bluuebunny/crossref_metadata_2025 huggingface dataset:
P3753Does empagliflozin modulate the autonomic system among patients with type 2 diabetes and coronary artery disease? Insights from the Holter sub-study of the EMPA-Heart CardioLink-6 Randomised Trial
Authors: Garg V , Verma S , Connelly K A , Yan A T , Sikand A , Garg A , Dorian P , Zuo F , Leiter L A , Zinman B , Juni P , Verma A , Quan A , Mazer C D , Ha A C T
Published: October 2019

Introduction

The mechanism behind how empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, reduces all-cause and cardiovascular mortality among patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) is unknown. Autonomic tone, as reflected by changes in heart rate variability (HRV), is an established prognosticator in patients with CAD and/or heart failure.

Purpose

To assess if empagliflozin treatment changes HRV in subjects with T2DM and CAD.

Methods

In the double-blind EMPA-Heart trial, 97 subjects with T2DM and CAD were randomised to empagliflozin 10 mg/day or placebo for 6 months and underwent 24-hour Holter monitoring at baseline and 6 months. Using automated algorithms, time and frequency HRV domain measures were obtained (standard deviation of NN intervals (SDNN); SD of the average NN intervals for each 5-minute segment (SDANN); root mean square of successive RR interval differences (rMSSD); % interval differences of successive NN intervals >50 ms (pNN50); ratio of low to high frequency (LF/HF)). Changes of these HRV parameters were calculated over 6 months. Between-group differences in HRV parameters were compared using ANCOVA.

Results

Complete Holter data (baseline and 6-month) were available for 68% (n=66) of the cohort. The average heart rate (HR) at baseline/6 months was 69.5±9.8 bpm/72.8±8.1 bpm and 76±10.4 bpm/76.5±10.6 in the placebo group and empagliflozin group, respectively. Both groups had similar changes in average HR over 6 months. Key Holter data are summarised in the table. SDNN and SDANN were higher in the placebo vs. empagliflozin group at 6 months; no significant difference was noted for all other measures.

Empagliflozin 10 mg/day (n=33) Placebo (n=33) Adjusted difference between Empagliflozin and Placebo (ANCOVA) Baseline, Mean (SD) 6-month, Mean (SD) Baseline, Mean (SD) 6-month, Mean (SD) Mean, (95% CI) P-value SDNN (ms) 100.49 (43.74) 98.05 (38.86) 109.35 (30.02) 125.08 (43.83) −18.55 (−34.28, −2.82) 0.022 SDANN (ms) 86.84 (39.34) 83.76 (35.53) 94.70 (28.52) 118.28 (77.41) −20.24 (−37.27, −3.21) 0.021 rMSSD (ms) 27.00 (11.84) 27.22 (13.48) 28.00 (11.58) 27.17 (9.38) −1.23 (−6.02, 3.55) 0.608 pNN50 (%) 7.81 (7.59) 8.32 (9.51) 8.26 (7.8) 6.93 (5.35) 0.51 (−2.61, 3.62) 0.746 LF/HF ratio 1.63 (0.52) 1.65 (0.51) 1.53 (0.43) 1.83 (0.82) −0.08 (−0.38, 0.22) 0.602

Conclusions

Among subjects with T2DM and CAD, changes in HRV over 6 months were similar in the empagliflozin and placebo arms suggesting that the mortality benefit conferred by empagliflozin is not associated with positive modulation of autonomic tone.

Acknowledgement/Funding

This trial was supported by an unrestricted investigator-initiated study grant from Boehringer Ingelheim.
P3756Diverse activation patterns during persistent atrial fibrillation characterised by dipole density non-contact mapping
Authors: Shi R , Chen Z , Butcher C , Zaman Z , Boyalla V , Wang Y K , Riad O , Sathishkumar A , Norman M , Haldar S , Jones D G , Hussain W , Markides V , Wong T
Published: October 2019

Background

Global simultaneous recording of activation during atrial fibrillation (AF) can elucidate underlying mechanisms contributing to AF maintenance. A better understanding of these mechanisms may allow for a personalised ablation strategy to treat persistent AF.

Purpose

To characterise left atrial endocardial activation patterns during AF using a novel non-contact dipole density mapping.

Methods

Activation patterns were characterised into three sub-types: (i) focal with centrifugal activation (FCA); (ii) localised rotational activation (LRA); (iii) localised irregular activation (LIA). Continuous activation patterns were quantified and distributed in the left atrium.

Results

A total of 144 persistent AF segments with 1068 activation patterns from 25 patients were analysed. The most common pattern was LIA (63%), which consist of four disparate features: slow conduction (45%), pivoting (30%), collision (16%) and acceleration (7%). LRA was the second commonest pattern (20%). FCA (17%) arose frequently from the PVs/ostia. Continuous AF activations comprise multiple combinations of FCA, LRA and LIA, transitioning from one to the next without a discernible order. Preferential conduction areas were typically seen in mid-anterior (48%) and lower-posterior (40%) walls where dominant activations were made up of LRA and LIA.

Conclusion

AF is characterised by heterogenous activation patterns that vary between individuals. Clinical implications of individualised ablation strategies guided by dipole density mapping will have to be determined.

Acknowledgement/Funding

None
P3770Interatrial block: a prognostic factor for atrial fibrillation in cryptogenic stroke patients
Authors: Mendieta Badimon L G , Guasch E , Weir D , Aristizabal D , Llull L , Mont L , Bayes De Luna A , Sitges M
Published: October 2019

Background

Atrial fibrillation (AF) is a well-known risk factor for ischemic stroke. Interatrial block (IAB), resulting from a conduction delay in Bachmann's bundle, is an electrical abnormality that, especially in its advanced (A-IAB) form, has been associated with atrial fibrotic cardiopathy and remodeling, sharing a common pathologic substrate with AF. Therefore, IAB has been proposed as a marker of atrial electromechanical dysfunction that may predispose to the development of AF. We hypothesized that IAB could be a marker of AF in patients with cryptogenic stroke (CS).

