the correlation between MDCT-derived LVEF and echocardiographic LVEF (r=0.590, p<0.001) (Figure).

Conclusions

Assessment of LV GLS and LVEF on dynamic MDCT data provides similar values to those obtained with echocardiography and could be used in the risk-stratification of severe AS patients undergoing TAVI.