bluuebunny/crossref_metadata_2025 huggingface dataset:
P592Myocardial strain measurement with cardiovascular magnetic resonance in professional soccer athletes
Authors: Jimenez Franco V , De La Pena-Almaguer E P A , Jerjes-Sanchez C J S D , Trevino Ortiz A T O
Published: October 2019

Background

Over the last decade, cardiovascular screening in sports has gained interest due to the presence of sudden cardiac death in apparently healthy athletes. In these specific group of patients, a reliable evaluation of the ventricular dimensions and volumes by non-invasive methods is of utmost importance to rule out potentially lethal cardiomyopathies. Cardiovascular magnetic resonance (CMR) has emerged as a corner stone in the characterization of the athlete's heart and contributing to diagnosis of underlying diseases. Strain evaluation by CMR adds information regarding ventricular mechanics and little, or no data has yet been described in professional soccer players.

Purpose

We evaluated cardiac deformation by measuring endomyocardial global longitudinal strain (GLS) by CMR in professional soccer players (First Division Mexican Soccer League) compared to sedentary controls. Secondary objectives were to evaluate structural and morphological changes as compared to healthy and deconditioned controls.

Methods

We performed a monocentric, non-randomized, observational and control study, that evaluated the GLS by CMR in professional soccer players compared to healthy and deconditioned controls. Primary end point was percentage of GLS by feature tracking method. Secondary end point included diastolic and systolic left ventricular diameters, left and right ventricular volumes, left ventricular and right ventricular ejection fraction, ventricular mass and cardiac output.

Results

From January 2017 to March 2018, information was gathered from CMR studies in 37 subjects, 20 of them being high performance athletes, and 17 healthy sedentary subjects. The GLS by CMR showed a non-significant trend towards a higher negative deformation percentage of athletes as compared to the control group of deconditioned participants: (−22.0±2.0% vs. 20.9±2.05%, p=0.36). There were no differences in the cardiac output and the indexed cardiac output (6.0 L/min and 3.2 L/min/m2 vs. 6.1 L/min and 3.1 L/min/m2; p=NS). Athletes had higher systolic (42.9 mm vs. 35 mm; p<0.0001) as well as diastolic LV diameters (60.5 mm vs. 51 mm; p<0.0001). LV mass and indexed mass were significantly greater in the group of soccer players (145 gr and 75 gr/m2 vs. 109 gr and 52 gr/m2 respectively; p<0.0001). We found no difference in the LVEF 60±2.5%; p=0.55).

Conclusion

Despite athletes having higher LV mass and diameters, we found no difference in ventricular deformation values as evaluated GLS by CMR, which in turn may represent a normal and physiological adaptation. Further studies are warranted to reproduce these results.
P594Cardiac magnetic resonance imaging in lung transplant assessment: the clinical significance of right ventricular-pulmonary arterial coupling and right ventricular trabecular complexity
Authors: Sarri G , Halim K , McCurry M , Pierce I , Asaria P , Chen Z , Rahman-Haley S , Simon A , Carby M , Reed A , Wong J
Published: October 2019

Introduction

Right ventricular (RV) dysfunction complicating lung disease is prognostic in patients undergoing lung transplantation. However key metrics are not clear.

Purpose

We assessed RV-pulmonary arterial (PA) coupling and RV trabecular complexity through cardiac magnetic resonance (CMR) imaging in patients undergoing lung transplant assessment.

Methods

Between 2013 and 2018, 91 consecutive patients underwent lung transplant assessment with echocardiography and CMR (1.5T - Siemens). RV trabecular complexity was assessed by its fractal dimension (FD) on CMR, using freely available code (FracAnalyse). RV functional adaptation to increased afterload was assessed with the RV-PA coupling index (stroke volume (SV)/RV end-systolic volume (ESV) ratio).

Results

91 patients (median age 53±15 years, 54% male) were analysed; 97% had underlying lung disease. Median follow up period was 23.8 months. Tricuspid regurgitation was echo-detected in 71 patients; 74% (53 patients) had echo-diagnosed pulmonary hypertension (PH). 85%, 10%, and 4% of PH patients were categorized to WHO PH classification Groups 3, 5 and 1 respectively. Mean LV and RV ejection fraction (EF) were 62±1.01% and 51±15.5%.

SV/ESV correlated to CMR indexed RV end-diastolic volume (RVEDVi), indexed RV end-systolic volume (RVESVi), RV EF, right atrial area and echo mean pulmonary artery pressure (mPAP) (r −0.437, r −0.646, r 0.824/all p<0.001; r −0.290/p 0.005; r −0.348/p 0.003 respectively). Global FD also correlated to these parameters (r 0.371, r 0.369/both p 0.001; r −0.245/p 0.021; r 0.352, r 0.403/both p<0.001). RV FD did not differ significantly in patients with PH. Survival was predicted by SV/ESV ratio, RVEF, RVEDVi, RVESVi, and mPAP on univariate analysis (Table).

