bluuebunny/crossref_metadata_2025 huggingface dataset:
480Right ventricular dysfunction is associated with late mortality in severe aortic stenosis: results from a multi-centre outcome study in patients undergoing aortic valve replacement
Authors: Rigolli M , Musa T A , Treibel T A , Loudon M , Vassiliou V S , Captur G , Singh A , Chin C , Dobson L E , Pica S , Malley T , Foley J R J , Bijsterveld P , Law G R , Myerson S G
Published: October 2019

Background

The right ventricle (RV) is relatively understudied and often not routinely assessed in aortic stenosis (AS). However, there are several potential reasons for its importance. RV function is sensitive to left-sided afterload changes which can result in pulmonary hypertension (PH) in severe AS. PH is also a recognised predictor of poor prognosis in AS, but RV afterload and function can be difficult to assess. Cardiovascular magnetic resonance (CMR) may reveal unrecognised RV dysfunction and simultaneously evaluate other prognostic markers in AS.

Purpose

To investigate preoperative RV function assessed by CMR in severe AS and its association with mortality after aortic valve replacement (AVR).

Methods

674 severe AS patients listed for either surgical or percutaneous AVR at six cardiothoracic centres underwent preoperative CMR (for ventricular function, mass and scar) along with echocardiography for valve severity. Scans were core-lab analysed for LV and RV volumes, function and scar quantification. Eight patients were excluded due to inadequate RV image quality for a total of 666 patients finally included. All-cause mortality was tracked for a minimum of 2 years after AVR.

Results

107 (16%) of severe AS undergoing invasive AVR had a RV ejection fraction (RVEF) <55%. CMR detected overt RV dysfunction (RVEF <50%) in 61 (9%) patients. During a median 3.6 years follow-up, 145 (22%) patients died. Baseline RV dysfunction was the most powerful predictor of all-cause mortality (hazard ratio [HR] 2.5, 95% CI 1.6–3.9, p<0.0001). RV function was independent from other clinical characteristics but associated with signs of LV maladaptation (LV ejection fraction [LVEF] and late gadolinium enhancement [LGE]). The strongest Cox multivariable model for all-cause mortality accounted for RV dysfunction, age and LGE (adjusted HRs 1.7, 1.1, 2.2, respectively). Even early stages of pre-procedural RV dysfunction (RVEF 45–50%) were associated with reduced long-term survival.

Cox and Kaplan-Meier for all-cause death

Conclusion

One out of 6 patients with severe AS undergoing valve replacement manifests a reduction in RV function detectable by CMR. Those with RV dysfunction (RVEF<50%) have a 2.5-fold increase in all-cause mortality after AVR at 3.6 years. Whilst RV dysfunction is associated with LV maladaptation (LGE, LVEF), it is a powerful independent factor associated with all-cause mortality and impacts survival even at early stages. Thus, the RV appears to be important in cardiac adaptation to AS and longevity after AS intervention.

Acknowledgement/Funding

British Heart Foundation and National Institute of Health Research
P305Prognostic value of relative apical sparing pattern of longitudinal strain in patients with severe aortic stenosis
Authors: Saito M , Imai M , Wake D , Higaki R , Sumimoto T , Inaba S
Published: October 2019

Background

The relative apical sparing pattern (RASP) of left ventricular longitudinal strain (LS) is determined on the strain polar map, while global longitudinal strain (GLS) is measured using speckle-tracking echocardiography and is frequently associated with cardiac amyloidosis (CA). According to recent reports, some elderly patients with aortic stenosis (AS) suffer from transthyretin CA and have a poor prognosis. Accordingly, we aimed to investigate the association of RASP and outcome of patients with severe AS.

Methods

We retrospectively studied 157 consecutive patients (age: 81±10 years, 33% men) with severe AS (mean transaortic pressure gradient: 49 mmHg) and preserved ejection fraction (>50%). After measuring GLS, RASP was semi-quantitatively and quantitatively assessed. Semi-quantitative RASP (sRASP) was defined as reduction of LS (more than −10%), showing light red or blue in ≥5 segments out of the basal six segments, relative to apical LS (less than −15%) showing red. This analysis was independently performed in a blinded manner by two observers. Quantitative RASP (qRASP) was calculated using the following formula: average apical LS/(average basal LS + average mid-ventricle LS), then qRASP ≥1 was determined as positive according to the previous paper. Patients were followed up to determine their outcomes, i.e., sudden cardiac death or unexpected admission due to heart failure over a median duration of 1.9 years. Concordance of sRASP was assessed using the kappa statistic, and a Cox proportional hazards model was used to assess the association between the parameters and primary outcome.

Results

The consistency in the observations of the two sonographers in identifying sRASP was found to be excellent (κ = 1.00). sRASP and qRASP were observed in 24 (15%) and 42 (27%) patients, respectively, and were significantly associated with the primary outcome (n=44; 28%). The representative case is shown in figure (left panel). Further, positive sRASP was associated with the outcome after adjusting for the Euro score, NYHA ≥II, and GLS (hazard ratio = 2.69, p=0.01). The model based on these covariates significantly improved following the addition of sRASP (Figure; right panel). In addition, sRASP was observed in four patients out of 50 patients who underwent aortic valve replacement. Of these, one patient had the primary outcome (25%). On the other hand, in the remaining 46 patients without sRASP, four patients had the outcome (9%).

Figure 1

Conclusions

RASP was observed in some patients with severe AS and has been shown to have increasing importance in predicting adverse cardiac events in such patients.
P314Osteopontin stimulates cell cycle in neonatal cardiomyocytes
Authors: Rotem I , Schary Y , Shaihov - Teper O , Konfino T , Leor J
Published: October 2019

Introduction

Macrophages control myocardial regeneration in the neonatal heart and repair in the adult heart. Osteopontin (OPN) is a macrophage-derived protein which is upregulated following tissue injury. While OPN regulates cell adhesion, spreading and migration, its role in myocardial regeneration is unknown.

