bluuebunny/crossref_metadata_2025 huggingface dataset:
P5697J-wave elevation in the inferior leads is a predictor of lethal ventricular arrhythmia initiated by premature ventricular contractions with right bundle branch block and superior axis
Authors: Munetsugu Y , Kawamura M , Ogawa K , Ochi A , Onishi Y , Ito H , Onuki T , Kobayashi Y , Shinke T
Published: October 2019

Background

Lethal-ventricular-arrhythmia (VA) could be sometimes initiated by idiopathic Premature Ventricular Contractions (PVCs) originated form inferior wall. Furthermore, J-wave elevation in inferior leads was sometimes associated with lethal-VA. However, it was unclear the relationship between these PVCs and J-wave elevation in patients with lethal-VA.

Purpose

The aim of this study was to investigate the relationship between PVCs and J-wave elevation.

Methods and results

We studied 32 patients who underwent radiofrequency (RF) ablation of idiopathic PVCs with RBBB and superior axis. These PVCs were originating from inferior wall of left ventricular. Lethal-VA was defined as ventricular fibrillation (VF) or ventricular tachycardia (VT) with loss of consciousness (LOC). Among 32 patients, 3 had VF and 2 had VT with LOC. Other 27 had non-lethal-VA. Baseline clinical characteristics were not significantly difference between lethal and non-lethal-VA. The ratio of J-wave elevation in lethal-VA was significant higher as compared to those with non-lethal-VA (5/5 (100%) vs. 3/27 (11.1%), p<0.0001). Furthermore, no patients had recurrence of lethal-VA with J wave elevation in inferior leads after RF ablation of these PVCs with RBBB and superior axis,

Conclusions

We speculated that J-wave elevation in inferior leads might be a predictor of lethal-VA initiated by PVCs with RBBB and superior axis. RF ablation of these PVCs were useful method of treating lethal-VA.

Acknowledgement/Funding

None
P5718Effects of the fluoroquinolones moxifloxacin and levofloxacin on the QT subintervals: sex differences in ventricular repolarization
Authors: Taubel J , Prasad K , Rosano G , Van Langenhoven L , Fernandes S , Sugiyama A
Published: October 2019

Background

The effects of medicines affecting cardiac repolarization can be further evaluated by assessing the balance of inward and outward currents. These can be detected in the ECG by analysing the QT subintervals. Pure hERG potassium channel block was shown to prolong both early repolarization (J-Tpeak) and late repolarization (Tpeak-Tend), whereas multichannel blockers may shorten or have no effect on J-Tpeak.

The gender dependency of ventricular repolarization is also well known. Recently, Matsukura indicated that moxifloxacin significantly increased J-Tpeak and Tpeak-Tend and females in their study were more sensitive than males to the drug-induced J-Tpeak prolongation and QTcF.

Purpose

The purpose of the present study is to use data from two Thorough QT (TQT) studies to characterize the differences in depolarization (QRS), early repolarization (J-Tpeak), and late repolarization (Tpeak-Tend) between moxifloxacin and levofloxacin and further define the sex differences in QTc and subintervals.

Methods

Data from two TQT studies were used to further investigate the impact of moxifloxacin (400 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using validated algorithms for measurement of QRS, J-Tpeak and Tpeak–Tend intervals. Concentration-effect analyses were performed to establish a potential relationship between the ECG effects and the concentrations of the two fluoroquinolones as typically males and females also show differences in plasma concentrations due to differences in body weight.

Results

The relationships between moxifloxacin and levofloxacin plasma concentrations and their respective predicted ΔΔQTcF, ΔΔQRS, ΔΔJ-Tpeakc and ΔΔTpeak-Tend values are shown in Fig 1.

The plasma concentrations were higher for females than males in both drugs.

Moxifloxacin was shown to be a more potent prolonger of QTcF and had a pronounced effect on J-Tpeakc, consistent with its effects on both IKr and IKs channels while levofloxacin had little effect on J-Tpeakc. For moxifloxacin, the concentration-effect modelling showed a greater effect for females on QTcF and J-Tpeakc while for levofloxacin the inverse was true. Based on the assumption that repolarization reserve of females relies to a greater extent on IKs channels it would be reasonable to assume that they are more affected by a medicine that blocks IKs in addition to IKr.

Figure 1

Conclusions

This study showed that levofloxacin elicited a smaller ΔΔQTcF and ΔΔJ-Tpeakc prolongation when compared to moxifloxacin. The results of this study also showed a different pattern of sex difference in repolarization after administration of both drugs. which may suggest a difference in expression of IKs and possibly IKr channels.
P5728Association of systolic blood pressure and cardiovascular outcomes at different age groups in the healthy general population: a nationwide prospective cohort study
Authors: Jung M H , Ihm S H , An S J , Yi S W
Published: October 2019

Background

Uncertainties remain regarding the effect of blood pressure on various cardiovascular outcomes in different age groups.

Purpose

We aimed to identify 1) whether a systolic blood pressure (SBP) of 130–139 mm Hg elevates cardiovascular disease (CVD) mortality and 2) whether SBP shows a linear association with cause-specific CVD mortality in all age groups among individuals without known hypertension and CVD.

Methods

We used the Korean National Health Insurance sample data (n=429,220). Participants were categorized into three groups by age (40–59, 60–69, and 70–80 years).

