bluuebunny/crossref_metadata_2025 huggingface dataset:
6115Influence of microvascular function and coronary flow in the diagnostic precision of resting full-cycle ratio
Authors: Tamargo Delpon M A , Gutierrez Ibanes E , Diez-Delhoyo F , Gonzalez-Saldivar H , Rivera A R , Casado A , Vazquez M E , Sanz R , Soriano J , Elizaga J , Fernandez-Aviles F J
Published: October 2019

Introduction

Resting full-cycle ratio (RFR) has been recently described as a non-hyperemic index of coronary stenosis with good concordance with Fractional Flow Reserve (FFR). However, there is no information concerning the influence of microvascular function and coronary flow on RFR results.

Purpose

To determine if the accuracy of this novel parameter might be influenced by changes in microvascular function.

Methods

133 patients admitted in our center between July 2016 and December 2017 underwent coronary physiology study of an angiographically intermediate lesion. 67 subjects presented with AMI and an intermediate lesion in a non-culprit artery, and 66 subjects stable coronary disease. We performed FFR, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR) and Resistance Reserve Ratio (RRR) in all of them. We calculated RFR retrospectively from the pressure tracings.

Results

Coronary physiology parameters showed a non-normal distribution and are presented as median [IQR]: FFR 0.86 [0.79–0.92]; CFR 2.05 [1.4–2.95]; IMR 20.5 [14–32.55]; RRR 2.5 [1.85–3.63]; RFR 0.897 [0.83–0.94]. Patients with abnormal CFR displayed lower RFR values although FFR was not markedly affected (Table 1). These findings remained irrespective of the clinical scenario at presentation.

61 patients had a CFR lower than 2. Correlation between RFR and FFR was not significantly different in patients with abnormal CFR than in those with normal CFR (0,73 vs 0,88; p=0,067) (Figure 1); however, overall binary agreement between RFR and FFR was worse in patients with a low CFR (69% vs 83%; p=0,047).

48 patients had a high IMR (>25). Linear correlation between RFR and FFR was similar in patients with high and normal IMR (0,81 vs 0,83; p=0,784); likewise, binary concordance showed no significant difference between both groups (77% vs 75%, p=0,78).

The mean difference between RFR and FFR was 0,025. This was only influenced by CFR: patients with a low CFR had a smaller difference than those with a normal CFR (0,012 vs 0,035; p=0,019).

Physiology parameters by CFR group Normal CFR (≥2) Low CFR (<2) P-value FFR 0.88 [0.82–0.93] 0.84 [0.79–0.92] 0.14 RFR 0.91 [0.88–0.95] 0.86 [0.80–0.92] 0.0009 IMR 16.5 [13–27] 25 [16–45.5] 0.002 RRR 3.6 [2.7–4.9] 1.7 [1.3–2.1] <0.0001 Physiological coronary parameters (Median [IQR]) according to CFR.

Correlation between RFR and FFR by CFR

Conclusion

RFR has good overall correlation and concordance with FFR. However, RFR has a lower diagnostic accuracy in patients with a low CFR.

Acknowledgement/Funding

None
6125High wall shear stress predicts plaque rupture of the aortic arch: computational fluid dynamics model and non-obstructive general angioscopy study
Authors: Kojima K , Hiro T , Ebuchi Y , Morikawa T , Migita S , Tamaki T , Mineki T , Akutsu N , Murata N , Kitano D , Sudo M , Fukamachi D , Takayama T , Hirayama A , Okumura Y
Published: October 2019

Background

Wall shear stress (WSS) has been considered as a major determinant of aortic atherosclerosis. Recently, non-obstructive general angioscopy (NOGA) was developed to be able to visualize a variety of its atherosclerotic pathology, including in vivo ruptured plaque (RP) in the aorta. We, therefore, investigated the relationship between NOGA derived RP in the aortic arch and the stereographic distribution of WSS by using computational fluid dynamics modeling (CFD) on three-dimensional CT angiography (3D-CT).

Methods

We investigated 30 consecutive patients who underwent 3D-CT before and NOGA during coronary angiography. WSS in the aortic arch was measured with an application of CFD based on finite element method by using uniform inlet and outlet flow conditions. Aortic RP was detected by NOGA.

Results

The maximum and mean values of WSS were 67.2±29.2 Pa and 2.4±0.6 Pa. A total of 18 RPs was detected by NOGA. The patients with a distinct RP showed a significantly higher maximum WSS in the whole aortic arch, and the greater and lesser curvature of the aortic arch than those without it (73.3±29.0 Pa vs 50.4±15.2 Pa, p=0.035, 95.0±27.5 Pa vs 42.8±25.2 Pa, p=0.003, 70.8±29.3 Pa vs 46.1±11.9 Pa, p=0.013, respectively), whereas there was no significant difference in the mean WSS between those with and without it. In a multivariate analysis, the maximum value of WSS was an independent predictor of RP in the aortic arch (odds ratio 1.05, 95% confidence interval 1.01–1.13, p=0.019).

Representative picture of WSS and NOGA

Conclusions

Aortic RP detected by NOGA was strongly associated with the higher maximum WSS in the aortic arch derived by CFD using 3D-CT. Maximum WSS may explain the underlying mechanism of not only aortic atherosclerosis, but also aortic RP.
6132Trends in mortality from heart failure between 1980 and 2016
Authors: Santos S C , Villela P B , Klein C H , Queiroga D , Oliveira G M M
Published: October 2019

Background

Heart failure (HF) is a highly prevalent disease with high mortality rates worldwide, representing the final stage of a large set of cardiovascular diseases.

Purpose

To evaluate the trend of mortality rates fromHF, by sex and Brazilian geoeconomic region, between 1980 and 2016.

Methods

Time series analysis of the underlying causes of death from HF between 1980 and 2016. Population and death-related data were obtained from the Information Technology Department of the Brazilian Unified Health System (DATASUS/MS). Annual crude mortality rates per 100,000 inhabitants were calculated. Standardized rates were estimated according to the age structure of the Brazilian population in the year 2000. Mortality rates were evaluated in all federal units (FedUs) that comprise the Braziliangeoeconomicregions (Northern, Northeastern, Southeastern, Southern and West-Central).