Purpose

We aimed to test the hypothesis that OPN stimulates cardiomyocyte proliferation.

Methods and results

Mouse neonatal cardiomyocytes were treated with a serum-free medium for 24 hours. Immunofluorescent staining showed that these cells expressed the OPN receptor CD44 (Fig. 1A). To assess cell expansion, we used MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colorimetric assay. OPN preserved cardiomyocyte count in a low glucose medium for 24 hours, compared with no OPN treatment (Fig. 1B). Staining for phosphohistone (pH)3, a marker of nucleus division, showed a higher expression of pH3 in cardiomyocytes after OPN treatment (Fig. 1C). Immunoblotting revealed that OPN induced the phosphorylation of cell-cycle activity proteins, known as yes-associated protein (YAP)1, and extracellular signal-regulated kinase (ERK)2, while it decreased the phosphorylation of the YAP1 inhibitor, the large tumor-suppressor kinase (LATS)1/2 (Figs. 1D and 1E). Gene expression analysis revealed that OPN upregulated the transcriptional enhancer factor TEF-1 (TEAD1), which interacts with YAP1 (Fig. 1F), connective tissue growth factor (CTGF) and cyclin-dependent kinase 1 (CDK1), which are YAP downstream targets (Figs. 1G and 1H). Furthermore, OPN significantly upregulated cyclin B1, a regulator of the mitotic (M) phase (Fig. 1I). Moreover, OPN may promote positive feedback by upregulating the expression of CD44, SPP-1 (Figs. 1J and 1K). Finally, administration of OPN to adult mouse improved cardiac remodeling and function after myocardial infarction.

Conclusions

OPN stimulates cell-cycle activity in neonatal cardiomyocytes through YAP1 activity, independently from the HIPPO-YAP signaling pathway. Because macrophages are a major source of OPN after injury, our findings could explain the essential role of macrophages in neonatal heart regeneration and adult heart repair.

Acknowledgement/Funding

Israel Science Foundation
P315In-vivo and vitro mitochondrial transfer from adipose-derived mesenchymal stem cell to ischemic cardiomyocyte
Authors: Mori D , Miyagawa S , Kawamura T , Hata H , Ueno T , Toda K , Kuratani T , Kurata H , Nishida H , Sawa Y
Published: October 2019

Background

Although transplantation of human Adipose-derived Mesenchymal stem cell (hADSC) shows efficacy in the treatment of ischemic cardiomyopathy, its therapeutic mechanisms have not been fully elucidated. It has been already reported that mitochondria transfer to recipient cells have impact on resistance to injury and tissue regeneration, however this phenomenon has not been elucidated in the damaged heart. Therefore, we hypothesized that ADSC transfer own mitochondria to cardiomyocytes in-vivo and in-vitro under ischemic condition, resulting in the functional recovery of cardiomyocyte.

Method and result

Transplantation of hADSC (group A) to the heart surface or sham operation (group C) was performed in rats that were subjected to LAD ligation 2 weeks prior to the treatment (n=10 each). The number of transplant cell was 1x106/body. Three days after transplantation, transferred hADSCs' mitochondria were observed in recipient cardiomyocytes histologically (Figure). Quantitative PCR analysis revealed that mitochondrial genome of recipient myocytes increased over time. The cardiac function assessed with echocardiography was significantly better in group A. Furthermore, live-imaging of hADSC transplantation revealed the suspected transfer of mitochondria to beating heart.

In-vitro, the co-culture of rat cardiomyocytes (rCM) and hADSC was observed with time-lapse photography and demonstrated mitochondrial transfer under the hypoxic condition. The measuring the oxygen consumption rate (OCR) of these cells showed that OCR of rCM was reinforced by co-culture with hADSC conspicuously.

Figure 1

Conclusion

Mitochondrial transfer from hADSC to rCM was suggested in-vivo and in-vitro ischemic condition and suspected to be related to functional recovery of ischemic cardiomyocyte.
P318Exosomes mediate myocardial regeneration of cardiac progenitor cells in a swine model of dilated cardiomyopathy
Authors: Hirai K , Goto T , Ousaka D , Ohtsuki S , Oh H
Published: October 2019

Introduction

Stem cell therapy has been shown to improve cardiac function. The mechanisms of therapeutic efficacy are considered the secretion of paracrine factors but the details are still unknown.

Hypothesis

Exosomes are extracellular vesicles containing bioactive substances such as proteins, messenger RNAs and micro RNAs. We hypothesized that exosomes may be the main paracrine factors to mediate therapeutic efficacy of cardiosphere-derived cells (CDCs).

Methods

Farm pigs (30 kg, n=10) were treated by intracoronary administration of 10,000 microspheres (100–300 μm) into three vessels. Two weeks later, 9.0×106 CDCs pretreated by exosome inhibitor (EI; 20μM of GW4869) or DMSO as controls were selectively infused into three coronary arteries. Evaluation of ejection fraction (EF) was performed before cell infusion and 1 month after protocol treatment.

Results

Pigs developed diffuse hypokinetic heart failure (baseline EF 37.1%±2.1%) and randomly assigned into two groups (CDCs with EI: n=5, CDCs with DMSO: n=5). No serious adverse events were found during the CDCs infusion. Significant improvement of EF was observed in CDCs with DMSO group (37.1%±2.1% to 42.5%±3.0%; P=0.01), whereas no change was found in CDCs with EI group (37.1%±2.4% to 36.2%±2.9%; P=0.58). Myocardial fibrosis stained by picrosirius red was significantly reduced in CDCs with DMSO group compared with CDCs with EI group (9.5±3.6% versus 17.3±5.3%; P<0.01).