Results

A positive and graded association was generally observed between SBP and overall and cause-specific CVD mortality regardless of age, except for ischemic heart disease (IHD) mortality in those aged 70–80 years. Among those aged 70–80, the hazard ratios (HRs) (95% CIs) for overall CVD mortality were 1.08 (0.92–1.28), 1.14 (0.97–1.34), and 1.34 (1.14–1.58) for SBP values of 120–129, 130–139, and 140–149 mm Hg, respectively, compared to SBP <120 mm Hg. For total stroke mortality, the corresponding HRs were 1.29 (1.02–1.64), 1.37 (1.09–1.72), and 1.52 (1.20–1.93), while for IHD mortality, the corresponding HRs were 0.90 (0.64–1.26), 0.86 (0.62–1.19), and 1.29 (0.93–1.78). Nonlinear associations were significant for IHD (Fig 1).

Figure 1

Conclusion

In the elderly Korean population, SBPs of 130–139 mm Hg elevated total stroke mortality, but not IHD mortality, compared to normal BP, and a linear association was not observed for IHD mortality in the range <140 mm Hg. Regarding an appropriate diagnostic cutoff for hypertension, an individualized approach considering each person's organ susceptibility is needed for the elderly population.

Acknowledgement/Funding

None
P5730Do hypertensive women with coronary artery disease benefit from lowering systolic blood pressure under 130 mmHg? Long-term mortality in the INternational VErapamil SR-trandolapril STudy (INVEST)
Authors: Sava R I , Chen Y , Taha Y K , Gong Y , Smith S M , Cooper-Dehoff R , Keeley E C , Pepine C J , Handberg E M
Published: October 2019

Background

Hypertension (HTN) and coronary artery disease (CAD) are a prevalent combination in women, however limited data are available to guide blood pressure (BP) management. We hypothesize older women with HTN and CAD may not derive the same prognostic benefit from systolic BP (SBP) lowering <130 mmHg.

Purpose

To investigate the long-term mortality implications of different achieved SBP levels in hypertensive women with CAD.

Methods

Long-term, all-cause mortality data were analyzed for 9216 women, stratified by risk attributable to clinical severity of CAD (women with prior myocardial infarction or revascularization considered at high, all others at low risk) and by age (50 - <65 or ≥65 yo). The prognostic impact of achieving mean in-trial SBP <130 (referent group) was compared with 130 to <140 and ≥140 mmHg using Cox proportional hazards, adjusting for demographic and clinical characteristics.

Results

During 108,838 person-years of follow-up, 2945 deaths occurred. High risk women (n=3011) had increased long-term mortality in comparison to low risk women (n=6205) (adjusted HR 1.38, CI 1.28–1.5, p<0.001). Within risk groups, crude mortality percentages decreased according to BP values (table). As expected, high risk women were more likely to be ≥65 yo (68.68% vs. 50.51%, p<0.0001) or have SBP ≥140 mmHg (43.08% vs. 31.18%, p<0.0001). In adjusted analyses, an SBP ≥140 mmHg was associated with worse outcomes than SBP <130 mmHg in the entire cohort (HR 1.3, CI 1.2–1.5, p<0.0001) and when stratifying by risk (low risk group, HR = 1.47, CI 1.28–1.7, p<0.0001; high risk group, HR = 1.71, CI 1.01–1.35, p=0.03). In analyses stratified by age and risk, women ≥65 years and at high risk had decreased mortality in the 130 - <140 SBP category vs. <130 mmHg (HR 0.812, 95% CI 0.689–0.957, p=0.0133; figure).

Women and deaths by risk and SBP group Group SBP category Women (n) Mortality (n) Mortality (%) High risk <130 773 338 44 130–<140 941 414 44 ≥140 1297 694 54 Low risk <130 2187 390 18 130–<140 2083 451 22 ≥140 1935 658 34 SBP = systolic blood pressure; n = number; % = percent per each group.

Mortality adjusted HRs

Conclusion

In women ≥65 yo with hypertension and prior myocardial infarction and/or coronary revascularization enrolled in INVEST, a SBP between 130 to <140 mmHg was associated with lower all-cause, long-term mortality versus SBP <130 mmHg.

Acknowledgement/Funding

The main INVEST (International Verapamil [SR]/Trandolapril Study) was funded by grants from BASF Pharma, Ludwigshafen, Germany; Abbott Laboratories, A
P5733IABP use in patients with STEMI complicated by cardiogenic shock: time for rehabilitation?
Authors: Somaschini A , Cornara S , Demarchi A , Mandurino Mirizzi A , Puccio S , Galazzi M , Camporotondo R , Crmi M , Ferlini M , Gnecchi M , Oltrona Visconti L , De Servi S , De Ferrari G M
Published: October 2019

Background

Evidence from a large randomized clinical trial has led international guidelines to downgrade to Class III the recommendation level for the routine use of intra-aortic balloon pump (IABP) in patients with STEMI complicated by cardiogenic shock (CS). Despite this, its use in clinical practice remains high.

Purpose

The aim of our study was to evaluate whether IABP use could provide a prognostic benefit in a large real-world population of STEMI patients undergoing primary PCI (pPCI).

Methods

Our registry included 2958 consecutive patients undergoing primary pPCI for STEMI in our department from 2005 to 2017. The presence of a persistent (>30 min) systolic blood pressure <90 mmHg and signs of pulmonary congestion or impaired end organ perfusion needing catecholamine infusion qualified for CS. Among patients with CS we compared mortality between those with and those without IABP in the whole population and in the pre-specified subgroup with anterior STEMI. Univariate (cross-tables and Kaplan-Meier curves with log-rank test) and multivariate mortality analysis (Cox regressions) were performed.