Results

In Brazil, of the 35,348,374 deaths recorded between 1980 and 2016, 3.2% had HF as the underlying cause. The crude mortality rates from HF in both sexes showed a similar reduction trend over the period. In men, those rates ranged from 13.77 in 1980 to 6.69 per 100,000 inhabitants in 2016, while in women, those rates ranged from 13.15 in 1980 to 7.27 per 100,000 inhabitants in 2016 (Figure 1). Despite the relative stability in the last decade, the standardized rates (Figure 1 - Std) showed a similar trend, but with lower values at the end of the study period. Of all FedUs, only Maranhão (Northeastern region) showed a mortality rate similar to that observed in 1980 (10.44 per 100,000 inhabitants in 1980 and 10.65 per 100,000 inhabitants in 2016). All the other FedUs showed a reduction over the period. The FedUs of the Southeastern, Southern and West-Central regions had the highest reductions, especially Espírito Santo (Southeastern region), Rio Grande do Sul (Southern region) and the Federal District, which decreased from 38.98, 53.34 and 28.56 in 1980 to 3.43, 8.49 and 4.33 per 100,000 inhabitants in 2016, respectively.

Figure 1

Conclusions

The crude and standardized mortality rates from HF decreased in the last 37 years, probably because of the better control of risk factors and the advances in HF treatment. The most important reductions occurred in the richest regions of the country, which may be related to the improvement of socioeconomic factors.
P4987Long term follow up after comparison of two strategies in a chest pain unit: exercise echocardiography and multidetector computed tomography
Authors: Pineiro-Portela M , Peteiro-Vazquez J , Bouzas-Mosquera A , Martinez-Ruiz D , Yanez-Wronenburger J C , Pombo F , Vazquez-Rodriguez J M
Published: October 2019

Introduction and objectives

Up to 5% patients with acute chest pain present an acute coronary syndrome (ACS). This study aimed to compare peak exercise echocardiography (ExE) and multidetector computed tomography (MCT) in patients referred to a chest pain unit.

Methods

203 patients with ≥1 cardiovascular risk factors, no ischemic ECG changes and negative biomarkers were randomized to ExE (n=103) or MCT (n=100). The endpoints were hard events (cardiovascular death and non-fatal myocardial infarction), combined events (hard events and revascularizations), and combined events plus readmissions during follow-up. Cost of either strategy was also investigated.

Results

Mean age was 64±11 years and 131 patients were male. Hypertension was seen in 71%, hypercholesterolemia in 74%, diabetes mellitus in 28%, and smoking in 21%. Most of the patients had a low TIMI risk score (68% TIMI I and 32% TIMI II). Mean follow-up was 4,7±2,7 years. Invasive angiography due to positive/nonconclusive results was performed in 34 of the patients, 103 submitted to SE and in 27 of the 100 submitted to MCT (33% vs. 27%, p=0.15). A final diagnosis of acute coronary syndrome was achieved in 53 patients (30 [88%] in the ExE group and 23 [85%] in the MCT group, p=0.12). There were no significant differences between groups in hard events (5 [5%] patients in the ExE group and 7 [7%] in the MCT group, p=0,42), combined events (35 patients [34%] in the ExE group and 29 [29%] in the MCT group), and combined events plus readmissions (43 [42%] patients in the ExE group and 41 [41%] in the MCT). The median stay in hospital was 7 (5–10) days in the ExE group and 8 (5–10,25) in the MCT group (p=NS). For patients with negative results by either technique the mean stay was less than 8 hours. There were no differences in the global cost, although it was lower for patients with negative ExE (557 € vs. 706 €, p<0,02) as compared to those with negative TCM.

Conclusions

Both MCT and ExE are equally effective for the stratification of patients with low to moderate probability of ACS admitted to a chest pain unit. The cost was similar with both strategies, although significant lower in ExE when negative studies were compared.
P4988Beta-blockers in diabetes with stable coronary heart disease - a cause for concern?
Authors: Malik A H , Shetty S , Kar K , El Accaoui R
Published: October 2019

Background

Beta-blocker (BB) therapy is a cornerstone for the treatment of coronary heart disease (CHD). The evidence of the benefit from long-term BB therapy in diabetic patients with stable CHD is scarce. This meta-analysis summarises the evidence relating to the BB therapy in diabetic patients with stable CHD.

Methods

A meta-analysis was performed according to PRISMA and MOOSE guidelines for reporting of systematic reviews of observational studies. PubMed, Embase, and Cochrane central were searched and two authors independently screened studies for eligibility. The quality of studies was assessed with the Newcastle Ottawa scale. The primary outcome of interest was all-cause mortality, cardiovascular (CV) mortality and major adverse cardiovascular events (MACE) in diabetic patients with and without BB therapy. A generic inverse variance model was used to pool the odds ratio or hazards ratio from included studies to calculate the overall effect estimate. The significance threshold was set at p-value <0.05. Heterogeneity was assessed by I2.

Results

Four non-randomized studies with 9,515 participants were selected for the analyses. Four studies were post-hoc analyses of randomised controlled trials, and 1 article was an analysis of a nationally representative survey. In a fixed effects model, BB therapy in diabetic patients with stable CHD was found to be associated with increased risk of CV mortality, and MACE (27%, and 32% respectively; p-value <0.05) and was not associated with a reduction in all-cause mortality (HR 1.12; 95% CI 0.94–1.33; p-value =0.22).

Conclusion

BB therapy in diabetic patients with stable CHD appears to be linked to higher mortality. Large randomised trials are needed in this population to confirm these findings.

