bluuebunny/crossref_metadata_2025 huggingface dataset:
P1251Percutaneous coronary intervention versus medical therapy for coronary lesions with positive fractional flow reserve (FFR) but preserved coronary flow reserve (CFR). A substudy of the COMPARE-ACUTE
Authors: Haeck J D , Zimmermann F M , Van 'T Veer M , Neumann F J , Triantafyllis A S , Abdel-Wahab M , Omerovic E , Boxma-De Klerk B M , Pijls N H , Richardt G , Tonino P A , Johnson N P , Smits P C
Published: October 2019

Introduction

International guidelines recommend performing percutaneous coronary intervention (PCI) on stable coronary lesions with a positive fractional flow reserve (FFR) to improve clinical outcomes. It remains unclear if FFR positive lesions with preserved coronary flow reserved (CFR) might be better treated medically.

Purpose

This study compared clinical outcomes between PCI and medical therapy for stable FFR-positive lesions with preserved CFR.

Methods

We performed a substudy of the randomized, multicenter COMPARE-ACUTE trial in which treated ST-elevation myocardial infarction patients with stable non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperaemic pressure gradients, we computed the so-called pressure bounded-CFR (pb-CFR) and classified lesions as low (<2) or preserved (≥2). Our primary end point was a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events (MACCE) at 12 months.

Results

A total of 980 lesions from 885 subjects were included in this sub-study due to availability of baseline and hyperaemic pressure gradients. For the 462 lesions with FFR≤0.80, 249 had a pb-CFR<2 while 29 had a preserved CFR (pb-CFR≥2). The rate of MACCE at 1 year did not differ significantly between subjects with FFR≤0.80 and pb-CFR<2 versus FFR≤0.80 and pb-CFR≥2 (24% vs. 30%, p=0.44). Because of randomization, baseline characteristics were well balanced between subjects with FFR≤0.80 and pb-CFR≥2 who were treated by PCI or medical therapy. Importantly for subjects with FFR≤0.80 and pb-CFR≥2, MACCE occurred more frequently when treated medically compared with PCI (50% vs. 0% respectively, p=0.01).

Conclusions

In this post-hoc substudy from a large randomized controlled trial of 885 subjects with 980 lesions, a preserved pb-CFR≥2 did not associate with an improved clinical outcome when FFR≤0.80. Subjects with FFR-positive coronary lesions but a preserved pb-CFR experienced significantly worse clinical outcomes when treated medically instead of with PCI. These data suggest that a stenosis with a FFR≤0.80, even when pb-CFR remains preserved, benefits from treatment with PCI.

Acknowledgement/Funding

Maasstad Cardiovascular Research, Abbott Vascular and St. Jude Medical
P1458Telemonitoring of patients with chronic heart failure (CHF): evaluation of mortality, costs and utilization
Authors: Franz W M , Rabbe S , Schreyoegg J , Blankart R , Hager L , Lehner M
Published: October 2019

Background

The telemonitoring program aims at optimizing the treatment for high risk CHF patients (NYHA II-IV) of a German sickness fund. All participants were equipped with remote monitoring devices such as body-scale, blood pressure monitor or 12-channel ECG system. With these devices information are collected in electronic medical records and analysed by a medical professional, who contacts the patient according to a predefined algorithm aiming for early interventions in order to prevent emergency hospitalization. The 24/7 intervention program is supported by coaching modules related to co-morbidities. All patient related data were provided by the sickness fund.

Methodology

For the evaluation the patient collective of a German sickness fund was screened for eligibility. Inclusion criteria are at least one inpatient stay due to heart failure or related conditions within the past 24 months before the start of the program as well as at least one outpatient diagnosis of heart failure or heart failure related diseases. Exclusion criteria are defined to eliminate patients with diagnoses such as cancer treatments, dialysis or mental illnesses.

After the first selection of all relevant patients for the study population patients are assigned to either intervention or control group. To ensure pre-treatment balance on important characteristics between treatment- and control group different methods such as propensity score matching and propensity weighting are used. For these methods patient characteristics e.g., on costs, medications and comorbidities are used for the period of 24 months before the start of the intervention. Intervention groups were enrolled in 11 waves. The observation period was 24 months (Q3/2015-Q2/2017). In a first analysis total health care costs consisting of inpatient and outpatient care, pharmaceutical as well as medical aids were analysed. Following this outpatient contacts, length of hospital stays and the number of prescribed drugs related to heart failure will be analysed. Further, mortality will be used as an outcome parameter.

Results

Preliminary results for the Gamma regression after propensity score matching on 714 patients in each group suggest a significant negative effect of the intervention of 0,1431 (p=0,005) for the total cost in the study, leading to an average decrease in cost of −2.187€ per patient. There were 998 hospitalizations accounted for in the intervention group vs. 1197 hospitalizations in the control group.

These effects appear to be driven by a decrease in inpatient costs, while costs in other areas such as outpatient care or drugs increased slightly.

Conclusion/Outlook

The preliminary results using propensity score matching suggest a sizable cost reduction for patients in the telemedical treatment group. Results on utilization and outcomes are still pending.

Acknowledgement/Funding

Funding by IKK Suedwest and SHL Telemedicine
P1462Return to physical activity among women following newly diagnosed dilated cardiomyopathy or myocardial infarction
Authors: Burch A E , Kutyifa V , Erath J W , Assmus B , Bondermann D , Russo A M
Published: October 2019

Background

Resuming activity following a new diagnosis of dilated cardiomyopathy (DCM) or myocardial infarction (MI) is important for improvements in morbidity and mortality. Activity is also associated with an improved ejection fraction (EF) and lower risk of reinfarction. Patient management could benefit from having normative values and expected gains in activity early following diagnosis of DCM or MI.