Results

CS occurred in 246 patients (8.3%); among these patients, 145 (60%) had anterior AMI. Mortality at 30 days was 3.7 in inferior vs 7.1% in anterior STEMI (p<0.001). In these two groups of patients, IABP was used in 32% and 66.7% of cases, respectively. In the whole CS group, IABP use was associated with a lower 30-day mortality (39% vs 53%, p=0.020 – see figure panel A); this figure was confirmed at multivariable analysis (HR 0.49, 95% CI 0.27–0.87, p=0.016) after adjusting for age, CK peak, triple-vessel disease, eGFR and all-TIMI bleeding during hospital stay. IABP use in CS patients was not associated with major complications or an increased rate of Hb drop (>3 mg/dL) during hospital stay. In the subgroup of patients with anterior STEMI, there was a marked survival benefit at univariate analysis (30-day mortality 41% vs 61%, p=0.013 – see figure panel B), confirmed at multivariable analysis (HR 0.40, 95% CI 0.19–0.88, p=0.023) after adjusting for the same variables of the previous model. In the subgroup of patients with inferior STEMI, IABP use was not significantly associated with a lower 30-day mortality (32% vs 41%, p=0.380).

Figure 1

Conclusion

In the present large real-world cohort of unselected patients with STEMI, the use of IABP in case of CS was found to improve survival. This finding suggests that IABP could still play a role in patient with STEMI complicated by CS, especially when additional risk features are present, such as anterior MI. We suggest that additional careful prospective studies are needed before abandoning or markedly limiting the use of IABP in this clinical setting.
P5736Mortality in infarct-related cardiogenic shock patients treated with an microaxial pump: influence of timing and predicted risk
Authors: Schaefer A , Werner N , Westenfeld R , Moller J E
Published: October 2019

Background

In-hospital mortality in acute myocardial infarction-related cardiogenic shock (AMI-CS) remains high at ∼40%. No prospective trials have been finished investigating the influence of mechanical support in AMI-CS. We compared observed to individually predicted mortality using CardShock-, Shock II-, and SAVE-scores in AMI-CS patients treated between 2013 and 2017 with an Impella microaxial pump, who met the IABP-Shock II-trials inclusion/exclusion criteria in order to determine whether standardised use of an Impella microaxial flow-pump in AMI-CS is associated with lower than predicted mortality rates and whether timing of implantation or selecting patients based on predicted risk is meaningful.

Methods

We analyzed data from 166 consecutive AMI-CS patients meeting the inclusion/exclusion criteria of the IABP-Shock II-trial (age 65±12 years), who received an Impella microaxial pump and compared observed vs. individually predicted mortality using CardShock-, Shock II-, and SAVE-scores. 39% (n=65) had been resuscitated before Impella implantation.

Results

Overall 30-day mortality was 43%. Mortality was higher in resuscitated patients (50% vs. 36%, p=0.0324) and when Impella was implanted post-PCI (Impella-pre-PCI: 29%, Impella-post-PCI: 50%, p=0.0130). In all score systems predicted mortality was significantly higher than observed mortality on Impella support for individuals with highest predicted risk (IABP-Shock II predicted 77% vs observed 44%, p=0.010; CardShock predicted 77% vs observed 51%, p=0.017; SAVE predicted 81% vs observed 56%, p<0.001).

Conclusion

In the absence of prospective trials, our retrospective analysis encourages the use of active mechanical circulatory support by Impella microaxial pumps in high-risk patients with AMI-CS and supports the concept of early implantation prior to PCI.
P5742Prognostic model of the development of the first atherothrombotic stroke
Authors: Shishkova V , Stakhovskaya L , Adasheva T V , Remennic A , Valyaeva V
Published: October 2019

Aim

The study of the relationship between various parameters: clinical-anthropometric, biochemical, metabolic, vascular-inflammatory, molecular-genetic and the development of the first ischemic stroke, and the development of a prognostic model for determining the probability of its occurrence.

Material and methods

196 patients who underwent the first ischemic stroke and 119 people who did not suffer a stroke, corresponding to age, place of residence and nationality to a group of patients, were examined. The main anthropometric, clinical, biochemical and metabolic parameters were assessed; markers of vascular inflammation and endothelial dysfunction. Genotyping of single nucleotide polymorphisms of genes: IL8, ADIPOQ, ADIROR, APOB, APOC-IV, BDNF, GRM3 using ready-made TaqMan probes was carried out.

Results

Based on the results of the correlation analysis, the following parameters were statistically significant with the first ischemic stroke: weight, BMI, WC, homocysteine, insulin, adiponectin, cystatin C, ApoA1, Apo B, OHL, XC-HDL, LDL, TG, CRB-sh, glucose, uric acid, IL-1b, IL-4, IL-6, IL-8, TNF-a, VEGF-A. The binary logistic regression method was used to construct the forecast model. The final independent model includes the following independent variables: weight, diabetes, adiponectin, Apo A1, IL-1b, IL-4, ADIPOQ (rs17366743), GRM3 (rs2228595), R2 value of Nagelkerk was 0.839. The percentage of agreement between the model and the “training sample” was 90.7%. The percentage of consent of the model with the “independent sample” was 87.1%, the overall percentage of the model's agreement for all patients was 89.8%. In accordance with the received data, the ROC-curve (Receiver Operating Characteristic) was constructed, the area under the ROC-curve was 0.92.

Conclusion

Based on the data obtained in this study, a probability model for the development of the first ischemic stroke was obtained. Of all the parameters studied in the study, the largest contribution to the probability of development of the first ischemic stroke, according to the model obtained, is made by the parameters: diabetes, adiponectin, Apo A1, IL-4.

Acknowledgement/Funding

None
P5743Overweight and obesity in adolescent men in Sweden and risk of early stroke
Authors: Rosengren A , Robertson J , Schaufelberger M , Aberg D , Schioler L , Aberg M
Published: October 2019

Background

Increasing numbers of stroke cases in the young are reported in many countries, potentially at least partly due to rising rates of overweight and obesity. Most data on the effect of obesity on stroke is derived from middle aged populations; there is a comparative lack of information on the effect of excessive body weight in young people.