Methods

We retrospectively screened a cohort of CS patients with no prior history of AF, and collected their demographic, cardiovascular risk factors and other co-morbidities, stroke severity and resultant functional disability (NIHSS and mRS scales), CHA2DS2-VASc score, baseline 12-lead ECG, transthoracic echocardiogram, and neuroimaging studies on admission. All patients underwent continuous ECG monitoring for at least 48h. Forty-eight (64%) patients underwent additional out-patient 24h Holter monitoring following hospital discharge. P-wave (PW) analysis of baseline ECG classified patients into three groups: normal p-wave duration (N, PW <120 ms), partial IAB (P-IAB, PW ≥120 ms) and advanced IAB (A-IAB, PW ≥120 ms and biphasic morphology in leads DII, DIII and aVF). AF episodes (defined as irregular supraventricular arrhythmias without detectable PWs lasting >30 s), frequent premature atrial contractions (PACs) (>1%) and atrial tachyarrhythmia episodes (runs of >3 consecutive PACs) were detected on 24h Holter readings. Ischemic brain lesions were classified as cortical, subcortical or lacunar in relation to their localization and maximal diameter.

Results

Out of the 80 consecutive CS patients identified, 5 were excluded due to poor quality ECG readings. A high prevalence of both P-IAB (n=30, 40%) and A-IAB (n=23, 30.7%) was found in the final analysis with 75 CS patients. No differences were found between demographics, cardiovascular risk factors and co-morbidities, NIHSS, mRS and CHA2DS2-VASc scores, left atrial size and left ventricular ejection fraction among the 3 ECG categories. Cortical ischemic brain lesions were more frequent in patients in the IAB groups than in the N ECG group. After a mean follow-up of 522 days, AF was clinically diagnosed in 13 patients (17%), with an increasing risk in accordance to the severity of the IAB (p<0.05) (Figure 1A). 24h Holter readings showed greater frequency of PACs and atrial tachyarrhythmia episodes in patients with IAB (p<0.05) (Figure 1B).

Figure 1

Conclusions

In CS, IAB is associated with a greater risk to develop AF and its presence identifies a subgroup of patients with probable atrial fibrotic cardiopathy that could potentially benefit from early oral anticoagulation in secondary prevention.
P3772Risk factors for future development of atrial fibrillation are not evident among apparently healthy individuals with paroxysmal atrial fibrillation
Authors: Koshiyama M , Tamaki K , Ohsawa M
Published: October 2019

Background

Atrial fibrillation (AF) is one of the important factors of cardiovascular morbidity and mortality and to find not only patients with persistent AF but also individuals with paroxysmal AF among apparently healthy people is a crucial strategy for decreasing number of patients with serious cardio-embolic stroke. However, screening ability using previously known risk factors for future development of AF has not been examined in individuals with paroxysmal AF.

Methods

A total of 59730 male individuals, aged 40 years or older who underwent multiple comprehensive physical check-ups including 12 lead electrocardiogram (ECG) from 2012 to 2015 were enrolled. Persistent AF was defined a case that consecutively manifested AF till the last checkup. Paroxysmal AF was defined as a case who transiently manifested AF in each of the checkup and subsequently manifested sinus rhythm at the last checkup. Non-AF was defined as a case that never manifested AF in any of checkup. Age-adjusted prevalence rates and their 95% confidence intervals of known-risk factors in the first survey were estimated by logistic regression analysis separately by the three groups (non-AF (n=58602), paroxysmal AF (n=392) and persistent AF (736)).

Results

Age-adjusted prevalence rates (95% confidence interval) of risks factors for AF are shown in the table. Already known risk factors were evidently manifested in persistent AF group, however, prevalence rates of these factors in paroxysmal AF group were not different from the rates in non-AF group.

Conclusion

The repeated measurements of ECG study indicated that individuals who would develop paroxysmal AF in the near future did not have typical risk factors for AF and a screening test using risk factors for AF have no chance to find a high-risk individual for paroxysmal AF.
P3787Incidence, risk predictors, and mortality risk of new heart failure in an incident hospitalised atrial fibrillation cohort: a Western Australia population-based study, 2000–2010
Authors: Weber C , Hung J , Hickling S , Nedkoff L , Murray K , Li I , Briffa T
Published: October 2019

Background

Atrial fibrillation (AF) is a risk factor for heart failure (HF) and new HF onset is associated with increased mortality.

Purpose

To determine the incidence, risk predictors and mortality risk of a new HF hospitalisation event in patients after incident AF hospital admission.

Methods

This was a contemporary, population-based retrospective cohort study which included all Western Australian residents, aged 25 to 94 years, who survived an incident hospitalisation for AF, between 2000 and 2010. Patients hospitalised with AF that had no previous AF or HF hospitalisations up to 15 years beforehand were identified. Time to first-ever HF hospitalisation in the three years following incident AF was assessed using Kaplan-Meier methods, accounting for all-cause death as a competing risk. Cox proportional hazards models were used to determine independent predictors of HF. The association of first HF with subsequent survival was estimated using a time-dependent HF variable with other risk covariates in a proportional hazards model.

Results

The cohort comprised of 34 999 patients, 56.8% male, with a mean age of 71.0 (SD 13.1) years. Females were on average 6 years older than males (P<0.001). Among the cohort, 20.4% had died from any cause at 3-year follow-up. The cumulative incidence of a first HF hospitalisation event at 3 years (n=4298), after accounting for death as a competing risk, was 12.3% (95% CI 11.9%-12.6%). Most HF hospitalisations (56.2%) occurred within the first year after incident AF admission (median of 279 days; IQR 64–649 days). Of the incident HF hospitalisations, 88.9% were an emergency admission. Independent predictors of an increased risk of HF hospitalisation included older age and a history of hypertension, diabetes, excessive alcohol consumption, myocardial infarction, chronic obstructive pulmonary disease, valvular heart disease, and chronic kidney disease (all P<0.0001). Incident AF patients who were hospitalised for first HF had an adjusted hazard ratio of 2.89 (95% CI; 2.71–3.08) for all-cause mortality (P<0.0001).