Acknowledgement/Funding

None
P4996The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload
Authors: Koop A M C , Videira R F , Ottaviani L , Poels E M , Van De Kolk K W , Lourenco A , Nascimento D S , De Windt L J , Falcao-Pires I , Berger R M F , Da Costa Martins P A
Published: October 2019

Introduction

Heart and neural crest derivatives expressed-2 (Hand2) has been identified as an important embryonic basic helix-loop-helix-transcription factor, with different functions in the development of the first and second heart field, from which the left and right ventricle originate, respectively. Our previous work revealed that Hand2, under conditions of left ventricular (LV) pressure overload, is re-expressed in the adult heart and activates a “fetal gene” program contributing to pathological cardiac remodeling. Ablation of cardiac expression of Hand2 resulted in protection to cardiac stress and attenuated maladaptive remodeling.

Purpose

In this study, we aimed at unraveling the role of Hand2 during cardiac remodeling in response to right ventricular (RV) pressure overload induced by pulmonary artery banding (PAB).

Methods

Hand2F/F and MCM− Hand2F/F mice were treated with tamoxifen (control and knockout, respectively) and subjected to six weeks of RV pressure overload induced by PAB. Echocardiographic and MRI derived hemodynamic parameters, and molecular remodelling were assessed for experimental groups and compared to sham-operated controls (Fig. 1a). RNA sequencing and gene ontology enrichment analysis were performed to compare the dysregulated genes between the pressure overloaded RV of the control and Hand2 knockout mice.

Results

After six weeks of increased pressure load (Fig. 1b), levels of Hand2 increased in the control banded animals but, as expected, remained absent in the knockout hearts (Fig. 1c). In contrast to the what was previously observed for the pressure overloaded LV, in the pressure loaded RV, Hand2 depletion resulted in more severe remodelling and dysfunction as reflected by increased hypertrophic growth, increased RV end-diastolic and end-systolic volumes as well as decreased RV ejection fraction (Fig. 1d–g). In addition, RNA sequencing revealed a distinct set of genes that are dysregulated in the pressure-overloaded RV, compared to the previously described pressure-overloaded LV. These include components of the extracellular matrix structure, collagen assembly and organization and several types of collagens. Genes associated with inflammation response, adhesion and muscle organization were also affected in the RV of the Hand2 KO mice (Fig. 1h).

Figure 1

Conclusion

Cardiac-specific depletion of Hand2 is associated with severe cardiac dysfunction in conditions of RV pressure overload. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressure overload. This study highlights the need to better understand the molecular mechanisms driving pathological remodelling of the RV, in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure.
P5008Empagliflozin in a real-world chronic heart failure population
Authors: Rocha M L , Cunha G C , Gomes R M , Morais R , Campos L , Araujo I , Fonseca M C
Published: October 2019

Introduction

Heart Failure (HF) is a burdensome syndrome with significant mortality, morbidity and costs. Its prognosis is further aggravated by diabetes mellitus (DM). The EMPA-REG OUTCOME trial suggested that empagliflozin significantly reduced HF hospitalizations compared to placebo in patients with DM.

Purpose

We aimed to investigate which patients with chronic HF and DM in the outpatient setting could have been enrolled in the main empagliflozin trial.

Methods

This analysis is based on a retrospective cohort enrolling chronic HF patients who consecutively attended the HF appointment between January and July 2018. Of these, those with concomitant DM were selected and further analysed. The key EMPA-REG OUTCOME trial inclusion criteria [(i.e., hemoglobin A1c 7–10%, high cardiovascular (CV) risk and glomerular filtration rate [GFR] ≥30mL/min/1,73m2) were considered. Further, the European Medicine Agency (EMA) restriction (GFR>60mL/min/1,73m2) was also considered in an additional analysis.

Results

Of 316 patients with HF, 114 (36%) concomitantly had DM. Mean age was 74±10 years, 63% were male and most (54%) had preserved left ventricular ejection fraction. Ischemic (51%) and hypertensive (27%) HF were the most often observed etiologies. According to the inclusion criteria, 21 (18.4%) (or 5.3% when further considering the EMA restriction) HF patients could have been potentially enrolled in the main trial and derive a HF hospitalization reduction benefit from starting empagliflozin. The remainder would be excluded due to GFR<30mL/min/1.73m2 (2.6%), absence of “high CV risk” as per trial's definition (7%), HbA1c off target (18,4%) or a combination of the above criteria (53.6%). In light of the new Standards of Medical Care in Diabetes 2019, controlled patients with HbA1c off target (i.e., <7% or >10%) could be switched to a SGLT2 inhibitors, hence possibly expanding the indication to start empagliflozin to 36.8% of our HF cohort.

Figure 1

Conclusions

Roughly 1 in every 5 patients with HF and DM could have been enrolled in the main empagliflozin trial, as per key inclusion criteria, and potentially derive CV benefit from it. Thus, only a minority of our cohort shared the features for EMPA-REG OUTCOME trial inclusion, limiting the extrapolation of the trial's observed CV benefits to our HF cohort. Indeed, whether these benefits also expand to overall HF cohort is eagerly awaited by ongoing trials.

Acknowledgement/Funding

None
P5011Impact of guideline-recommended medical therapy at discharge on long-term mortality in patients with or without left ventricular dysfunction after primary PCI for STEMI
Authors: Radomirovic M , Milasinovic D , Mehmedbegovic Z , Jelic D , Zobenica V , Zaharijev S , Zivkovic I , Pavlovic A , Dudic J , Obreski A , Dolicanin A , Vukcevic V , Asanin M , Stankovic G
Published: October 2019

Background

Clinical practice guidelines provide class I recommendation for the use of angiotensin-converting enzyme inhibitors (ACE-I) and beta-blockers in patients with prior myocardial infarction and left ventricular (LV) dysfunction, whereas their use in patients without LV dysfunction is considered to be a class IIa recommendation.

Purpose

Our aim was to comparatively assess the impact of ACE-I and/or beta-blockers on 3-year mortality in patients with or without impaired left ventricular (LV) function undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).

