bluuebunny/crossref_metadata_2025 huggingface dataset:
P2245Sex differences in the in-vivo markers of platelet activation among patients with ischemic heart disease: insights from the EVA study
Authors: Raparelli V , Romiti G F , Sperduti N , Santangelo G F , Vano M , Recchia F , Proietti M , Lenzi A , Basili S
Published: October 2019

Background/Introduction

Ischemic heart diseases (IHD) are not synonymous with obstructive flow-limiting coronary artery disease (CAD), especially in women. Platelet dysfunction is suggested as a potential mechanism favouring ischemia in non-obstructive CAD. However, it is unknown whether sex differences in platelet function of patients with non-obstructive CAD exist.

Purpose

We assessed for sex differences in in-vivo markers of platelet activation among patients with the acute coronary syndrome and chronic stable angina, with or without obstructive CAD

Methods

From the “Endocrine Vascular disease Approach” (EVA) study, we selected IHD patients undergoing urgent or elective coronary angiography with complete baseline clinical characteristics and angiographic data. Non-obstructive CAD was defined as the presence of coronary stenosis <50%. Thromboxane B2 (TxB2) and soluble P-selectin (sP-s) were measured at baseline. A sex-stratified analysis of platelet biomarkers was performed.

Results

Among two-hundred-seventy-seven patients (mean age 67±11, 37% women), non-obstructive CAD was documented in 25% of patients. Acute coronary syndrome (ACS) was the reason for angiography in 61% of cases. Women had more frequently ACS, as compared with men (54.8% vs 41.3%, p=0.001), with predominantly non-obstructive CAD. Median serum TxB2 (121.5 [92.7–174.0] vs 103.5 [83.0–140.2] pg/ml, p=0.005) and plasma sP-s (27.0 [18.7–35.0] vs 22.0 [16.0–30.0] ng/ml, p=0.006) levels were higher in patients with ACS as compared with the ones with stable chronic angina. The median concentration of TxB2 was significantly increased in women as compared with men, regardless of the clinical presentation and the coronary stenosis degree (all comparison, p<0.001). However, women with non-obstructive CAD were the group with the highest serum levels of TxB2 (140.0 [111.0–152.0] pg/ml). Sex differences in the plasma sP-s level were also observed among patients with stable chronic angina (women, 26 [20.0–34.0] vs men, 21 [16.6–27.7] ng/ml, p=0.002) and with non-obstructive CAD (women, 26 [20.5–34.5] vs men, 18.5 [16.6–26.0] ng/ml, p=0.003).

Conclusion(s)

Women with IHD and non-obstructive CAD had increased level of TxB2 and sP-s as compared with men, independently by the clinical presentation. Further investigations are warranted to verify the role of platelet hyperactivation in the pathogenesis of myocardial ischemia with non-obstructive coronary artery disease among women.

Acknowledgement/Funding

Scientific Independence of Young Researchers Program (RBSI14HNVT) - Ministry of Education, University and Research (MIUR)
P2252Hyperglycemia drives myeloid CD34+ stem cells differentiation towards pro-inflammatory and senescent monocyte subpopulations
Authors: Vinci M C , Vigorelli V , Raucci A , Genovese S , Pompilio G
Published: October 2019

Background/Introduction

Diabetes is characterized by a chronic low-grade inflammatory status mediated by cellular senescence and alterations of the circulating cytokine profile and of innate immune system cell components. An abnormal expansion of intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocyte subpopulations with highly inflammatory and senescent-associated secretory phenotype (SASP) have been observed in T2DM patients with cardiovascular (CV) complications. It is unknown whether CD34+ hematopoietic stem cells (HSCs), players of CV prognosis, are involved in this process.

Purpose

To assess whether hyperglycemia might induce a pro-inflammatory priming of hematopoietic CD34+ HSCs that through senescence and acquisition of SASP skew their myeloid differentiation into more aggressive monocyte populations.

Methods

CD34+ cells were purified from cord blood of healthy donors and expanded in normal-glucose (NG; with 30 mM mannitol for osmotic control) or high-glucose (HG; 30 mM) serum-free medium plus cytokines. The cell were counted after 10, 20 and 30 days. The expression of p27, p21 RELA/p65, IL6, TNFα genes and telomere length was assessed by qPCR and secreted cytokines by ELISA. Apoptosis, ROS and monocyte subpopulations were evaluated by flow cytometry after Annexin V, CellRox and CD14/CD16 staining respectively.

Results

CD34+ HSCs cultured in HG (HG-CD34+) displayed a significant proliferation impairment when compared to their osmotic control (NG-CD34+). This loss of glucose tolerance was associated with a significant increase in mitochondrial ROS production (n=6; p≤0.01) without induction of apoptosis as showed by flow cytometry analysis for Annexin V. Moreover, qPCR assay revealed a significant telomere shortening (n=4; p≤0.05) and up-regulation of cyclin-dependent kinase inhibitors p27 and p21 in HG-CD34+cells (n=13; p≤0.05) along with an enhanced expression and secretion of TNFα (n=9; p≤0.05) and IL6 (n=10; p≤0.05) in HG-CD34+ when compared with NG-CD34+. SASP phenotype in HG-CD34+ was associated to a significant up-regulation of RELA/p65 gene in HG-CD34+ when compared with NG-CD34+ (n=8; p≤0.05). Furthermore, we found that in vitro HG-CD34+ differentiation into myeloid lineage generated higher levels of pro-inflammatory intermediate (n=3; p≤0.05) and non-classical (n=3; p≤0.01) monocyte subsets when compared with the normoglycemic counterpart.

Conclusion(s)

These data suggest that HG exposure primes HSCs myeloid differentiation towards inflammatory and senescent monocyte subpopulations.