Conclusion

Hospitalisation for HF is a frequent and troublesome problem in patients after incident AF admission, and is independently associated with increased risk of mortality. The clinical predictors of new HF occurrence highlight the importance of assessment and comprehensive management of associated risk factors and comorbid diseases in order to prevent HF morbidity and mortality in AF patients.

Acknowledgement/Funding

NHMRC CRECOI Scholarship
P3794MOODS: a novel risk score to identify patients with atrial fibrillation and sleep apnoea
Authors: Kadhim K , Elliott A , Middeldorp M , Hendriks J , Gallagher C , Mahajan R , McEvoy R D , Lau D , Sanders P , Linz D
Published: October 2019

Background

Sleep-disordered breathing (SDB) is an important risk factor for developing atrial fibrillation (AF), and treatment of concomitant SDB can improve AF rhythm outcomes. Diagnosis of SDB requires sleep studies which can pose a significant time and resource burden. We sought to develop a prediction score based on clinical characteristics that can help identify AF patients who require further assessment for SDB.

Methods

Prospectively-collected data for 442 consecutive patients treated for AF from 2009 to 2017 were analysed. All patients were considered candidates for rhythm-control and therefore referred for sleep studies. The diagnosis of SDB was confirmed using in-lab polysomnography and classified using the apnoea-hypopnoea-index (AHI), with cut-offs of ≥15/hr and ≥30/hr indicating moderate-to-severe and severe SDB respectively. Patients treated up to 2015 formed the derivation cohort (n=311) and the remainder (n=113) formed the validation cohort. Multivariate logistic regression analysis was used to identify clinical variables predictive of moderate-to-severe SDB. A risk score model was developed based on regression coefficients and tested using receiver-operating-characteristics analyses on the validation cohort.

Results

Overall, mean age was 60±11 years, mean body mass index (BMI) was 30±5 kg/m2 and 69% were men. The prevalence of moderate-to-severe SDB was 33.7%. There were no significant differences in baseline characteristics between the derivation and validation cohorts. Male gender (score=1), overweight (BMI: 25–29 kg/m2, score=2), obesity (BMI≥30 kg/m2, score=3), diabetes (score=1), and stroke (score=2) were significantly independently predictive of moderate-to-severe SDB and formulated the score. The score performed well to predict moderate-to-severe SDB with a C-statistic of 0.73 (95% CI: 0.67–0.79, P<0.001) in the derivation cohort, and 0.67 (95% CI: 0.57–0.77, P<0.001) in the validation cohort. As a rule-out test, a score of ≤3 had a negative predictive value of 77% for moderate-to-severe SDB (91% for severe SDB). A score of ≥4 had an intermediate positive likelihood ratio (PLR) of 2 for moderate-to-severe SDB (2.2 for severe SDB), while a score of ≥5 had a high PLR of 6.5 and 6.8 for moderate-to-severe SDB and severe SDB respectively.

Sensitivity and specificity table

Conclusion

A novel risk score comprising clinical characteristics can identify patients with AF likely to benefit from further assessment for SDB. Application of this model may aid optimise resource utilisation and facilitate timely patient care.
P3796Prediction of severe sleep apnea in patients with nocturnal bradycardia or conduction disorders
Authors: Szajerska-Kurasiewicz A , Loboda D , Simionescu K , Golba A , Dzierzawa M , Szady T , Kucia-Kuzma S , Turski M , Golba K S
Published: October 2019

Background

According to the 2018 ACC/AHA/HRS Bradycardia Clinical Practice Guidelines an effective treatment of obstructive sleep apnea (OSA) can prevent the need to implant a pacemaker.

The aim of the study was to create a prediction model of high risk of OSA in patients with bradycardia or conduction disorders during sleep and referred for pacemaker implantation.

Methods and results

The polysomnography was performed in 118 (20 female) high-cardiovascular risk patients; aged 60.1±11.7 years; body mass index (BMI) 32.65±7.1. Sleep-disordered breathing (SDB) as an apnea/hypopnea index (AHI) ≥5 per hour was observed in 101 (85.6%) subjects including moderate SDB (AHI≥15) in 28 (27.7%) and severe SDB (AHI≥30) in 43 (42.6%) subjects.

The risk of severe SDB increased with increasing BMI; if ≥30kg/m2 (AUC=0.725, sensitivity 81.4%, specificity 55.4%, p<0.0001), the neck size; if ≥43cm (AUC=0.74, sensitivity 60.0%, specificity 75.7%, p<0.0001).

The ECG Holter was performed in 93 patients and revealed in 27 of them bradycardia and/or conduction disorders during sleep: episodes of bradycardia <40 beats per minute in 19 (20.4%), sinus arrest in 7 (7.5%) and an atrioventricular block in 8 (8.6%). The neck size, BMI and AHI in these patients were larger: 45.8±4.0 vs. 42.6±3.0 cm (p=0.081), 37.5±8.4 vs. 30.4±5.5kg/m2 (p=0.0003) and 38.0±22.5 vs. 21.7±21.4 (p=0.0016) respectively.

When age, sex, BMI and neck size were taken into consideration using multivariate modeling the BMI and sex if male were revealed as independent predictors of clinically significant SDB (AHI ≥15); (p=0.0001, AUC for model 0.820) (figure 1).

Figure 1. Receiver-operating characteristic curve showed the best cut-off value of BMI >34,9 kg/m2 (sensitivity 72,73, specificity 78,12) to predict nocturnal bradycardia or conduction disorders in patients with sleep apnea and AHI index ≥15.