Purpose

Assess the change in activity among women for the first 30 days after hospital discharge following a new DCM diagnosis or MI.

Methods

Female adult patients prescribed a wearable cardioverter defibrillator (WCD) for a diagnosis of DCM (n=3550) or MI (n=1422) with low EF were included. Step count was measured by WCD accelerometer. Change in activity over time was analyzed, including weekly percentage gains.

Results

Women with DCM were significantly younger (64, SD = 13) than women post-MI (67, SD = 12). Median daily step count across the entire 30-day period was 4093 (IQR: 2123–6609). Women with DCM demonstrated a higher step count compared to women post-MI, 4405 (IQR: 2348–6986) and 3352 (IQR: 1644–5709), respectively, even after correcting for the difference in age between the groups. The greatest increases in activity for all occurred from week 1 to week 2. Women with DCM or post-MI had a 15.4% and 19.1% increase, respectively. Incremental increases in activity continued throughout the month.

Conclusion

Physical activity among women with newly diagnosed DCM or MI and a low EF increased within the first 30 days. The most significant increase occurred from week 1 to week 2. This data can be used as a benchmark to develop and assess prescriptive activity programs for women.
P1465Artificial intelligence in echocardiography - Steps to automatic cardiac measurements in routine practice
Authors: Karuzas A , Sablauskas K , Skrodenis L , Verikas D , Rumbinaite E , Zaliaduonyte-Peksiene D , Ziuteliene K , Vaskelyte J J , Jurkevicius R , Plisiene J
Published: October 2019

Introduction

The growth of artificial intelligence (AI) use in echocardiography over the past years has been exponential, proposing new paths to overcome inter-operator variability and experience of the operator. Even though the applications of AI are still in their infancy within the field of echocardiography, the potential of AI implies future directions and is eager to assist for accuracy and efficiency of manual tracings. Deep learning, a subset of machine learning algorithms, is gaining popularity in echocardiography as a state of the art in visual data analysis.

Purpose

To evaluate deep learning for two initial tasks in automated cardiac measurements: view recognition and end-systolic (ES) and end-diastolic (ED) frame detection.

Methods

A total of 230 patients' (with various indications for study) 2D echocardiography data was used to train and validate neural networks. Raw pixel data was extracted from EPIQ 7G, Vivid E95 and Vivid 7 imaging platforms. Images were labeled according to their view: parasternal long axis (PLA), basal short axis, short axis at mitral level, apical two, three and four chambers (A4C). Additionally, ES and ED frames were labeled for A4C and PLA views. Images were de-identified by applying black pixel masks to non-anatomical data and removing metadata. Convolutional Neural Network (CNN) architecture was used for the classification of 6 different views. A total of 34752 and 3972 (5792 and 662 per view) frames were used to train and validate the network, respectively. Long-term Recurrent Convolutional Network (LRCN) combining temporal and spatial cognition was used for ES and ED frame detection. A total of 195 and 35 sequences with a length of 92 frames were used to train the LRCN.

Results

CNN for view classification had an AUC of 0.95 (sensitivity 95%, specificity 97%). Accuracy was lower for visually similar views, namely apical three-chamber and apical two-chamber. Training for ES and ED detection was achieved when training LRCN for regression instead of classification of each frame. LRCN for cardiac cycle evaluation had an average Framed Difference (aFD) of 2.31 (SD±2.15) for ED and 1.97 (SD±2.04) frames for ES detection which corresponds to error rate of about 0.04 s.

Conclusion

Determining echocardiographic view and evaluating cardiac cycle are the first steps in automating cardiac measurements. We have demonstrated the potential of two deep learning algorithms in accomplishing these tasks. Initial results are promising for the development of neural networks for cardiac segmentation and measuring of anatomical structures.
P1471Multimodality imaging of left ventricular function and volumes in patients with acute and chronic myocardial injury - Novel insights
Authors: Drabik L , Kwiecien E , Mazurek A , Urbanczyk M , Szot W , Kostkiewicz M , Banys R P , Brzyszczyk-Marzec M , Skubera M , Iwaszczuk P , Plazak W , Prokop-Staszecka A , Majka M , Podolec P , Musialek P
Published: October 2019

Introduction

The three main techniques to evaluate myocardial function and volumes: two-dimensional echocardiography (TTE), gated single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (cMRI), have important differences in accessibility and practicality.

Purpose

We aimed to evaluate: TTE, SPECT and cMRI in the measurement of left ventricular ejection fraction (LVEF), left ventricular end-diastolic (LVEDV) and left ventricular end-systolic volumes (LVESV) in patients with acute and chronic myocardial ischemic injury.

Methods

Consecutive patients with first large acute myocardial infarction (AMI) [LVEF ≤45% and/or cMRI infarct size ≥10% of left ventricle, 2–5 days after pPCI, n=10] and patients with chronic ischemic heart failure (CIHF) [LVEF ≤45% by SPECT, NYHA class II or III, n=10] were enrolled. Multimodality imaging using the study techniques was performed within 36 hours.

Results

LVEF measured with TTE, SPECT and cMRI did not differ between both groups (AMI: 41±2.5%, 37.9±2.7%, 41±2.7%; p=0.07, CHF: 29.6±3.2%, 29.7±3.0%, 32.9±4.9%; p=0.42). LVEDV and LVESV evaluated by SPECT were +33.6%, +38.2% higher in the AMI group and +40.7%, 40.4% higher in the CIHF group compared with TTE (p<0.001). When measured with cMRI they were +52.1%, +50.5%, +31.5%, +25.5% higher (AMI, CIHF group, respectively), compared with TTE (p<0.001).