Acknowledgement/Funding

This work was supported by Ricerca Finalizzata, Ministero della Salute [PE-2011-02348537]
P2256Aging and inhibition of Nox4 and Nox1 exacerbate perivascular inflammation in spontaneous hypertension
Authors: Nosalski R , Mikolajczyk T , Siedlinski M , Maciag J , Guzik T J
Published: October 2019

Introduction

Hypertension is associated with enhanced NADPH oxidase activation and increased accumulation of immune cells leading to perivascular inflammation. However, while aging and oxidative stress are a major factor for the development of hypertension, their effect on perivascular inflammation remains unclear.

Purpose

We aimed to establish the interaction between aging, oxidative stress and perivascular inflammation.

We hypothesize that the modulation of oxidative stress, by NADPH oxidase inhibition, could affect perivascular inflammation during the aging.

Methods

Using flow cytometry, we studied leukocyte infiltration in the perivascular adipose tissue (PVAT) in 1-, 3-, 6- and 12-month-old SHR (Spontaneously Hypertensive Rats) and normotensive WKY (Wistar-Kyoto) rats (n=5–12). Additionally, 1-month-old rats were treated with GKT137831 or ML171 (60mg/kg; NOX1/4 and NOX1 inhibitor, respectively) for 4 weeks. Blood pressure (PB) was measured by tail cuff. Statistical analysis was performed using two-way ANOVA or t-test. Data are presented as means±SEM.

Results

Aging in SHRs was associated with an increase of BP (139±4 vs. 180±4 vs. 203±3 vs. 209±3, mmHg) and an elevation of PVAT leukocytes (2090±164 vs. 2255±359 vs. 2502±496 vs. 3255±408, cell/mg) in 1-, 3-, 6- and 12-month-old rats, respectively. These effects were not seen in WKY.

These were associate with similar changes of NK cells (p int <0.001) and macrophages (p int <0.001) in the SHR PVAT. Within T cell compartment, TH17 cells in PVAT were only elevated with age in SHR (1.04±0.08% vs. 1.89±0.2%, 1.08±0.1% vs. 2.03±0.2%, 1.71% vs. 4.37±0.5%, WKY vs. SHR, 3-,6- and 12-months, respectively, p int<0.001).

While an age-related increase of Nox4 mRNA in the vessels was observed in both groups, this increase was more dynamic in SHRs, (p int <0.05). Furthermore, 5-, 6- and 9-fold induction of Nox1 mRNA was observed in the vessels of 3-, 6- and 12-months-old SHRs, respectively (p<0.01).

Interestingly, GKT137831 increased BP in both WKY and SHR rats (p<0.01, 2-way ANOVA). This was accompanied by the elevation of leukocytes (988±180 vs 147±188 cell/mg, 1487±945 vs 1878±164 cell/mg) and macrophages (107±14 vs. 153±14 cell/mg, 228±26 vs. 298±42 cell/mg) in PVAT of both WKYs and SHRs treated with GKT137831. Moreover, GKT137831 treatment significantly increased (p int<0.01) percentage of TH17 in PVAT of both normotensive (1.4±0.2% vs. 2.5±0.2%) and hypertensive (2.3±0.1% vs. 2.9±0.1%) animals. On the contrary, ML171 treatment, inhibiting only Nox1, in turn protected against an increase of PVAT leukocytes especially among macrophages, TH17 cells (p<0.01).

Conclusion

Aging and spontaneous hypertension is associated with a trajectory of BP elevation and perivascular inflammation. This state is hastened after NOX1/4 inhibition, while ML171 treatment protects against perivascular inflammation.

Acknowledgement/Funding

National Science Centre 2013/11/N/NZ4/00310
P2259Cognitive function and adherence to treatment in patients with chronic heart failure and reduced left ventricular ejection fraction: relation and prognostic meaning
Authors: Solonovych A S , Voronkov L G
Published: October 2019

Background

Poor adherence to treatment increases risk of hospitalization and has negative impact on quality of life and clinical prognosis in chronic heart failure (CHF). Cognitive impairment (CI) is observed in more than half of patients (pts) with CHF and may affect their adherence to treatment. Nevertheless, association between cognitive function (CF) and adherence to treatment in CHF pts is studied insufficiently.

Purpose

To establish relationship between the state of CF and adherence to treatment in pts with CHF and reduced left ventricular ejection fraction (rLVEF).

Methods

124 pts with stable CHF and rLVEF (<40%) NYHA II-III non older than 75 years old were examined. Besides routine clinical examination, standard neuropsychological tests (MMSE, Schulte test, the HADS scale) were used. To assess adherence to treatment, Morisky-Green questionnaire (MGQ) was used. CI was defined as MMSE ≤26 points. Statistic methods included descriptive statistics, Mann-Whitney U-test, Spearman's rank correlation, Kaplan-Meier method. The difference was considered statistically significant at p<0.05.

Results

CI was observed in 85 (68.5%) of pts. The presence of CI was associated with significantly lower survival rate (fig. 1). According MGQ poor adherence to treatment was observed in 37 (43.5%), moderate – in 30 (35.3%), good adherence – in 18 (21.2%) of pts. After distribution of pts to three groups depending on their adherence to treatment (0–2 poor, 3-moderate, 4-good adherence), it was found that they significantly differed in MMSE and Shulte test results (p=0.006 and p=0.038 respectively). At the same time, groups were comparable by HADS anxiety and depression scores. The number of MGQ points directly correlated with MMSE (r=0.186, p=0.038).