Methods

The analysis included 4425 patients admitted for primary PCI during 2009–2015 from a prospective, electronic registry of a high-volume tertiary center, who survived initial hospitalization, and for whom information on LV function and discharge medication were available. Patients were stratified according to LV systolic dysfunction, defined as LVEF <40%. Unadjusted and adjusted Cox regression models were created to investigate the impact of beta-blocker and/or ACE-I therapy on 3-year mortality.

Results

22.9% (n=1013) had LV dysfunction, 23.0% (n=1017) received either an ACE-I or a beta-blocker and 72.2% received both medications at discharge (n=3197). The concurrent use of both ACE-I and beta-blockers was not different in LVEF≥40% vs. LVEF<40% (72.4% vs. 71.7%, p=0.43). The use of at least one of the guideline-recommended medications was associated with a significantly lower 3-year mortality in both patients with LVEF≥40% (18.7% if neither was used, 11.2% if either a beta-blocker or an ACE-I were used and 9.4% if both were used, p=0.001), and LVEF<40% (55.4% if neither was used, 32.5% if either a beta-blocker or an ACE-I were used and 22.9% if both were used, p<0.001) (Figure). After adjusting for significant mortality predictors including older age, diabetes, hypertension, renal failure, previous stroke, Killip class ≥2 and non-culprit chronic total occlusion (CTO), the concurrent use of both a beta-blocker and an ACE-I remained independently associated with lower 3-year mortality in both patients with LVEF<40% (HR 0.30, p<0.001) and LVEF≥40% (HR=0.41, p=0.001). The use of a single agent was independently associated with lower mortality in patients with LVEF<40% (HR 0.45, p=0.002), but not in patients with LVEF≥40% (HR 0.61, p=0.07).

Conclusions

Guideline-recommended use of both a beta-blocker and an ACE-I in post-MI patients was associated with a lower 3-year mortality regardless of the LV function, whereas using only one of the two agents was associated with improved prognosis only in patients with LV dysfunction, but not in patients without LV impairment.
P5016Usefulness of different electrocardiographic patterns as predictors of in-hospital mortality in acute pulmonary embolism
Authors: Alarcon P , Bilbao J A , Melchiori R , Cigalini I M , Scatularo C E , Jauregui J C , Bernal M I , Aboy J M , Ortego J , Schmidt P , Figueroa A V , Garcia Zamora S , Thierer J , Zaidel E J , Bonorino J
Published: October 2019

Background

Many electrocardiographic (ECG) patterns may be present in acute pulmonary embolism (PE), but their prevalence and association with in hospital mortality (IHM) are less well established.

Objective

Assess the correlation between different ECG patterns and IHM in patients (Pts) with PE using a whole country dataset.

Methods

Prospective multicenter registry which included Pts with acute PE hospitalized in 75 academic centers from October 2016 to November 2017. We considered the following ECG patterns: sinus tachycardia, pulmonary P waves, Q waves in DII-aVF leads, negative T waves in V1-V4, ST segment elevation in aVR and V1, atrial fibrillation or atrial flutter (AF/AF), right bundle branch block (RBBB), ST segment depression, S1Q3T3 pattern or Qr in V1. Statistical analysis was carried out using de STATA version 13.1. A value of p<0.0.5 was considered statistically significant.

Results

We included 684 Pts; mean age 63.8±16.7 years (43% male). Global IHM was 12%. The most prevalent ECG patterns were sinus tachycardia (51.7%), S1Q3T3 (24.5%), negative T waves in V1- V4 (16%), RBBB (9.9%), AF/AF (8.6%). Four ECG patterns remained statistically significant predictors of IHM on multivariate analysis: AF/AF (OR: 3.81; CI 95% 1.82–7.95, p<0.01), pulmonary P waves (OR: 3.81; CI 95% 1.2–12, p<0.04), RBBB (OR: 2.71; CI 95% 1.39–5.30, p<0.01) and sinus tachycardia (OR: 2.05; CI 95% 1.18–3.54, p<0.04).

ECG pattern and in-hospital mortality.Multivariate analysis Electrocardiographic pattern OR CI 95% p value AF/AF 3.81 1.82–7.95 <0.01 Pulmonary P waves 3.81 1.20–12.00 <0.04 RBBB 2.71 1.39–5.30 <0.01 Sinus tachycardia 2.05 1.18–3.54 <0.04 Q waves in DII-aVF 0.93 0.32–2.64 0.89 ST segment depression 1.07 0.39–2.96 0.80 Negative T waves in V1-V4 0.93 0.47–1.81 0.83 S1Q3T3 pattern 0.75 0.39–1.41 0.37 Qr in V1 2.07 0.63–6.73 0.22 ST segment elevation in aVR 2.38 0.79–7.15 0.12

Conclusions

We corroborate the usefulness of the ECG as a prognostic tool in acute PE. Four simple ECG patterns (AF/AF, Pulmonary P waves, RBBB and sinus tachycardia) were associated with a higher IHM and therefore should be considered for PE risk stratification.
P5269The impact of sarcomeric mutations on myocardial fibrosis and ventricular diastolic function in hypertrophic cardiomyopathy (SADS-TW HCM registry study)
Authors: Chen C.-Y , Lin L.-Y , Lin Y.-H , Wang Y.-C , Lee J.-K , Wu C.-K , Lin L.-C , Chen W.-J , Lin P.-C , Ho L.-T , Liu Y.-B , Lai L.-P , Hwang J.-J , Juang J.-M
Published: October 2019

Background

Hypertrophic cardiomyopathy (HCM) may manifest as diastolic dysfunction. The degree of myocardial fibrosis quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) imaging is positively correlated with the risk of sudden cardiac death, whereas the impact of sarcomeric mutations on the ventricular diastolic function and myocardial fibrosis is unclear.

Purpose

We aimed to investigate the difference of the ventricular diastolic function and the degree of myocardial fibrosis between the HCM patients with and without sarcomeric mutation.

Methods

From 2014 to 2018, we prospectively enrolled 55 unrelated patients with HCM as defined by the 2014 European Society of Cardiology guideline. All enrolled patients underwent next-generation sequencing screening of 20 sarcomeric genes and CMR examination for the evaluation of left ventricular (LV) function, mass and LGE.