All patients (n=91) Alive (n=77) Dead (n=14) Alive vs dead HR CI p value median/mean/counts (SEM/IQR) median/mean/counts (SEM/IQR) median/mean/counts (SEM/IQR) p value CMR RVESVI (ml/m2) 35 (20) 33 (18) 54 (41) <0.001 1.03 1.02, 1.04 <0.001 CMR RVEF (%) 51 (15.5) 53 (13) 38 (15) 0.001 0.93 0.90, 0.93 <0.001 RV-PA coupling SV/ESV 1.06 (0.64) 1.13 (0.61) 0.57 (0.38) <0.001 0.10 0.02, 0.46 0.003 6 minute walk test distance (m, n=90) 290 (188) 300 (190) 190 (264) <0.05 0.99 0.99, 1.00 0.13 Transplanted 22 15 7 0.04 2.39 0.80, 7.17 0.12 Echo mPAP (mmHg, n=71) 27 (10.7) 27 (9) 33 (14.8) <0.05 1.05 10.1, 1.05 0.008

Conclusion

RV functional adaptation to afterload assessed by CMR may predict survival among patients with underlying lung disease referred for lung transplant assessment. Fractal analysis of RV trabecular complexity correlated with metrics influencing RV remodelling and contractility, although not survival. Assessment in a larger cohort is required to determine utility of these metrics.
P596Early markers of right ventricular involvement in experimental chronic postcapillary pulmonary hypertension
Authors: Garcia Lunar I , Jorda P , Pereda D , Ascaso M , Santiago E , Sanchez J , Galan C , Fuster V , Ibanez B , Garcia-Alvarez A
Published: October 2019

Background

In chronic pulmonary hypertension (PH), the main cause of death is right ventricular (RV) failure. However, the onset of RV dysfunction varies significantly among patients. Early recognition of RV maladaptation would be highly relevant.

Purpose

To identify cardiac magnetic resonance (CMR)-derived parameters affected in early stages of PH before the development of RV dysfunction.

Methods

Experimental chronic PH was generated by pulmonary vein banding in 76 pigs whereas 14 animals underwent sham operation. Animals were followed-up monthly with right heart catheterization (RHC) and immediate CMR for a maximum of 9 months. CMR exams included a T1-mapping sequence to quantify equilibrium-extracellular volume (ECV) at the RV insertion points. Pairs of RHC and CMR examinations were compared among controls and PH with normal RV ejection fraction (RVEF≥55%) or reduced (REVF<55%) using ANCOVA test with Bonferroni correction. All procedures followed the “Principles of laboratory animal care”.

Results

In the presence of PH confirmed by RHC and normal RVEF, the RV displays significant hypertrophy and increased myocardial native T1 and ECV, despite preserved ventricular dimensions and PA flow (Fig 1B). In advanced stages of the disease, RV-AP uncoupling and reduced PA pulsatility develop together with RV dilatation and failure (Fig 1C).

CMR parameters in sham and PH animals Sham controls (n=25 evaluations) PH with normal RVEF (n=155 evaluations) PH with low RVEF (n=70) RVEF (%) 62±5 61±4 47±8# RVEDV (mL/m2) 73±18 83±17 111±29# RVESV (mL/m2) 28±8 32±8 61±25# RV mass (g/m2) 17±4 23±5* 30±11# PA area (cm2/m2) 5.5±1.2 6.3±1.6 8.7±2.2# Native T1 anterior RVIP (ms) 983±75 1043±78* 1055±90# ECV anterior RVIP (%) 27±5 31±6* 36±7# Native T1 inferior RVIP (ms) 959±68 1022±71* 1032±99# ECV inferior RVIP (%) 25±5 31±6* 36±7# PA pulsatility (%) 29±6 27±7 21±3# Ea/Emax 40±16 47±11 97±65# RVEDV: RV end-diastolic volume; RVESV: RV end-systolic volume; RVIP: RV insertion point. *p<0.05 1 vs. 2; #1 vs. 3.

NativeT1: control, PH-normal RV, RV dysf

Conclusion

RV hypertrophy and ECV expansion are early mechanisms in RV adaptation to postcapillary PH, whereas ventricular and PA dilatation, RV-PA uncoupling and reduced pulsatility appear in more advanced stages concurring with systolic dysfunction.