Conclusions

We confirmed the therapeutic efficacy of CDCs and these effects were mainly mediated by exosomes.
P319Proliferative induced cardiomyocyte precursor cells obtained by direct reprogramming and transcriptional selection
Authors: Bachamanda Somesh D , Klose K , Juerchott K , Krueger U , Kunkel D , Kurtz A , Falk V , Gossen M , Stamm C
Published: October 2019

Objective

Enriched populations of proliferative induced cardiomyocyte precursors (iCMPs) generated from cardiac fibroblasts (CF) could represent a potential population for use in therapeutic application. We developed a protocol for generation of iCMPs from cardiac fibroblasts by genetic reprogramming followed by transcriptional selection and induced maturation.

Methods

Cardiac fibroblasts were reprogrammed into induced cardiomyocyte precursor cells (iCMPs) via transduction with cardiomyogenesis-related transcription factors Gata4, Mef2c, TBX5 and Myocd. Pure population of iCMPs were obtained by molecular beacons (MB) based selection of MYH6/7 expression. The transcriptome was profiled by RNA sequencing. For maturation iCMPs were treated with 5'-azacytidine and cultured in medium containing ascorbic acid and TGFβ1. The cells were monitored regularly for formation of sarcomere structures, cardiac marker expression and contractions. iCMPs were transplanted into MI mice and monitored for 6 weeks. At the end of 6 weeks, the mice were sacrificed and hearts were explanted and cryopreserved to examine the heart structure and scare size. Cardiac function was monitored by echocardiography.

Results

iCMPs expressed troponin T, α-actinin and myosin heavy chain (MHC) protein observed by immunocytology. These iCMPs could robustly proliferative and maintain a stable phenotype. Global transcriptome analysis revealed that the iCMP gene expression profile is unique from those of the parental CFs and adult CMs. With Gene Ontology (GO) analysis, we found that iCMPs show upregulation of genes associated with cardiac development, differentiation and morphogenesis while they showed downregulation of genes associated to cell-proliferation in comparison to their parental CFs. Evaluation of selected gene sets showed downregulation of non-myocyte genes, upregulation of transcription factors and upregulation of certain functional and structural genes like ion channel genes and contractile genes. Maturation studies showed that iCMPs gradually changed morphology after stimulation with 5-Aza, as seen in immunofluorescence staining. Cells expressing cTnT showed formation of sarcomeric striations. In vivo translational studies showed reduction of heart function in control groups treated with PBS or CF whereas the iCMPs group showed an improvement in function, reflected by left ventricular ejection fraction and fractional shortening as evaluated by echocardiography. Additionally we noticed an improvement in left ventricular wall thickness at diastole in mice transplanted with iCMPs.

Conclusions

Gene expression pattern suggests that these iCMPs represent an intermediate state of cardiogenic population that can be expanded to yield therapeutic cell doses. When transplanted to mouse hearts following myocardial infarction, they improved cardiac function.
P320Heart failure with mid-range (HFmrEF) or recovered (HFrecEF) ejection fraction: differential determinants of transition
Authors: De Maria R , Macera F , Gorini M , Battistoni I , Iacoviello M , Iacovoni A , Palmieri V , Pasqualucci D , Leonardi G , Pagnoni N , Montagna L , Floresta M , Midi P , Pulignano G , Mortara A
Published: October 2019

Background

Heart failure with mid-range ejection fraction (HFmrEF) has been identified as a multi-faceted phenotype that may encompass both patients with mild disease or those who from previous HFrEF recover EF (HFrecEF)

Purpose

To describe clinical characteristics and factors associated with phenotype transition at follow-up.

Methods

From 2009 to 2016, 1194 patients with baseline EF<50% and a second echocardiographic determination during clinically stability at a median of 6 months were enrolled in the IN-CHF Registry. Based on EF at enrollment, 335 (28%) had HFmrEF and 859 (72%) had HFrEF. We compared baseline clinical characteristics and predictors associated with follow-up reclassification to HFmrEF or full EF recovery

Results

When compared to HFrEF patients, those with HFmrEF had less often an ischemic etiology, advanced symptoms and a HF admission in the previous year. No other differences were found in clinical characteristics and drug therapy (Table).

At a median follow-up of 6 months, 30% of HFrEF patients improved EF by 14 (9) units: 21% showed partial EF recovery (transition to HFmrEF) and 9% had full EF recovery. Conversely among HFmrEF patients 22% improved EF, by 9 (5) units, to full recovery, and 18% deteriorated by 1.5 (5.5) units sloping to HFrEF.

By multivariable logistic regression analysis, variables associated with EF recovery at 6-month follow-up differed between baseline phenotypes. Within HFrEF, ischemic etiology (OR 0.46, 95% CI 0.33–0.64) and NYHA class III-IV symptoms (OR 0.57, 95% CI 0.38–0.68) were associated with a lower likelihood of EF recovery, while a history of HF<6 month correlated with a higher likelihood of EF recovery (OR 2.44, 95% CI 1.76–3.39). Within HFmrEF, while ischemic etiology (OR 0.66, 95% CI 0.19–0.68) was also associated with a lower likelihood of EF recovery, a history of atrial fibrillation at enrollment correlated with higher likelihood of EF recovery (OR 2.66, 95% CI 1.37–5.17) by 6 month-follow-up.

At a median follow-up of 36+28 months mortality was 4.6% vs 6.9% in HFrecEF vs non-recovered patients (log rank p=0.08).

Baseline characteristics HFrEF vs HFmrEF

Conclusions

HFmrEF patients showed a less severe clinical picture than HFrEF patients, but had EF recovery less often. EF improvement is negatively associated with ischemic etiology in both phenotypes, and positively associated with atrial fibrillation in HFmrEF and a short history of HF in HFrEF.
P323Haemodynamic implications of mitral regurgitation in heart failure with preserved ejection fraction
Authors: Tamargo Delpon M A , Masaru O , Reddy Y N , Pislaru S , Egbe A , Borlaug B A
Published: October 2019

Background

Mild to moderate mitral regurgitation (MR) is a common finding in heart failure with preserved ejection fraction (HFpEF). MR is often considered to be an innocent bystander, yet little data is available regarding its implications.