Results

After comparing the results with several public databases (Taiwan Biobank, gnomAD, HGMD, ClinVar) and performing in silico analyses (SIFT, Polyphen-2, PROVEAN, REVEL, CADD), 24 pathogenic variants were identified in 22 HCM patients. Although there were no differences in demographic data and clinical presentations between the mutation-positive and mutation-negative groups, the degree of LGE (14.2±14.3 vs 6.2±8.9%, p=0.015) and left atrial diameter (4.54±0.63 vs 4.00±0.49 cm, p<0.001) were significantly higher in the mutation-positive group, whereas the LV ejection fraction, mass, strain rates, peak ejection and filling rates, peak intra-LV and tricuspid regurgitation pressure gradient were similar in both groups.

Table 1. Comparisons of the CMR parameters of HCM patients with and without sarcomeric mutation Sarcomeric mutation (+, M+), Sarcomeric mutation (−, M−), Control (C), M+ vs M− M+ vs C M− vs C n=21 n=34 n=36 P-value P-value P-value PER/LVEDV, L/s −4.73±1.18 −5.03±1.19 −3.49±0.78 0.361 <0.001* <0.001* PFR/LVEDV, L/s 4.05±1.00 3.74±1.25 5.52±1.20 0.341 <0.001* <0.001* Global radial diastolic strain rate, /s −2.49±0.99 −2.74±1.51 −2.68±0.88 0.527 0.210 0.846 Global circumferential diastolic strain rate, /s 0.89±0.19 0.92±0.30 1.49±0.32 0.684 <0.001* <0.001* Global longitudinal diastolic strain rate, /s 0.64±0.19 0.62±0.24 0.95±0.27 0.744 <0.001* <0.001* C: control; LVEDV: left ventricular end-diastolic volume; M+: sarcomeric mutation (+); M−: sarcomeric mutation (−); PER: peak ejection rate; PFR: peak filling rate. *p<0.05.

Conclusions

The HCM patients with sarcomeric mutations had a higher degree of LV myocardial fibrosis than patients without mutations, which may imply that these mutations accelerate myocardial fibrosis in HCM. Nonetheless, there was no difference in diastolic function between the patients with and without sarcomeric mutation.

Acknowledgement/Funding

None
P5278Myocardial abnormalities in people living with Human Immunodeficiency Virus (PLWH) detected using cardiovascular magnetic resonance (CMR)
Authors: Manmathan G P R , Kotecha T , Chacko L , Brown J , Little C , Knight D , Kinloch S , Barber T , Johnson M A , Burns F , Fontana M A , Rakhit R D
Published: October 2019

Background

Antiretroviral therapy (ART) has dramatically improved the prognosis in PLWH with survival nearing that of HIV negative people. PLWH may develop significant comorbidities as they age including cardiovascular disease (CVD) such as myocardial infarction, sudden cardiac death, heart failure, as well as subclinical evidence of myocardial inflammation. Overall, ART treated patients are at an increased CVD risk with some studies quoting a 2.2 fold relative risk.

Aim

To assess the incidence of functional, structural and tissue characterisation changes in PLWH using CMR with multiparametric mapping

Methods

39 PLWH (34 men, mean age 55.8±10.9, mean duration of HIV 17.8±9.29 years) and 29 healthy volunteers (20 men, mean age 45.1±8.3) underwent CMR with late gadolinium enhancement (LGE) imaging, T1 and T2 mapping.

Results

Of PLWH, only 7 scans (18%) were normal. LV ejection fraction was significantly lower and LV mass significantly higher compared to controls. Native T1, a marker of diffuse fibrosis or increased myocardial water content was no different between the groups. T2, a more specific marker of myocardial oedema, was elevated in PLWH. Sixteen PLWH (41%) had evidence of LGE including 8 with an ischaemic pattern (7 sub-endocardial and one transmural) and 8 with a non-ischaemic pattern (5 with mid-wall enhancement and 3 with RV insertion point LGE. No controls had evidence of LGE.

Student t-Test: PLWH versus controls PLWH (n=39) Control (n=29) P-value LVEF (%) 59±15 67±5 <0.01 iLVM 79±24 56±13 <0.01 Native T1 (ms) 1021±52 1001±41 0.116 T2 (ms) 48±2 46±2 <0.05 LGE 16 (41%) 0 (0%) <0.001 LVEF (%) = Left Ventricular Ejection Fraction; iLVM = Indexed Left Ventricular Mass (g/m2); LGE = Late Gadolinium Enhancement.

Conclusion

This study identifies a number of cardiac changes associated with HIV and prolonged treatment with ART. The elevated LV mass may be associated with hypertension, commonly found in PLWH. The elevated myocardial T2 compared to controls may be due to chronic inflammation associated to prolonged HIV exposure. There was no evidence of diffuse fibrosis but focal areas of non-ischaemic scar were a common finding which may relate to previous myocarditis or HIV-related cardiomyopathy. A fifth of PLWH also had evidence of previous myocardial infarction.

We propose to image asymptomatic PLWH to further classify, diagnose and treat a vulnerable group of patients who are now described as having a normal life expectancy.
P5282Comparison of cardiovascular magnetic resonance ejection fraction and left ventricular volumes by long axis feature tracking strain analysis versus standard short axis stack contour tracing
Authors: Vasquez M , Puntmann V , Nagel E
Published: October 2019

Introduction

Cardiovascular magnetic resonance (CMR) feature tracking (FT) is based on the recognition of endocardial features obtained during standard CMR cine imaging to be tracked and followed throughout the cardiac cycle. Global longitudinal strain (GLS) has been proposed as a superior measure for diagnosis and prognosis than ejection fraction (EF). However, EF remains an important primary parameter to describe cardiac function. A rapid determination of GLS based on three long axis views (LAX) allows for a simultaneous calculation of EF without additional imaging or post-processing promising a significant reduction of scan and post-processing time.