Acknowledgement/Funding

The CNIC is supported by the Ministerio de Ciencia, Innovaciόn y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence
P604Clinical feasibility assessment of a novel Quantitative Multi-contrast Atherosclerosis Characterization (qMATCH) sequence for carotid plaque quantification
Authors: Cho I , Jung M S , Jung H G , Xie Y , Wang N , Kim W D , Li D , Chang H J
Published: October 2019

Background

Conventional protocol contrast MRI (cMRI) for evaluating carotid artery atherosclerosis is clinically under-utilized due to complex scanning procedures and long scan time. Recently, the Quantitative Multi-contrast Atherosclerosis Characterization (qMATCH) has been proposed, which allows comprehensive and quantitative assessment of atherosclerosis including MRA, dark-blood vessel wall morphology, and T1/T2 mapping with an 8-minute single scan (Figure1). However, the diagnostic accuracy and feasibility of qMATCH has not been validated in clinical circumstances.

Purpose

To evaluate the diagnostic accuracy of quantitative plaque analysis of qMATCH compared with cMRI

Method

We prospectively enrolled 43 patients who have carotid plaques diagnosed by carotid ultrasound. cMRI was performed along with qMATCH scan. All imaging data were acquired with a clinical 3T scanner using a 64-channel head & neck coil. In the current analysis, we evaluated the diagnostic accuracy of qMATCH in the quantitative assessment of carotid plaque. Plaque area measurements using dark-blood wall images with qMATCH were compared with corresponding cross-sectional T1/T2-weighted images with cMRI as references values (Figure 2). These inter-technique comparisons included linear regression with Pearson correlation and Bland-Altman analyses to assess the mean inter-technique differences (biases) and limits of agreements.

Result

Among 90 segments, mean plaque areas measured by cMRI and qMATCH were 43.83±21.21 mm2 and 42.47±19.23mm2, respectively (mean differences, −1.36±8.12mm2; p for a paired t-test, 0.073). Correlation coefficient showed excellent correlation between plaque areas measured by cMRI and qMATCH (r=0.943, p<0.001) (Figure 3). Bland-Altman plot showed excellent agreement in plaque areas between the two methods (Figure 4).

Conclusion

Quantitative carotid plaque burden analysis by a novel sequence with qMATCH is feasible and accurate compared with conventional MRI. Given that qMATCH can reduce scan time and allow quantitative relaxometry mapping, fast and accurate carotid plaque analysis would be feasible. Further studies to evaluate the accuracy of qualitative plaque analysis should be performed to confirm the “all-in-one” assessment of carotid atherosclerosis using qMATCH.
P613Cardiac magnetic resonance imaging derived left ventricular mechanical function in patients with atrial fibrillation and left atrial low voltage zones
Authors: Ulbrich S , Schoenbauer R S , Kirstein B , Tomala J , Huo Y , Mayer J , Richter U , Piorkowski J , Gaspar T , Mascherbauer J , Piorkowski C
Published: October 2019

Background

The relation of left atrial low voltage zones (LVZ) to left ventricular function in patients undergoing pulmonary vein isolation (PVI) is not known.

Objective

To explore the relationship of left atrial low voltage zones (LVZ) on left ventricular function in patients with atrial fibrillation.

Methods

From June to Nov. 2018, 107 (mean age 67y, 70 men, 73 persistent AF) consecutive patients with symptomatic AF underwent a PVI with LVZ mapping. Before PVI the left ventricular ejection fraction (EF) and stroke volume (SV) were measured by cardiac magnetic resonance imaging (CMR). From feature-tracking of CMR-cine images left ventricular global, systolic and diastolic longitudinal strains (GLS), circumferential strains (GCS) and radial strains (GRS) were calculated.

Results

Of 59 patients CMR scanning in sinus rhythm was performed, LVZ were present in 24 patients.

LVEF was significantly lower in patients with left atrial LVZ (62±9% vs. 55±15%) (p=0,03). Left ventricular stroke volume was significantly decreased by the extent of LVZ (94±23 vs. 72±21ml), (p=0,03).

The left ventricular diastolic strains during ventricular filling (caused by atrial contraction) of GLS (r=−0,52), GCS (r=−0,65) and GRS (r=−0,65) were highly signifcantly correlated to the occurence and extent of LVZ (each p<0,001 respectively).

The only systolic ventricular strain was GLS, which decreased (r=−0,3, p=0,03) by the occurance of atrial low voltage.

Conclusion

The active, atrial part of diastolic left ventricular filling properties is impaired by the occurrence and extent of left atrial LVZ. In patients with left atrial LVZ the left ventricular stroke volume and ejection fraction is decreased already in sinus rhythm. It seems possible that atrial mechanical dysfunction and presence of atrial low voltage maybe predicted by LV diastolic strain analysis.
P632Long-term benefits of cardiac rehabilitation in patients with diabetes mellitus after percutaneous coronary intervention
Authors: Romero Reyes M J , Rodriguez Delgado R , Esteve Ruiz I , Otte Alba C , Mora Pardo J A , Molano Casimiro F J
Published: October 2019

Introduction

After percutaneous coronary intervention (PCI), patients with diabetes have a worse prognosis than non-diabetics and are at increased risk of recurrent cardiovascular events, hospitalization and higher mortality.