Purpose

We aimed to determine whether body mass index (BMI) at age 18 predicted early stroke events among men in Sweden.

Methods

Population-based Swedish cohort study of conscripts (n=1,668,921; mean age at baseline, 18.3 years) who enlisted during 1968–2005. Follow-up was done through linkage to the nationwide Swedish patient and death registries. Risk of a first hospitalization for stroke (any type) during follow-up (5–46 years) was calculated with Cox proportional hazards models. Objective baseline measures of fitness and cognition were included in the models in a second set of analyses.

Results

During follow-up there were 12,512 first hospitalizations for stroke (mean age at diagnosis, 48.5 (SD 9.4) years, maximum 64 years). Compared with men with BMI of 18.5 to 20.0 kg/m2, men with BMI 20 to <22.5 and 22.5 to <25.0 kg/m2 had hazard ratios (HR) of 1.06 (1.00–1.12) and 1.23 (1.14–1.31), respectively, for hospitalization for stroke, after adjustment for age, year of conscription, comorbidities at baseline, parental education, blood pressure, IQ, muscle strength, and fitness. Those with a BMI of ≥35 kg/m2 had an HR of 3.33 (2.46–4.51) for an event before the age of 65, compared to slim men. The multiple-adjusted risk per 1-unit increase in BMI was 1.07 (95% CI, 1.06–1.08).

Conclusion

We found a rise in risk of early hospitalisation for stroke detectable already at normal levels of body weight at age 18, and rising to more than 3-fold in the highest weight category. Given increasing levels of body weight, and prevalence of overweight, obesity, and severe obesity in young adults, the increased incidence of stroke in the young may potentially partly be explained by rising body weight, with an obvious potential for prevention.
P5744Sleep-disordered breathing assessed by holter-monitoring is associated to worsened one-year clinical outcomes in ischemic stroke patients: a cardiopulmonary coupling analysis
Authors: Kang D O , Kim C K , Park Y , Jang W Y , Kim W , Choi J Y , Choi C U , Na J O
Published: October 2019

Background

Sleep-disorder breathing (SDB) using polysomnography is closely associated to poor functional and clinical outcomes in ischemic stroke patients. The cardiopulmonary coupling analysis using Holter-monitoring (CPC-Holter analysis) is an emerging feasible modality to investigate SDB.

Purpose

We investigated the association between SDB defined by CPC-Holter analysis and one-year clinical outcome in patients with acute ischemic stroke.

Methods

Total 666 patients with acute ischemic stroke who underwent Holter-monitoring were enrolled. The CPC-Holter analysis was conducted and SDB was defined as the presence of narrow-band (NB) coupling during sleep time. Primary outcome was recurrent ischemic stroke, and secondary outcome was major adverse cerebrovascular event (MACE), a composite of recurrent ischemic stroke, transient ischemic attack, and all-cause mortality within one year since discharge.

Result

The NB coupling was present in 205 (30.8%) of 666 patients with mean age of 64.1±12.8 years. The NB group showed significantly higher incidence of both recurrent ischemic stroke (8.3% vs. 1.4%, p<0.001) and MACE (14.9% vs. 3.0%, p<0.001) within one-year. In multivariate analysis, presence of NB coupling remained as an independent predictor of both recurrent ischemic stroke and MACE (HR: 4.81; 95% CI: 1.73–13.4; p=0.003; and HR 4.17; 95% CI: 1.74–10.0; p<0.001, respectively). The results were consistent after propensity-score matched analysis with 164 patient pairs (C-statistics=0.757).

One-year clinical outcomes Overall population (n=666) PSM population (n=328) no NB (=461) NB (n=205) Log-rank p-value OR (95% CI) no NB (n=164) NB (n=164) Log-rank p-value OR (95% CI) Recurrent ischemic stroke 6 (1.4) 14 (8.3) <0.001 5.73 (2.20–14.9) 3 (2.0) 11 (8.1) 0.026 3.85 (1.07–13.8) Transient ischemic attack 3 (0.7) 3 (1.7) 0.275 2 (1.3) 3 (2.1) 0.633 Hemorrhagic stroke 0 (0.0) 2 (1.2) 0.027 0 (0.0) 2 (1.5) 0.148 Total death 3 (0.7) 9 (4.8) 0.001 2 (1.3) 3 (1.9) 0.641 MACEs 12 (3.0) 25 (14.9) <0.001 4.63 (2.06–10.4) 7 (5.2) 17 (13.1) 0.030 2.95 (1.06–8.21) Data are expressed as n (%). CI = confidence interval; MACE = major adverse cardiovascular event; NB = narrow-band; OR = odds ratio.

One-year clinical outcomes

Conclusion

SDB assessed by CPC-Holter analysis at early phase of ischemic stroke is a powerful prognostic marker for predicting one-year adverse clinical outcomes. The CPC analysis using Holter-monitoring is a useful modality and could be easily applied to predict clinical outcomes in acute ischemic stroke patients.
P5752Which is the best stenting technique for coronary bifurcation lesions? Evidence from a network meta-analysis of randomized clinical trials
Authors: Chiabrando J , Lombardi M , Vescovo G M , Biondi Zoccai G , Abbate A , Wohlford G , Berrocal D H , Guzman L
Published: October 2019

Background

Bifurcation lesions represent 20% of all coronary lesions treated by percutaneous coronary interventions (PCI). Although provisional technique with 1 stent in the main branch and balloon angioplasty of the side branch is considered the standard approach, the implantation of 2 stents is often being pursued with a wide variety of bifurcation stenting techniques. We thus conducted a systematic review and network meta-analysis of randomized clinical trials (RCTs) to compare clinical cardiovascular outcomes involving stenting techniques in coronary bifurcation lesions.