There was a strong positive correlation between LVEF derived from TTE and SPECT (r=0.81, AMI; r=0.92, CIHF), TTE and cMRI (r=0.89, AMI; r=0.75, CIHF), SPECT and cMRI (r=0.88, AMI; r=0.76, CIHF; all p<0.01). As well as for LVEDV (r=0.79, 0.88; 0.90, 0.85; 0.76, 0.87; all p<0.05) and LVESV measurements (r=0.90, 0.91; 0.94, 0.89; 0.85, 0.85, all p<0.05).

Figure 1

Conclusions

There is a strong correlations between TTE, SPECT, and cMRI in the assessment of left ventricular function in patients with AMI or CIHF. However, TTE appears to significantly underestimate left ventricular volumes in relation to SPECT and cMRI.
P1482Preclinical diastolic dysfunction assessed by left atrial strain and association with incident heart failure
Authors: Potter E , Ramkumar S , Yang H , Kawakami H , Negishi K , Marwick T H
Published: October 2019

Background

Left atrial strain in the reservoir phase (LASr) measures passive LA stretch and is a sensitive marker of left ventricular diastolic dysfunction (DD). However, reduced LASr has not been prospectively validated against clinical heart failure (HF) endpoints and its place in diastology evaluation is unclear.

Aim

We sought whether DD grades defined by previously validated ranges of LASr predicted incident HF and whether reclassifying indeterminate diastolic function based on reduced LASr could facilitate assessment of HF risk.

Methods

Community dwelling elderly subjects were recruited and underwent baseline clinical and echocardiographic assessment. Where imaging was suitable, speckle-tracking echocardiography assessed LASr and subjects were assigned DD grades based on published ranges: normal >35%, grade 1 24–35%, grade 2 19–24%, grade 3 <19%. Current ASE/EACVI recommendations were used to identify those with indeterminate function; LASr-defined DD (LASr-DD) was defined as LASr ≤23%. Follow-up was ≤2 years and incident HF adjudicated by Framingham criteria.

Results

Of 610 subjects (age 71±5 yrs., 46% male) LASr analysis was feasible in 590 (97%); average LASr was 39% (IQR 34–43%). Incident HF was associated with LASr-DD grade, occurring in 8 (36%) with grade ≥2, 14 (10%) with grade 1 and 39 (9%) with normal function (p<0.001). Adjusted odds ratio for incident HF for LASr-DD grade ≥2 was 3.12 (95% CI 1.06–9.1, p=0.038) Diastolic function was indeterminate in 147 (24%) subjects; of 144 (98%) with LAS analysis, 6 (75%) of those with LASr-DD vs. 15 (11%) with normal LASr experienced incident HF (p<0.001).

Univariable Multivariable* OR (95% CI) p-value OR (95% CI) p-value LASr-DD grade:   1 1.13 (0.59–2.15) 0.7 0.84 (0.42–1.69) 0.63   ≥2 5.7 (2.26–14.5) <0.001 3.12 (1.06–9.1) 0.038 *Adjusted for age, hypertension, diabetes, BMI, global longitudinal strain, E/e', LA volume index, LV mass index (all p<0.1 on univariable analysis).

Incorporating LA strain in practice

Conclusion

DD defined by LASr is predictive of HF for grades ≥2 independent of other diastolic measures. Indeterminate diastolic function with LASr ≤23% is associated with incident HF. LASr may complement current diastolic function assessment recommendations.

Acknowledgement/Funding

Baker Heart and Diabetes Institute
P1486Semi-automated volume-strain loops: a new tool in TTE to assess diastolic dysfunction
Authors: Hubert A , Le Rolle V , Galli E , Hernandez A , Donal E
Published: October 2019

Aim

This work aims to evaluate a novel semi-automatic tool for the assessment of volume-strain loops by transthoracic echocardiography (TTE). The proposed method was evaluated on a typical model of left ventricular (LV) diastolic dysfunction: the cardiac amyloidosis.

Method

18 patients with proved cardiac amyloidosis were compared to 19 controls, from a local database. All TTE were performed using Vivid E9 or E95 ultrasound system. The complete method includes several steps: 1) extraction of LV strain full traces from apical 4 and 2 cavities views, 2) estimation of LV volume from these two traces by spline interpolations, 3) resampling of LV strain curves, determined for the same cardiac beat, (in apical 4-, 2- and 3- cavities views) as a function of pre-defined percentage increments of LV-volume and 4) calculation of the LV volume-strain loop area. (Figure 1, panel B)

Results

(Table 1): LVEF was similar between both groups whereas global longitudinal strain was significantly lower in amyloidosis group (−14.4 vs −20.5%; p<0.001). Amyloidosis group had a worse diastolic function with a greater left atrial volume index (51 vs 22ml/m2), a faster tricuspid regurgitation (2.7 vs 2.0 m/s), a greater E/e' ratio (17.3 vs 5.9) with a p<0.001 for all these indices. Simultaneously, the global area of volume-strain loop was significantly lower in amyloidosis group (36.5 vs 120.0%.mL). This area was better correlated with mean e' with r=0.734 (p<0.001) than all other indices (Figure 1, panel A).