Purpose

The purpose of this work is to compare the LV volumes and EF obtained during assessment of GLS based on CMR feature tracking with standard analysis of a short axis (SAX) stack used as the reference standard.

Methods

75 consecutive patients underwent a routine clinical scan obtaining a full SAX stack as well as 3 standard LAX views using either 3-Tesla or 1,5-Tesla clinical scanners. We determined LV volumes and EF based on the reference standard as well as feature tracking analysis with additional GLS. A p value <0.01 was considered statistically significant.

Results

Mean EF was 45.9% using standard SAX (range, 13%-72%) and 51.1% using triplanar feature tracking (r=0.950; p<0.0001, figure 1A). Bland-Altman analysis showed a systematic bias of 5,27%; without proportional bias (figure 1B). End-diastolic volumes (r=0,975; p<0.0001) and end-systolic volumes (r=0.985; p<0.0001) demonstrated similar results. Mean GLS was −17.3% (range: −30,7% to −3,3%) and was significantly correlated with standard EF (r=−0,884; p<0.0001). Classification of EF into categories: reduced, mid-range or preserved (<40%, 40–49%, ≥50%) remain unchanged in 79% of patients when using EF by feature tracking analysis. Twelve of 16 reclassifications occurred in the mid-range category.

Figure 1

Conclusion

There is a good correlation between EF obtained by rapid post-processing of GLS with EF based on a full SAX stack resulting in an identical categorization in 79% of patients. Reduction of EF within the mid-range might be best assesses by the standard SAX stack.
P5316Birthweight, childhood growth patterns and left ventricular structure at midlife: Northern Finland 1966 Birth Cohort Study
Authors: Korpela N , Kaikkonen K , Auvinen J , Tulppo M P , Junttila J , Perkiomaki J , Jarvelin M.-R , Huikuri H V , Kiviniemi A M
Published: October 2019

Background

Higher cardiac left ventricular (LV) mass (LVM) has independently been associated with cardiovascular risk and mortality. Changes in LV structure have been observed in children with obesity. However, information about the long-term influence of early growth on LV structure is limited.

Purpose

To explore the associations between early growth patterns, specifically birth weight, age and body mass index (BMI) at infant BMI peak and at childhood BMI rebound, and LV structure at midlife.

Methods

At the age of 46, a sample of the participants of the Northern Finland Birth Cohort 1966 took part in follow-up examinations. A randomly selected subpopulation was enrolled to echocardiographic examinations (n=1124). BMI at various ages in childhood was calculated from frequent anthropometric measurements collected from child welfare clinical records. Age and BMI at BMI peak (n=541, mean age 9.0 months) and at BMI rebound (n=657, mean age 5.8 years) were derived from random effect models.

Results

Birth weight (n=1124), BMI at BMI peak and at BMI rebound were directly associated with LVM (beta [standardized]: 0.171, 0.186 and 0.223, respectively, p<0.001 for all) and LVM index (LVMI) (beta: 0.146, 0.120 and 0.120, respectively, p<0.01 for all) at midlife. All the associations, except that between BMI at BMI peak and LVMI, remained significant after adjustments for gender, adult blood pressure, heart rate, antihypertensive medications, heart diseases and diabetes (p<0.05 for all). Significant interaction between gender and age at BMI rebound was observed in LVMI. Age at BMI rebound was inversely associated with LVMI in both genders, the association being stronger in males (beta: −0.212, p<0.001) compared to females (beta: −0.117, p=0.025) and independent of potential confounders. There were direct univariate associations of birth weight and BMI at BMI peak and rebound with LV relative wall thickness (p=0.009–0.019), which were largely explained by potential confounders. However, the association of birth weight with LV relative wall thickness retained its significance even after relevant adjustments (beta: 0.097, p=0.001). After additional adjustments for adult BMI, only associations of birth weight and BMI at BMI peak with LVM remained significant, which, however, did not remain significant after additional adjustment for adult height.

Conclusions

This study shows that birth weight and early growth patterns are associated with LV structure at midlife, which is largely explained by adult BMI. Therefore, the relationship between early growth patterns to LV structure in the adulthood may be largely explained by their strong tracking to obesity and related cardiovascular risk factors at midlife and to some extent by normal somatic growth.
P5323HDL-C and all-cause mortality in a high-risk population: impact of LDL-C
Authors: Dhindsa D , Sandesara P B , Liu C , Topel M , Mehta A , Allard-Ratick M , Sperling L , Quyyumi A
Published: October 2019

Background

Previous studies have shown increased cardiovascular (CV) risk with both high (>60mg/dl) and low concentrations of high-density lipoprotein cholesterol (HDL-C). The effect of elevated HDL-C levels (>60mg/dL) at differing LDL-C concentrations on outcomes is unknown.

Purpose

To study the relationship between elevated HDL-C levels (>60mg/dl) in relation to LDL-C concentration (greater vs less than 70mg/dL) and adverse CV outcomes in an at-risk population.

Methods

Participants included 5,746 individuals (mean age 63.3±12.4 years, 35% female, 23% African American) enrolled in the cardiovascular biobank. Individuals were stratified by HDL-C categories (<30, 31–40, 41–50, 51–60 and ≥60 mg/dL) and LDL-C categories (≥70 and <70 mg/dL). A Cox proportional hazards model was used to examine the association between HDL-C and adverse outcomes, with HDL-C 41–50 mg/dL as the reference group. All models were adjusted for age, race, sex, body mass index, hypertension, smoking, triglycerides, heart failure history, myocardial infarction (MI) history, diabetes, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use, beta blocker use, statin use, aspirin use, estimated glomerular filtration rate, obstructive coronary artery disease.