Conclusions

In patients who are being considered for a pacemaker implantation for bradycardia or conduction disorders during sleep, with BMI >30kg/m2 or the neck size over 43cm screening for sleep apnea syndrome is reasonable.
P3800Defibrillation for right ventricular dysfunction - An echocardiographic method for therapy selection
Authors: Montenegro Sa F , Almeida J , Fonseca P , Oliveira M , Goncalves H , Primo J , Braga P
Published: October 2019

Introduction

Cardiac resynchronization therapy (CRT) is recommended for heart failure (HF) patients with left ventricular ejection fraction (LVEF) <35% and QRS>130 mseg. We aim to identify if baseline transthoracic echocardiographic (TTE) data can predict the need for defibrillation therapies in a primary prevention HF population referred for CRT implant.

Methods

We analyzed 119 consecutive HF patients in primary prevention referred for CRT implantation between 2004 and 2016. All patients underwent TTE before implantation. During a mean follow-up time of 58.4±33.9 months, all patients were evaluated with device interrogation every 6 months. In order to determine which parameters can predict sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) occurrence, a multivariate analysis was performed including previous medical history, baseline laboratorial, electro and echocardiographic data.

Results

We included 86.6% (n=106) males, mean age at implant 65.5±9.7 years. A CRT-defibrillator (CRT-D) was implanted in 82 (64.2%) patients and a VT or VF was documented in 16 patients (13.4%). Baseline characteristics are presented in the table. After multivariate analysis, baseline right ventricular dysfunction (defined as TAPSE≤18mm) was an independent predictor for VT or VF occurrence (OR=4.83, 95CI 1.67–6.25, p=0.002).

Baseline characteristics VT/VF (n=16) No VT/VF (n=103) P-value Age (years, mean ± SD) 62,4±7,9 66,2±9,5 0,135 Female gender (n, %) 2 (12,5) 14 (15,1) 0,572 Ischemic cardiomyopathy (n, %) 7 (43,8) 21 (22,6) 0,073 NYHA III + IV (n, %) 13 (81,3) 76 (73,8) 0,984 QRS width (mseg, mean ± SD) 168,5±19,5 177,6±22,2 0,142 Atrial fibrillation (n, %) 5 (31,3) 17 (18,3) 0,089 LVEF (%, mean ± SD) 24,6±4,8 26,3±6,3 0,302 TAPSE (mm, mean ± SD) 14,9±4,9 17,9±4,3 0,034 PASP (mmHg, mean ± SD) 48,5±9,4 43,5±14,6 0,419 Mitral regurgitation (moderate or greater, n, %) 5 (31,3) 24 (28,9) 0,077 iVol (mL/m2, mean ± SD) 134,2±36,6 128,7±44,1 0,690 CRT-D implantation (n, %) 16 (100,0) 60 (64,5) 0,002

Conclusion

In a real-world HF population, right ventricular dysfunction defined by echocardiography was an independent predictor for VT or VF occurrence. This may help more accurate patient selection for CRT-D implantation.
P3805Mortality predictors and outcome in patients after upgrade from implantable cardioverter-defibrillator to cardiac resynchronization therapy in comparison to CRT-D de novo implantation
Authors: Jedrzejczyk-Patej E , Mazurek M , Kowalska W , Bugajski M , Konieczny-Kozielska A , Kozielski J , Podolecki T , Kowalski O , Kalarus Z , Sredniawa B , Lenarczyk R
Published: October 2019

Background

Over a quarter of all cardiac resynchronization therapy (CRT) implants are upgrades from previous devices, mainly from implantable cardioverter-defibrillator (ICD). In comparison to CRT with defibrillator (CRT-D) de novo implantation, upgrade from ICD to CRT-D carries higher risk of complications. Limited number of studies evaluated predictors of death in patients undergoing upgrade from ICD to CRT-D.

Aim

To determine mortality predictors and outcome in patients undergoing upgrade from ICD to CRT-D in comparison to subjects with CRT-D de novo implantation.

Methods

Study population consisted of 595 consecutive patients with CRT-D implanted between 2002 and 2015 in tertiary care university hospital, in a densely inhabited, urban region of Poland (480 subjects [84.3%] with CRT-D de novo implantation; 115 patients [15.7%] upgraded from ICD to CRT-D).

Results

The median follow-up was 1692 days (range: 457–3067). All-cause mortality in patients upgraded from ICD was significantly higher than in subjects with CRT-D implanted de novo (43.5% vs. 35.5%, P=0.045). On multivariable regression analysis, left ventricular end-systolic diameter (HR 1.07, 95% CI 1.02–1.11, P=0.002), creatinine level at baseline (HR 1.01, 95% CI 1.00–1.02, P=0.01), NYHA IV class at baseline (HR 2.36, 95% CI 1.00–5.53, P=0.049) and cardiac device-related infective endocarditis (CDRIE) during follow up (HR 2.42, 95% CI 1.02–5.75, P=0.046) were identified as independent predictors of higher mortality in patients with CRT-D upgraded from ICD.

Conclusions

Mortality rate in patients upgraded from ICD is higher in comparison to CRT-D de novo implanted subjects, and reaches almost 45% within 4.5 years. Left ventricular dimensions, creatinine level, high NYHA class at baseline and infective endocarditis during follow up are independent mortality predictors in patients with CRT-D upgraded from ICD.
P3807Impact of unipolar vs bipolar left ventricular pacing using a quadripolar lead on heart failure hospitalization in patients undergoing cardiac resynchronization therapy
Authors: Mittal S , Stivland T , Wold N , Hammill E , Stein K M
Published: October 2019

Background

Unipolar (uni) pacing from a bipolar left ventricular (LV) pacing lead in cardiac resynchronization therapy (CRT) patients (pts) has been associated with worse outcomes than bipolar (bi) pacing (MADIT CRT and ALTITUDE analyses). However, it is unknown whether the same is true with quadripolar LV pacing leads.

Purpose

To determine whether there is a difference in heart failure hospitalization (HFH) following CRT implantation in pts undergoing uni vs. bi LV pacing.