Table 1 Amyloidosis (N=18) Controls (N=19) p Global strain-volume loop area (%.mL) 36.5±21.3 120.0±54.2 <0.001 Global longitudinal strain (%) −14.4±3.8 −20.5±1.8 <0.001 Left ventricular ejection fraction (%) 62±7 65±5 0.08 Left atrial volume index (ml/m2) 51±22 22±5 <0.001 E/A 1.72±0.97 2.07±0.45 0.17 Mean e' 5.5±1.3 14.4±2.8 <0.001 Mean E/e' 17.3±5.4 5.9±1.4 <0.001 Tricuspid regurgitation velocity (m/s) 2.7±3.8 2.0±0.3 <0.001

Figure 1

Conclusion

LV volume-strain loop area appears a very promising new tool to assess semi-automatically diastolic function. Future applications will concern the integration of LV volume-strain loop area as novel feature in machine-learning approach.
P1488Single wave mitral inflow pattern caused by left ventricular diastolic dyssynchrony in patients with heart failure
Authors: Takemoto K T , Hirata K , Akasaka T A
Published: October 2019

Background

Mitral E and A waves could fuse to form a single wave in tachycardia. Patients with heart failure (HF) occasionally show single wave mitral inflow despite of non-tachycardiac condition.

Purpose

To investigate mechanisms of single wave mitral inflow in HF patients with sinus rhythm and normal heart rate.

Methods

A total of 60 HF patients, including 20 single wave (SW), 20 impaired relaxation (IR) and 20 pseudonormalized (PN) mitral inflow patterns were retrospectively enrolled. All the patients were in sinus rhythm under 85 bpm. Patients with bundle branch blocks and first-degree heart block were excluded. We compared basic echo measurements, magnitude of left ventricular (LV) diastolic dyssynchrony, isovolumic relaxation time (IRT) and BNP levels among 3 groups. Diastolic dyssynchrony was determined as standard deviation of interval between aortic valve closure and peak early diastolic wave of longitudinal strain across 16 LV myocardial segments using 2D speckle tracking echocardiography.

Results

There was no significant difference in heart rate among 3 groups. Patients with SW showed significantly large magnitude of diastolic dyssynchrony (4.1±1.1) compared to those with IR (2.7±0.7) and PN (2.9±0.9ms), respectively. Likewise, IRT of SW (7.1±2.7) was longer than IR (3.2±0.8) and PN (2.4±0.9ms). BNP level in patients with IR (153±111) was significantly lower than those with SW (558±432) and PN (523±263pg/ml).

Representative cases

Conclusion

HF patients with SW could be caused by LV diastolic dyssynchrony and their BNP levels are comparable to those with PN.
P1494Usefulness of longitudinal strain adjusted to regional thickness in hypertrophic cardiomyopathy
Authors: Mansencal N , Utado S , Hauguelf-Moreau M , Mallet S , Charron P , Szymanski C , Dubourg O
Published: October 2019

Background

In hypertrophic cardiomyopathy (HCM), longitudinal strain analysis allows to early detect left ventricular (LV) contraction abnormalities despite preserved LV ejection fraction. In current software, the width of the region of interest (ROI) is the same over the entire myocardial wall, and might analyze partially LV hypertrophic segments.

Purpose

The aim of this study is to evaluate a novel software for strain analysis with an adjustable ROI according to each segment thickness.

Methods

We included 110 patients: 55 patients with HCM (HCM group) and 55 healthy subjects (age- and sex-matched control group). All patients underwent echocardiography using a Vivid 9 GE system and measurements were performed using EchoPAC software. Global longitudinal strain (GLS) and regional strain for each of the 17 segments was calculated with standard software (for 2 groups) and with software adjusted to the myocardial wall thickness (for HCM group).

Results

GLS was significantly decreased in the HCM group as compared to the control group (−15.1±4.8% versus −20.5±4.3%, p<0.0001). In HCM group, GLS (standard method versus adjusted to thickness) were not significantly different (p=0.34). Interestingly, regional strain adjusted to thickness was significantly lower than standard strain in hypertrophic segments, especially in basal inferoseptal segment (p=0.0002), median inferoseptal segment (p<0.001) and median anteroseptal segment (p=0.02). Strain adjusted to thickness was still significantly lower in the most hypertrophic segments (≥20 mm) (−3.7±3%, versus −5.9±4.4%, p=0.049 in the basal inferoseptal segment and −5.7±3.5% versus −8.3±4.5%, p=0.0007 in the median inferoseptal segment). Analysis of strain adjusted to thickness had a better feasibility (97.5% versus 99%, p=0.01).

Conclusion

Analysis of longitudinal strain adjusted to regional thickness is feasible in HCM and allows a better evaluation of myocardial deformation, especially in the most LV hypertrophic segments.
P1497Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome - Insights from exercise echocardiography
Authors: Yakupoglu H Y , Saeed S , Manivarmane R , Senior R , Lyon A R , Khattar R S
Published: October 2019

Introduction

Takotsubo syndrome (TTS) is an acute heart failure syndrome usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, approximately 10% of patients have persistent symptoms and seek further medical advice.

Purpose

To determine the cardiovascular haemodynamic and LV contractile response to exercise in these TTS survivors with ongoing symptoms.

Methods

This was a case-control study of 20 symptomatic patients with previous TTS referred for treadmill exercise echocardiography (EE), and 20 age-, sex- and ethnicity-matched control subjects with normal treadmill EE. Among the TTS group, EE was performed at a median of 8 months (mean 17±21 months) following the index event. Demographic characteristics, resting and EE data were collected. LV ejection fraction (EF) was measured at rest and peak stress. Global longitudinal and circumferential strain (GLS, GCS) were measured at rest.

