bluuebunny/crossref_metadata_2025 huggingface dataset:
P735Interleukin-33 induced eosinophilia restores perivascular adipose tissue function in obesity
Authors: Saxton S , Potter R J , Withers S B , Grencis R , Heagerty A M
Published: October 2019

Background/Purpose

Perivascular adipose tissue (PVAT) is essential in the modulation of vascular tone. Recently we have shown that resident eosinophils play a vital role in regulating PVAT function. In obesity, eosinophil numbers are reduced and PVAT anticontractile function is lost, resulting in increased vascular tone, which will contribute to development of hypertension and type-2 diabetes. Evidence suggests that eosinophilia resulting from parasitic infection may be useful in improving glucose tolerance; therefore, we investigated the effects of eosinophilia on PVAT function in health and obesity.

Methods

Control mice and a high fat fed mouse model of obesity were administered intraperitoneal injections of interleukin-33 (IL-33, 0.1μg) over a five day period. Blood pressure, blood glucose and plasma insulin were measured and compared with un-injected control and obese mice. Wire myography was used to assess the vascular contractility of mesenteric arteries (<250μm, +/− PVAT) from both injected and un-injected control and obese mice in response to noradrenaline. ELISAs and immunohistochemistry were used to examine eosinophil numbers.

Results

High fat feeding induced significant elevations in blood pressure, blood glucose and plasma insulin, which were reduced using IL-33 injections. Eosinophilia was confirmed in blood plasma using an eosinophil cationic protein ELISA. Using wire myography, mesenteric arteries from control mice PVAT exerted an anticontractile effect on the vessels, which was enhanced in control mice injected with IL-33. In obese mice, the PVAT anticontractile effect was lost, but was restored in IL-33 injected obese mice. Using immunohistochemistry, we confirm that eosinophils numbers in PVAT were reduced in obesity and increased in IL-33 treated PVAT.

Conclusions

IL-33 injections induced eosinophilia in both control and obese mice. IL-33 treatment restored PVAT function in obesity, and enhanced the anticontractile function of PVAT in healthy animals. In addition, only five consecutive injections of IL-33 reversed development of hypertension and type-2 diabetes in obese mice. These data suggest that IL-33 induced eosinophilia presents a novel approach to treatment of hypertension and type-2 diabetes in obesity.

Acknowledgement/Funding

British Heart Foundation
P741Next generation miRNA sequencing and changes in coagulation measured by thrombelastography (TEG) in patients with cardiovascular disease
Authors: Kreutz R , Ipe J , Kassab K , Kanuri S , Gao H , Liu Y , Skaar T
Published: October 2019

Background

Thrombelastography (TEG), an ex-vivo clotting assay can identify subjects at high risk of subsequent coronary thrombotic events. Synthesis of clotting factors is subject to post-translational regulation, which is modulated at least in part by miRNA.

Hypothesis

We hypothesized that miRNA sequencing may identify specific miRNA linked with measures of hypercoaguability by TEG.

Methods

Kaolin activated thrombelastography was performed in platelet poor citrate plasma from 61 subjects referred for cardiac catheterization. Time to clot formation (R), clot stabilization time (K), and maximal fibrin clot strength (MA) was measured. Next generation miRNA sequencing was done from RNA isolated from whole blood samples, which includes miRNA derived from leukocytes and platelets. Prediction of miRNA gene targets was performed with targetscan.

Results

Sequencing resulted in quantification of 371 distinct miRNA from whole blood samples. We found 13 miRNA correlating with alteration in TEG-R, 33 miRNA correlating with TEG-K, and 21 miRNA correlating with TEG-MA. Coagulation factors or genes associated with coagulation were found to be among predicted targets in 49 out of these 67 miRNA. Most common predicted targets included factors II, V, VII, X, XIII, fibrinogen, plasminogen-activator inhibitor, and tissue factor. Factor XIIIA1 was highly conserved gene target by miR-96-5p (one of only 3miRNA predicted for this gene). MiR-96-5p correlated with clot stabilization time (ρ=-0.26, p=0.047) which has been shown to be dependent on FXIIIa activity. MiR-22-3p was significantly correlated with TEG-K (ρ=0.28, p=0.034) and was only miRNA with highly conserved target site for prothrombin (Factor II).

Conclusions

In patients with cardiovascular disease miRNA sequencing combined with coagulation phenotype in silico analysis may identify novel links to coagulation that are associated with increased thrombotic risk.

Acknowledgement/Funding

Charles Fisch Cardiovascular Research Award endowed by S. Knoebel
P766The impact of a nurse-led heart failure service on complex device need
Authors: Graby J , Tibbs G , Giblett D , Dayer M , Gosling O
Published: October 2019

Introduction

The prevalence of left ventricular systolic dysfunction (LVSD) continues to rise. It is recognised that optimal medical therapy can improve ejection fraction (EF) in a proportion of patients. A nurse-led Heart Failure Service (HFS) was established in a district general hospital to deliver this, and previous analysis has demonstrated its efficacy in optimising HF drugs to recognised therapeutic doses.

Complex devices (Implantable Cardiac Defibrillators [ICDs] or Cardiac Re-synchronisation Therapy Devices [CRTs]) are established treatments for HF patients if on Optimal Medical Therapy (OMT). The European Society of Cardiology (ESC) and National Institute for Clinical Excellence (NICE) guidelines have expanded their role with a broad cohort of patients eligible for this therapy.

Aim

We sought to determine how many patients, who at baseline had an indication for device therapy, improved after OMT to an extent that they no longer had an indication for device therapy.

Methods

A retrospective analysis was undertaken of the HFS database over a 5 year period recording ECG for QRS duration & morphology, surveillance of EF, device outcome. Exclusion criteria: Baseline EF >35%; device in-situ or listed for prior to HFS referral; no identifiable baseline EF or ECG.