Aim

Determine the pathophysiologic correlates of MR in HFpEF

Methods

We retrospectively studied 280 patients with invasively proven HFpEF. MR was absent (None or trivial) in 163 subjects (Non-MR-HFpEF), and present in 117 (MR-HFpEF; 78 mild and 39 moderate MR). 247 subjects also underwent invasive cardiopulmonary exercise testing.

Results

At rest, MR-HFpEF subjects displayed higher pulmonary artery pressures (PAP), PCWP, and pulmonary vascular resistance (PVR; Table). During exercise, PAP and PCWP were not significantly different among groups, but MR-HFpEF displayed reduced ability to enhance cardiac output (CO) in response to heightened metabolic demand (oxygen consumption, VO2; Figure).

Baseline characteristics and haemodynamic characterization at baseline and peak exercise Baseline characteristics Non-MR-HFpEF (N=163) MR-HFpEF (N=117) p value Age 66±11 71±10 0.0002 Female (%) 56 69 0.02 AFib (%) 13 38 <0.0001 Nt proBNP 192 [66, 557] 870 [401, 2135] <0.0001 E/E' 12.3±5.5 15.6±7.2 0.0006 LVEF (%) 64±6 62±6 0.0001 RV fractional area change (%) 51±9 47±10 0.0001 Mean PA (mmHg) 25±7 28±9 0.001 Mean PCWP (mmHg) 15±5 17±6 0.0002 PVR (Woods) 2.0±1.1 2.5±1.4 0.015 CO (L/min) 5.5±1.6 4.8±1.3 0.12 Peak exercise hemodynamics Non-MR-HFpEF (N=152) MR-HFpEF (N=95) p value Mean PA (mmHg 45±10 46.5±10 0.07 Mean PCWP (mmHg) 32±6 31±6 0.6 PVR (Woods) 1.8±1.6 2.7±2.4 0.002 CO (L/min) 9.1±3 7.2±3 0.01 P value adjusted for age, gender and BMI.

CO change in response to VO2 increase

Conclusion

The presence of even mild MR in HFpEF is associated with more adverse hemodynamics, greater pulmonary vascular dysfunction and impaired CO reserve with exercise. Further study is required to better understand the natural history and treatment for MR in HFpEF.

Acknowledgement/Funding

None
P335Prevalence of transthyretin cardiac amyloidosis in a community-based heart failure population
Authors: Lindmark K , Pilebro B , Solekrans L , Wixner J , Anan I , Suhr O , Lindqvist P
Published: October 2019

Introduction

Cardiac wild type (wt) transthyretin (ATTR) amyloidos causes hypertrophic, restrictive cardiomyopathy in older patients and is generally considered underdiagnosed. However, its prevalence remains poorly investigated. Scintigraphy using bone tracers, e.g. Tc-PYP and Tc-DPD, is a highly sensitive and specific method for detection of cardiac ATTR and has revolutionised diagnostics The aim of this study was to describe the prevalence of wtATTR amyloidosis in our heart failure population.

Methods

Our University Hospital is the sole provider of specialised heart care in an area with around 150 000 inhabitants, 37 600 of which are older than 60 years. Medical records for all living patients in the area with a diagnosis of heart failure, hypertensive heart disease or cardiomyopathy between 2010 and May 2018 were scrutinized (n=2237). 95% of these patients had an echocardiographic exam available for re-evaluation. All patients withseptal thickness >14 mm who had no previous DPD scintigraphy or genetic diagnosis of sarcomeric hypertophic cardiomyopathy were offered DPD scintigraphy (n=131). Eight patients died prior to and 38 patients declined work up, mainly due to old age.

A DPD uptake of grade 2 or higher was considered diagnostic in absence of signs of AL amyloidosis.

Results

Adding up patients found during the screening effort and those with an already known diagnosis of wtATTR amyloidosis, 26 patients had wtATTR. Their men age was 84 years and 90% were male.

Conclusions

The study gives us an estimated prevalence of disease warranting specialized heart failure treatment of 1/1500 in the population older than 60 years. Cardiac wtATTR amyloidosis is common in patients with heart failure and increased LV wall thickness, especially among the older male patients. Therefore we recommend a liberal use of bone scintigraphy in this group.
P343Comparison of Focal Impulse and Rotor Modulation Ablation (FIRM) only versus second-generation cyroballoon ablation in patients with paroxysmal atrial fibrillation
Authors: Tilz R , Lyan E , Heeger C , Fink T , Liosis S , Brueggemann B , Meyer-Sarai R , Sano M , An D , Eitel C , Vogler J
Published: October 2019

Background

Rotors have been postulated to be a major driver of atrial fibrillation (AF). Initial studies demonstrated, that focal impulse and rotor modulation (FIRM) might be an effective therapy for the treatment of paroxysmal AF (PAF). However, data about FIRM-guided ablation strategies without PVI is sparse.

Objective

To compare the safety and efficacy of FIRM-guided catheter ablation (without PVI; FIRM arm) and second generation cryoballoon (CB2, CB2 arm) based PVI in patients with paroxysmal atrial fibrillation (PAF) and de-novo catheter ablation of AF.

Methods

In this retrospective single-center study patients with PAF undergoing de-novo ablation of PAF between February 2016 and January 2017 were enrolled. Patients treated with FIRM-guided AF ablation as a standalone therapy without PVI were included and compared with patients undergoing CB2 based PVI. All patients in the FIRM arm were part of the randomized multicenter FIRMAP AF trial (results of this trial will be presented at this meeting). In patients undergoing FIRM-guided ablation, 3D electroanatomical mapping of both atria was performed. Rotor mapping using FIRM technology was conducted in spontaneous or induced AF. The procedural endpoint was the elimination of all rotors and focal impulses; no PVI was performed in those patients. In the CB2 arm, CB based PVI with the procedural endpoint of isolation of all veins was performed. Procedural data and arrhythmia-free survival after 12 months were compared.