Results

All 20 TTS patients were Caucasian postmenopausal females (mean age 63.5±6.6 years). There were no significant differences in body mass index (BMI), resting heart rate (HR) and the prevalence of cardiovascular risk factors compared to controls. Resting systolic and diastolic blood pressure (SBP, DBP) were higher in TTS patients (144±17 mmHg versus 128±18 mmHg, and 81±10 mmHg versus 74±9 mmHg, respectively). A comparative analysis of the resting and stress echo data is given in Table 1. The stress echo data showed similar exercise time and peak HR, but higher peak SBP in TTS patients. TTS patients had blunted contractile response to exercise with lower peak LVEF, ΔLVEF (exercise minus resting EF) and peak wall motion score index (WMSI) compared to controls. Among the 20 TTS patients, 12 had exercise-induced wall motion abnormalities: 6 involved the apical segments and 6 developed global dysfunction. In these 12 patients, the mean ΔLVEF was reduced (4%). In the other 8 patients, the ΔLVEF was 16% and pooled the TTS cohort had blunted contractile response with exercise compared to controls (ΔLVEF 8% vs. 19% in the control group, p=0.001).

Table 1

Conclusions

Our study shows that symptomatic patients with previous TTS have a blunted contractile response to exercise manifest as reversible apical or global LV dysfunction. These findings might indicate the need for treatment. Further systematic investigation of the therapeutic and prognostic implications of this reversible exercise-induced myocardial dysfunction is needed.
P1518Impact of psychological risk factors on cardiovascular prognosis in patients after coronary artery bypass grafting: data from a 5-year-follow-up study
Authors: Raykh O I , Sumin A N , Korok E V
Published: October 2019

Psychosocial stress is acknowledged as one of risk of development of cardiovascular pathology. The interrelation between existence personality type D and prevalence of atherosclerosis is recently established. However, predictive value of type D personality in different cultures and the countries are not fully understood.

Purpose

Study aim was to investigate the association of type D personality with the development of cardiovascular complication in patients in five years after coronary artery bypass grafting (CABG).

Materials and methods

Evaluation of psychological status and combined risk of nonfatal (strokes, nonfatal myocardial infarctions, repeat procedures of revascularization and hospitalization due to relapse or progression of angina pectoris) and fatal (general and cardiovascular mortality) cases before and in five years after CABG. Patients with chronic ischemic heart disease (n=602, 112 (18.5%) females and 490 (81.5%) males, mean age=57.7±7.3 years.) who had had CABG were included in the study. Who were formed in two groups: patients with the presence of type D (n=134) and patients without type D (n=468). The study of the psychological status was carried out using questionnaire DS-14. Analysis of long-term results were assessed using the Kaplan–Meier method.

Results

During the 5 years frequency of fatal cases in both groups amounted 8.3% and 8.1% (p=0.145), in turn nonfatal end-points in group with type D amounted 31.8%, and 15.9% in group without type D (p=0.044). Presence of type D personality at initial examination increased 3.21 times combined risk of nonfatal and fatal cases (OR 3.21, 95% CI 2.02–6.14, p=0.002). In long term period there were no differences in survival between groups type D and without type D (95.5% vs. 96.8%), There were differences in groups type D and without type D in nonfatal events (strokes, nonfatal myocardial infarctions, secondary endpoint: repeat procedures of revascularization and hospitalization due to relapse or progression of angina pectoris) (respectively, 97.1% vs 88.0%, (p=0.34).

Conclusion

Type D patients had a greater risk for nonfatal cardiac events compared with non Type D patients. Accumulated proofs indicate that in detection of patients at risk of development of stress induced cardiac complications after CABG it is reasonable to use approach which involves consideration of personality type.
P1522Validating a new device for precise assessment of pulse wave velocity in arteries of various structures in patients in different age groups
Authors: Olszewski R , Sondej T , Sieczkowski K , Obiala K , Jannasz I , Targowski T , Dobrowolski A P
Published: October 2019

Background

Arterial stiffness (AS) is a process that develops with age and obesity, but is also an independent predictive factor for the development of hypertension, and cardiovascular complications. Measuring the pulse wave velocity (PWV) is the most common method of assessing arterial stiffness. Two methods of PWV evaluation dominate in the world (carotid-femoral and brachial-ankle). However, recent studies have indicated that the age-related increase in PWV was not even uniform in different arteries and the AS gradient is a better predictor of mortality than the classic PWV one. So we need the devices for a more accurate assessment of AS in different areas. Our group constructed a precise, multi-site system (M3S) for the simultaneous, real-time, synchronous measurement of PWV. M3S has a maximum of eight photopletysmographic (PPG) detectors – Fig. 1A.

Aim

The purpose of the study is to validate the PWV measurement by M3S device against a gold standard (SphygmoCor XCEL) for patients in different age groups.

Methods

Measurements collected from 62 subjects (36 young [19–24], 26 older [62–89]) using the M3S were compared with simultaneously recorded SphygmoCor XCEL measurements. With the 59 paired PWV values, we investigated the agreement between the M3S prototype and the SphygmoCor XCEL device using Pearson correlation analysis and Bland-Altman plot. We also performed analysis on the determinants and reproducibility of PWV measured with both devices.

Results

The correlation coefficient for PWV measured with the two devices was 0.87 (p<0.001) – Fig. 1B. Compared with the SphygmoCor XCEL device, the M3S prototype slightly underestimated PWV by r=−0.47 m/s (±1.96 standard deviations SD: +2.2 m/s, r=−3.2 m/s). The coefficient of variation (CV) between the difference and the average of the M3S and SphygmoCor XCEL measurements was 19% (p=0.10) – Fig. 1C.