Results

502 patients were analysed and 264 patients met criteria for a new device or upgrade at baseline – 191 male (72%), 73 female (28%), median age 73 (IQR 64–80).

76/97 (78%) of potential CRT candidates (Pacing or Defibrillator component) were male. 16/97 (16%) improved to an EF >35% (median age 68 [IQR 64–72], 14 male [88%], 2 female [12%]). 4/16 (25%) of these patients underwent pharmacological or electrical cardioversion, which can contribute to EF improvement.

There were 167 potential ICD candidates (115 male [69%]). 53 /167 (32%) improved to an EF >35% (median age 68 [IQR 56–75], 33 male [61%]). 7/53 (13%) of these patients had other treatments that can also improve EF (cardioversion, 4; re-vascularisation, 2; valvuloplasty, 1).

69/264 (26.1%) patients did not require a device after optimal therapy had been delivered.

Conclusions

We have demonstrated that in a significant proportion of HFS patients, the delivery of high quality OMT translates into an improvement in EF.

Not all patients that strictly “meet guideline criteria” will be offered a device, nor will all patients take up offer of a device. However, this improvement in EF is likely to benefit the patient symptomatically and prognostically, and carry a significant cost saving to healthcare institutions. A cost analysis study will be undertaken to further assess this.
P870A genetic risk score is associated with increased coronary plaque burden but not specific plaque features: a coronary computed tomography study
Authors: Christiansen M K , Nissen L , Winther S , Frost L , Johansen J K , Jensen H K , Botker H E , Bottcher M , Nyegaard M
Published: October 2019

Background

Genetic risk scores (GRSs) based on risk variants identified from genome-wide association studies (GWASs) predict coronary artery disease (CAD) risk. However, it is unknown whether the GRS is associated with coronary plaque burden or specific high-risk plaque features responsible for the clinical disease onset.

Purpose

To investigate if a GRS is associated with coronary plaque burden and specific plaque characteristics, in patients with suspected stable CAD referred for coronary computed tomography angiography (CTA).

Methods

We consecutively included and genotyped 1645 patients undergoing coronary CTA. Using LDPred, a previously validated GRS was calculated as the weighted sum of the number of CAD risk variants identified from the CARDIoGRAMplusC4D GWAS meta-analysis. Plaques were evaluated using an 18-segment model and characterized by stenosis severity (0%, 1–49%, 50–69%, 70–100%) and composition (calcified (>80% calcified), mixed-calcified (50–80% calcified), mixed-soft (20–50% calcified), or soft (<20% calcified)). The segment stenosis score and the coronary artery calcium score (CACS) were used as measures of plaque burden. Multivariate regression models were used to assess the effect per standard deviation (SD) of the GRS with adjustment for age, sex, hypertension, hypercholesterolemia, BMI, chest pain symptoms, and active smoking.

Results

For each SD increase in the GRS, the segment stenosis score increased with 49% (p=8.6e-27) and CACS increased with 110% (p=2.3e-24). The GRS was associated with a higher risk of plaque stenosis >50% (OR: 1.74, p=3.2e-15), calcified (OR: 1.65, p=3.0e-16), mixed-calcified (OR: 1.64, p=1.5e-8), mixed-soft (OR: 1.44, p=1.6e-6), and soft plaques (OR: 1.40, p=3.0e-6), and all coronary vessels were more often affected with plaques (all p-values <1.0e-4).

When analyzing the plaque characteristics (3007 plaques in 849 patients), the GRS was associated with stenosis severity (OR per severity category: 1.15 (p=0.005), but not with extent of calcification, proximal location, or presence in any of the major coronary vessels (all p-values >0.05).

GRS and Plaque burden

Conclusion

The GRS was strongly associated with the extent and severity of CAD at coronary CTA, but not any specific plaque characteristics per se. The results may suggest that polygenic risk based on large CAD-GWAS increases CAD risk through increased coronary plaque burden rather than specific plaque features.
P878Prevalence and prognosis of patients with myocardial infarction with nonobstructive coronary arteries: a nationwide registry based study
Authors: Janosi A , Ferenci T , Andreka P
Published: October 2019

Background

There are conflicting data about the proportion and prognosis of patients (pts) with acute myocardial infarction (AMI) with nonobstructive coronary arteries (MINOCA).

Purpose

To define the incidence and prognosis of MINOCA pts in different types of AMI.

Methods

The Hungarian Myocardial Infarction Registry (HUMIR) is a nationwide, mandatory database in which the clinical and demographic informations of patients with AMI are recorded. Between January 1, 2014 and June 30, 2018, a total of 45,223 AMI (ST-elevation myocardial infarction (STEMI) n=22,469) pts were registered. After excluding pts with previous AMI, PCI, CABG, and congestive heart failure, 2003 MINOCA pts were found (MINOCA group), while 43,220 AMI pts had obstructive coronary artery disease (MI-CAD group).

Results

The proportion of pts with MINOCA disease was 4.4% among the total pts with AMI. The prevalence was higher in the non ST-elevation myocardial infarction (NSTEMI) group (n=1546, 6.8%) than in the STEMI (n=457, 2.0%) group. The pts with MINOCA disease were slightly younger compared to the pts with MI-CAD (mean age 64.0±14.4 vs. 65.5±12.2 years respectively). The proportion of women was higher in the MINOCA group than in the MI-CAD group (55.7% vs. 36.5%). At discharge, pts with MINOCA disease were less likely to be prescribed certain drugs compared to the pts with MI-CAD. These include aspirin (85.4% vs. 95.6%), RAAS blockers (83.8% vs. 90.4%), statins (86.2% vs. 94.7%), β-blockers (86.8% vs. 89.8%) for the MINOCA and MI-CAD groups respetively. At the 1-year follow-up, the incidence of new AMI events was 1.6% in the MINOCA group compared with 5.0% in the MI-CAD group (HR=2.79). All-cause mortality was higher among the pts with MI-CAD compared to the pts with MINOCA disease. In the MINOCA group, among the pts with NSTEMI, men and women had similar outcomes at 30 days, but men had somewhat higher mortality at one and two years. In contrast, in the STEMI group, women had higher mortality compared to men at all time points during the study (Table 1).