Results

FIRM-guided and CB2 based AF ablation was performed in 22 and 86 patients, respectively. Follow up was completed in 20 and 79 patients LA diameter differed between groups. Otherwise, baseline characteristics did not differ between the FIRM group (mean age 60±11 years, 59.1% males) and the CB2 group (mean age 62±13, 62.4% male).

Arrhythmia-free survival including a 90-day blanking period was 25.0% (15/20) in the FIRM group and 86.1% (11/79) in the CB2 PVI group (p=0.000; Figure 1). Procedure duration was significantly longer in the FIRM group (152 [120; 176] minutes) compared to the CB2 PVI group (122 [110; 145] minutes) (p=0.031), whereas radiation dose was lower in the FIRM group (1266 [1027; 2281] cGy·cm2 vs. 3020 [1677; 4215] cGy·cm2). Adverse events (groin complications) occurred in 1 patient (1.2%) in the CB2 PVI group and 5 patients (22.7%) in the FIRM group.

Figure 1. Kaplan-Meier-survival curve dem

Conclusion

De novo ablation of PAF using a FIRM-guided AF ablation only (without PVI) is associated with poor arrhythmia-free survival after 12 months compared to CB2 PVI. These results underline the importance of PVI as the first-line approach in catheter ablation of AF.
P346More procedural complications in female patients undergoing pulmonary vein ablation in atrium fibrillation: results from 12,430 patients in the Netherlands Heart Registry
Authors: Mol D , Houterman S , De Jong J S , De Groot J R
Published: October 2019

Introduction

Pulmonary vein isolation (PVI) has become a cornerstone of the treatment of atrial fibrillation (AF). Several technologies have been developed to improve procedural and long-term outcomes. Depending on type of AF and rhythm recording used, 1-year freedom of AF varies between 55–82%. However, severe complications are reported in 1–3%.

Purpose

To describe procedural complications of PVI with either single tip radiofrequency ablation (STRF), multi electrode phased RF ablation (PVAC) or cryoballoon (CB).

Methods

Data was extracted from the Netherlands Heart Registry in which 14 Dutch heart centres participate. Procedural complications in patients treated with the 3 different ablation modalities (STRF, PVAC and CB ablation) were compared. Complications included: pericardial tamponade, persistent phrenic nerve palsy (PNP) beyond 24hrs, thromboembolic events, vascular- and bleeding complications. Patient characteristics: gender, age, BMI, CHA2DS2 -VASc, type of AF and previous left atrium ablation were assessed in a univariate and multivariate regression model.

Results

In total, 12,430 patients were included (STRF n=5,106, PVAC n=2,341, CB n=4,983) between January 2013 and December 2017, of whom, 69% were male, 74% had a history of paroxysmal AF, 24% persistent AF and 2% longstanding persistent AF. The incidence of complications within 30 days was 3.6%. Pericardial tamponade requiring intervention, occurred more frequently in the STRF group (STRF: 0.8% vs PVAC 0.3% vs CB 0.3% p= <0.01). PNP was present in 0.1% of patients after STRF ablation, in 0.2% of patients after PVAC ablation and in 1.5% of patients treated with CB ablation (p= <0.001). Thromboembolic events were observed in 0.4% with no statistical difference between the 3 modalities. Patients treated with STRF had more vascular complications (STRF 1.7% vs PVAC 1.2% vs CB 1.3% p= <0.001). In the PVAC and CB group there were significant less bleeding complications (STRF: 1.1% vs PVAC: 0.5% vs CB: 0.7% p=0.01). Female patients and patients with a higher CHA2DS2-VASc had an increased risk for pericardial tamponade, vascular- and bleeding complications (figure) with adjusted odds ratios for female patients of 2.97 (95% CI 1.77–5.00), 2.24 (95% CI 1.41–3.56) and 2.84 (95% CI 1.88–4.28) respectively.

Univariate analysis

Conclusion

PVI was associated with a complication rate of 3.6%. Compared to PVAC and CB ablation, patients treated with STRF ablation more often developed a pericardial tamponade and vascular- and bleeding complications. PNP occurred most frequent in patients undergoing CB ablation. Female gender and CHA2DS2-VASc were independent predictors for pericardial tamponade, vascular- and bleeding complications.
P581Electronic health records (EHRs) data validation in atherosclerotic/cardiovascular clinical phenotypes
Authors: Cruz N , Serrano M , Lopez A , Medrano I H , Lozano J , Coll B
Published: October 2019

Background

Research efforts to develop strategies to effectively identify patients and reduce the burden of cardiovascular diseases is essential for the future of the health system. Most research studies have used only coded parts of electronic health records (EHRs) for case-detection obtaining missed data cases, reducing study quality and in some case bias findings. Incorporating information from free-text into case-detection through Big Data and Artificial Intelligence techniques improves research quality. Savana has developed EHRead, a powerful technology that applies Natural Language Processing, Machine Learning and Deep Learning, to analyse and automatically extracts highly valuable medical information from unstructured free text contained in the EHR to support research and practice.

Purpose

We aimed to validate the linguistic accuracy performance of Savana, in terms of Precision (P), Recall (R) and overall performance (F-Score) in the cardiovascular domain since this is one of the most prevalent disease in the general population. This means validating the extent to which the Savana system identifies mentions to atherosclerotic/cardiovascular clinical phenotypes in EHRs.