Figure 1. A. Block diagram of M3S measurement system with configuration for PWV validation. B. Relationship between PWV for SphygmoCor XCEL (carotid-femoral) and M3S (forehead-toes (right, left mean). C. Bland-Altman plot for the analysis of the difference between the SphygmoCor XCEL and M3S devices.

Conclusion

This technique used by the M3S could provided a multi-site measurement of PWV. It can be potentially extended for measurement and non-invasive characterization of global arterial stiffness with the possibility of calculating the different AS gradients.
P1544Circulating secretoneurin concentrations provide incremental prognostic information to established risk indices in patients with moderate to severe aortic stenosis
Authors: Brynildsen J , Myhre P L , Lyngbakken M N , Klaeboe L G , Stridsberg M , Christensen G , Edvardsen T , Omland T , Rosjo H
Published: October 2019

Background

Secretoneurin (SN) concentrations provide important prognostic information in patients with myocardial dysfunction. Whether preoperative SN concentrations improve risk assessment in patients with moderate to severe aortic stenosis (AS) is unknown.

Methods

We included 57 patients with moderate to severe AS referred for presurgical evaluation and recorded all-cause mortality during follow-up. All patients were examined with comprehensive echocardiography, electrocardiogram (ECG), and high-sensitivity cardiac troponin T (hs-TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements.

Results

Median (quartile 1–3) SN concentration in the AS patients was 141 (121–163) pmol/L. Lower estimated creatinine clearance and use of diuretics, but not standard ECG or echocardiographic indices and cardiac biomarkers, were associated with increasing SN concentrations. In total, 15 patients (26%) died during 3.5 years median follow-up. SN concentrations were higher in non-survivors than survivors: 156 (133–209) vs. 140 (116–155) pmol/L, p=0.007. The optimal cut-off concentration for SN in discriminating long-term mortality was 147 pmol/L (sensitivity 67% [95% CI 38–88%], specificity 74% [58–86%]) and patients with SN concentrations above the optimal cut-off had worse prognosis than patients below the cut-off (Figure; p=0.005 with the log-rank test). Higher SN concentrations were associated with increased risk of mortality after adjustment for clinical risk factors, echocardiographic and ECG variables, hs-TnT and NT-proBNP concentrations, and whether patients were subjected to aortic valvular surgery (n=34): hazard ratio per lnSN 15.13 (95% CI 1.05–219.00); p=0.046. Receiver operating characteristics area under the curve for SN to predict mortality was 0.74 (95% CI 0.60–0.88) compared to 0.73 (0.59–0.87) for hs-TnT and 0.67 (0.51–0.82) for NT-proBNP.

Conclusions

SN concentrations seem to reflect additional pathophysiology to established risk indices and improve risk assessment in patients with moderate to severe AS.
P1549Serum soluble Klotho is associated with extent of coronary artery calcification in patients with stable angina pectoris undergoing percutaneous coronary intervention
Authors: Koga S , Ikeda S , Akashi R , Yamagata Y , Yonekura T , Kawano H , Maemura K
Published: October 2019

Background

Klotho, which was originally identified as an aging suppressor, is a key regulator of bone and mineral metabolism. Transmembrane and soluble forms of Klotho protein have been identified. The transmembrane form serves as an obligate co-receptor for fibroblast growth factor 23 (FGF23). However, the physiological importance of soluble form of Klotho has not been determined.

Purpose

The present study aimed to test the hypothesis that circulating soluble Klotho levels can predict the presence or extent of coronary artery calcification (CAC) in patients with coronary artery disease.

Methods

We analyzed CAC of culprit lesions in patients with 75 stable angina pectoris who were not on dialysis and were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). Arc and length of each calcium within the culprit lesion was measured by IVUS. The main outcome measure was the calcium index; a volumetric IVUS-derived measure which was calculated as total calcium length/lesion length × maximal calcium arc/360°. Low calcium index was defined as calcium index <0.042 of the first quartile value. Serum Klotho and FGF23 were measured before PCI. Patients were divided into two groups according to median serum Klotho value: low-Klotho (n=37, ≤460 pg/mL) and high-Klotho group (n=38, >460 pg/mL).

Results

Compared with patients with low-Klotho, those with high-Klotho had higher estimated glomerular filtration rate (eGFR) (69±20 vs. 55±16 mL/min/1.73 m2, p<0.001), lower FGF23 levels (51±24 vs. 67±41 pg/mL, p=0.010). Patients with high-Klotho had significantly lower calcium index than those with low-Klotho (0.17±0.21 vs. 0.24±0.23, p=0.043). Serum Klotho levels correlated significantly and inversely with calcium index (r=−0.31, p=0.006). The correlation between Klotho and calcium index was pronounced at analysis in patients with eGFR <60 mL/min/1.73 m2 (r=−0.52, p<0.001). Logistic regression analysis showed that high-Klotho is a sole significant independent factor associated with low calcium index (odds ratio 7.17, p=0.004). Presence of high-Klotho had high sensitivity and negative predictive value for identifying low calcium index (83% and 92%, respectively).