Mortality among MINOCA and MI-CAD pts Mortality MINOCA (n=2003) MI-CAD (n=43,220) MINOCA – STEMI MINOCA – NSTEMI Men (n=218) Women (n=239) Men (n=669) Womenr (n=877) 30-day 5.9% [4.9–7.0] 8.4% [8.1–8.7] 8.7% [4.9–12.4] 13.4% [9–17.6] 4.3% [2.8–5.9] 4.4% [3.1–5.8] 1-year 12.5% [11.0–14.0] 15.6% [15.3–16.0] 12.1% [7.6–16.4] 20.3% [15–25.2] 12.2% [9.6–14.7] 10.8% [8.7–12.8] 2-year 16.7% [14.9–18.5] 19.9% [19.5–20.3] 18.2% [12.4–23.6] 23.6% [17.8–29] 16.9% [13.8–20] 14.3% [11.7–16.7] 95% confidence interval in brackets.

Conclusion

The population-level incidence of MINOCA disease was 4.4% in AMI; the incidence was higher in the NSTEMI group compared to the STEMI group (6.8% vs. 2.0%). Despite the benign anatomy, the long-term prognosis is poor, especially in women after STEMI: 1 out of 4 pts died at the two-year follow up.

Acknowledgement/Funding

None
P931Direct left ventricular wire pacing during transcatheter aortic valve implantation
Authors: Stapor M , Trebacz J , Wiewiorka L , Ostrowska-Kaim E , Nawara-Skipirzepa J , Sobczynski R , Konstanty-Kalandyk J , Musial R , Trebacz O , Zmudka K , Kapelak B , Legutko J
Published: October 2019

Background

Rapid ventricular pacing is mandatory during balloon valvuloplasty or balloon-expandable transcatheter aortic valve implantation (TAVI). Traditionally right ventricular (RV) lead pacing was used. Direct left ventricular (LV) wire pacing is considered safe and effective in balloon-expandable TAVI (EASY-TAVI study).

Aim

The purpose of this study is to determine whether a direct LV wire pacing during TAVI reduces procedure duration and complications in population of unselected patients.

Methods

LV pacing was provided via commercially available pre-shaped guide wires. The cathode was connected to the tip of the wire and the anode to a needle inserted into subcutaneous tissue of the groin.

Results

143 patients underwent transfemoral TAVI. Self-expandable (79,7%), balloon-expandable (18,2%) and mechanically-expandable (2,1%) valves were implanted. LV pacing was dominant (57,3%) and its efficacy was 97,6%. Procedural duration was shorter in LV pacing group (83.7±20.3 vs. 88±33.5 min, p=0.0203). LV pacing required higher radiation dose (754.7±586.4 vs. 547.7±394 mGy, p=0.0168) and more contrast agent (157.8±56.8 vs. 134.8±61.8 ml, p=0.0072). There was no cardiac tamponde in LV pacing group in comparison with 2 in RV pacing group (3%, p=0.3438). In RV pacing group more patients required blood transfusion (21.5% vs. 7.3%, p=0.0075). Pacing method did not affect the outcome or length of hospitalization.

TAVI complications LV wire pacing RV lead pacing p Valve displacement 1 (1.2%) 1 (1.5%) 0.4998 Second valve (bail-out) 1 (1.4%) 3 (4.9%) 0.1021 Perivalvular regurgitation (more than mild) 6 (7.1%) 5 (7.8%) 0.4583 Cardiac tamponade 0 (0%) 2 (3%) 0.3438 Postprocedural permanent pacemaker 4 (5.1%) 10 (16.4%) 0.0025 Cerebrovascular accident 3 (3.8%) 1 (1.6%) 0.8506 VARC-2 bleeding 5 (5.9%) 5 (7.6%) 0.3923 Maximum creatinine level (umol/l) 114.6±45.8 116.9±92.8 0.5351 Lowest hemoglobin (g/dl) 11±7.3 10.1±1.6 0.6967 Blood transfusion 6 (7.3%) 14 (21.5%) 0.0075 Hospitalization (days) 7.1±7.2 8.2±10.6 0.3142 In-hospital mortality 1 (1.2%) 1 (1.6%) 0.8506

Conclusions

Direct LV wire pacing during TAVI is simple, reproducible and safe, provides stable stimulation with a low rate of complications and a potential reduction in procedural time.
P945Abnormalities in ankle-brachial indices are independently associated with new-onset atrial fibrillation
Authors: Tseng A , Girardo M , Atwal D , Firth C , Shipman J , Liedl D , Cooper L , Wennberg P , Shamoun F
Published: October 2019

Introduction

Lower extremity physiologic studies are an important non-invasive diagnostic tool in peripheral arterial disease (PAD). PAD and atrial fibrillation (AF) are associated with increased cardiovascular and all-cause mortality.

Purpose

To evaluate the association between PAD and new-onset AF and the risk of stroke.

Methods

We performed a study of all patients without AF undergoing ankle-brachial index (ABI) for any indication between January 1996 to June 2018. The ABI cut-off were as follows: abnormal ABI (0–0.99), normal ABI (1.00–1.39) and poor vessel compressibility (PC) (1.40+). Demographic, comorbidity, and outcome variables were extracted using the electronic medical record.