Purpose

The aim of our study was to evaluate the impact of cardiac rehabilitation (CR) in this high-risk group of patients.

Methods

We performed a retrospective cohort study of 318 consecutive patients with type 2 diabetes mellitus (DM2) who underwent PCI in our hospital between 2004 and 2011. We classified the patients in two cohorts according to their participation (n=154) or not (n=164) in a CR programme. We collected the events ocurring during a median follow-up of 9 years.

Results

Using multivariate logistic regression, we found that CR participation was associated with significantly reduced all-cause mortality (53% vs 23%, OR 2.10; IC 95%; 1.16–3.82; p 0.014) and cardiac mortality (3.9% vs 23.8%, OR 8.69; IC95% 2.80–26.99; p<0.0005). CR aslo associated with a singnificant decrease in a heart failure hospitalization (26.6% vs 10.6%, OR 2.4; IC 95% 1.06–5.52; p<0.035). No significant differences were observed in non fatal myocardial infarction, stent restenosis and non fatal stroke.

Basal characteristics Rehabilitation (n=153) No Rehabilitation (n=164) P vaule Male sex 138 (86.4%) 100 (61.0%) <0.0005 Age (years) 59 (38–74) 65 (47–74) <0.0005 Hypertension 113 (73.9%) 111 (67.7%) NS Hypercholesterolemia 112 (73.7%) 115 (70.1%) NS HbA1c ≥7% 88 (66.2%) 73 (64.6%) NS Prior myocardial infarction 24 (15.6%) 32 (19.5%) NS Chronic kidney disease 6 (3.9%) 19 (11.6%) 0.012 FEVI <50% 30 (20%) 39 (25%) NS Three vessel disease 53 (34.4%) 58 (35.4%) NS Incomplete revascularization 80 (51.9%) 81 (49.4%) NS Drug-eluting stent 110 (78.6%) 127 (80.4%) NS Stent length 22.4±11.9 24.6±14.8 NS Stent diameter 2.7±0.3 2.8±0.4 NS

Conclusion

CR participation after PCI is associated with lower all-cause mortality, cardiac mortality and heart failure hospitalization rates in patients with DM2 during long-term follow-up.
P647An audit of possible familial hypercholesterolaemia in general practice
Authors: Gallagher J , McGuckin M , Behan D , Harrington P
Published: October 2019

Background

Familial hypercholesterolaemia (FH) is an autosomal dominant condition associated with elevated total cholesterol and low-density lipoprotein (LDL). It confers an increased risk of premature cardiovascular disease and associated mortality. It is estimated that the majority of patients with FH in Ireland are undiagnosed and structured care programmes are not available.

Purpose

To undertake an audit of those patients in a general practice with possible FH

Methods

A retrospective audit was carried out on the patients attending a GP practice. Inclusion criteria for the study were as follows:

LDL level >4.9mmol/L

Triglyceride level (<2mmol/L)

Data was collected from the patients' clinical notes and patients were interviewed to acquire additional details not available in the clinical notes where possible. A Dutch Lipid Clinic Network Score (DLCNS) was calculated for each patient.

Results

Of 5,438 patients with a LDL recorded 284 patients fulfilled the inclusion criteria. 52.4% were female. Mean age 60 years old (range: 19–95 years). The highest LDL level recorded for these patients ranged from 5.0 - 8.6 mmol/L, with a mean value of 5.4 mmol/L. The mean most recent LDL level was 3.6mmol/L (range: 1.0–6.3 mmol/L). 42 patients (14.8%) had a family history of premature coronary and/or vascular disease in line with DLCNS criteria. 9 patients (3.2%) had a personal history of premature cardiovascular disease. The DLCNS was calculated for each patient based on the information available. 225 patients (79.2%) had a score of 3, 36 patients (12.7%) had a score of 4, 12 patients (4.2%) had a score of 5 and 6 patients (2.1%) had a score of 6. This equates to 273 patients (96.1%) with a possible diagnosis of FH, and 6 patients (2.1%) with a probable diagnosis of FH. The mean most recent systolic blood pressure reading for these patients was 128mmHg, and diastolic 76mmHg. 51 patients (18%) were current smokers, 83 (29.2%) were ex-smokers, and 111 (39%) had never smoked. Smoking status was unknown for 38 patients (13.4). 128 patients (45%) were on lipid-lowering treatment at the time of this audit. 60 (21.1%) were on high intensity treatment, 68 (23.9%) were on medium intensity treatment and none were on low intensity treatment. 24.3% of patients were at target LDL. There were 5 patients (1.8%) currently receiving ezetimibe and 1 (0.4%) on fenofibrate.