Methods

All pts enrolled in the NAVIGATE study were implanted with a CRT-D (RESONATE, Boston Scientific) using a quadripolar LV lead (ACUITY X4 Spiral Long, Spiral Short, or Straight). Pts were followed, and data collected on HFH and mortality. Vectors were programmed at the discretion of the implanter. Outcomes were adjusted for age, gender, NYHA class, ischemic etiology, conduction disorder pattern, EF, LV lead location, and LV lead shape.

Results

The study cohort included 2080 pts; 1781 pts had bi and 299 pts had uni LV pacing. Bi LV had higher % female, NYHA II/III, non-ischemic, LBBB, spiral shape, lateral and apical locations. During follow-up, the adjusted likelihood of HFH was significantly lower in pts undergoing bi LV pacing (HR 0.75, 0.58–0.97, p=0.027, Figure). Mortality was similar between the two groups.

Conclusions

In this large prospective study, uni LV pacing was associated with significantly greater likelihood of need for HFH during a 4-year follow-up period. These data suggest that routine programming in a bi configuration may be better for post-CRT pts. However, further study is needed to confirm causality and mechanism of this finding.
P3829Antiarrhythmic effects of Sacubitrilat (LBQ657) on Ca2+ homeostasis in ventricular cardiomyocytes
Authors: Eiringhaus J , Wuensche C , Herting J , Hasenfuss G , Sossalla S , Fischer T
Published: October 2019

Background and objectives

Simultaneous inhibition of neprilysin and angiotensin II receptors by sacubitril/valsartan was shown to significantly reduce morbidity and mortality in heart failure patients compared to sole interference with the renin angiotensin system. Beneficial effects of increased levels of natriuretic peptides following neprilysin inhibition have been suggested, whereas direct effects of sacubitrilat on myocardial Ca2+ cycling properties remain elusive.

Methods and results

Under basal conditions the combination of active neprilysin-inhibitior sacubitrilat (LBQ657) and angiotensin II receptor inhibitor valsartan did not influence diastolic Ca2+ spark frequency (CaSpF) nor arrhythmogenic SR Ca2+ leak in murine ventricular cardiomyocytes (confocal microscopy, n CMs/hearts=80/7 vs. 100/7, P=0.91/0.99). In contrast, sacubitrilat/valsartan treatment significanty reduced CaSpF by 35±9% and SR Ca2+ leak by 45±9% in CMs that had been put under catecholaminergic stress (isoproterenol 10nM, n=81/7 vs. 62/7, P<0.001 both). This effect could be clearly be attributed to the neprilysin inhibitor sacubitrilat as sole sacubitrilat treatment also reduced both parameters by similar degrees (reduction of CaSpF by 57±7% and SR Ca2+ leak by 76±5%; n=101/4 vs. 108/4, P<0.01 both) whereas sole valsartan treatment did not affect diastolic SR Ca2+ leak. Of note, systolic Ca2+ release, SR Ca2+ load and Ca2+ transient kinetics of murine CMs were not compromised upon treatment with sacubitrilat (epifluorescence microscopy, n=41/6 vs. 39/6). Importantly, sacubitrilat/valsartan in combination as well as sacubitrilat alone also reduced diastolic CaSpF and SR Ca2+ leak by 40–74% in human left-ventricular CMs from patients with end-stage heart failure (n=71/8 vs. 78/8, P<0.05).

Conclusion

This study demonstrates that neprilysin-inhibition directly exerts beneficial effects on Ca2+ homeostasis in human heart failure. We can show for the first time that neprilysin-inhibition by sacubitrilat yields a strong reduction of arrhythmogenic SR Ca2+ leak without affecting systolic Ca2+ release. These effects might contribute to the mortality benefit of sacubitril/valsartan treatment in the PARADIGM Study.

Acknowledgement/Funding

THF was funded by the Deutsche Forschungsgemeinschaft (DFG) through the SFB 1002 (A11). SS is supported by the Marga und Walter Boll-Stiftung.
P3837Both left atrial and left ventricular multilayer longitudinal strain are impaired in early stages of arterial hypertension in postmenopausal women
Authors: Sokolova M V , Kolesnyk M Y
Published: October 2019

Background

Left ventricular (LV) hypertrophy and left atrial (LA) dilation are powerful prognostic predictors in arterial hypertension (AH). However, their use is limited in the early stages of hypertensive heart disease. LV and LA global longitudinal strain (GLS) are promising diagnostic markers for identification of early myocardial dysfunction. The purpose of the study was to evaluate the longitudinal deformation of left heart chambers in hypertensive postmenopausal women prior to LV hypertrophy and LA dilation development.

Methods

The study enrolled 100 postmenopausal hypertensive women (mean age 57.5±4.1 years), divided into 2 groups, and 26 healthy females (control group). The 1st group included 32 women with structurally normal hearts and the 2nd group consisted of 68 females with LV hypertrophy (LV mass index >95 g/m2) and LA dilation (LA volume index >34 ml/m2). LV multilayer GLS was calculated with 2D speckle tracking echocardiography. LA GLS was computed by averaging 12 segmental values with both P- and R- wave ECG-triggering. Strain was measured in contractile and reservoir phase, calculating GLS as sum of these values with P-wave variant, and as maximal peak of curves with R-wave method. The data are presented as median and interquartile range.

Results

The LV GLS was significantly lower in hypertensive women with structurally normal hearts in all myocardial layers compared to healthy females (table). The LA longitudinal strain was reduced due to the deterioration of reservoir phase. The reduction of LA GLS in hypertensive women with structurally normal hearts was detected using R-wave triggering method only (opposite to P-wave method).