Results

Overall, 34,441 patients (mean age 66.8±14.3, 57.3% male, 88.2% white) were included in the study with a median follow-up of 7.2 years (interquartile range, 3.0–12.9 years). Multivariate Cox proportional hazard analysis showed increased risk of new-onset AF for male sex, older age, hypertension, coronary artery disease, cerebrovascular disease, chronic kidney disease stage III or greater, congestive heart failure, chronic obstructive pulmonary disease, and cancer (all p<0.0001). After adjustment, ABI results were significantly associated with new-onset AF, particularly poorly-compressible vessels (adjusted HR: 1.42 (1.30–1.55), p<0.0001) compared to abnormal ABI (adjusted HR: 1.12 (1.05–1.20), p=0.0012). Patients with atrial fibrillation were more likely to experience ischemic stroke (39.2% versus 16.1%, p<0.0001).

Conclusion

Abnormalities in ABI results, particularly poorly-compressible vessels, are independently associated with new-onset atrial fibrillation in a large ambulatory cohort. While the mechanism cannot be assessed, common inflammatory mechanisms and increased vascular stiffness may play an important role. Identification of AF in these at-risk patients may improve cardiovascular outcomes.
P961Investigator versus Core Lab evaluation of coronary blood flow in PCI of patients in cardiogenic shock: a substudy of the CULPRIT-SHOCK trial
Authors: Zeitouni M , Barthelemy O , Rouanet S , Guedeney P , Hauguel-Moreau M , Hage G , Overtchouk P , Brugier D , Vignolles N , Kerneis M , Silvain J , Collet J P , Vicaut E , Thiele H , Montalescot G
Published: October 2019

Background

Thrombolysis In Myocardial Infarction (TIMI) flow is a prognostic factor which assessment is complex in life-threatening situations. Because TIMI flow evaluation by site investigator (SI) is subject to bias, independent Core-Laboratory (CL) adjudication is the reference standard in clinical trials.

Purpose

To evaluate the concordance between CL and SI in the evaluation of the culprit artery TIMI flow, and the associated prognosis in the CULPRIT-SHOCK trial.

Methods

All patients of the CULPRIT-SHOCK trial with CL adjudications were included in this analysis. CL adjudicators were blinded to patient's characteristics and outcomes: pre and post-PCI TIMI flows were solely evaluated on the basis of coronary angiograms. SI determined the TIMI flow before and immediately after PCI of the culprit lesion. The concordance was determined by Cohen's κ coefficient. A multivariate analysis was used to evaluate 1) factors of discordance 2) the association between each method of evaluation and the mortality at 30 days and 1 year.

Results

Among CULPRIT-SHOCK patients, 663 patients were eligible for this analysis. Of the 214 patients adjudicated TIMI flow 3 by CL before PCI, SI over-estimated the obstruction to TIMI flow 0–1-2 in 121 (56.5%). Of the 139 patients scored TIMI flow 0–1-2 by CL after PCI, SI over-graded their results to TIMI flow 3 in 79 (56.8%). Overall, the K coefficient of agreement was 0.44, 95% CI [0.36; 0.51] before PCI and 0.44, 95% CI [0.35; 0.53] after PCI. Mechanical circulatory support and culprit left main were the main factors of discordance of TIMI flow after PCI. The association between TIMI flow 0–1-2 after PCI and 30-days mortality was significant, whether adjudicated by SI or CL (figure). Post-PCI TIMI-flow 0–1-2 was associated to 1-year mortality only when evaluated by SI (figure).

Association between TIMI and mortality

Conclusions

In comparison to the independant CL evaluation, SI overestimated the severity of coronary slow flow before PCI, and the success of PCI in improving coronary flow. The level of agreement between CL and SI was moderate. While both evaluations predicted 30-days mortality, only SI scoring was associated to 1-year mortality.

Acknowledgement/Funding

European Union Seventh Framework Program, the German Heart Research Foundation, German Cardiac Society.
P966Clinical impact of target vessel on long term cardiac survival in patients with chronic total occlusion treated by percutaneous coronary intervention
Authors: Bernardini A , Berteotti M , De Gregorio M G , Migliorini A , Carrabba N , Vergara R , Pennesi M , Valenti R
Published: October 2019

Background

Chronic total occlusions (CTOs) occur in 15–35% of patients with significant coronary artery disease who undergo coronary angiography. The rationale of percutaneous CTO revascularization is the improvement in survival and in quality of life, mainly reducing angina symptoms and increasing LVEF. The clinical impact of target vessel has been investigated in previous studies, with controversial results.

Purpose

The aim of this study, based on a large scale single-center registry, is to determine the impact of different target vessel successful CTO percutaneous coronary intervention (PCI) on long-term survival in a “real world” population.

Methods

All consecutive patients who attempted a CTO-PCI from 2004 to 2015 in our Hospital department were included in a CTO-PCI Registry. CTO was defined as a coronary obstruction with TIMI flow grade 0 with an estimated duration of >3 months. Patients with multiple CTO were excluded. Long-term mortality was assessed by Kaplan-Meier and Cox multivariable analysis.

Results

A total of 1235 patients attempted PCI for CTO; patients were stratified into two main groups according to the CTO carrying vessel: LAD-CTO (n=360) and not-LAD CTO (n=875). Cardiac survival rate at 5 years was lower in LAD-CTO patients compared with not-LAD CTO patients (85±3% vs. 90±2%; p=0.001), but when a successful CTO-PCI was achieved, there was no statistical difference between the two groups (89±3% vs. 93±1%; p=0.095). On the other side, a failure of the CTO PCI in LAD vessel was associated with a worse outcome (67±8% vs. 85±4%; p=0.001). Completeness of revascularization carried a significant survival benefit independently from the target vessel CTO (LAD CTO group 94±2% vs. not-LAD CTO group 95±1%; p=0.256), but an incomplete revascularization was associated with a worse outcome in LAD-CTO patients (67±6% vs. 81±4%; p<0.001). By multivariable Cox analysis, age >75 years, diabetes, left ventricular ejection fraction <40%, complete revascularization and LAD-CTO were independently related to death.