Results

Over a median follow-up of 6.2 years (25th-75th percentiles = 3.3–8.0 years), a total of 286 MIs, 691 CV deaths and 1,093 all-cause deaths occurred. Individuals with HDL-C ≥60 mg/dL (n=632) had an increased risk of all-cause mortality with an LDL-C ≥70mgdL (HR 1.59; 95% CI=1.10–2.29, p=0.013) after adjustment for the aforementioned variables. This association was not statistically significant with LDL-C <70mg/dL (HR 1.16; 95% CI 0.60–1.21, p=0.66). There was no statistically significant difference for CV death or MI at elevated HDL-C in either group.

Conclusion

Elevated HDL-C levels is associated with increased all-cause mortality with an LDL-C ≥70mg/dL, though does not appear to be associated with worse outcomes when LDL-C is <70mg/dL.
P5326Effect of evolocumab on lipoprotein(a) levels: results across 15 studies
Authors: Toth P P , Jones S R , Monsalvo M L , Elliott-Davey M , Lopez J A G , Banach M
Published: October 2019

Background/Introduction

Elevated levels of lipoprotein(a) (Lp[a]) have been associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Elevated Lp(a) is relatively refractory to lifestyle change and pharmacologic intervention.

Purpose

To examine the effect of evolocumab on Lp(a) in a range of clinical trial populations, including hypercholesterolaemia/mixed dyslipidaemia, statin-intolerance, diabetes mellitus, and heterozygous familial hypercholesterolaemia (HeFH) at different timepoints up to 5 years.

Methods

Fifteen phase 2 and phase 3 double-blind and open-label extension studies, with a minimum 12 weeks duration that used approved doses of evolocumab (140 mg every 2 weeks [Q2W] or 420 mg once monthly [QM]) were included in this analysis. Studies were pooled on the basis of patient population, duration, and comparator groups (of which the MENDEL-1, -2, GAUSS-1, -2, and LAPLACE-2 atorvastatin cohort studies employed ezetimibe comparators). The effect of evolocumab on percent change from baseline in Lp(a) was examined.

Results

In short-term studies, evolocumab led to a median percent change in Lp(a) from baseline to week 12 of −21.2% to −33.3% overall (Table). Results were similar for both evolocumab doses with median percent change ranging from −22.0% to −38.2% for 140 mg Q2W and −20.0% to −33.3% for 420 mg QM. In long-term studies (1 to 5 years), percent change in Lp(a) ranged from −23.8% to −33.3%.

Patient populations Percent change from baseline in Lp(a), median (Q1, Q3), % Ezetimibe comparator trials Placebo comparator trials Evolocumab Ezetimibe Evolocumab Placebo 12-week studies   Hypercholesterolaemia/mixed dyslipidaemia (YUKAWA-1, -2, LAPLACE-TIMI-57, LAPLACE-2, MENDEL-1, -2) −22.0 (−39.4, 0.0), n=760 0.0 (−11.8, 14.6), n=387 −26.3 (−44.7, −5.0), n=1838 0.0 (−10.4, 15.4), n=1179   Statin intolerance (GAUSS-1, -2) −23.1 (−42.0, −3.3), n=223 0.0 (−16.7, 3.6), n=126 – –   HeFH (RUTHERFORD-1, -2) – – −21.2 (−38.1, −7.0), n=263 0.0 (−4.2, 15.3), n=150   Type 2 diabetes (BANTING, BERSON) – – −33.3 (−55.6, −16.7), n=833 0.0 (−16.2, 16.7), n=425 Long-term studies   1-Year (DESCARTES) – – −28.4 (−49.2, −6.0), n=535 −5.5 (−20.5, 0.9), n=272   2-Year (OSLER-2)†‡ −23.8 (−44.4, 0.0), n=3077 – – –   5-Year (OSLER-1)† −33.3 (−51.3, −11.1), n=941 – – – †All patients received evolocumab in the OSLER studies. ‡OSLER-2 was a 3-year study; however, only 2-year data were available for Lp(a).

Conclusion

Evolocumab reduces Lp(a) in a variety of patient populations at 12 weeks with sustained lowering over 5 years.

Acknowledgement/Funding

Amgen Inc.
P5327Are we being able to meet current guidelines LDL-cholesterol goals in very high risk patients? How many of them could benefit of PSCK9 inhibition by the FOURIER/ODYSSEY and NICE criteria?
Authors: El Andere T , Soto J A T , Moreira I S , Wamser M N , Freitas H C , Almeida M P C , Goncalves R M , Zatz H P , Araujo D B , Sulzbach M L , Bertolami A , Faludi A A
Published: October 2019

Background/Introduction

With increasing evidence of LDL-cholesterol (LDL-c) lowering and a subsequent reduction in cardiovascular events, guidelines of different parts of the world aim for lower LDL-c goals by risk stratification. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has been able to reduce up to 60% LDL-c levels, with further reduction in cardiovascular outcomes.

Purpose

Our aim was to evaluate the proportion of very high risk patients in a tertiary cardiology center that met LDL-c goal of less than 50mg/dL proposed by the Brazilian Society of Cardiology (BSC) guidelines. Furthermore, we assessed the number of patients that were receiving adequate statin intensity therapy and could benefit from PCSK9 inhibition by the FOURIER/ODYSSEY and by the National Institute for Health and Care Excellence (NICE) criteria.

Methods

We screened 2180 consecutive patients from March, 2018 to February, 2019 for cardiovascular risk factors, cholesterol and glycemic levels, and current medical therapy at use. Patients were stratified by level of risk, and compliance to recommended statin therapy was evaluated. We then analyzed how many of the very high risk patients, that were in use of high intensity statin therapy, met the inclusion LDL-c levels of the FOURIER/ODYSSEY trials (≥70mg/dL) and the NICE recommendations (≥140mg/dL) for the introduction of PCSK9 inhibitors.

Results

Of the 2180 patients enrolled to our study, 1225 (56.2%) patients were at very high cardiovascular risk level. Of these patients, 136 (11.1%) met LDL-c BSC guideline levels. Using the LDL-c target of 70mg/dL, an additional 320 (26.1%) patients were below target range. When analyzing statin therapy at use, 913 (74,5%) were receiving adequate statin therapy. Of the very high risk patients in adequate statin treatment, 617 (65.9%) by the FOURIER/ODYSSEY criteria and 88 (9.4%) patients by the NICE criteria would benefit from PCSK9 inhibitors.