Methods

The project was conducted in 3 Spanish sites and the system was validated using a corpus that consisted of 739 EHRs, including the emergency, medical and discharge records, written in free text. These EHRs were randomly selected from the total number of clinical documents generated during the period of 2012–2017 and were fully anonymized to comply with legal and ethical requirements. Two physicians per site reviewed records (randomly selected) and annotated all direct references to atherosclerotic/cardiovascular clinical phenotypes, following the annotation guidelines previously developed. A third physician adjudicated discordant annotations. Savana's performance was automatically calculated using as validation resource the gold standard created by the experts.

Results

We found good levels of performance achieved by Savana in the identification of mentions to atherosclerotic/cardiovascular clinical phenotypes, yielding an overall P, R, and F-score of 0.97, 0.92, and 0.94, respectively. We also found that going through all the EHRs and identifying the mentions to atherosclerotic/cardiovascular clinical phenotypes, the expert spent ∼ 60h while Savana ∼ 36 min.

Conclusion(s)

Innovative techniques to identify atherosclerotic/cardiovascular clinical phenotypes could be used to support real world data research and clinical practice. Overall Savana showed a high performance, comparable with those obtained by an expert physician annotator doing the same task. Additionally, a significant reduction of time in using automatic information extraction system was achieved.
P606High intermodality variability in ejection fraction measured by echocardiography, cardiac magnetic resonance and single photon emission computed tomography in chronic coronary artery disease patients
Authors: Stokke T M , Sarvari S I , Bjerring A W , Haugaa K H , Elahi M T , Hoedemakers S I , Rademakers F , Monaghan M , Sicari R , Engvall J , Nagel E , Zamorano J L , Ukkonen H , D'hooge J , Edvardsen T
Published: October 2019

Background

Clinical treatment strategies are often based on measurement of left ventricular ejection fraction (LVEF). There is limited evidence about variations in LVEF when measured by different imaging modalities.

Purpose

To investigate the intermodality variability of LVEF measured by two-dimensional echocardiography (2DE), three-dimensional echocardiography (3DE), cardiac magnetic resonance (CMR), and single photon emission computed tomography (SPECT) in patients with chronic coronary artery disease (CAD).

Methods

Patients from a multicenter study (DOPPLER-CIP – Determining optimal noninvasive parameters for the prediction of left ventricular remodeling in chronic ischemic patients) with chronic CAD were included. LVEF was measured by CMR and at least one additional modality. In each modality, LVEF was measured by a core laboratory independently of the other modalities. Measurements of LVEF by CMR were compared to 2DE, 3DE and SPECT using correlation and Bland-Altman plots.

Results

A total of 343 patients were included. Mean age was 63.9±8.3 years and 253 (74%) were males. Mean LVEF by CMR was 61.8±11.6%. Correlations between CMR LVEF and other modalities were moderate for 2DE and 3DE, and good for SPECT (Figure A-C). CMR had significantly greater correlation to SPECT, compared to 2DE and 3DE. Bland-Altman plots indicated relatively wide limits of agreement between all modalities, ranging from 31% to 42% (Figure, D-F). Mean absolute difference of LVEF between CMR and other modalities were 8.5% for 2DE, 9.0% for 3DE, and 8.3% for SPECT. The percentage of measurements that fell within a range of 5% difference compared to CMR LVEF was 41% for 2DE, 34% for 3DE and 37% for SPECT (all p>0.05).

Conclusions

In a multicenter study with chronic CAD patients, LVEF assessed by CMR had better correlation to SPECT, compared to 2DE and 3DE. However, there was considerable variability among all three modalities that were compared to CMR. Awareness of these variations are important in clinical management.
P608Exercise testing and multi-parametric CMR assessment in patients with Ebstein anomaly
Authors: Radke R M , Bietenbeck M , Meier C , Orwat S , Baumgartner H , Yilmaz A
Published: October 2019

Background

Ebstein anomaly (EA) is a rare congenital heart disease characterized by an apically displaced tricuspid valve. It is associated with tricuspid valve regurgitation and right heart dilatation leading to significant morbidity. While echocardiography remains the mainstay of routine outpatient cardiac imaging, assessment of right ventricular (RV) anatomy and function is still challenging. Cardiovascular magnetic resonance imaging (CMR) has been shown to be of advantage in these patients being free from acoustic window limitations and offering superior volume quantification. In the present study, parameters obtained from cardiopulmonary exercise testing (CPET) were compared to conventional and novel CMR parameters in patients with EA.

Methods

In this prospective single centre study, N=17 patients with EA (mean age = 33.8±12.7yrs; N=10 females) underwent clinical assessment, CPET and multi-parametric CMR. Maximal work load (maxWL) and peak oxygen uptake (maxO2) were derived from CPET. CMR studies were performed on a 1.5-T Philips scanner and respective CMR parameters comprised a) anatomical, b) functional and c) myocardial deformation values of both ventricles.

Results

The majority of patients presented in NYHA class I or II (mean NYHA = 1.6±0.7) and with normal or mildly elevated NT-proBNP values (mean NT-proBNP = 189±158pg/ml). CPET-based maxWL was 147.14±55 watts and maxO2 19.32±5 ml/kg/min. CMR-based mean LVEF was 57.1±6.4% and RVEF was 46.5±11.1%, respectively. Deformation imaging revealed (amongst others) a LV global longitudinal strain (LV-gLS) of −13.7±3.0 and a RV global longitudinal strain (RV-gLS) of −14.7±5.0. Non-ischemic presence of late-gadolinium-enhancement was documented in 36% of our patients. Comprehensive correlation analysis revealed a substantial correlation a) between LV-gLS and NYHA class (r=0.64, p=0.01), but not between RV-gLS and NYHA class (r=0.19, p=0.46), b) between serum NT-proBNP levels and maxO2 (r=−0.53, p=0.03) as well as maxWL (r=−0.63, p=0.02), and c) between LV-EF and LV-gLS (r=−0.64, p=0.01).