Conclusion

A significant number of patients had a LDL >5mmol/l in this audit. Only 45% were on lipid lowering treatment and 24.3% were at a target LDL. This highlights the needs for structured programmes for screening and management of FH in primary care.

Acknowledgement/Funding

Funded by an unrestricted grant from Amgen
P648Screening and treatment of familial hypercholesterolemia in a French sample of ambulatory care: a retrospective longitudinal cohort study
Authors: Ferrieres J , Banks V , Pillas D , Ricci L , Dova-Boivin M , Vannak J V , Desamericq G
Published: October 2019

Background

Familial hypercholesterolemia (FH) is largely underdiagnosed as there are typically no clinical symptoms prior to the first cardiovascular (CV) event. We conducted a study which utilised ambulatory care electronic medical record (EMRs) to alert physicians to possible cases of FH. Specifically, physicians were alerted to LDL-C levels >190 mg/dL (suggesting a risk of FH) and invited to complete the Dutch Lipid Clinic Network score (DLCN).

Purpose

Describe characteristics, comorbidities and clinical management of patients diagnosed with definite or probable FH in an ambulatory care setting.

Methods

All patients with a DLCN score of definite/probable FH (score higher or equal than 6; index event) between January 2016 and September 2018 were identified in the THIN® database (The Health Improvement Network; an anonymized EMR powered by GERSDATA, a Cegedim Health Data Division). These fully anonymized data were collected by 2000 General Practitioners (GP), 130 cardiologists and 40 endocrinologists, receiving 5.5 million patients regularly in their office. Sociodemographic, laboratory measurements, comorbidities, lipid-lowering therapies (LLT), visits to specialists, LDL-C and hospitalizations were collected and analysed at baseline, and 1, 2, 3, 6 months, and 1 year thereafter.

Results

From 999 anonymous patients with a DLCN score, 98 (10%) FH patients were identified (38 [39%] definite FH, 60 [61%] probable FH) while remaining fully anonymous, 9 (9%) of whom already had genetic testing. Mean (SD) age was 57.4 (14.3) years; 56 (57%) patients were female, half (51/98 [52%]) were diagnosed with pure hypercholesterolemia (ICD-10 code: E78.0) and 9 (9%) had a personal history of CV event. 93 patients (95%) had a LDL-C measurement prior to DLCN assessment (definite FH, 36/38 [95%]; probable FH, 57/60 [95%]). Among screened FH patients, 61.2% had LDL-C between 190 to 250 mg/dL and 16.3% had LDL-C higher than 250 mg/dL. At the time of DLCN assessment, one third (30/98 [31%]) of patients were not receiving any LLT, one third ([35%] 34/98) were receiving statins alone, 19% (19/98) receiving LLT combination with statin, and 15% (15) other LLTs. Moderate statin intensity was prescribed in 20% (20/98) of patients; high intensity statin, 17%, (17/98); low intensity, 10% (10/98). No improvement on LLT use (including use of high statin intensity) was observed over the 12-month follow-up.

Conclusion

This is the first study in France that use EMR to screen possible FH patients and support GPs in identifying patients that need to be treated. Our data highlight the need to screen, diagnosis and treat potential FH patients in ambulatory care settings. Longer follow-up is needed to evaluate the impact of FH assessment on referral to specialists, LLT and clinical outcomes.

Acknowledgement/Funding

Amgen
P658CHA2DS2-VASc score calibration in anticoagulated vs non-anticoagulated patients in a healthcare area
Authors: Baluja A , Lopez-Canoa N , Rodriguez-Manero M , Lopez-Pardo E , Agra-Bermejo R , Cordero-Fort A , Garcia-Seara J , Fernandez-Lopez X A , Varela-Roman A , Gonzalez-Melchor L , Alvarez-Escudero J , Martinez-Sande J L , Gonzalez-Juanatey J R
Published: October 2019

Introduction

Atrial fibrillation (AF) is a highly prevalent heart disease, affecting a significant proportion of patients over 65 years old. The CHA2DS2-VASc score predicts 1 year risk of a thromboembolic (TE) event and is well validated against several populations. However, calibration may vary if there is subgroup heterogeneity.

Purpose

To compare the CHA2DS2-VASc score calibration, in patients with or without anticoagulation (AC) in a real population of AF patients in our healthcare area.

Methods

Patients with an episode with atrial fibrillation/flutter were selected from a general population in a healthcare area (383,000 subjects), with 21/12/2013 as a cut-off date. Patients with valve disease, anticoagulation or antiplatelet therapy were identified.