Conclusions

Serum Klotho values were independently and inversely associated with the degree of CAC assessed by IVUS. These findings have important clinical implications for serum Klotho as a biomarker that reflects the extent of CAC.
P1551A genetic risk score predicts recurrent events after myocardial infarction in young adults
Authors: Rincon L M , Sanmartin M , Alonso G L , Rodriguez J A , Muriel A , Casas E , Navarro M , Carbonell A , Lazaro C , Fernandez S , Jimenez Mena M , Fernandez Golfin C , Esteban A , Garcia Bermejo M L , Zamorano J L
Published: October 2019

Background

To evaluate whether a genetic risk score (GRS) improves the prediction of recurrent events in young non-diabetic patients presenting with an acute myocardial infarction and identifies a more aggressive form of atherosclerosis in this population.

Methods and results

We performed a prospective study including 81 consecutive non-diabetic patients aged below 55 y.o. presenting with an acute myocardial infarction (48±6 y.o., 89% male). A comprehensive study including serum biomarkers, genetic testing and cardiac CT was performed. We studied the association of a GRS composed of 11 genetic variants with a primary composite end-point (all-cause mortality, recurrent acute coronary syndrome, and cardiac re-hospitalisation). After a median follow-up of 4.1 (3.5 - 4.4) years 24 recurrent events were documented. A significantly higher prevalence of 9 out of 11 risk alleles was noted compared with general population. The GRS was significantly associated with recurrent events, especially when baseline LDL-cholesterol levels were elevated. Compared with the low-risk GRS category, the multivariate-adjusted hazard ratio for recurrent events for the intermediate-risk GRS category was 10.2 (95% CI 1.1–100.3, p=0.04) and for the high-risk GRS was 20.7 (2.4–181.0, p=0.006) when LDL-C ≥2.8 mmol/L. Inclusion of the GRS improved the C statistic (ΔC statistic =0.086), the continuous Net Reclassification Index (30%) and the Integrated Discrimination Improvement (0.05) compared with a multivariate clinical risk model. Cardiac CT detected coronary calcified atherosclerosis and numerous plaques but it had a limited value for prediction of recurrences. No association was observed between extracellular matrix metabolism biomarkers and GRS or recurrent events in this population.

Cox regression analysis between GRS terciles and LDL-C Univariate analysis Multivariate analysis* HR (95% CI) p-value HR (95% CI) p-value* Low GRS 1 1 Intermediate GRS 2.0 (0.7–5.8) 0.21 LDL-C≤110 mg/dL (≤2.8 mmol/L) 1.0 (0.3–4.0) >110 mg/dL (>2.8 mmol/L) 10.2 (1.1–100.3) 0.04 High GRS 3.0 (1.0–9.2) 0.05 LDL-C≤110 mg/dL (≤2.8 mmol/L) 0.3 (0.1–1.9) >110 mg/dL (>2.8 mmol/L) 20.7 (2.4–181.0) 0.006 *Multivariate model adjusted for GRACE risk score and LDL-C and interaction. There was a strong interaction between GRS terciles and LDL-C (p<0.01).

Recurrent events based on genetic risk

Conclusions

A multilocus genetic risk score identified non-diabetic young patients at increased risk for recurrent events after a myocardial infarction. The significance of LDL-cholesterol in relation to genetic predisposition for recurrences merits further evaluation.

Acknowledgement/Funding

Instituto de Salud Carlos III (PI12/0564, PI14/01152 and PI15/00667), the CIBERCV and the Spanish Society of Cardiology (2015/CC)
P1604Validating previously reported Brugada syndrome-associated common variants identified in caucasian population in the Han Chinese BrS cohort in Taiwan: SADS-BrS registry
Authors: Juang J.-M , Chen C Y , Liu Y B , Lin L Y , Ho L T , Huang H C , Lai L P , Hwang J J , Wu C K , Lin T T , Yu C C , Lu T P , Chattopadhyay A , Yu Q Y , Lin J L
Published: October 2019

Background

Brugada syndrome (BrS) is a sudden arrhythmic death. The prevalence of BrS is higher in the Southeast Asian populations than that in Caucasian patients. A previous genome-wide association study (GWAS) has reported 13 SNPs significantly associated with BrS. However, no study was performed to validate whether these SNPs are enriched in BrS patients in Han Chinese (HC).

Purpose

Evaluating the common variants previously reported in Caucasian BrS patients could be generalized to HC BrS patients in Taiwan

Methods

We genotyped 200 unrelated BrS patients using Affymetrix TWB Array (N=653,291 SNPs, a customized array for HC in Taiwan). The controls are obtained from the Taiwan Biobank (N ≈ 16,000) using the same array. An imputation workflow was shown in Figure 1. To confirm the accuracy of the imputed genotype of each variant, Sanger sequencing was performed in 10% of randomly selected cases.

Results

Among the 3 most important common variants (rs11708996 in SCN5A, rs10428132 in SCN10A and rs9388451 in HEY2/NCOA7) reported in the previous GWAS mainly conducted in Caucasian BrS patients, 2 of them (rs10428132 and rs9388451) were successfully replicated in the HC population in Taiwan (P<0.01). We also found that the differences of minor allele frequency (dMAF: the MAF of cases minus the MAF of controls) of the two variants were relatively smaller between the BrS cases and healthy controls in HC population compared with that in Caucasian populations (dMAF, rs9388451: 0.15 (Caucasian) vs −0.07 (HC); rs10428132: 0.28 (Caucasian) vs 0.11 (HC)). For the remaining 10 common variants reaching genome-wide significance (P=5×10–8) in Caucasian BrS patients, 9 of them were also significantly enriched in the HC BrS patients after the Bonferroni correction (P<0.05/12=0.0042). We next analyzed the variants identified in the previous GWAS on ECG traits (PR interval, QRS duration, QTc interval, and heart rate) in the Caucasian population. Among the reported 75 variants associated with ECG traits, 5 common variants (rs6798015 (PR), rs1760876 (QRS), rs6795970 (PR/QRS), rs2074238 (QTc) and rs314370 (heart rate)) were significant after Bonferroni correction (P<0.05/75=0.00066).