Survival curves of CI vs non-CI pts

Conclusion

Insufficient adherence to treatment accessed by MGQ is observed in majority of CI pts with CHF and rLVEF. Adherence to treatment is reliably associated with cognitive status of pts, which, in turn, related to poor clinical outcome.
P2428Comparison of Newtonian and non-Newtonian rheology in calculation of endothelial shear stress
Authors: Thondapu V , Poon E K W , Revalor E , Zhu S , Dijkstra J , Serruys P , Ooi A , Barlis P
Published: October 2019

Background

Although blood is a non-Newtonian fluid, most clinical computational fluid dynamic (CFD) studies assume blood to be a Newtonian fluid with constant viscosity. At higher blood flow rates in larger arteries, the two models should present similar results, and the Newtonian assumption can be considered acceptable. However, whether the Newtonian assumption is valid in patient-specific coronary arteries under pulsatile flow has not been evaluated.

Purpose

To compare CFD results using Newtonian and non-Newtonian models of blood in order to determine whether the Newtonian assumption can be considered valid in patient-specific coronary arteries.

Methods

Coronary arteries of 16 patients were reconstructed from fusion of angiography and intracoronary optical coherence tomography imaging. Pulsatile CFD simulations using Newtonian and non-Newtonian models were performed to calculate endothelial shear stress (ESS). The absolute and percent difference in time-averaged and instantaneous ESS values (calculated as non-Newtonian minus Newtonian) were compared on a point-to-point basis. The percent area of the vessel exposed to proatherogenic ESS values (considered <1 Pa) in each model was also calculated.

Results

The Newtonian and non-Newtonian models produce similar qualitative distributions of ESS. However, quantitative comparison shows that compared to the Newtonian results, the non-Newtonian model estimates significantly higher time-averaged ESS (2.04±0.63Pa versus 1.59±0.54Pa, 95% CI 0.39–0.49, p<0.001) throughout the cardiac cycle. This results in significantly greater estimate of area exposed to ESS <1Pa in the Newtonian model (50.43±14.16% versus 37.20±13.57%, 95% CI 11.28–15.18, p<0.001). Instantaneous ESS plotted through the cardiac cycle indicates the greatest divergence in ESS values occurs at the transition between end-systole and early diastole, at approximately 0.35 seconds (FIGURE).

Conclusions

Despite similar qualitative ESS distributions, Newtonian and non-Newtonian simulations provide significantly different quantitative ESS values. This suggests that in patient-specific simulations of coronary blood flow, the non-Newtonian model may increase accuracy of ESS measurements. We hypothesize that using a non-Newtonian model may improve the diagnostic accuracy of abnormal ESS to predict clinically significant progression of atherosclerosis, however further study is necessary.
P2437Screening for cardiac relaxation abnormalities using surface ECG wavelets for identifying high-risk cardiac phenotypic abnormalities
Authors: Piccirilli M , Shrestha S , Kagiyama N , Hu L , Kulkarni H , Sengupta P P
Published: October 2019

Background

The impairment of myocardial relaxation is a strong predictor of all-cause mortality and has been proposed to be a potential tool for cardiovascular (CV) risk stratification. We investigated a novel signal-processed electrocardiography (spECG) technique to extract the features of abnormal myocardial relaxation as a screening tool to identify high-risk CV patients.

Methods

Time–frequency-energy features extracted from continuous wavelet-transformed spECG (Fig. A) were obtained in 1,006 cases. A machine learning model was trained for predicting abnormal myocardial relaxation as a screening tool for detecting high-risk CV patients. High-risk CV phenotype was defined as presence of LV hypertrophy, advanced LV diastolic dysfunction (grade 2 or 3), LV ejection fraction <50%, and/or significant valvular heart disease.

Results

After training with 5-fold cross validation using data from 810 patients, the machine learning model when tested in an independent hold-out validation set of 180 cases, showed an area under receiver-operating characteristic curve (AUC) of 0.83 (p<0.001) for prediction of myocardial relaxation impairment (Fig. B). A prediction of abnormal relaxation was associated with older patients (64±11 vs. 45±16 years old, p<0.001) with a higher prevalence of coronary artery disease (23% vs. 7%, p=0.004), hypertension (70% vs. 40%, p<0.001), and diabetes (30% vs. 9%, p=0.001). Furthermore, a prediction of abnormal myocardial relaxation was associated with increased likelihood of high-risk CV phenotypes (Odds ratio: 3.93, p<0.001) including LV hypertrophy (Odds ratio: 2.62, p=0.028), advanced LV diastolic dysfunction (Odds ratio: 11.4, p=0.020), and LV ejection fraction <50% (Odds ratio 10.5, p=0.025). Age and gender modified the prediction of abnormal relaxation with higher diagnostic value seen for patients under 60 years (Fig C, AUC: 0.88, p<0.001) and in male patients (Fig D, AUC: 0.87, p<0.001). The algorithm for abnormal relaxation also showed robust prediction of LV ejection fraction <50% (Fig E, AUC: 0.91, p<0.001) in male patients. spECG showed significant net reclassification improvement (0.47, p<0.001) and integrated discrimination improvement (0.16, p<0.001) over traditional surface ECG interpretation using Glasgow score for predicting abnormal relaxation and other high-risk phenotypic presentations.

ROC curves

Conclusion

The spECG provided a robust prediction of abnormal myocardial relaxation and may be a valuable screening strategy for early detection of high-risk cardiac structural and functional abnormalities.
P2438Deep learning model for atrial fibrillation detection based on single beat morphology
Authors: Baalman S W E , Schroevers F E , Oakley A , Ramos L A , Lopes R R , Van Der Stuijt W , Brouwer T F , Knops R E , De Groot J R
Published: October 2019

Background

The electrocardiogram (ECG) is commonly used, but most recent rhythm discrimination algorithms still lack both specificity and sensitivity. Deep learning techniques have shown promising results in the classification of physiological signals like ECGs.

Purpose

To develop and test a deep learning (DL) model to discriminate between atrial fibrillation (AF) and sinus rhythm (SR).