The CHA2DS2-VASc score was calculated as stipulated in the European Society of Cardiology guidelines. A CHA2DS2-VASc score of 0 is considered to be low risk for TE events (0% at 1 year), score of 1 intermediate risk (0.6% rate at 1 year), and greater than 1 high risk (3% rate at 1 year).

Quantitative variables are presented as mean and standard deviation (SD). Categorical variables were presented as frequencies and percentages. A logistic regression was fitted to predict 1-year risk TE outcomes with CHA2DS2-VASc as the only covariate. Model calibration was assessed using the predicted versus actual probabilities of TE events. All analyses were performed using R v.3.4 (R Core Team, Vienna, Austria) with the packages rms and ggplot2.

Results

CHA2DS2-VASc was calculated in 7990 patients with AF. A total of 1824 patients were excluded either due to valvular disease (846) or due to previous antiplatelet treatment (1047). From them, 143 patients were excluded for an incomplete follow-up time (<1 year).

As of December 31, 2015, 67 stroke cases had been notified from 6023 patients (1.1%) (Table 1). Mortality rate was 181 (3%) at 1 year.

Patients presented overall low risks of stroke with a poor score calibration. Higher scores presented risks that were lower than predicted by CHA2DS2-VASc. Event rate at 1 year was similar regardless of the AC regime at the initial date, and also similar to a previous cohort of anticoagulated patients (Lip et al.). This similarity may indicate confounding by later AC therapy initiation, before the final assessment date.

Table 1. Comparison of thromboembolic event rates in several studies % (No-AC) % (AC) % Lip 2010 % Poli 2011 % Friberg 2012 % Okumura 2014 0.01 0.01 0.02 4.5 4.5 1 AC: anticoagulation.

CHA2DS2VASc score calibration

Conclusion

Higher CHA2DS2-VASc scores are not associated to higher risks of stroke in our healthcare area, in patients with non-valvular AF and without antiplatelet therapy.
P687Is sacubitril/valsartan useful in patients with cancer and heart failure? Data from HF-COH Spanish multicenter registry
Authors: Martin Garcia A , Mitroi C , Chaparro M , Moliner P , Martinez-Monzonis A , Martin-Garcia A C , Asla C , Castro A , Gual-Capllonch F , Marco I , Sanchez-Pablo C , Antunez Ballesteros M , Lopez Sendon J L , Sanchez P L , Lopez-Fernandez T
Published: October 2019

Current guidelines recommend sacubitril/valsartan (S/V) for patients (p.) with heart failure and reduced left ventricular ejection fraction (LVEF) but there is lack of evidence of its efficacy and safety in p. with cancer and heart failure. Our aim was to analyze the potential benefit of S/V in specific cardio-oncology clinics.

Methods

We performed a retrospective multicenter registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all p. treated with S/V. Clinical and echocardiographic data, NYHA functional class, type of neoplasms and anti-tumoral treatment were described. Median follow-up was 7.2 [7.9] months.

Results

Sixty-one p. were included (median age was 64 [21] years old; 64%women, 43% hypertensive, 54% dyslipidemics and 28% diabetics). Most of p. (97%) had cancer therapy related cardiac dysfunction (CTRD) with a median time from anti-cancer therapy to CTRD of 40 [132] months. Breast (46%) and hematological (38%) cancers were the most frequent neoplasms, 31% of p. had metastatic disease and 71% had been treated with anthracyclines. In 5% S/V was initiated at CTRCD diagnosis while in 95% S/V was started to improve clinical status in p. already treated with ACE inhibitors or ARBs. 87% were on beta-blocker therapy and 74% on mineralocorticoid receptor antagonists.Maximal S/V titration dose was achieved in 8.2% of p. (24/26mg: 43%; 49/51mg: 33%) S/V was discontinued in 4 p. (reasons: 2 hypotension; 1: renal failure; 1: pruritus)

Baseline NT-proBNP levels, functional class, and LVEF improved at the end of follow-up in p. who continued with S/V (all p values ≤0.01). No statistical differences were found in creatinine clearance or potassium serum levels. Table

Patient parameters before and after S/V Before S/V After S/V P value LVEF (%) 33 [7] 39.5 [15] <0.001 Creatinine (mg/dl) 0.9 [0.4] 0.9 [0.5] 0.15 Creatinine clearance (ml/min) 73 [30] 75 [37] 0.22 Potassium serum levels (mg/dl) 4.5 [0.5] 4.5 [0.6] 0.42 Systolic arterial pressure (mmHg) 116 [23] 112 [27] 0.025 Diastolic arterial pressure (mmHg) 70 [13] 68 [10] 0.498 NT-proBNP (pg/ml) 1831 [3132] 842 [1919] 0.007 NYHA 2.2±0.6 1.6±0.62 <0.001 Values are median [interquartile range] or mean ± standard derivation; S/V: sacubitril-valsartan; LVEF: left ventricle ejection fraction.