Left heart chambers longitudinal strain Parameter Control group 1st group 2nd group p LV GLS endo, % −23.75 (−20.3; −25.15) −21.25 (−19.6; −22.35)* −21.2 (−20.14; −22.9)* 0.047 LV GLS mid, % −21.4 (−18.5; −22.6) −19.1 (−17.8; −20.45)* −19.1 (−17.95; −20.15)* 0.03 LV GLS epi, % −18.7 (−16.75; −20.2) −16.95 (−15.95; −18.5)* −17.1 (−15.96; −18.05)* 0.03 P-wave triggering   LA LS in contractile phase, % −15.75 (−13.41; −16.37) −15.38 (−13.69; −17.77) −14.99 (−12.97; −16.89) 0.47   LA LS in reservoir phase, % 17.19 (15.4; 20.2) 13.19 (8.8; 18.03)* 13.54 (10.45; 16.19)* 0.0004   LA GLS, % 31.01 (25.11; 35.59) 28.37 (24.29; 32.5) 26.73 (23.21; 30.54)* 0.02 R-wave triggering   LA GLS, % 38.3 (34.54; 43.43) 33.63 (30.11; 36.28)* 30.77 (26.23; 36.11)* 0.0002 *p<0.05 compared to control group.

Conclusions

LV multilayer and LA GLS are reduced prior to LV hypertrophy and LA dilation development in hypertensive postmenopausal women and may be considered as early signs of myocardial dysfunction.
P3839Hypertension or hypertrophic cardiomyopathy? Using cardiovascular magnetic resonance imaging to unmask the great imitator
Authors: Keteepe-Arachi T , Malhotra A , Basu J , Parry-Williams G , Ensam B , Miles C , Dassanayake S , MacLachlan H , Ibrahim B , Papdakis M , Tome M , Khong T , Sharma S , Anderson L
Published: October 2019

Background

Structural cardiac adaptations due to hypertension (HTN) present a diagnostic challenge when differentiating from hypertrophic cardiomyopathy (HCM), using traditional imaging techniques such as echocardiography (echo). Cardiac magnetic resonance imaging (CMR) offers reproducible anatomical, functional quantification and myocardial tissue characterisation which discriminates between hypertension and HCM.

Purpose

To identify hypertensive individuals with undiagnosed HCM using CMR imaging.

Methods

100 consecutive hypertensive patients underwent CMR at a tertiary centre dedicated blood pressure clinic (55% male, mean age 51 years). In keeping with ESC guidelines, end diastolic wall thickness (EDWT) ≥15mm identified individuals within the “grey zone” between hypertension and with a potential HCM diagnosis. 19 individuals were referred on to the dedicated inherited cardiac conditions clinic for further evaluation. Four patients expressed a definitive LV phenotype and were diagnosed with HCM. CMR parameters were compared in three groups: Hypertensive (HTN), “grey zone” Hypertensive (GZH) and HCM.

Results

CMR demonstrated end diastolic wall thickness (EDWT) >11 mm in 50% of hypertensives. 73% of the referred patients were Afro-Caribbean (AC) and all 4 HCM patients were AC. All referrals demonstrated EDWTs ≥14mm, 9 (47%) demonstrated late gadolinium enhancement of which 3 (16%) had HCM. Three had asymmetrical septal hypertrophy – 2 were in the HCM cohort and one underwent endomyocardial biopsy confirming HTN. Left ventricular mass index (LVMI) was significantly higher in GZH compared to HTN (p<0.0001) and in HCM compared to HTN (p=0.0004). EDWT was significantly greater in GZH compared to HTN (p<0.0001) and in HCM compared to HTN (p=0.0002). There was no significant difference in these parameters between GZH and HCM.

Table 1. P-values for CMR data in hypertensive (HTN), gray zone hypertensive (GZH) and hypertrophic cardiomyopathy (HCM) cohorts CMR Parameter HCM vs. HTN GZH vs. HTN GZH vs. HCM EDVI NS p=0.025 NS EDWT p=0.0002 p<0.0001 NS LVMI p=0.0004 p<0.0001 NS

Conclusion

This study reports a 4% prevalence of HCM among hypertensive patients - 20 x greater than in the general population - which would be left undiagnosed using echo alone. Screening hypertensive individuals with CMR is not routine but we advocate its use in these individuals especially in Afro Caribbeans and in those in the “grey zone”, to identify undiagnosed HCM, which has significant implications for lifestyle modification and family screening.

Acknowledgement/Funding

Cardiac Risk in the Young
P3840Impact of potent P2Y12 inhibitors in adverse events reduction in diabetic patients with Acute Coronary Syndromes. An analysis from ACHILLES Registry
Authors: Esteve Pastor M A , Ruiz-Nodar J M , Rivera-Caravaca J M , Orenes-Pinero E , Tello-Montoliu A , Veliz-Martinez A , Carrillo-Aleman L , Candela E , Sandin Rollan M , Lozano T , Macias-Villanego M J , Pernias-Escrig V , Nunez-Martinez L , Vicente-Ibarra N , Marin F
Published: October 2019

Background

Diabetic patients (DM) with an acute coronary syndrome (ACS) have a worse prognosis than non-diabetic patients. The new P2Y12 inhibitors, both ticagrelor and prasugrel, have shown efficacy in cardiovascular event reduction in patients with DM and ACS.

Purpose

The main objective of this study was to analyze the use of antiplatelet agents, prognosis and adverse events during the follow-up in diabetic patients admitted after an acute coronary syndrome.

Methods

These patients belong to ACHILLES registry. All patients with type 1 ACS were included prospectively in a national, prospective and multicenter registry. We analyzed baseline characteristics and comorbidities focusing on the presence of DM and the use of potent antiplatelet agents (ticagrelor and prasugrel) in those patients. After 1 year of follow-up, adverse events in diabetic patients were analyzed according to the type of antiplatelet used [clopidogrel vs new antiplatelet drugs (NAD)].

Results

Of 1,717 patients, 1,294 patients [mean age 65.0±13.3 years, 952 (73.6%) male] were finally analyzed (excluding patients discharged with oral anticoagulation). Diabetic patients had high prevalence of cardiovascular risk factors such as hypertension (54.9% vs 81.1%; p<0.001), dyslipidemia (50.7% vs 72.8%; p<0.001) or chronic kidney disease (22.1% vs 31.9%; p<0.001). Diabetic patients had also higher rate of non-invasive management of ACS compared to non-diabetic patients (4.5% vs 9.1%; p=0.002). At discharge, the use of NAD in patients with DM was 40.4% compared to 50.8% in non-diabetic patients (p<0.001).