Methods

For the development of the DL model we used 1499 ECGs sampled at 500 Hz of patients diagnosed with AF. All ECGs were labeled by two experienced investigators. Only ECGs labeled as SR or AF were included in the dataset. To simplify the learning process, solely the first ECG channel was used. The ECG waveforms were preprocessed using the Fourier cosine series to correct for baseline wander. Input data was generated by normalizing and scaling all different heartbeats by centralizing the R peak, leading to 15744 single heart beat samples of 80 data points (figure A). Multiple feedforward architectures were tested with different numbers of layers, filters and activation functions. The models were trained by equally splitting the data (50%SR, 50%AF) in a training (65%), validation (25%) and test set (15%). The best performing model was chosen based on the accuracy.

Results

A total of 1469 ECGs (1061 (72%)SR, 408 (28%)AF) were included. The model with the best performance was a feedforward model consisting three dense layers with ReLU activation and four dense layers with Linear activation. Training of the model was performed in 32 epochs. Validation of the model resulted in an accuracy of 96% (figure B), precision of 95% and recall of 96%.

Conclusions

The morphology based deep learning model developed in this study was able to discriminate atrial fibrillation from sinus rhythm with a fairly high accuracy using a limited size dataset and only one lead.
P2440Increased mortality with high versus normal ejection fraction in elderly women
Authors: Haghi A , Playford D , Stewart S , Bulsara M , Strange G
Published: October 2019

Mortality with impaired left ventricular ejection fraction (LVEF) has been clearly demonstrated. However, the prevalence and significance of increased LVEF (beyond the guideline-recommended normal range) in the community is unclear. We used the National Echo Database Australia (NEDA) to compare mortality in patients with normal and high LVEF.

Methods

NEDA contains echo data (>530,000, years 1997–2017) from laboratories (N=14) across Australia, linked to the National Death Index (NDI). 331,344 individuals aged >18 years (n=172,251 [52%] men, age=60.8±18.0 years and 152,095 [48%] women, 60.9±19.2 years) had a mean follow up of 5.4 person-years and 63,142 fatal events. LVEF using Method Of Discs (MOD) could be calculated in 116,544 individuals. We compared mortality in those with normal LVEF (52–72% for males and 54–74% for females) compared with high LVEF (>72% and >74% for males and females, respectively).

Results

Mortality was 11% higher in females with high LVEF vs females with normal LVEF. On multivariable logistic regression, high ejection fraction remained an independent predictor of mortality after correction for age, gender and body mass index. High LVEF was positively associated with female gender, age and diastolic dysfunction. Of 96,033 individuals in the study population, there were 46,876 males (48.8%), mean age 61.19±17.09 years, not significantly different from their female counterparts. 44,282 males had normal LVEF (52–72%) as opposed to 2,594 with high LVEF (>72%). In females, 46,186 had normal LVEF (54–74%) and 2,971 had high LVEF.InCox proportional hazard models, the hazard ratio (HR) for mortality in males with normal EF was 1.105 for age (95% CI 1.102 to 1.07) and 1.074 (95% CI 0.988 to 1.167) for high LVEF (p<0.001 for all outputs). In females, the corresponding adjusted HR was 1.107 for age (95% CI 1.105 to 1.110) and 1.140 for high LVEF (95% CI 1.057 to 1.230).

Conclusion

High LVEF, particularly in older women, is associated with increased mortality compared with an LVEF within the reference range. Further study is required to evaluate possible mechanisms for worse outcomes in patients with high LVEF.
P2443Diagnostic performance of 2d-echocardiography versus cardiac catheterization in assessing left ventricular end-diastolic pressure: a meta-analysis
Authors: Acosta K , Cano J , Esposo E , Shiu L , Masbang A
Published: October 2019

Introduction

Heart failure (HF) is a major public health problem that affects 23 million people worldwide. The global incidence and prevalence rates of HF are approaching epidemiologic proportions, as evidenced by the relentless increase in the number of HF hospitalizations, the growing number of HF deaths, and the spiraling costs associated with the care of HF patients. Its diagnosis may be challenging because symptoms are nonspecific. Determination of left ventricular filling pressure (LVFP) is important to interpret equivocal symptoms so as to optimize therapy. Catheterization remains to be the gold standard; however, it is not practical to submit many patients with clinical suspicion of HF to invasive studies. Although echocardiographic indices are recommended by recent guidelines (Level IIIB), studies have shown conflicting results on its diagnostic performance.

Purpose

This study aims to identify the diagnostic performance of 2D-echocardiography compared with cardiac catheterization in assessing LV end-diastolic pressure (LVEDP) among adult patients with suspected HF using a meta-analysis of observational studies.

Methods

Eight studies with a total of 1,153 patients with suspected HF who underwent simultaneous evaluation of echocardiographic estimates of LVFP and invasive measurement of LVEDP by cardiac catheterization were included in the final analysis after extensive searching. Review Manager 5.3 was used to the assess the sensitivity and specificity of E/e' lateral, septal and average, and left atrial volume index (LAVI). Meta-Disc was applied to obtain pooled estimates, receiver operating characteristic curve (ROC) and area under curve (AUC) using a 95% confidence interval.

Results

Overall, pooled estimates for E/e' septal >15, E/e' lateral >12, E/e' average >13 and LAVI >34 have significant diagnostic values with pooled sensitivity of 62% (95% CI 0.54 to 0.69), 39% (95% CI 0.33 to 0.45), 81% (95% CI 0.73 to 0.87) and 53% (95% CI 0.46 to 0.61) respectively; pooled specificity of 59% (95% CI 0.53 to 0.65), 87% (95% CI 0.81 to 0.91), 72% (95% CI 0.65 to 0.78) and 69% (95% CI 0.57 to 0.79) respectively; and pooled AUC of 0.624, 0.8486, 0.8190 and 0.69 respectively.