Conclusion

Our preliminary data suggest that serum markers such as NT-proBNP and novel CMR parameters such as LV-gLS – but not RV-gLS - correlate with CPET-derived exercise parameters in patients with EA. The predictive value of these parameters regarding cardiac disease progression in EA has to be evaluated in future follow-up studies.
P614Comparison of echo parameters with cardiac MRI in the assessment of right ventricular function
Authors: Agasthi P , Venepally N R , Mookadam F , Jokerst C E , Marcotte F , Brown L , Semkiv O I , Wang P , Konduru S , Fath A R , Arsanjani R
Published: October 2019

Introduction

Systolic right ventricular (RV) function has prognostic significance both in acquired and congenital heart diseases. However accurate assessment of RV ejection fraction (EF) with transthoracic echocardiography (TTE) remains challenging due to the complex geometric shape of the RV. Magnetic resonance imaging (MRI) remains the gold standard modality for assessment of RV function; however the cost and availability limits the regular use of MRI in clinical practice. The RV strain measured by speckle tracking (RVS) is a novel method of assessing RV EF.

Purpose

The purpose of the study was to assess the accuracy of RVS compared RV fractional area change (FAC%), tricuspid annular peak systolic excursion (TAPSE) and Doppler tissue imaging-derived isovolumic acceleration and peak systolic velocity (S') at the lateral tricuspid annulus in the assessment of impaired RV EF.

Methods

We retrospectively identified patients who had a cardiac MRI between 2012- 2017 and only included patients with a TTE within 1 month of the MRI for our final analysis. Baseline characteristics, TTE and MRI parameters were extracted from chart review. RV strain was measured retrospectively using ECHOINSIGHT software. Four TTE parameters including RVS, TAPSE, S' and FAC% were tested for accuracy to identify impaired RV EF (defined as EF<45%) using receiver operator curves.

Results

The study cohort included 500 patients with mean age 55 yr ± 18 and right ventricular systolic pressure 33.7±13.6 mmHg. The proportion of female gender, diabetes, hypertension and obstructive sleep apnea were 38%, 15.6%, 43% & 19.8% respectively. The area under ROC for TAPSE, S', FAC% and RVS were 0.58 (95% confidence interval [CI] 0.51–0.65, p=0.03), 0.59 (95% CI 0.52–0.66, p=0.03), 0.67 (95% CI 0.61–0.73, p=0.03) and 0.70 (0.64–0.76, p=0.03) for assessing RV EF <45%.

Conclusion

Right ventricular strain most accurately detected impaired right ventricular ejection fraction as obtained by MRI.

Acknowledgement/Funding

None
P638High intensity interval exercise training improves endothelial function in patients with heart failure with preserved ejection fraction
Authors: Deljanin Ilic M , Kocic G , Simonovic D , Pavlovic R , Ilic S , Petrovic D , Ilic B
Published: October 2019

Background

Cardiac rehabilitation has traditionally invoved low-to moderate intensity continuous exercise training (MICT). There is growing evidence that high intensity interval exercise training (HIIT) shows similar or greater efficacy compared with MICT. However, the relationship between the training modality and its effects on endothelial function still remains to be elucidated.

Purpose

To evaluate the impact of high intensity interval exercise training versus low-to moderate intensity continuous exercise training on circulating blood markers of endothelial function: the stable end product of nitric oxide (NOx), S–nitrosothiols (RSNO–reservoir for bioavailable nitric oxide), dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in patients (pts) with heart failure with preserved ejection fraction (HFpEF).

Methods

A total of 43 pts with HFpEF (mean age 57.5±6.8y) admitted at residential rehabilitation center were enrolled in the study. Patients were randomized to HIIT, (HIIT group, n=20) and MICT, (MICTgroup, n=23). At baseline and 3 weeks later, in all pts values of NOx, RSNO, ADMA and SDMA were determined and exercise test was performed.

Results

After 3 weeks NOx increased significantly in both groups: in HIITgroup (from 34.7±7.5 to 48.5±8.3 μmol/l, P<0.0001), in MICTgroup (from 35.0±9.5 to 42.5±10.0 μmol/l, P<0.05), and value of NOx after 3 weeks was higher in HIIT than in MICT group (P<0.05). Value of ADMA as well of SDMA decreased in both groups after 3 weeks, and this decrease was significant in HIIT group: ADMA in HIIT group (from 0.305±0.055 to 0.250±0.077 μmol/l, P<0.005) and in MICT group (from 0.325±0.069 to 0.280±0.140 μmol/l, ns); SDMA in HIIT group (from 0.285±0.050 to 0.240±0.060 μmol/l, P<0,005) and in MICT group (from 0.270±0.080 to 0.247±0.063 μmol/l, ns). Value of RSNO significantly increased in both groups, with higher increase in HIIT group: in HIIT group (from 3.0±1.5 to 5.1±1.7 μmol/l, P<0.001), in MICTgroup (from 3.2±1.7 to 4.5±2.3 μmol/l, P<0.05). Compared to the baseline, at the end of the study, exercise capacity (METs) was significantly higher in both groups (P<0.0001). Higher increase in METs in HIIT group during exercise training (by 39.8%), compared to increase in MICT group (by 27.2%), resulted in significantly higher exercise tolerance in HIIT than in MICT group at the end of the study (P<0.02). In both groups, adverse events during or after exercise training, were not occurred.

Conclusions

In pts with HFpEF high intensity interval exercise training as well as low-to moderate intensity continuous exercise training induced favorable modification of endothelial function, expressed through increase of NOx and RSNO, and decrease of ADMA and SDMA. More significant increase of NOx and RSNO, and significant decrease of ADMA and SDMA gives an advantage to HIIT over MICT exercise training in patients with HFpEF.
P651Prevalence of hypertriglyceridemia in statin treated high risk patients who might benefit from treatment with icosapent ethyl for secondary prevention in clinical practice - Results of DYSIS
Authors: Gitt A K , Horack M , Lautsch D , Ferrieres J
Published: October 2019

Background

Patients with elevated triglyceride (TG) levels are at increased risk for ischemic events. In the recently published REDUCE-IT-Study among patients with elevated triglyceride levels who were receiving statin therapy, the risk of major ischemic events, including cardiovascular death, was significantly lower with 2 g of icosapent ethyl twice daily than with placebo. Little is known about how many patients in clinical practice might benefit from this additional treatment.