After 1 year of follow-up, 64 (5.0%/year) patients had a new ACS, 46 (3.6%/year) patients died due to cardiovascular causes, 76 (6.1%/year) died for any cause and 28 (2.2%/year) patients had a major bleeding events. The use of clopidogrel in diabetic patients was associated with an increase in all-cause mortality [HR 2.90; 95% CI (1.27–6.629), p=0.011] and in MACE [HR 2.14; 95% CI (1.22–3.77), p=0.008.] Diabetic patients treated with NAD had no differences in terms of major bleeding but those patients presented a significant reduction in cardiovascular mortality and MACE with NAD use.

Event Free Survival according NAD Use

Conclusions

Patients with DM and ACS had high prevalence of concomitant cardiovascular risk factors but lower use of NAD compared with non-diabetic patients, despite DM patients had greater baseline risk. The use of NAD therapy was associated with a significant reduction in all-cause mortality, cardiovascular mortality and MACE without differences in major bleeding events.
P3843Ischemic-bleeding balance according to history of prior bleeding in patients with acute coronary syndrome during treatment with dual antiplatelet therapy
Authors: Dominguez Erquicia P , Raposeiras Roubin S , Abu-Assi E , D'Ascenzo F , Manzano Fernandez S , Saucedo J , Simao Henriques J P , Ariza Sole A , Cespon Fernandez M , Munoz Pousa I , Caneiro Queija B , Cobas Paz R J , Dominguez Rodriguez L M , Iniguez Romo A
Published: October 2019

Introduction

ESC guidelines recommend short-term dual antiplatelet therapy (DAPT) in patients with high bleeding risk. In this sense, patients with prior admissions by bleeding are considered of high-risk of bleeding. With our study, we aimed to show the ischemic-bleeding profile of patients with prior bleeding in comparison with those without prior bleeding during treatment with DAPT.

Methods

The data analyzed in this study were obtained from the fusion of 3 clinical registries of ACS patients: BleeMACS (2004–2013), CardioCHUVI/ARRITXACA (2010–2016) and RENAMI (2013–2016). All 3 registries include consecutive patients discharged after an ACS with DAPT and undergoing PCI. The merged data set contain 26,076 patients. A propensity-matched analysis was performed to match the baseline characteristics of patients with and without prior admission by bleeding. The impact of prior prior bleeding in the ischemic and bleeding risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For ischemic risk we have considered a new acute myocardial infarction, whereas for bleeding risk we have considered major bleeding defined as bleeding requiring hospital admission. Follow-up time was censored by DAPT suspension/withdrawal.

Results

From the 26,076 ACS patients, 1,105 have PAD (4.2%). During a mean follow-up of 12.2±4.8 months, 964 patients died (3.7%), 640 had myocardial infarction (2.5%) and 685 had major bleeding (2.6%). After propensity-score matching, we obtained two matched groups of 1,101 patients. In comparison with patients without prior bleeding, those with prior bleeding had higher risk of major bleeding (sHR 2.03, 95% CI 1.33–3.11, p=0.001) with similar risk of myocardial infarction (sHR 0.98, 95% CI 0.61–1.59, p=0.945), in comparison with those without PAD. The cumulative incidence of myocardial infarction was 31 and 32 per 1,000 patients/year in patients with and without prior bleeding, respectively. The cumulative incidence of major bleeding was 63 and 29 per 1,000 patients/year in patients with and without prior bleeding, respectively. The difference between myocardial infarction rate and major bleeding rate was −32 and +3 per 1,000 patient-years in patients with and without prior bleeding (Figure).

Conclusions

Patients with ACS and prior history of bleeding have a significant increment of bleeding risk during treatment with DAPT. In these patients, short-term DAPT (6 months) should be recommended.
P3852Twenty-eight-year temporal trends of treatment strategy and short-term outcomes in patients with high-risk pulmonary embolism: impact of ESC guidelines changes
Authors: Hosokawa Y , Yamamoyo T , Tanida A , Matsuda J , Sangen H , Nakata J , Tara S , Shimizu W
Published: October 2019

Background

Thrombolysis has been recommended for high-risk pulmonary embolism (PE) in ESC guidelines, used as a reference in Japan. Recently, indication of thrombolysis for acute PE has been limited with recent guideline revision. Little is known regarding trends of treatment strategy and mortality in high-risk PE patients.

Purpose

To clarify temporal trends of treatment strategy and short-term outcomes in high-risk PE patients.

Methods

A retrospective analysis of therapeutic interventions and short-term outcomes was performed for 52 consecutive high-risk PE patients including cardiac arrest. According to timing of ESC guidelines update (2000, 2008 and 2014), patients were divided into four time periods: 1992 to 2000, 2001 to 2008, 2009 to 2014, and 2015 to 2018.

Results

Mean age and proportion of male were not different over the period. Nosocomial case decreased from 100% to 25% (p<0.01). Postoperative cases (relative contraindication for thrombolysis) included 43% of all patients. Cardiac arrest and VA-ECMO use were 42% and 21% of all patients. Any thrombolytic therapy including catheter-directed intervention showed a non-significant decrease trend (92%-87%-71%-44%, p=0.067). Temporary or retrieval IVC filter insertion showed a significant downward trend (36%-80%-54%-22%, p=0.025). The entire study 30-day mortality was 23%. There was no significant difference in 30-day mortality over the periods (14%-27%-14%-44%, p=0.303). However, major bleeding decreased significantly (71%-40%-7%-22%, p=0.004) (Table).