Conclusion

2D echocardiography have significant diagnostic performance compared with cardiac catheterization in assessing LVEDP among adults with suspected HF. Guidelines may be updated using this meta-analysis.
P2448Evolution of clinical quality activities within a national echocardiography database: seven-year trends from the GenesisCare Outcomes Registry
Authors: Eccleston D , Cehic D , Cross D , Srivastava P
Published: October 2019

Introduction

Despite rapid technologic advances and sustained growth, less attention has been focused on quality in imaging than in other areas of cardiovascular medicine. To address this deficit, the ACC proposed additional areas of effort such as data standardisation, structured reporting identifying key data elements and imaging registries. We explored these changes within a large multi-centre Australian registry.

Methods

From 2010–2014 we introduced direct online entry of echocardiographic studies into an electronic database, selection and auditing of key data elements and quality improvement pathways to maximise completeness of data acquisition and reporting across 4 states. We compared completeness of key data elements (AV peak velocity, EF, E/E', LA area, rhythm, RVSP) by time and state using de-identified data.

Results

464,688 echocardiographic procedures were captured from 2011 to 2018.

Data completeness improved significantly from 2011 to 2018 (72.0±26.8 vs 88.2±13.5%, p=0.02). Inter-practice variability fell from 2011 to 2018 for both EF and E/E', p<0.002

Conclusion

Identification, systematic capture and auditing of key echo data elements can significantly improve the quality and reduce inter-practice variability of echo data. Developing a national database allows rapid adoption of local quality improvements.

Acknowledgement/Funding

None
P2450The atrial electromechanical conduction delay with ultrasound based two-dimensional speckle-tracking predicts very late recurrence following catherter ablation for atrial fibrillation
Authors: Fujii A , Inoue K I , Kinoshita M K , Nagai T N , Sasaki Y S , Akazawa Y A , Higashi H H , Uetani T U , Aono J A , Nishimura K N , Ikeda S I , Yamaguchi O Y
Published: October 2019

Background/Introduction

Long-term efficacy following catheter ablation (CA) of atrial fibrillation (AF) remains unknown. Left atrial (LA) reverse remodeling following CA may be important to reduce the risk of very late recurrence (VLR).

Purpose

We hypothesize that improved mechanical conduction delay with myocardial strain is associated with LA reverse remodeling indicates efficacy following AF ablation. This study aimed to investigate the clinical utility of mechanical conduction delay to predict VLR in patients with AF undergoing CA.

Methods

We enrolled 114 consecutive patients undergoing initial CA in patients with AF from January 2012 to February 2014. 20 patients were excluded due to poor echocardiographic image quality. 38 patients had AF recurrence within 12 months after CA. Finally, 54 patients (age 62 years, 13 female, 15 persistent AF) were analyzed. Trans-thoracic echocardiography (TTE) was performed within 24 hours as baseline, and every 6–12 months following the initial CA as follow-up. We compared the TTE data with baseline and latest test when sinus rhythm was maintained. To assess atrial electromechanical conduction delay, we adopted a parameter based on speckle tracking echocardiography (EMT-ε), which was defined as the interval from the P- wave onset to the peak late diastolic longitudinal strain in the basal lateral wall of LA (Figure).

Results

Eleven patients had VLR after CA. In patients with VLR, left atrial volume index (LAVI) at baseline was significantly higher than those without VLR (49±17 vs 35±14 ml/m2, P<0.05). EMT-ε had no significant difference between two groups (225±52 vs 208±49 ms, P=NS).

During 58±22 months, LAVI and EMT-ε were significantly improved (LAVI: 38±16 vs 33±14 ml/m2, EMT-ε: 215±48 vs 197±45 ms, P<0.05, respectively). The change of LAVI had no significant difference between two groups (−2 (−10, 4) vs 33 (−13, 6) ml/m2, P=NS). EMT-ε shortening was significantly greater in AF-free patients than patients with VLR (−27 (−66, −3) vs 23 (−1, 79) ms, P<0.01). At a cut-off value of −9 ms, the change of EMT-ε predicted VLR with sensitivity (100%) and specificity (68.9%).

Conclusion(s)

The atrial electromechanical conduction delay could predict VLR after CA in patients with AF.
P2456Role of left atrial volume as simple and early predictor of cardiotoxicity
Authors: Cerrito L F , Schiavone A , Bergamini C , Dal Porto M , Benfari G , Dolci G , Setti E , Comunello A , Rossi A , Fiorio E , Ribichini F L
Published: October 2019

Background

It is crucial to predict and early detect Trastuzumab (TZ)-related cardiotoxicity (CT) in patients with HER2-positive breast cancer (BC). Although baseline left atrial (LA) volume and its changes over time assessed by echocardiography have been used as prognostic tool in various clinical conditions, up to now there are no well-defined LA-based parameters predictive of chemotherapy-related dysfunction.

Aim

To define the role of increased baseline LA indexed volumes (LAVI) and its changes over time as early predictors of TZ-related CT in a larger and well characterized cohort of BC patients.

Methods

HER-2 positive BC patients receiving TZ were retrospectively recruited. Patients underwent consecutive transthoracic echocardiography at baseline and then every three months. CT was defined as decrease in left ventricular ejection fraction (LVEF) to a value <50% or a decrease of >10 percentage points from baseline, according to our oncology unit.