Methods

The cross sectional, observational Dyslipidemia International Study (DYSIS) examined lipid goal attainment among statin-treated very high cardiovascular risk patients (defined as per 2011 EAS/ESC guidelines, including patients suffering from coronary heart disease, diabetes, chronic kidney disease or peripheral atherosclerotic disease) in Canada, Europe, Middle East countries and China. Data were collected under real life conditions in physicians' offices and hospital outpatient wards between 2008–2012. We examined the prevalence of mixed dyslipidemia with TG >135 mg/dl in high statin treated high risk patients in clinical practice.

Results

Of a total of 44,593 patients on very high cardiovascular risk, all on chronic statin treatment, 21,312 (47.8%) had mixed dyslipidemia with TG values >135mg/dl. Patients with elevated TG also had higher levels of total and LDL-cholesterol. The overall use of additional fibrates on top of statins was low (4.0%), but more frequent in patients with TG >135 mg/dl.

CVD patients with TG>135 mg/dl Pts with TG >135 mg/dl Pts with TG ≤135 mg/dl p-value OR (95% CI) n=21,312 (47.8%) n=23,281 (52.2%) Age (years) 65.4±10.1, 68.1±10.2 <0.0001 Females 42.2% 38.6% <0.0001 1.16 (1.12–1.21) Sedentary lifestyle 43.0% 37.6% <0.0001 1.25 (1.20–1.30) Risk factors/CV-disease   Hypertension 79.0% 74.9% <0.0001 1.26 (1.21–1.32)   Diabetes mellitus 56.3% 45.3% <0.0001 1.55 (1.50–1.61)   Ischemic heart disease 50.6% 54.4% <0.0001 0.86 (0.83–0.89)   Cerebrovascular disease 16.1% 17.7% <0.0001 0.90 (0.85–0.94)   Peripheral artery disease 8.1% 6.9% <0.0001 1.18 (1.10–1.27) Lipid lowering therapy   Rosuvastatin 11.3% 11.8% 0.13 0.95 (0.90–1.01)   Atorvastatin 38.2% 40.9% <0.0001 0.89 (0.86–0.93)   Simvastatin 41.9% 38.9% <0.0001 1.13 (1.09–1.18)   Other statins 8.6% 8.4% 0.12 0.96 (0.88–1.05)   Fibrates 5.5% 1.5% <0.0001 3.86 (3.40–4.37) Lipid Profile   Total Cholesterol (mg/dl) 185.6 159.0 <0.0001   LDL-Cholesterol (mg/dl) 102.1 88.9 <0.0001   Triglyderides (mg/dl) 189.5 95.7 <0.0001

Conclusion

Almost half of consecutive patients with cardiovascular disease treated with statins for secondary prevention in clinical practice suffer from TG levels >135 mg/dl and might benefit from additional treatment with icosapent ethyl with further reduction in subsequent major ischemic events, including cardiovascular death.

Acknowledgement/Funding

MSD
P667Aspirin in primary prevention. Risks and benefits. Up date 2019. A meta-analysis
Authors: Lobo L M , Masson G , Molinero G , Masson W , Giorgi M A , Siniawski D
Published: October 2019

The usefulness of aspirin in patients without a cardiovascular history continues to be a subject of controversy.

Objectives

1. Perform an updated meta-analysis on the use of aspirin in primary cardiovascular prevention. 2. Analyze the results by risk.

Methods

This meta-analysis was performed according to the PRISMA guidelines. The primary endpoint was cardiovascular death, AMI, and ischemic stroke. The measures of effect size are expressed as odds ratios. The level of statistical significance was established at 0.05.

Characteristics of the studies Trials Year N Follow-up Risk RTPDABMD 1988 5,139 5.5 Middle PHS 1989 22,071 5 Low HOT 1998 18,790 3.8 Middle TPT 1998 5,085 6.7 Middle PPP 2001 44,95 3.6 Low WHS 2005 39,876 10.1 Low JPAD 2008 2,539 4.4 Low POPADAD 2008 1276 6.7 High AAA 2010 3,350 8.2 Low JPPP 2014 14,464 5 Low ASCEND 2018 15,480 7.4 Middle ARRIVE 2018 12,546 5 Low ASPREE 2018 19,114 4.7 Low RTPDABMD, Randomised trial of prophylactic daily aspirin in British male doctors; PHS, Physicians' Health Study; HOT, Hypertension Optimal Treatment; TPT, Thrombosis Prevention Trial; PPP, Primary Prevention Project; WHS, Women's Health Study; JPAD, Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes; POPADAD, Prevention of Progression of Arterial Disease and Diabetes; AAA, Aspirin for Asymptomatic Atherosclerosis; JPPP, Japanese Primary Prevention Project; ASCEND, A Study of Cardiovascular Events in Diabetes; ARRIVE, Aspirin to Reduce Risk of Initial Vascular Events; ASPREE, Aspirin in Reducing Events in the Elderly.

Figure 1

Results

Thirteen works were considered for the analysis (Table 1). A total of 164,225 patients were included, 82,900 in the aspirin arm and 81,325 in the control group. A reduction of the primary endpoint was observed in the AAS group (OR 0.90, 95% CI 0.85–0.94). No differences by risk group (Figure 1). Risk of severe bleeding was significantly higher in patients treated with ASA (OR 1.45, 95% CI 1.34–1.56), this difference was maintained by risk (Figure 1).

Acknowledgement/Funding

None