Methods

We searched on Pubmed, Google Scholar, Embase and Cochrane Library, up to October 2018 for published and unpublished RCTs that compared clinical cardiovascular outcomes in patients with bifurcation lesions treated with 7different techniques (crush [Cr]; culotte [Cu]; double kissing crush [DKCr], mini-crush [mCr], routine T-stenting [RTS], T-stenting and small protrusion [TAP], and provisional (1 stent technique)). We performed a frequentist fixed-effect network meta-analysis to estimate relative risks (RR) of major adverse cardiovascular events (“MACE”, typically defined as death, myocardial infarction and target vessel revascularization), target vessel revascularization (TVR), target lesion revascularization (TLR), and stent thrombosis (ST).

Results

We identified 14 studies, yielding data on 4285 patients. DKCr and mCr yielded significant reductions in MACE, TVR, and TLR when compared with the 1-stent technique (RR 0.31–0.55 [all P<0.01] and RR 0.42–0.45 [all P<0.02], respectively) and with the rest of the bifurcation techniques (RR 0.44–0.55 [all P<0.05] for DKCr and RR 0.37–0.45 [all P<0.05] for mCr). On the other hand, Cu and Cr were associated with an increased risk for ST compared to 1-stent technique (RR 3.25–4.27 [both P<0.05]) and to DKCr (RR 3.02–3.99 [both P<0.05]). We found no heterogeneity nor inconsistency between studies.

Conclusions

The various PCI bifurcation stenting techniques are associated with different cardiovascular outcomes, with double kissing crush and mini crush being more effective than others, including the 1-stent approach, whereas culotte and crush are associated with increased risk of stent thrombosis.

Acknowledgement/Funding

None
P5973Regional left ventricular myocardial work and response to cardiac resynchronization therapy
Authors: Kostyukevich M V , Van Der Bijl P , Vo N M , Ajmone Marsan N , Delgado V , Bax J J
Published: October 2019

Background

Myocardial work, assessed by speckle tracking echocardiography, reflects mechanical efficiency of the left ventricle. In heart failure patients, characterization of acute changes in regional (septal and lateral) left ventricular (LV) myocardial walls after cardiac resynchronization therapy (CRT) may enhance understanding of CRT response.

Objective

To evaluate the interaction between CRT response and components of myocardial work of the lateral wall and septum in patients with heart failure.

Methods

Regional LV myocardial work was calculated by integrating non-invasive blood pressure measurements, timing of mitral and aortic valve opening and closure and speckle tracking-derived LV longitudinal strain. From pressure-strain loops, constructive work (CW) and wasted work (WW) were calculated. CRT response was defined as a decrease in LV end-systolic volume ≥15% at 6 months follow-up. Changes in CW and WW of the septal and lateral walls prior to (baseline) and within the first 5 days after CRT implantation were compared between CRT responders and non-responders.

Results

At baseline, measurement of regional CW and WW was performed in 168 patients treated with CRT (71% men, 66±10 years). At 6 months, 59% of patients were CRT responders. CRT responders more frequently had non-ischemic heart failure than non-responders (54% vs 36%; p=0.027). At baseline, CRT responders were characterized by a significantly higher septal WW (270.5 [160.0; 451.5] mmHg% vs. 210.5 [106.3; 336.5] mmHg%; p=0.038) and lateral CW (989.5 [574.0; 1439.0] mmHg% vs. 689.0 [463,3; 1140.0] mmHg%; p=0.005). On multivariable analysis, only CW of the lateral wall at baseline was independently associated with CRT response (HR 1.001; 95% CI, 1.000–1.001; p=0.048).

Immediately after CRT implantation, measurement of regional CW and WW was feasible in 115 patients. CRT responders showed improvement in CW (433.0 [254.5; 686.5] mmHg% to 664.5 [424.5; 977.8] mmHg%; p<0.001) and WW (305.0 [169.0; 461.3] mmHg% to 145.0 [80.0; 306.3] mmHg%; p=0.005) of the septum whereas the lateral wall demonstrated a significant decrease in CW (1036.5 [561.0; 1402.0] to 818.0 [491.0; 1154.3] mmHg%; p=0.005) and increase in WW (132.5 [80.3; 269.3] to 198.5 [107.5; 331.0] mmHg%; p=0.025). Non-responders showed only a decrease in WW of the septum (202.8 [102.9; 332.5] to 168.5 [67.6; 258.4] mmHg%; p=0.049).

Conclusion

CRT responders are characterized by increased WW of the septum and CW of the lateral wall at baseline, which are corrected immediately after CRT implantation. Constructive work of the LV lateral wall at baseline is independently associated with CRT response.

Acknowledgement/Funding

Study was supported by ESC Research grant 2018
P5976Prediction of ventricular arrhythmias with mechanical dispersion assessed by strain echocardiography: a systematic review and meta-analysis
Authors: Kawakami H , Nerlekar N , Haugaa K H , Edvardsen T , Marwick T H
Published: October 2019

Background

Recent studies have demonstrated that left ventricular mechanical dispersion (LVMD) assessed by speckle tracking might be a powerful marker in risk stratification for ventricular arrhythmias (VA). We sought to perform a systematic review and meta-analysis to i) assess the prognostic value of this parameter (previous studies were predominantly single-center), ii) define the value relative to other parameters, iii) identify the most appropriate cutoff for designating risk.

Purpose

To assess the association between LVMD and the incidence of VA.