Results

Eligible patients were 280, mean age 56±12 years. Mean follow-up (FU) was 15±5 months and CT occurred in 64 patients (22,9%). Baseline LAVI showed to be associated with development of CT (p=0,003), and to predict its onset, Odds Ratio (OR) per 5 ml/mq LAVI increase 1,32 (95% CI 1,07: 1,62), p=0,006. After multivariate adjustment (age, systolic arterial pressure, anthracycline treatment) baseline LAVI remained an independent predictor of CT: OR 1,25 (95% CI 1,00- 1,56), p=0,04. LAVI showed an increasing trend that has been evident since the very beginning (at three months) and continued over time. LAVI dilation appeared to be small on average, but became significant in patients with subsequent CT (Figure 1). Early LAVI dilation (0–3 months) was able to predict CT OR 1.22 (CI 1.03–1.47) p=0.02 per 5 ml/mq increase, Even when adjusted for baseline LAVI, age, and systolic arterial pressure, OR 1.31 (CI 1.07–1.58), p=0.004. In patients who had mitral regurgitation at baseline, there was no significant worsening of regurgitation overtime.

Conclusion

Baseline LAVI, as assessed by routine practice, provides an incremental predictive value about CT risk over the other known clinical features. On top, LAVI dilation over time seems to begin before LVEF decreases, and hence could anticipate the development of left ventricular dysfunction. Even if LAVI is a simple and well known echocardiographic measurement, it could be used in this newborn context to stratify patients after validation with prospective studies.
P2457Left atrial strain parameters predict clinical outcomes in patients with HFmrEF and HFpEF
Authors: Vrettos A , Al Saikhan L , Matiti L , Plymen C , Low B , Nihoyannopoulos P
Published: October 2019

Background

Heart failure with preserved ejection fraction (HFpEF) and with mid-range ejection fraction (HFmrEF) are conditions sharing similar diagnostic criteria and symptoms. Left ventricular (LV) diastolic dysfunction has often been considered central to the pathophysiology of both, as determined by current conventional echocardiographic measures of elevated filling pressure and/or an increased in left atrial (LA) volume. However, the independent prognostic importance of LA function, beyond clinical predictors and LV features, in those groups remains unclear.

Aims

To evaluate the prognostic value of LA function measured by speckle tracking echocardiography in patients with new diagnosis of HFpEF and HFmrEF.

Methods

A total of 171 consecutive patients diagnosed with HFpEF with an Ejection Fraction (EF) ≥50%, or HFmrEF with an EF of 40–49% were prospectively enrolled and followed up. Follow-up was completed in 134 patients with HFpEF (n=100) and HFmrEF (n=34) for a median period of 57 months. Baseline characteristic and comorbidities were recorded, as well as conventional resting echocardiographic parameters of systolic and diastolic function. Left atrial phasic function was analysed using 2D-Specle Tracking. Peak-atrial longitudinal strain (PALS) and peak-atrial contraction strain (PACS) were measured, reflecting LA reservoir and pump function respectively. We looked at the relationship of traditional parameters of systolic and diastolic function and LA strain, with the following cardiovascular (CV) events: acute coronary syndromes, new atrial fibrillation, cerebrovascular events, HF-related admissions and cardiac deaths.

Results

During a median follow up period of 57 months (range 11.10), of 134 patients, 42 (31%) had at least one CV event, 10 (8%) out of whom had at least one HF-related hospitalization and 5 (4%) had cardiac death. 92 patients (69%) remained event-free. In univariate analysis, lower PALS and PACS were associated with increased risk for the composite endpoint of all CV-events (PALS OR=0.92 p<0.01 and PACS OR=0.92 p<0.05), but only PALS predicted HF admissions (PALS OR=0.86 p<0.05). In multivariate analysis after adjusting for LV EF, E/e' and LAVi, PALS remained significant at predicting CV-events (OR=0.91 p<0.05) and HF admissions (OR=0.85 p<0.05), but PACS did not. Amongst all echocardiographic parameters measured, PALS had the greatest Area Under the Curve at Receiver Operating Characteristics analysis (AUC=0.78 p<0.05) and a PALS value of <23% best predicted future HF-related admissions (sensitivity 0.9, specificity 0.6).

Conclusion

LA dysfunction in HFpEF and HFmrEF is associated with a higher risk of CV events and HF hospitalizations. The association of LA strain with HF hospitalization remained significant after adjustment for systolic and diastolic parameters.
P2461The presence of L wave was associated with non-invasively estimated left atrial stiffness in heart failure patients
Authors: Masai K , Goda A , Ohta Y , Oshita T , Asakura M , Ishihara M
Published: October 2019

Background

The mid-diastolic L wave is recorded as mid-diastolic mitral forward flow with conventional Doppler echocardiography. L wave is occasionally detected in heart failure (HF) patients but its mechanism of occurrence is still unknown. It is hypothesized that L wave was induced by a positive atrioventricular gradient caused by left atrial filling via pulmonary veins, and the magnitude of the L wave is augmented by increasing ventricular stiffness. We speculate that also Left atrium (LA) function will relate with the presence of L wave because the L wave flow occurs passing LA. LA function has been known to have reservoir, booster pump and conduit function. It is reported that LA conduit function related to LA stiffness. The aim of this study is to clarify the association between LA functions and presence of L wave in HF patients.

Methods and results

Eighty two patients who admitted to our hospital for HF were enrolled in this study. We performed echocardiography before discharge. LA speckle-tracking strain was analyzed by an external software program using apical 4 chamber view. Reservoir function was measured as peak strain value at end systole, and booster pump function was measured as the value of atrial contraction. Conduit function was calculated as the difference of the peak value at end systole and atrial contraction. There were 23 patients who had L wave before discharge and 59 patients without L wave. Transmitral E wave (E) and left atrial volume index (LAVI) were higher in patients with L wave than in those without L wave. LA reservoir strain was not different in two groups, but poster pump strain was lower and conduit strain was higher in patients with L wave than those without. LA reservoir strain and booster pump strain weakly correlated with A wave velocity (r=0.39 p=0.004, r=46 p=0.001) and LAVI (r=−0.23 p=0.0383, r=−0.31 p=0.005), but conduit strain had no correlation with A wave (r=0.12 p=0.26) and LAVI (r=−0.04 p=0.67). In multivariate regression analysis for the presence of L wave with A wave velocity, LAVI and LA conduit strain, LA conduit strain remained independent predictors of the presence of L wave (HR 1.12 95% CI 1.04–1.23; p=0.004).