Conclusions

In a “real world” population, LAD-CTOs were associated with a lower cardiac survival rate when compared to other vessel CTOs; however, this survival gap was no longer significant when a successful CTO PCI was performed. The survival benefit was even greater when a complete coronary revascularization was achieved.
P1019Validation of a risk score to predict the need for pacemaker implantation after transcatheter aortic valve replacement
Authors: Kiani S , Kamioka N , Caughron H , Dong A , Patel H , Lisko J , Gleason P , Stewart J , Grubb K , Greenbaum A , Devireddy C , Guyton R , Leshnower B , Babaliaros V , Hoskins M
Published: October 2019

Background

New conduction abnormalities necessitating pacemaker implantation (PMI) is a common occurrence after TAVR. There is an increased rate of PMI in the those receiving the most contemporary implanted valve, the Edwards Sapien-3 (S3), compared to prior generation balloon expandable valves. We previously described predictors of PMI in a large cohort. Herein we sought to validate these predictors of PMI in a subsequent validation cohort.

Methods

We evaluated all patients undergoing first time elective TAVR with S3 at our institution (n=326). We developed a risk score based on a predictive model we have previously described. Patients received one point for each of the following: history of syncope, oversizing of the valve >16%, baseline right bundle branch block morphology, and two points for a QRS duration >115 ms. We performed regression analysis of the risk score and need for PMI. We also evaluated the performance of the risk score using ROC analysis.

Results

Thirty patients (8%) of the total cohort had need for PMI after S3 implantation. Those with PMI had a higher rate of pre-existing infra-nodal conduction system disease – including QRS duration >115ms (57% vs. 20%, p<0.001) and right bundle branch block (RBBB) morphology (47% vs. 10%, p<0.001) - as well as more frequent valve oversizing >15.7% (47% vs. 23%, p<0.01). There was no significant difference in a history of syncope (10% vs. 8%, p=0.72) between groups. The PMI risk score had an area under the curve of 0.753 on ROC analysis. The PMI risk score was significantly associated with PMI (OR 2.37; 95% CI [1.64–3.34], p<0.001).

Rate of PMI Stratified by Risk Score

Conclusions

The PMI risk score was strongly predictive of the need for PMI after implantation of the S3 valve in a large validation cohort. The PMI risk score performed well in sensitivity analysis. This PMI risk score represents a simple tool to help further risk stratify patients being considered for TAVR.
P1020Feasibility of pediatric probes in transesophageal echocardiography guiding of left atrial appendage closure in adults
Authors: Maarse M , Klaver M N , Swaans M J , Boersma L V A
Published: October 2019

Introduction

Transesophageal echocardiography (TEE) is essential in the guidance of left atrial appendage closure (LAAC). Current practice often requires general anesthetics (GA) to endure a standard size probe during LAAC procedures. Smaller probes for pediatric purposes have been developed and might be useful for the guidance of LAAC in adults, eliminating the need for general anesthetics (GA) and reducing procedure times.

Methods

In this prospective observational registry study patients were analyzed retrospectively to determine feasibility of pediatric TEE probes in adults for LAAC guidance. A standard set of LAA measurements, device compression and peri-device leakage was evaluated during procedure and by a second observer. Follow-up imaging, performed between 1–6 months after LAAC, was viewed by two independent reviewers for device positioning, peri-device leakage and thrombus formation.

Results

A total of 85 patients (56 male, mean age 72±7 years) were included. All patients underwent LAAC (76 Watchman, 9 Amplatzer Amulet), in 28 patients (33%) LAAC was combined with pulmonary vein isolation (PVI). The S8–3t micro-probe was used in 41 patients (48%) and the S7–3t mini-probe was used in 44 (52%). In 76 (38 mini-TEE, 38 micro-TEE) LAAC was successful, 7 of 9 failed procedures were due to unsuitable anatomy. Complete closure was achieved in 61/76 (80%, 29 mini-TEE, 32 micro-TEE), minimal residual flow was seen in 15/76 (20%, 8 mini-TEE, 7 micro-TEE). Device compression was comparable for mini- and micro-TEE and in accordance with recommendations. No GA was needed in 93% of the patients, none of these procedures were prematurely terminated because of discomfort. No serious probe related complications were seen. Follow-up imaging was performed 80±24 days after LAAC. Most patients (95%) underwent TOE with a standard probe for follow-up imaging, 5% of the patients underwent cardiac CT. Follow-up imaging showed similar proportions of patients with complete LAA closure (74%) or minimal residual flow (23%), while 2 patients had significant peri-device flow: 1 due to significant change in device position and 1 due to increase of peri-device leakage present during implant. In 1 patient device-related thrombus was seen and in 1 patient device embolization to the abdominal aorta occurred.

Conclusions

The use of pediatric probes in the guidance for LAAC in adults is a safe, effective, and attractive alternative avoiding the need for general anesthesia.
1171Myocardial perfusion mapping in cardiac amyloidosis - exploring the spectrum from infiltration to ischaemia
Authors: Chacko L , Kotecha T , Martinez-Naharro A , Brown J , Knight D , Steriotis A , Little C , Moon J , Gilmore J , Hawkins P , Rakhit R , Patel N , Xue H , Kellman P , Fontana M
Published: October 2019

Background

Cardiac involvement is the main driver of outcome in systemic amyloidosis, but the relationship between amyloid deposits and outcomes is not well understood. The simple explanation of physical, mechanical replacement of the interstitium by amyloid seems insufficient. Preliminary studies support the hypothesis that myocardial ischaemia could contribute to cell damage.