Methods

A systemic review of studies reporting the predictive value of LVMD for VA was undertaken from a search of Medline and Embase. LVMD was defined as the standard deviation of time from Q/R on ECG to peak negative strain from each LV segment. VA events were defined as sudden cardiac death, cardiac arrest, documented ventricular tachyarrhythmia, and appropriate implantable cardioverter defibrillator therapy. Hazard ratios (HRs) were extracted from univariable and multivariable models reporting on the association of LVMD and VA and described as pooled estimates with 95% confidence intervals (CIs). In a meta-analysis, the predictive value of LVMD was compared to that of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS).

Results

Among 3198 patients (weighted mean, 63 years, 30% female; 82% ischemic heart disease) in 12 published articles, 387 (12%) had VA events over a follow-up (17–70 months). Patients with VA events had a significantly greater mechanical dispersion compared with those without VA events (weighted mean difference, −20.3 ms; 95% CI, −27.3 to −13.2; p<0.01); 60 ms was found to be the optimal cutoff LVMD value for predicting VA events. Each 10 ms increment of LVMD was significantly and independently associated with VA events (HR, 1.19; 95% CI, 1.09 to 1.29; p<0.01). The predictive value of LVMD was superior to that of LVEF or GLS (Figure).

Figure 1

Conclusion

LVMD assessed by speckle tracking provides important predictive value for VA in patients with a number of cardiac diseases and appears to have superior predictive value to LVEF and GLS for risk stratification.
P5985New aspects of management of patients with long-term persistent atrial fibrillation before extracardiac interventions
Authors: Dzhioeva O , Resnik E , Nikitin I
Published: October 2019

Surgery in patients with atrial fibrillation is always an additional risk of thromboembolic complications. In the modern era of direct oral anticoagulants, the risk of bleeding is much lower, due to the lack of need for a Bridge, but at the same time, there is no clear position on the strategy of management of patients with long-term current atrial fibrillation in the tactics of rhythm control or heart rate control.

In our clinic we examined 772 before surgical intervention high risk. Of these, atrial fibrillation was diagnosed in 366 patients. 121 patients had a persistent or long-persistant form of arrhythmia. To determine the tactics, we performed a transesophageal echocardiographic study to assess intracardiac hemorheology. 109 studies were performed. 35 patients received rivaroxaban, 29 dabigatran, 19 apixaban, 26 patients did not receive anticoagulant therapy. Disorders of intracardiac hemorheology that do not allow to perform a planned cardioversion, such as blood clots and spontaneous contrast 3–4 degrees, were detected in 78% of patients not receiving anticoagulant therapy, 56% of patients receiving dabigatran, 52% of patients receiving rivaroxaban and 38% of patients receiving apixaban. Among patients with disorders of intracardiac hemorheology, unreasonably reduced doses were taken by 78% of patients. Patients with thrombotic disorders proposed to enter the perioperative period in accordance with the strategy of heart rate control and correction doses of anticoagulant therapy.

Thus, based on our observations, we recommend transesophageal echocardiography before elective surgery in all patients with persistant AF to determine the feasibility of restoring the sinus rhythm before surgery.
P5993Comprehensive characterization of experimental aortic valve stenosis by multiparametric MRI
Authors: Quast C , Zimmer S , Boenner F , Jacoby C , Gyamfi-Poku I , Piayda K , Erkens R , Niepmann S T , Adam M , Baldus S , Nickenig G , Kelm M , Floegel U
Published: October 2019

Background

Recently, we established an experimental model of moderate aortic valve stenosis (AS) aiming to mimic human disease progression closely. Functional and structural MRI of a mouse model in experimental aortic valve stenosis has not been accomplished so far.

Purpose

Here, we aimed at developing comprehensive MRI approach for simultaneous assessment of changes in valvular, left ventricular and aortic morphology and function.

Methods

Male 12-week-old wildtype mice (C57Bl/6) were subjected to wire injury of the aortic valve to induce aortic valve stenosis. High resolution MRI at 9.4T was used to monitor subsequent functional and structural changes in the aortic valve, the ascending aorta, the left ventricle and aortic flow patterns.

Results

MRI permits accurate planimetry of the orifice and the thickness of the aortic valve, allows a reliable three-dimensional mapping of transvalvular aortic flow, simultaneously depicts aortic regurgitation in 3D fashion and permits assessment of left ventricular changes due to AS. In our model we observed a reduced valve orifice and an increase in valve thickness. Homogenous flow pattern under control converted to heterogenous and turbulent flow with progression of AS associated with increased aortic strain, aortic wall and left ventricular wall thickness.

Conclusions

In a murine model of aortic valve stenosis MRI is capable to reliably display a three-dimensional transvalvular aortic flow profile with concomitant quantification of structural and functional changes in aortic valve, left ventricle, and ascending aorta. This comprehensive functional imaging at high resolution and distinct reproducibility offers for the first time serial assessment of disease progression in an experimental model of aortic valve stenosis.
P5998The Phosphodiesterase 4D interacting protein averts volume overload - but not pressure overload-induced pathological myocardial remodeling
Authors: Mohamed B A , Elkenani M , Jakubiczka-Smorag J , Bader M , Hasenfuss G , Toischer K
Published: October 2019

Background

Although volume- and pressure-overload (VO and PO, respectively) are hemodynamic stress, each results in distinct phenotypes. The Phosphodiesterase 4D interacting protein (PDE4DIP) is a protein involved in cardiac muscle contraction and suggested to play a role in cardiomyopathy. We previously identified Pde4dip transcript as being downregulated in VO but upregulated in PO.

Objective

We wanted to address whether Pde4dip deletion would alter the progression of pathological myocardial remodeling and heart failure (HF) following hemodynamic stress.