Table 1 1992–2000 (n=14) 2001–2008 (n=15) 2009–2014 (n=14) 2015–2018 (n=9) p Age (years) 54±12 59±17 64±13 65±16 0.224 Male 29% 13% 29% 44% 0.269 Any thrombolytic therapy 92% 87% 71% 44% 0.067 Catheter-directed therapy 86% 87% 71% 0% <0.01   with thrombolytics (92%) (83%) (90%)   without thromboloytics (8%) (17%) (10%) Only intravenous thrombolysis 8% 7% 7% 44% 0.038 Temporary/retrieval IVC filter 36% 80% 54% 22% 0.025 ICU stay (days) 15±14 10±18 5±4 8±8 0.206 30-day mortality 14% 27% 14% 44% 0.303 Major bleeding 71% 40% 7% 22% 0.004

Conclusion

The temporal analysis identified a decreased trend in any thrombolytic therapy and IVC filter insertion in high-risk PE. The study also found a decreasing trend in major bleeding.
P3853Mortality of surgical redo aortic valve replacement versus transcatheter aortic valve-in-valve implantation in patients with degenerated aortic bioprosthesis: a meta-analysis
Authors: Sanchez Recalde A , Pardo A , Salido Tahoces L , Mestre J L , Hernandez Antolin R , Sanmartin M , Zamorano J L
Published: October 2019

Background

Transcatheter valve-in-valve (tVIV) implantation for degenerated aortic bioprosthesis has become an alternative to surgical aortic valve replacement (sAVR) in the past few years. However, some concerns have been raised regarding to the long-term safety and efficacy of tVIV. The objective was to compare the clinical and echocardiographic outcomes of tVIV implantation with redo cAVR.

Methods

After an extensive search of PubMed we included 7 observational studies (3 used propensity score matching) comparing tVIV versus sAVR in 762 patients The primary endpoint was all-cause mortality determined from the longest available survival data. Other outcomes of interest were stroke, permanent pacemaker implantation, paravalvular leak, hospital stay and postoperative aortic valve gradient. The review was conducted according to the MOOSE recomendations. Der Simonian and Laird random effects model was used to estimate summary measures and their 95% CI.

Results

Patients in the tVIV group were significantly older (78 vs 73 y.o.) and had a higher baseline risk compared to those in the re-sAVR group (Euroscore 19.7 vs 14.3). There was no statistical difference in procedural or 30-day mortality 5.4% vs 5.3% in tVIV and sAVR, respectively (RR 0.98, 95% CI 0.54–1.80; p=0.96], and long-term mortality (from 6 month to 5 years) 18.7% versus 16.5% (RR 1.13, 95% CI 0.80–1.60; P=0.50). The risk of stroke was similar (1.5% in tVIV vs 2.4% in sAVR, p=0.47). tVIV was associated with a significantly lower rate of permanent pacemaker implantations 6.9% vs 12.1% (RR 0.58, 95% CI 0.36–0.94; P=0.03) and shorter hospital length stay (7 days vs 12 days, p=0.02). However, echocardiographic postoperative aortic valve gradients were lower in sAVR group than in tVIV (RR 1.83, 95% CI 0.75–2.91, p<0.001).

30-day and long-term mortality

Conclusion

This meta-analysis suggests that patients with aortic degenerated bioprosthesis treated with tVIV have similar 30-day and long-term mortality with lower need of permanent pacemaker and length stay than sAVR. Thus tVIV is a valid alternative to standard surgical treatment.
P4129cMR-Pulmonary transit time and pulmonary blood volume have an additional prognostic value over cMR-right ventricular ejection fraction in predicting mortality in HF-rEF patients
Authors: Houard L , Langet H , Militaru S , Rousseau M F , Pouleur A C , Gerber B L
Published: October 2019

Background

Assessment of congestion and cardiac function has been shown to have both therapeutic and prognostic implication for the management of patient with CHF. Pulmonary transit time (PTT) assessed by cMR is a novel parameter, which reflects not only hemodynamic congestion but also LV and RV function.

Purpose

We sought to explore the prognostic value of the pulmonary transit time assessed in seconds (PTT) and in beats (PTB) and the pulmonary blood volume indexed (PBVi) above conventional well-known risk factors including cMR-RVEF and estimated pulmonary artery pressure (eSPAP) in predicting outcomes. PBVi is defined by the product of PTB and the stroke volume indexed to body surface area.

Methods

401 patients in sinus rhythm with a LVEF <35% (age 61±13 years; 25% female) underwent a cMR and an echocardiography. Patients were followed for a primary endpoint of overall mortality.

Results

Average cMR-LVEF was 23±7%, cMR-RVEF was 43±15%, average estimated systolic pulmonary pressure (eSPAP) was 33±12mmH, average PTT was 11±6s, PTB 8.9±5.6 bpm and average PBVi 305.5±254.9ml/m2. After a median follow-up of 6 years, 182 reached the primary endpoint. In univariate cox regression, age, ischemic cardiomyopathy, hypertension, diabetes, NYHA class III-IV, eSPAP >40mmHg, E/A ratio, e/e'ratio, cMR-RVEF, LV scar, PTT, PTB, PBVi, GFR, beta blockers and diuretics were associated with overall mortality. For the multivariate analysis, a baseline model was created where age, ischemic etiology, NYHA functional class III-IV, eSPAP >40 mmHg, beta-blockers and cMR-RVEF were found to be significantly and independently associated with the primary endpoint. PTT (X2 to improve = 5.3, HR: 1.03; 95% CI: [1.01; 1.06]; P=0.015), PTB (X2 to improve = 11.8, HR: 1.06; 95% CI: [1.03; 1.09]; P<0.001) and PBVi (X2 to improve = 7.7, HR: 1.08; 95% CI: [1.03; 1.14]; P=0.002) showed a significantly additional prognostic value over the baseline model (p<0.001).

Conclusion

Pulmonary transit time and pulmonary blood volume provide higher prognostic information over well-known risk factors including cMR-RVEF and eSPAP with high power to stratify prognosis in HF-rEF and might be promising tools to identify patients at higher risk among HF patients.

Acknowledgement/Funding

Fond National de recherche scientifique (FNRS)