Purpose

(1) To assess myocardial ischaemia in cardiac amyloidosis. (2) To compare patients with cardiac amyloidosis to patients assessed on invasive coronary angiography (ICA) to have normal coronary physiology (NCP), microvascular dysfunction (MVD) and triple vessel coronary disease (3VD). (3) To assess correlation of perfusion mapping to markers of disease severity and prognosis.

Methods

86 patients and 20 healthy volunteers (HV) underwent CMR at 1.5T (Siemens) with standard cine, PSIR-LGE, T1, T2, Extracellular Volume (ECV) mapping and adenosine stress with myocardial blood flow (MBF) mapping. Thirty-eight patients also underwent ICA with 3 vessel assessment of Index of Microcirculatory Resistance and Fractional Flow Reserve: 7 had cardiac amyloidosis, 8 had NCP, 15 had MVD and 8 had 3VD.

Results

Cardiac amyloidosis patients had severe reduction in stress MBF and myocardial perfusion reserve (MPR) (1.22ml/g/min±0.70 and 1.62±0.63) compared to HV (3.21ml/g/min±0.64, p<0.001 and 4.17±0.78, p<0.001), NCP (2.66±0.56, p<0.001 and 2.51±0.43, p=0.036) and MVD (2.10±0.31, p<0.001 and 2.29±0.87, p=0.014) with the degree of reduction being similar only to patients with 3VD (1.44±0.54, p=1.000 and 1.64±0.68, p=1.000) (Figure 1). Rest MBF was also lower in amyloidosis than HV. Cardiac amyloidosis stress MBF and MPR inversely correlated with amyloid burden (ECV, r=−0.715, p<0.001, transmurality of LGE, p<0.01), systolic dysfunction (EF, r=0.405, p<0.01), and blood biomarkers (NT-proBNP (r=−0.678, p<0.001) and Troponin T (r=−0.628, p<0.001)). There was a correlation between stress MBF and native T1 (r=−0.588, p<0.001) but not T2 (p=0.591). Stress MBF and MPR were early disease markers, being elevated in patients with early cardiac amyloid infiltration (raised ECV, no LGE, P<0.01 vs HV).

Conclusion

Myocardial ischaemia is common in cardiac amyloidosis – with stress MBF and MPR similar to that of patients with 3VD. The reduction correlates with the degree of amyloid infiltration and markers of adverse prognosis, highlighting the potential role of myocardial ischaemia as a key mechanism in the pathophysiology of cardiac amyloidosis.
1384MitraClip treatment of functional mitral regurgitation - A meta-analysis
Authors: Noutsias M , Matiakis M , Ali M , Abate E , Ahmadzada B , Novruzlu R , Bigalke B , Rigopoulos A
Published: October 2019

Moderate-to-severe or severe functional mitral regurgitation (FMR) is associated with higher rates of hospitalizations and with increased mortality in heart failure with reduced left ventricular ejection fraction (HFrEF). Transcatheter mitral valve repair by MitraClip® implantation (TMVrMC) may effectively reduce severe MR, and is associated with symptomatic improvement. However, the long-term clinical effects of this procedure are not well defined.

Aims

We analyzed outcomes for rehospitalization and survival in heart failure patients with moderate-to-severe or severe functional mitral regurgitation (FMR) treated by either medical treatment (MT) only TMVrMC+MT by meta-analysis.

Methods and results

By systematic search of bibliographic databases, we evaluated publications comparing heart failure patients with FMR treated by MT only versus treatment by MT combined with TMVrMC. Studies with a minimum of 25 enrolled patients and a follow/up period of at least 12 months were deemed eligible for this meta-analysis. We identified n=7 studies enrolling 2,884 HFrEF patients, divided into two study arms: TMVrMC+MT (n=1,618), versus FMR patients receiving MT only (n=1,266). At 12 months, there was a significant reduction in all-cause mortality favoring TMVR+MT (OR: 0.67; CI 95% 0.55–0.81), as well as a reduction of unplanned rehospitalizations (OR: 0.69; 95%; CI 0.53–0.89), compared with the MT only patients. At 24 months, there was a significant reduction of all-cause mortality in the TMVrMC+MT patient group (OR: 0.50; CI: 95%: 0.38–0.66; p<0.001). TMVrMC+MT was associated with significantly lower rates of unplanned re-admissions for heart failure compared with MT only at 12 months (OR: 0.69; 95% CI: 0.53–0.89; p<0.001) and at 24 months (OR: 0.53; 95% CI: 0.39–0.71; p<0.001). In one publication, a survival benefit of TMVrMC+MT over MT alone was shown at 5 years post intervention (HR: 0.75; 95% CI: 0.69–0.94; p=0.012) after weighting for propensity score and controlling for age.

Conclusions

This meta-analysis on n=2,884 patients with moderate-to-severe or severe FMR reveals that TMVrMC+MT, as compared with MT alone, is associated with a significant reduction of rehospitalizations and improvement of survival. These data imply additional evidence for TMVrMC in eligible heart failure patients with relevant FMR, which might be important for an update of the corresponding guidelines.
1423Adherence to triple component antihypertensive regimen is higher in single-pill combination than two-pill regimen: data from a randomized controlled trial using medication event monitoring system
Authors: Sung J , Ahn K T , Cho B R , Lee S Y , Kim B J , Kim D K , Park J I , Lee W S
Published: October 2019

Background

Simplicity of regimen is known to be an important determinant of medication adherence and using single-pill combination (SPC) in hypertension treatment resulted in better adherence and persistence than free-equivalent combination. However, this finding has been studied only in dual-component antihypertensive treatments and in observational studies using medication possession ratio as an index of adherence. Medication event monitoring system (MEMS) is considered to be the gold standard in estimating medication adherence.