Conclusions

Our experience suggests that S/V is well tolerated and improves functional class and left ventricular function parameters in patients with CTRCD.
P701The role of a phosphoinositide-3 kinase inhibitor in vascular inflammation
Authors: Chaudhry H , Cerutti C , Kodji X , Argunhan F , Ridley A , Brain S D
Published: October 2019

Background/Introduction

Cardiovascular inflammation is associated with endothelial damage, resulting in leukocyte trafficking and oedema formation, which results in a positive-feedback loop of inflammatory events.

Purpose

The phosphoinositide 3-kinase (PI3K) pathway has been shown to be upregulated in vascular disease conditions whereby its inhibitors potentially have beneficial effects. Hence this study was designed to examine the actions of PI-103, a PI3K non-selective inhibitor, on inflammatory responses.

Methods

Permeability assays were undertaken to quantify the effect of TNF-a in the presence and absence of PI-103 using FITC-dextran (40 kDa, 0.1 mg/ml) to measure levels of permeability in trans-wells plates using human microvascular endothelial cells (HMVEC).

In vivo analysis was carried out per the UK Home Office Animals (Scientific Procedures) Act 1986. CD1 mice were anaesthetised, to test PI-103 in a zymosan-induced model of dorsal skin inflammation on neutrophil accumulation (measured by myeloperoxidase) and oedema formation (measured by Evans Blue accumulation).

All data were analysed using 1-way or 2-way ANOVA with post-hoc test.

Results

PI-103 significantly reduced TNF-α induced microvascular endothelial cell permeability (Graph), thus impeding in vitro cytokine-induced inflammation. Whilst there was no effect on neutrophil accumulation in vivo, there was significant reduction in weight of treated areas and oedema formation, which was inhibited by PI-103 (Table 1).

Effect of PI-103 in vivo Control 30 mg/kg PI-103 Tyrode solution Zymosan (μg/ml) Tyrode solution Zymosan (μg/ml) 10 30 100 10 30 100 MPO/Protein (U/mg) 0.66±0.26 1.42±0.07 1.40±0.14 1.68±0.12* 0.60±0.11 1.23±0.32 1.36±0.25 1.59±0.21* Oedema Volume (mm3) 0.00±0.00 3.26±1.76 11.70±2.21 21.50±4.67 2.20±1.53 1.05±1.05 3.27±0.74 5.52±1.58 Mice were pre-treated with PI-103 i.p. for 30 min, i.d injected with zymosan (50 μl/site) for 4 hr, followed by ex vivo MPO assay, weight and oedema volume measurements. Oedema was quantified by measuring: width (x), height (y) and depth (z) from each of the i.d. sites; volume of oedema = ((π/6)xyz). N=6 independent experiments in duplicates; *p<0.05 between Tyrode solution vs zymosan groups.

Effect of PI103 in vitro on permeability

Conclusions

Our findings show that the PI3K non-selective inhibitor, PI-103 (as well as a PI3K α-selective inhibitor), reduces endothelial activation and inhibits inflammatory oedema formation. We conclude that there is a potential for PI3K inhibitors to act as anti-oedema agents in cardiovascular-related inflammatory conditions.

Acknowledgement/Funding

British Heart Foundation
P703The small conductance Ca2+-activated K+-channel inhibition tool compound AP14145 protected the guinea pig heart from ventricular arrhythmia during hypokalemia whereas dofetilide was pro-arrhythmic
Authors: Bentzen B H , Abildgaard L , Edvardsson N G , Soerensen U S , Grunnet M , Diness J G
Published: October 2019

Background

Hypokalemia is commonly encountered in the clinic. Hypokalemia reduces the cardiac repolarization reserve and causes increases in intracellular calcium. This prolongs the QT-interval and increases the risk of ventricular arrhythmia; a risk that can be further exacerbated by concomitant administration of classical class 3 anti-arrhythmic agents.

Small conductance Ca2+-activated K+-channels (SK-channels) are a promising new atrial selective target for treatment of atrial fibrillation (AF). Under physiological conditions SK channels play an insignificant role in ventricular repolarization. However, this might change under hypokalemia because of concomitant increases in intracellur calcium.

Purpose

To study the effects of SK channel inhibition with the tool compound AP14145 or ICA under hypokalemic conditions as compared to the class 3 anti-arrhythmic agent dofetilide and time matched controls (TMC).

Methods

Guinea pig hearts were isolated and retrogradely perfused with normokalemic (4.5 mM K+) Krebs-Henseleit solution, followed by perfusion with drug or vehicle control. The perfusion was then changed to hypokalemic solution (2.5 mM K+) in presence of drug for 20 min, followed by 20 min perfusion with normokalemic solution in presence of drug. A total of 24 animals were included in the study and randomly assigned to 4 groups: ICA, AP14145, dofetilide or TMC. QT-interval, ventricular effective refractory period, extra systoles and incidence of ventricular tachycardia (VT) or fibrillation (VF) were recorded for each perfusion period.