Figure 1

Conclusions

The preliminary results indicated that 85% of common variants of SCN10A and HEY2/NCOA7 previously reported in Caucasian BrS patients are replicated in BrS patients in the HC population but not the common variant of SCN5A (rs11708996). Furthermore, the common variants of SCN10A and HEY2/NCOA7 related to cardiac depolarization or repolarization may also contribute to the development of BrS.

Acknowledgement/Funding

NTUH 106-S3469, NTUH106-S3458 and NTUH 106-018
P1612The ablation of VEGFR-1 signaling promotes angiotensin II induced cardiac dysfunction and sudden death
Authors: Tirronen A , Downes N L , Huusko J , Laakkonen J , Yla-Herttuala S
Published: October 2019

Introduction

Concentric left ventricular hypertrophy (LVH) and diastolic dysfunction develops as an adaptive response to pressure overload. Eventually this may lead to decompensated hypertrophy characterised by interstitial fibrosis, contractile dysfunction as well as changes in metabolism and electrophysiology, consequentially triggering heart failure. The molecular mechanisms involved in cardiac remodelling are not fully understood but maladaptive angiogenesis could promote the transition from adaptive LVH to decompensated heart failure. Angiogenesis is mediated by vascular endothelial growth factors but their role in LVH has remained unresolved.

Purpose

In this study, we wanted to investigate whether vascular endothelial growth factor receptor 1 (VEGFR-1) signaling has a role in the progression of LVH and development of heart failure.

Methods

We used wild type littermate controls and domain specific knock out mouse lacking the intracellular VEGFR-1 tyrosine kinase domain (VEGFR-1 TK−/−) and induced pathological hypertrophy with subcutaneous angiotensin II infusion. We examined the cardiac function with echocardiography and acquired surface ECG signal during the development of LVH. Mice were followed up for 14 days before sacrification and sample collection. Cross-sectional cardiac samples were stained with Masson's trichrome to assess the level of fibrosis and immunostained for lectin to determine capillary area. Additionally, we performed a CD31 whole mount staining to visualise capillary 3D network. To analyse changes in gene expression levels, we performed RT qPCR measurements.

Results

VEGFR-1 TK deficiency led to increased mortality (33.3%) and lack of adaptive LVH. Whereas wild type mice responded to angiotensin II infusion with a significant increase in ejection fraction (55.5% to 69.9%) within the first 6 days, VEGFR-1 TK−/− mice displayed a 5.2% decrease and without adaptive thickening of the LV anterior wall. The most striking difference was seen in LV volume, where wild type mice displayed a 63.3% reduction but in VEGFR-1 TK−/− mice it remained unaltered after angiotensin II infusion. Histological analyses showed that VEGFR-1 TK−/− mice displayed significant cardiomyocyte hypertrophy combined with ventricular dilatation but without changes in fibrosis or angiogenesis. ECG analysis revealed that VEGFR-1 TK−/− mice exhibited widening of the QRS complex, similar to human LVH, and this was accompanied by increased ANP/BNP levels.

Conclusions

In this study, we show that the ablation of VEGFR-1 TK signaling has an unexpected role in pressure overload inducing mortality. VEGFR-1 TK−/− mice displayed dilated LVH and a protracted response to angiotensin II infusion, suggesting that VEGFR-1 signaling is required for the adaptive response and concentric hypertrophy of the myocardium.
P1613Brown adipose tissue dysfunction has a critical role for the development of heart failure in murine pressure overload model
Authors: Yoshida Y , Shimizu I , Walsh K , Minamino T
Published: October 2019

Prognosis of severe heart failure is unacceptably high, and it is our urgent task to find therapies for this critical condition. It has been reported that low body temperature predicts poor clinical outcomes in patients with heart failure, however, underlying mechanisms and pathological implications are largely unknown. Brown adipose tissue (BAT) was initially characterized as a heat generating organ, and studies suggest that BAT has crucial roles for the maintenance of systemic metabolic health. Here we show that BAT dysfunction develops in a murine thoracic aortic constriction (TAC) model, and has a causal role for promoting pathologies in failing heart. TAC operation led to a significant reduction both in intraperitoneal and subcutaneous temperature. TUNEL-positive cells significantly increased in BAT during left ventricular (LV)-pressure overload, and in-vitro studies with differentiated brown adipocytes suggested that the chronic activation of adrenergic signaling promotes apoptosis in these cells. Gain of BAT function model, generated with BAT implantation into peritoneal cavity, improved thermogenesis and ameliorated cardiac dysfunction in TAC. In contrast, genetic model of BAT dysfunction promoted cardiac dysfunction. Metabolomic analyses showed that BAT dysfunction led to an increase of oxidized choline that promoted metabolic dysfunction in the failing heart. Electron microscope study showed that oxidized choline induced mitochondrial dysfunction in vitro as well as in vivo settings. Extracellular flux analyzerindicated that oxidized choline suppresses oxidative phosphorylation in mitochondria. We found that dilated cardiomyopathy patients have lower body temperature, and confirmed by metabolomic study that both choline and oxidized choline are increased in circulation. Maintenance of BAT homeostasis and suppression of oxidized choline would become a novel therapeutic target for heart failure.