Purpose

To investigate the superiority in adherence of triple-component SPC compared to equivalent two-pill regimen using MEMS

Methods

This is a multi-center open-label randomized controlled trial. Inclusion criteria were hypertensive patients whose clinic blood pressure is not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with combination antihypertensive regimen comprising two of three classes (angiotensin receptor blocker, calcium channel blocker and thiazide diuretics) for at least 4 weeks. Eligible patients were randomized either to single-pill (triple-component SPC, olmesartan/amlodipine/ hydrochlorothiazide 20/5/12.5 mg) or two-pill (dual-component SPC + one free pill, olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) groups and maintained for 12 weeks. Medications were dispensed in MEMS. Primary outcomes were the difference of percentage of dose taken (PDT) and percentage of days with prescribed dose taken correctly (PDTc) between single- and two-pill therapy, calculated from MEMS data.

Results

From 8 hospitals, 146 hypertensive patients were randomized into single- and two-pill groups. Final analysis was done in 65 and 66 patients in each group from which adherence index could be obtained. Baseline clinical characteristics of the two groups were not different. The single-pill group had significantly higher PDT and PDTc compared to the two-pill group. (median (25–75 percentile) (%), PDT 95.1 (87.9 - 100.0) vs 91.2 (79.8 - 96.5); PDTc 93.1 (79.8 - 96.5) vs 91.3 (70.7 - 96.4), p = both 0.04, by Wilcoxon rank sum test)

Percent dose taken

Conclusion

Single-pill combination of triple-component antihypertensive regimen showed superior adherence compared to equivalent two-pill therapy. Reducing pill burden by using SPC is a relevant strategy to enhance the adherence to multi-drug antihypertensive therapy.

Acknowledgement/Funding

Daiichi-Sankyo
2131Pragmatic clinical trials in cardiovascular medicine: trends over time in major medical journals
Authors: Sepehrvand N , Alemayehu W , Das D , Gupta A K , Gouda P , Ghimire A , Du A X , Hatami S , Babadagli H E , Verma S , Kashour Z , Ezekowitz J A
Published: October 2019

Background

Pragmatic trials provide results that may be more applicable to the population in which the intervention will be eventually applied and are discussed extensively in the current healthcare environment. The aim of this study was to investigate how pragmatic or explanatory cardiovascular (CV) randomized controlled trials (RCT) are, if this was changing over time, and if they were more or less likely to meet their primary endpoint.

Methods

Using the six top-ranked (based on impact factors) medical and CV journals, all CV-related RCTs that were published during the years of 2000, 2005, 2010 and 2015 were identified, data extracted and reviewed by 2 adjudicators. The PRECIS-2 tool was used to evaluate the level of pragmatism. PRECIS-2 uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis. A higher score indicates a more pragmatic score on an individual domain, and aggregated scores are a simplified formula across all domains. Cohen's D was used to quantify the mean difference relative to the variation.

Results

There were 616 RCTs, distributed evenly over the 2 decades, and 64% achieved their primary endpoint. The mean (±SD) PRECIS-2 score was 3.26±0.70 among 616 included RCTs. The level of pragmatism increased over time from a score of 3.07±0.74 in 2000 to 3.47±0.67 in 2015 (p<0.0001 for trend; Cohen's D relative effect size 0.57). The increase in pragmatism occurred mainly in the domains of eligibility, setting, intervention delivery, and primary endpoint (Figure). PRECIS-2 score was higher for neutral trials than those with positive results (p=0.0015) and in phase III/IV trials as compared to phase I/II trials (p<0.0001) (Figure). Furthermore, trials that involve more sites, with larger sample sizes, longer follow-ups, and those with mortality as the primary endpoint were found to be more pragmatic. There was no difference in the level of pragmatism between different sources of funding (public, industry, or both; p=0.52).

Study characteristics and pragmatism

Conclusion

The PRECIS-2 tool can be used for appraising trials to assess their placement in the pragmatic-explanatory continuum. The level of pragmatism increased over time in CV trials. Greater focus on the design and delivery of CV trials will be required for the broad application.

Acknowledgement/Funding

Dr. Sepehrvand receives scholarship from Alberta Innovates Health Solutions.
2424Long-term outcome of patients with biopsy-proven viral myocarditis: 12-year results from a late gadolinium enhancement cardiac magnetic resonance study
Authors: Seitz A , Greulich S , Ebadi N , Gruen S , Klingel K , Gawaz M P , Sechtem U , Bekeredjian R , Mahrholdt H
Published: October 2019

Purpose

Myocarditis is a common cardiac disease that is associated with significant mortality as demonstrated by several studies. Late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (CMR) is a valuable tool for risk stratification of patients with suspected myocarditis. Previous studies using CMR-LGE have reported a good negative predictive value over follow-up periods of 4–6 years, while its positive predictive value was only modest. However, there is a lack of data regarding the long-term prognosis (>10 years) of these patients. This study reports an extended long-term follow-up of a large cohort of patients with biopsy-proven viral myocarditis.

Methods

At initial presentation, all patients underwent endomyocardial biopsy and CMR for the work-up of suspected myocarditis or unclear cardiomyopathy and had evidence of virus in PCR analyses. The primary endpoints were: all-cause death, cardiac death, and the occurrence of sudden cardiac death (SCD).

Results

183 patients with biopsy-proven viral myocarditis were followed for a median of 11.5 years. At baseline, patients were 52 years old, 31% were females, and the median ejection fraction was moderately reduced (44%). Initial CMR assessment revealed LGE in 101 (55%) patients, while 82 (45%) patients had LGE-negative CMR. During the follow-up period, the following endpoints occurred in the overall cohort: all-cause death (n=71, 39%), cardiac death (n=50, 27%) and SCD (n=20, 11%). Most importantly, only a single LGE-negative patient experienced a SCD during this 12-year follow-up, while all other SCDs occurred in patients with LGE-positive CMR (1% vs. 19%, p<0.001). Consequently, the negative predictive value (NPV) of normal CMR-LGE regarding SCD was 98%. In addition, cardiac mortality (12% vs. 40%, p<0.001, NPV=88%) and all-cause mortality (20% vs. 54%, p<0.001, NPV=79%) were significantly lower in patients without LGE.