Methods

Pde4dip knockout (Pde4dip-KO) and age- and sex-matched wild-type (WT) mice were exposed to aortocaval shunt-triggered VO or transthoracic aortic constriction (TAC)-induced PO. Mortality rates were assessed and the cardiac structure and function were determined by serial echocardiography.

Results

The PDE4DIP protein levels decreased significantly in volume-overloaded hearts. However, pressure-overloaded hearts did not alter PDE4DIP protein levels, suggesting different posttranscriptional modifications that might affect the PDE4DIP protein expression in VO versus PO. The Pde4dip-KO Hearts were structurally and functionally normal in echocardiographic and morphometric analyses. However, Pde4dip deletion mildly attenuated the mortality rates in shunt-, but not in TAC-operated mice. A significant deterioration of left ventricle geometry and function was observed in volume-overloaded WT hearts at 12 weeks after shunt, but preserved cardiac function were noticed in shunt-operated Pde4dip-KO mice. On the other hand, TAC-operated WT and Pde4dip-KO mice exhibited a significant, but comparable deterioration of cardiac structure and function compared to sham mice.

Conclusion

Here we identified the PDE4DIP as an essential regulator of pathological myocardial remodeling following VO, but irrelevant to the development of cardiac dysfunction after TAC. Further investigations are warranted to dissect the possible mechanisms underlying the protective role of PDE4DIP deletion in the setting of VO.

Acknowledgement/Funding

This work was supported by DFG (SFB1002 project D04 to KT and D01 to GH; IRTG1816 to ME); BAM was funded by DSHF
P6003Coronary artery spasm: a consequence of impaired nitric oxide/hydrogen sulphide signalling?
Authors: Liu S , Nguyen T H , Imam H , Heresztyn T , Stafford I , Chirkov Y Y , Horowitz J D
Published: October 2019

Background

Coronary artery spasm (CAS) represents a major cause of patient morbidity, with variable clinical response to prophylaxis with calcium antagonists and generally poor symptomatic relief with organic nitrates. The precipitation of CAS with acetylcholine may reflect impaired nitric oxide (NO) release and/or signalling. We have recently demonstrated that platelets from patients with CAS exhibit markedly impaired anti-aggregatory responses to the NO donor sodium nitroprusside (SNP) (“NO resistance”).

Purpose

In the current experiments we sought to determine whether N-acetylcysteine (NAC), which is known to potentiate haemodynamic responses to organic nitrates, reverses NO resistance in platelets from CAS patients.

Methods

Patients with CAS were studied during acute (n=11) and chronic (n=24) phases of symptoms. NAC (10 g/24 hours) was infused together with low dose NTG (2.5 μg/min) in patients presenting with acute exacerbations, and platelets were studied ex vivo. In blood samples taken from chronic CAS patients, in vitro studies were performed to evaluate the possible role of H2S release (via cysteine formation) from NAC in putative potentiation of NO effect.

Results

(1) In acute patients, NTG/NAC infusion resulted in increases in platelet response to SNP (p=0.003);

(2) In vitro studies showed that incubation with NAC or the H2S donor NaHS potentiated SNP responses (Figure 1A);

(3) Effects of NAC were reversed by co-incubation with aminooxyacetic acid (AOAA) and D, L-propargylglycine (PAG), inhibitors of enzymatic cysteine bioconversion to release H2S (Figure 1B).

Figure 1

Conclusion

CAS-associated impairment of platelet NO signaling reflects a deficiency of the H2S/NO interaction, and can be reversed using exogenous H2S donors, including NAC.
P6006Pathogenesis of symptomatic crises in patients with coronary artery spasm: evidence for acute damage to vascular glycocalyx and to circulating platelets
Authors: Nguyen T H , Liu S , Imam H , Heresztyn T , Stafford I , Chirkov Y Y , Horowitz J D
Published: October 2019

Background

Coronary artery spasm (CAS) is known to occur commonly even in a “pure culture”, but little is known regarding the precipitation of the symptomatic crises which characterize this disorder. There have been recent reports of the occurrence of plaque erosion and intracoronary thrombosis during CAS crises. We have recently shown that (1) the anti-aggregatory effects of nitric oxide (NO) are impaired in CAS patient and (2) release into plasma of the endothelial glycocalyx component syndecan-1 (SD-1) occurs during acute episodes of CAS, suggesting glycocalyx erosion by inflammatory enzyme release.

Objective

In the current study, we sought to determine whether this phenomenon is accompanied by damage to circulating platelets and whether activation of mast cells may represent a possible precipitant.

Methods

In patients with acute episodes and chronic phases of CAS (n=10), as well as normal subjects (n=12), plasma concentrations of SD-1, of platelet-derived microparticles (PMPs), of the mast cell enzyme tryptase and of malondialdehyde (MDA), a measure of oxidative stress, were evaluated.

Results

The results are summarized in the table. Symptomatic crises were associated with substantial elevation of SD-1 concentrations and also those of PMPs and of tryptase, relative to chronic status. However, MDA concentrations did not vary significantly during acute episodes.

Impact of acute exacerbation of CAS on markers of glycocalyx shedding (SD-1), platelet activation (PMP counts), mast cell activation (tryptase) and oxidative stress (MDA) Parameter Acute CAS Chronic CAS p* Normal subjects** SD-1 (μg/L) 50.3±3.9 14.3±4.7 <0.0001 12.7±2.4 PMPs (counts) 24200±8100 4800±1010 0.02 10400±2900 Tryptase (μg/L) 4.4±0.4 4.1±0.4 0.03 <12.0 MDA (μM) 3.2±0.2 3.1±0.1 NS 3.09±0.15 *Acute vs. chronic; **provided for reference only.

Conclusion

(1) The combination of SD-1 release and formation of PMPs suggests that CAS crises reflect both glycocalyx “shedding” and platelet activation/apoptosis, a combination which would facilitate coronary thrombosis.