Conclusion

LA conduit function was not correlated with conventional echo parameters of LA function (A wave velocity and LAVI). The presence of L wave was associated with LA conduit strain.
P2462Left atrial appendage wall velocity evaluated by transthoracic echocardiography is a feasible parameter for predicting cardiac prognosis in patients with heart failure
Authors: Hashimoto N , Watanabe T , Tamura H , Tsuchiya H , Wanezaki M , Kato S , Nishiyama S , Arimoto T , Takahashi H , Shishido T , Watanabe M
Published: October 2019

Background

It was reported that left atrial (LA) remodeling is occurred in patients with heart failure (HF), and increased LA volume index (LAVI) is a feasible predictor for poor prognosis of HF. It was reported that LA remodeling is associated with LA appendage (LAA) dysfunction. We previously reported that LAA wall motion velocity (LAWV) obtained by transthoracic echocardiography (TTE) can noninvasively evaluate LAA dysfunction. However, it remains to be determined whether LAWV is useful for predicting poor prognosis in patients with HF.

Purpose

We investigated whether LAA dysfunction assessed by LAWV is associated with poor prognosis in patients with HF.

Methods

We performed TTE at discharge in 217 consecutive patients who hospitalized for HF (126 males, 71±13 years) and prospectively followed them up. LAWV was measured using Doppler tissue imaging at the LAA tip from the parasternal short-axis view on TTE imaging.

Results

There were 86 patients with cardiac events including 14 cardiac deaths and 72 rehospitalizations for HF during a median follow-up period of 404 days (interquartile range 168–748 days). LAWV was significantly lower in patients with cardiac events than in those without. LAWV was significantly decreased with advancing left ventricular diastolic dysfunction grade. Kaplan-Meier analysis demonstrated that significantly higher cardiac event rate was observed in patients with low LAWV (log-rank test, P=0.004). Cox multivariate hazard analysis revealed that LAWV was an independent predictor for cardiac events after adjusting for confounding factors (hazard ratio 0.57, 95% confidence interval 0.40–0.82, P<0.05). Further, we categorized the patients into 3 groups based on the median of LAWV and left atrial volume index (LAVI), and Kaplan-Meier analysis showed that patients with both low LAWV and high LAVI had the highest rate of cardiac events among 3 groups (log-rank test, P<0.001; Figure).

Figure 1

Conclusion

LAWV may be a feasible parameter for predicting cardiac prognosis in patients with HF.
P2463Advanced interatrial block is a surrogate for left atrial strain reduction which predicts atrial fibrillation and stroke
Authors: Lacalzada Almeida J , Armarnani Armarnani V , Garcia-Niebla J , Izquierdo-Gomez M M , Elosua R , Jimenez-Sosa A , Baranchuk A , De La Rosa-Hernandez A , Mari-Lopez B , Baez-Ferrer N , Duque-Gonzalez A , Laynez-Cerdena I , Barragan-Acea A , Bayes De Luna A
Published: October 2019

Background

The association between advanced interatrial block (aIAB) and atrial fibrillation (AF) is known as “Bayes' Syndrome”. There is little information on the prognostic role that new speckle tracking echocardiographic (STE) imaging techniques could play in it.

Purpose

We have examined the relationship between left atrial (LA) STE and the prediction of new-onset AF and/or stroke in IAB patients.

Methods

Observational study with 98 outpatients: 55 (56.2%) controls with normal ECG, 21 (21.4%) with partial IAB (pIAB) and 22 (22.4%) with aIAB. The end-point was new-onset AF, ischemic stroke, and the composite of both.

Results

During a mean follow-up of 1.9 (1.7–2.3) years, 20 patients presented the end-point (18 new-onset AF and 2 strokes): 8 (14.5%) in the control group, 3 (14.3%) in pIAB and 9 (40.9%) in aIAB, p=0.03. In multivariable comprehensive Cox regression analyses, a decrease of strain rate during the booster pump function phase (SRa) was the only variable independently related to the appearance in the evolution of the end-point, in the first model (age, P wave duration and SRa): HR 19.9 (95% CI, 3.12–127.5), p=0.002 and in the second (age, presence of aIAB and SRa): HR 24.2 (95% CI, 3.15–185.4), p=0.002.

Conclusions

In patients with IAB, a decrease in absolute value of LA SRa with STE predicts new-onset AF and ischemic stroke.

Acknowledgement/Funding

None
P2468Clinical and cardiac structural differences between paroxysmal and persistent/permanent non-valvular atrial fibrillation
Authors: Bhat A , Chen H H L , Khanna S , Gan C H , Menzies R , Nunes C M , MacIntyre R , Tan T C
Published: October 2019

Background

Atrial Fibrillation (AF) is a heterogeneous condition and is traditionally classified by duration (paroxysmal, persistent and permanent). There is a relationship between AF and left atrial (LA) remodeling, with increased likelihood of AF recurrence and maintenance with increasing LA volumes.

Purpose

To assess clinical and cardiac structural differences between the subtypes of AF.

Methods

We examined 1247 (68±13.4y; 50% men) consecutive admissions presenting to our institution with the primary diagnosis of AF. Repeat admissions (n=263) were excluded. Of remaining 984 subjects, a majority had diagnosed paroxysmal (72.2%), with lower numbers of persistent (23.4%) and permanent (4.4%) AF. Echo parameters of cardiac chamber size and function were examined in a subset of subjects with complete echo (n=646) performed during incident hospital admission.