Conclusions

With lower LDL-c goals, achievement of optimal LDL-c levels is now a challenge for current clinical practice. Even though many patients are receiving adequate guideline-based statin therapy, difficulty remains in achieving optimal treatment, especially in the higher risk stratum. These patients would benefit from PCSK9 inhibition, being the NICE criteria, a more cost-effective strategy, still applicable in a substantial portion of our patients.
P5329Montreal score and coronary artery calcification in the prediction of cardiovascular event in patients with familial hypercholesterolemia
Authors: Miname M , Bittencourt M S B , Jannes C E J , Pereira A C P , Krieger J E K , Santos R D S
Published: October 2019

Introduction

Familial hypercholesterolemia (FH) is characterized by elevated levels of LDL-C and early cardiovascular disease (CVD). However, the risk of CVD in HF is variable. The Montreal score was designed to stratify cardiovascular risk in the FH population. Coronary calcium score (CAC) is a tool that can be used to optimize CVD risk assessment in FH.

Purpose

The objective of this study is to evaluate whether CAC is superior to the Montreal score in cardiovascular risk discrimination in FH.

Methods

We Included 206 patients with molecular diagnosis of FH (36.4% men, mean age 45±14 years, mean baseline LDL-C: 269±70 mg/dL). All patients underwent CAC and were treated with maximum tolerated statin therapy. We evaluated cardiovascular risk factors and calculated Montreal score as prior publication. Cox regression analysis was performed to test the association of CAC with the incidence of cardiovascular events. CAC was transformed into LogCAC + 1 to optimize the distribution of the CAC as previously described. Area under the ROC curve was calculated for Montreal score and CAC.

Results

Patients were followed by a median of 3.7 years (interquartile range: 2.7 to 6.8 years). Mean Montreal score was 22±8, median of 22. CAC was positive in 105 individuals (51%) and 15 CVD events (7.2%) had occurred. Montreal score above the median was associated with CAC (OR: 8.36, 95% CI: 4.47–15.62, p<0.001), and there was a gradient of increase in the Montreal score with CAC increase (mean Montreal score for CAC = 0, CAC 1–100, CAC>100: 17±7, 23±7, 30±4, p<0.001). Univariate analysis showed that the following variables were associated with CVD occurrence: male gender, family history of early coronary disease, corneal arcus, HDL-c (protective), logCAC + 1 and Montreal score. Multivariate analysis was performed: model 1 with Montreal score and logCAC + 1, only logCAC + 1 was associated with the occurrence of CVD (RR: 3.886; 95% CI: 2.112–7.148, p<0.001). Model 2 with family history of early coronary disease, corneal arcus, logCAC + 1 and Montreal score, only the latter was not associated with the occurrence of CVD. CAC presents greater area under the ROC curve for CVD event discrimination compared to the Montreal score: 0.839 versus 0.685, p=0.0074.

Conclusion

The Montreal score is associated with CAC in FH, however CAC is superior than this clinical score in predicting the occurrence of CVD in FH.
P5330Evaluating lipid-lowering and anti-atherogenic effect of injectable curcumin in a rabbit model of atherosclerosis
Authors: Momtazi-Borojeni A A , Banach M , Majeed M , Sahebkar A
Published: October 2019

Background and purpose

The present study was aimed to evaluate lipid-lowering and anti-atherogenic effect of an intravenous (IV) curcumin in the rabbit fed high cholesterol diet (HCD).

Methods

New Zealand white male rabbits (4–6 months old, n=25, weight 2.286±0.256 kg)were fed on a normal chow enriched with 0.5% (w/w) cholesterol for 5 weeks. Atherosclerotic rabbits were randomly divided into three group, including a control group receiving intravenous (IV) injection of saline buffer, two treatment groups receiving IV injection of curcumin at two different dosages, 1and 10 mg/kg/week, for 4 weeks. Blood samples were collected from fasted rabbits at pre- (week 5) and post-treatment (week 11) points for analysis of serum lipid levels, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG), and total cholesterol (TC). Aortic arch atherosclerotic lesions were assessed using hematoxylin and eosin (H&E) staining.

Results

To evaluate curcumin's effects on the hyperlipidemic states and atherosclerosis plaque, HCD-fed rabbits were weekly treated with the injectable curcumin at the low (1mg/kg/week) and high (10 mg/kg/week) doses by 4 weeks. At week 4 in compared with the control group, low-dose curcumin could reduce serum levels of LDL-c, HDL-c, TG, and TC by −6.22% ±1.77, −35.24% ±12.49, −29.84% ±10.14, −14.19% ±5.19, respectively. In the case of high-dose curcumin, serum levels of LDL-c, HDL-c, TG, and TC were changed by −44.36%±3.24, 14.05% ±6.39, −25.92% ±5.57, −56.59% ±10.22, respectively, when compared with the control group at week 4. Low-dose curcumin after 4 weeks' treatment could reduce serum levels LDL-c, HDL-c, TG, and TC up to 103±28 mg/dL, 18.33±4.66 mg/dL, 97.5±31 mg/dL, and 356.5±19.5 mg/dL, respectively, when compared with the base line levels (week 0). High-dose curcumin after 4 weeks' treatment could decrease serum levels of LDL-c, HDL-c, TG, HDL-c, and TC up to 207±17.04 mg/dL, 15.5±0.5 mg/dL, 333±40 mg/dL, and 514.5±22.23 mg/dL, respectively (Figure). H&E staining declared that atherosclerotic lesion grades were significantly lower in the curcumin-treated groups than the control group.

Changes of lipids in rabbits on curcumin

Conclusions

The injectable curcumin at the low (1mg/kg) and high (10 mg/kg) could significantly improve dyslipidemia and alleviate atherosclerotic lesion in HCD-induced atherosclerotic rabbits.