(2) CAS crises are associated with mast cell activation, which may contribute to the above vascular/platelet damage.
P6147Access to essential cardiovascular medicines in Kerala, the state with the highest cardiovascular disease burden in India
Authors: Satheesh G , Puthean S , Ansil M , Unnikrishnan M K , Sharma A , Mishra S R , Jereena E
Published: October 2019

Introduction

The 2030 Agenda for Sustainable Development has prioritized the reduction of premature mortality due to NCDs – including cardiovascular diseases (CVD) - by a third. To achieve this goal, countries must achieve 80% availability of affordable essential medicines. Essential medicines as identified by the World Health Organization are those that meet the priority healthcare needs of majority population. Globally, India has the second highest CVD burden with over 1.7 million deaths annually, with the highest CVD morbidity and mortality rate in Kerala.

Purpose

To evaluate the availability, prices and affordability of essential CVD medicines in Kerala state to facilitate implementation of informed public health policy.

Methods

Using WHO/HAI methodology, we obtained data on availability and prices for 25 essential CVD medicines in a representative sample of 7 public-sector hospitals (survey anchors) and 37 private retail pharmacies located near the survey anchors in four districts. Additionally, we obtained the data from 10 government-subsidized discount pharmacies. We report availability as percentage of surveyed facilities where a given medicine was found. Median prices ratios (MPRs) were calculated by comparing consumer prices to the MSH International Reference Prices (IRPs). Medicines were considered affordable if the monthly supply costs less than one-day's wage of the lowest paid government worker.

Results

In the public-sector facilities (hospital and discount pharmacies combined), the mean (SD) availability of the surveyed CVD medicines was 52% (35.3%) for generic and 35.3% (20.7%) for originator brand (OB) version. 28% of surveyed medicines (including amlodipine, clopidogrel, losartan, metformin) were available in over 80% pharmacies. 12% (captopril, streptokinase and glyceryl trinitrate) were not available in any of the facilities.

In the private sector, mean (SD) availability of generic and OB versions was 64.4% (37.2%) and 43.7% (34.6%), respectively. MPR was 1.28 [range: 0.02 (insulin NPH) – 16.7 (simvastatin)] for both lowest-priced generics (LPG) and most-sold generics (MSG). The lowest paid government worker in Kerala would spend 0.06 - 3.48 days' wages for the monthly supply of essential CVD medicines in the private sector.

In government-subsidized discount pharmacies, mean availability was 49.3%. The generic medicine prices were 74% lower than in the private sector.

Conclusions

Availability of essential CVD medications in both public and private sector pharmacies fall short of the 80% target. In the private-sector, many essential CVD medications seem unaffordable especially considering the polypharmacy among CVD patients. Introducing policies to improve medicine availability in government-subsidized discount pharmacies is crucial in tackling Kerala's ever-increasing CVD burden.
P6153High risk plaque by coronary CTA predict cardiac events but not all-cause mortality: long term follow up
Authors: Senoner T , Plank F , Babieri F , Dichtl W , Beyer C , Friedrich G , Feuchtner G M
Published: October 2019

Background

Ultra long-term (10 years) outcome data of coronary computed tomography angiography (CTA) for coronary heart disease (CHD) screening are lacking. Novel CTA imaging biomarkers (“high-risk-plaque”) may improve risk stratification.

Aims

To define CT-imaging predictors for long–term outcomes.

Methods

1430 low-to-intermediate-risk patients (mean age 57.9 years; 44.4% females) were included into our prospective cohort study. Coronary Calcium Score (CCS) and CTA were performed. CTA was evaluated for: Stenosis severity (minimal<25%; mild<50%; moderate 50–70%; severe >70%) (CADRADS 1–4), total mixed plaque burden (G-score), high–risk-plaque criteria: 1) low attenuation plaque 2) Napkin-ring (“lunar-eclipse” sign) 3) spotty calcification 4) remodeling index

Primary endpoint was all-cause mortality, secondary endpoints cardiovascular mortality and composite (non-fatal and fatal) MACE.

Results

Over a follow-up of mean 10.55 years ±1.98 (range, 6.1–12.8), all-cause mortality rate was 106 (7.4%), cardiovascular mortality 25 (1.75%) and composite MACE 57 (4%).

In patients with negative CTA, cardiovascular mortality was 0% and composite MACE rate 0.2%.

Stenosis severity (CADRADS) was the strongest predictor for all 3 endpoints (p<0.001) on multivariate analysis (unadjusted and adjusted for risk factors, p<0.001) but calcium score >100 AU only predicted mortality on the unadjusted multivariate analysis (p=0.045) but not on the adjusted.

On multivariate analysis, G-score (p<0.0001), LAP<60HU and the Napkin-Ring predicted composite MACE (p<0.001) but not all-cause mortality, before and after adjusting for risk factors (p=0.007 and 0.001 for LAP<60HU and Napkin-Ring, respectively) while spotty calcification and remodeling index did not. 465 had calcium score zero and in 156 (33.5%) of those, noncalcified fibroatheroma were found (total rate, 11%), 4.9% had >50% stenosis. However only 1 patient with calcium score zero died while there were 6 MACE.

High risk plaque with “lunar eclipse”

Conclusions

Long-term prognosis is excellent if CTA is negative. Stenosis severity by CTA predicts all-cause and cardiovascular mortality, while calcium score predicts only mortality. Plaque burden and the high-risk plaque criteria LAP<60 and Napkin-Ring (syn. “lunar eclipse”) are strong predictors of MACE, but not all–cause mortality. Coronary CTA outperforms calcium scoring for risk stratification.