Results

There were significantly higher rates of diabetes mellitus (p=0.03), ischaemic heart disease (IHD; p=0.04) and peripheral vascular disease (PVD; p=0.02) in those with persistent/permanent AF compared to paroxysmal AF. No significant differences in age (p=0.19), BMI (p=0.42), OSA (p=0.05), or hypertension (p=0.76) was noted. There were significant differences in left ventricular (LV) mass and systolic function, LA size and function between the two groups (Table 1). Receiver operator curve analysis revealed that LAEF was a discriminator for persistent/permanent AF with an area under the curve of 0.689 (95% CI, 0.646 to 0.732; p<0.001).

Echo parameters in AF subtype Echocardiographic Parameters Paroxysmal AF (n=433) Persistent and Permanent AF (n=213) Significance (p value) LVEDD (cm) 4.8±3.0 5.0±0.9 0.29 LVESD (cm) 3.3±1.3 3.7±1.1 <0.01 IVS thickness (cm) 1.2±0.7 1.1±0.3 0.44 PW thickness (cm) 1.1±0.7 1.1±0.2 0.77 LV mass (g) 92.3±28.3 108.2±35.3 <0.01 LVEF (%) 56.1±14.1 47.4±16.8 <0.01 LA Expansion Index 89.4±69.1 53.4±40.3 <0.01 Min LA Volume indexed (ml/m2) 18.9±17.2 27.3±20.6 0.01 Max LA Volume indexed (ml/m2) 32.5±19.2 37.7±15.3 <0.01 LAEF (%) 41.8±16.4 31.5±13.6 <0.01

Conclusions

Our results suggest diabetes, IHD and PVD are associated with persistent/permanent AF. Additionally, greater LA remodeling and reduced atrial function was noted in this group, suggestive of an association between duration of AF electrical burden and LA remodeling and function.
P2477Assessment of intraventricular flow dynamics in acute heart failure studied by Vector Flow Mapping
Authors: Masuda K , Minami S , Stugaard M , Kozuma A , Takeda S , Nakayama T , Asanuma T , Nakatani S
Published: October 2019

Background

Although left ventricular (LV) flow dynamics should be closely related to LV morphology and function, little is known about how heart failure (HF) changes it. Pathline Analysis (PA), a recently developed software based on Vector Flow Mapping (VFM, Hitachi), enables us to trace the virtual blood particles entering to the LV in diastole and being ejected in systole. We investigated the change of flow dynamics in HF induced in dogs using PA.

Methods

In 15 open-chest dogs, HF was induced by intracoronary injection of microspheres. Color Doppler images of apical long-axis view were acquired using Prosound F75 (Hitachi) before and after HF and were analyzed by PA. We calculated the ratio of the numbers of entering particles in diastole and ejected particles in systole (ejection rate) and the distance reached by the particles in diastole corrected by the LV long-axis diameter (propagation distance). Apical and basal short axis images were acquired using GE Vivid E9 and were analyzed for peak rotation and peak twist.

Results

After inducing HF, LV end-diastolic pressure increased from 6±2 to 15±5 mmHg (p<0.001) and ejection fraction (EF), apical peak rotation and peak twist decreased significantly (EF; 58±5 to 36±8%, apical peak rotation; 14±5 to 3±2 degree, peak twist; 19±5 to 6±3 degree, p<0.05, respectively). PA showed most of the entering particles to the LV were ejected in the following systole at the control stage, but in HF, a significant part of the entering particles were not ejected and remained in the LV (Figure). Ejection rate decreased from 50±11 to 26±11% (p<0.001) and the propagation distance decreased from 85±9 to 66±13% (p<0.001) after inducing HF. There were significant relationships between indices obtained by PA and EF and peak twist (Table).

Conclusion

A significant part of inflow is not ejected directly to the outflow in the next systole and remains in the LV in HF, suggesting inefficient flow dynamics.
P2484SGLT2 inhibitors in diabetes with CKD
Authors: Malik A H , Yandrapalli S , Goldberg M , Jain D , Frishman W H , Aronow W S
Published: October 2019

Background

DM mellitus (DM) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular morbidity and mortality. Current guideline recommendations do not support the use of SGLT2 inhibitors in patients with CKD stage III or higher. We performed a comprehensive meta-analysis to evaluate their cardiovascular effects in patients with type 2 DM and CKD stage III or higher.

Methods

A comprehensive search was performed in PubMed, Cochrane central and Embase for randomized controlled trials (RCTs) evaluating the cardiovascular outcomes of SGLT-2 inhibitors in patients with type 2 DM and CKD defined as glomerular filtration rate of <60ml/min. There were no data available on patients with end-stage renal disease. We calculated treatment effects and associated standard errors from the corresponding odds ratio and confidence interval. These values were imputed in software R to perform meta-analysis via generic inverse variance method. Additionally, we conducted a network meta-analysis to compare the relative efficacy and safety of each agent.

Results

Data from 7 RCTs and 6,527 participants was available. In patients with type 2 DM and CKD, SGLT-2 inhibitor use resulted in a significant reduction of myocardial infarction (22%), heart failure hospitalization (39%), and major adverse cardiac events (20%) (all p-value<0.05). There was also a trend towards a reduction in stroke and cardiovascular mortality. In a network meta-analysis, canagliflozin was the most effective in reduction of MI, stroke and heart failure hospitalization. Empagliflozin performed better for the outcome of cardiovascular mortality, but the results failed to reach significance.

Conclusion

SGLT-2 inhibitors significantly improve cardiovascular outcomes in patients with type 2 DM and CKD stage III or higher. This meta-analysis confirms that renal dysfunction should not be a deterrent to the widespread utilization of SGLT-2 inhibitors. Further studies are needed to identify the mechanisms behind these improved cardiovascular outcomes

Acknowledgement/Funding

None