Conclusion

This cohort of biopsy-proven viral myocarditis demonstrates substantial mortality (39% in 11.5 years). However, absence of LGE on CMR was associated with favorable prognosis. This was applicable regarding all-cause and cardiac mortality, but most importantly with regard to SCD with a NPV of 98% over almost 12 years median follow-up.

Acknowledgement/Funding

This work was funded by the Robert-Bosch-Stiftung, Stuttgart, Germany and the Berthold-Leibinger-Stiftung, Ditzingen, Germany.
P1229Massive expansion of native human atrial cardiomyocytes through immortogenetics: generation of the hiAM cell lines
Authors: Harlaar N , Liu J , Volkers L , Ramkisoensing A A , Schalij M J , Klautz R J M , Van Brakel T J , Pijnappels D A , De Vries A A F
Published: October 2019

Background

Preclinical cardiac research greatly depends on animal-derived cellular models, thereby hampering clinical translation. While upcoming human pluripotent stem cell technology seems to decrease this gap between bench and bedside, its complex/multi-step protocol to produce cardiac muscle cells, its required expertise, and its trouble to produce large numbers of phenotypically homogeneous cardiomyocytes so far has limited broad application.

Purpose

We aimed to conditionally immortalize native human atrial cardiomyocytes to produce natural and standardized lines of these cells by gaining full control over their proliferation and differentiation.

Methods

Human fetal atria (gestational age 18 weeks) were dissociated and transduced with a lentiviral vector directing myocyte-specific and doxycycline-inducible expression of simian virus 40 large T antigen (here defined as immortogenetics). Addition of doxycycline to the culture medium pushed cardiomyocytes towards a proliferative phenotype. In total, 125 proliferating monoclones were isolated, expanded and screened for their cardiomyogenic differentiation capacity upon doxycycline removal. Selected clones were characterised using various molecular biological and electrophysiological assays.

Results

Upon doxycycline removal (i.e. under differentiation conditions), cells spontaneously reacquired a cardiomyocyte-like appearance as judged by phase-contrast microscopy and were observed contracting. Simultaneously, these cells stopped proliferating, which was accompanied by a drop in large T level, loss of Ki67 expression and the development of sarcomeres with striated α-actinin and troponin T staining patterns. These cells were tagged conditionally immortalized human atrial cardiomyocytes (hereinafter called hiAMs). Optical voltage mapping of hiAM monolayers revealed excitable cells showing homogeneous spreading of action potentials at 22,5±3,1 cm/s following 1-Hz point stimulation, with a mean APD80 of 139±22 ms. Monolayers of hiAMs could easily be created as big as 10cm2 while continuing to display homogenous conduction throughout the culture. Single-cell patch clamp recordings of a hiAM clone in current-clamp mode confirmed excitability with a resting membrane potential of −62,2±4,3 mV, peak potential of 39,4±3,9 mV and APD80 of 339±9 ms.

Excitable monolayer of hiAMs

Conclusion

We have generated first-of-a-kind lines of natural human atrial cardiomyocytes through immortogenetics, allowing massive cell expansion under proliferation conditions and robust formation of cross-striated, contractile and excitable cardiomyocytes after differentiation. Thereby, a user-friendly, clinically-relevant and much-anticipated research model has been produced, which application could range from multi-scale electrophysiological studies and drug response studies to disease modelling and myocardial regeneration.
P1456Evaluation of an enhanced, cloud-based AF-detection algorithm based on real-world arrhythmic recordings
Authors: Olsson A , Samuelsson M
Published: October 2019

Background

Cloud-based solutions offer the ability to centrally and continuously enhance detection algorithms for arrhythmias such as Atrial Fibrillation (AF) based on generated data.

Methods

The Coala Heart Monitor (Coala) system was evaluated by manual interpretation of 1,000 consecutive anonymous printouts of chest- and thumb-ECG waveforms, without any exclusion. The anonymized printouts were blinded from algorithm analysis, apart from gender and age within a 10-year span. The recordings were derived from actual Coala users in Sweden with no training, control or influence, under a defined time period. The prevalence of cardiac conditions in the user population was unknown. The blinded recordings were manually interpreted by a trained cardiologist.

The interpretation was compared with the automatic analysis performed by an algorithm in the Coala Cloud to evaluate ECG signal performance and calculate performance metrics.

An enhanced algorithm utilizing P-wave detection was then evaluated on the data set and compared with the performance metrics of the existing algorithm.

Results Metric Results with current algorithm Results with enhanced algorithm Prevalence of AF in the recordings 14.4% (143 of 990 recordings) 14.4% (143 of 990 recordings) Sensitivity for detecting AF 0.972 (95% CI = 0.930–0.992) 0.951 Specificity for detecting AF 0.946 (95% CI = 0.928–0.960) 0.976 Negative predictive value for detecting AF 0.995 (95% CI = 0.987–0.999) 0.992 Positive predictive value for detecting AF 0.751 (95% CI = 0.683–0.812) 0.872 Accuracy 0.950 0.973

Conclusion

The enhanced algorithm was found to improve the Positive Predictive Value for detecting AF as compared to the existing algorithm (0.872 vs 0.751). The reduced sensitivity for the enhanced algorithm was due to 3 consecutive recordings from a single individual who had misplaced the Coala with corresponding altered morphology of the ECG signal. The recordings were still reported as having an irregular rhythm by the algorithm.

The evolution demonstrates that cloud-based systems offer an ability to enhance detection accuracy by using reference data to train algorithms.