Results

Hypokalemia caused a small increase in QT-interval. Application of SK channel inhibitors did not cause further changes, whereas dofetilide prolonged QT compared to hypokalemia alone. During hypokalemia 3 out of 6 hearts in the TMC group developed VF (one spontaneously, two following S1S2 stimulation) whereas 4 out of 6 hearts developed VF in the dofetilide group (one spontaneously, three following S1S2 stimulation). In comparison only 1 heart out of 6 developed VF when treated with the SK channel inhibitor ICA (spontaneously) or AP14145 (following S1S2 stimulation).

Conclusion

Hypokalemia was associated with an increased risk of VF, an effect that was exaggerated by co-administration of dofetilide. In comparison, the structurally and functionally different SK channel inhibitors, ICA and AP14145, protected the heart from hypokalemia induced VF. These results with the tool compound AP14145 support that SK inhibition may be associated with a better safety and tolerability profile than dofetilide.

Acknowledgement/Funding

Innovation Fund Denmark
P727Metabolic and functional differences between male and female endothelial cells from umbilical cords (HUVEC) of twin pairs
Authors: Lorenz M , Blaschke B , Benn A , Hammer E , Witt E , Kirwan J , Fritsche-Guenther R , Gloaguen Y , Kramer F , Kappert K , Brunner P , Dreger H , Stangl K , Knaus P , Stangl V
Published: October 2019

Background

Personalised Medicine is one of the hallmarks of future medicine. Sex and gender differences exist in the incidence, clinical manifestation and outcome of cardiovascular diseases. Gonadal hormones are thought to account for most of these sex differences. However, besides hormones, sexual dimorphisms at the cellular level may also contribute to physiological and pathophysiological cardiovascular differences between women and men.

Purpose

To analyse intrinsic sex differences at the cellular level, we aimed to elucidate sex-specific differences in endothelial cell migration and energy metabolism under pro-migratory conditions in male and female HUVECs. To reduce biological variability, we used HUVECS obtained from umbilical cords from twin pairs of the opposite sex. These cells are exposed in utero to the same maternal environment, and therefore represent a valuable tool to study intrinsic sex-specific differences at the cellular level.

Methods

Vascular endothelial growth factor (VEGF)-stimulated migration was determined with IBIDI migration chambers. Sex-specific levels of proteins were studied using proteome profiling. Cellular metabolism was measured by Seahorse and levels of intracellular metabolites were analysed using GC-MS based technology.

Results

Female cells showed significantly higher VEGF-induced cell migration than male HUVECs. Proteomic profiling revealed a sex-specific response to VEGF treatment. Mitochondrial respiration rate was higher in VEGF-stimulated male HUVECs compared to female cells. Whereas mean glycolytic rates did not significantly differ between sexes, the ratio of glycolysis/mitochondrial respiration after VEGF stimulation was higher in female than in male HUVECs. Female cells had higher intracellular ATP levels after serum starvation and treatment with VEGF. Under both conditions, female cells showed altered levels of metabolite pools compared to male HUVECs.

Conclusions

Higher intracellular ATP and metabolite levels in female cells after serum starvation and VEGF may contribute to the observed functional sexual dimorphisms, and may also point to an increased stress tolerance of female cells. The results of our study provide a strong argument to discriminate between male and female cells in in vitro experiments.

Acknowledgement/Funding

The work was supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research).
P755The impact of levothyroxine on cardiac function in older adults with subclinical hypothyroidism: a randomized clinical trial
Authors: Gencer B , Moutzouri E , Blum M R , Feller M , Collet T H , Buffle E , Monney P , Gabus V , Muller H , Kearney P , Gussekloo J , Westendorp R , Scott D J , Bauer D C , Rodondi N
Published: October 2019

Importance

Subclinical hypothyroidism has been associated with heart failure, but no conclusive clinical trial assessed whether treating subclinical hypothyroidism with levothyroxine has an impact on cardiac function.

Objective

To assess the impact of levothyroxine treatment on cardiac function in subclinical hypothyroidism.

Design

This is a randomized, double-blind placebo-controlled, multicenter Swiss substudy within the TRUST trial.

Participants

Participants aged ≥65 years with subclinical hypothyroidism.

Intervention

Levothyroxine to achieve TSH normalization, or placebo including mock titrations.

Main outcome measures

Primary outcomes, assessed by echocardiography at the end of the trial were the left ventricular ejection fraction (LVEF, normal defined as >50%) for systolic function and the ratio between mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (e' (E/e' ratio) for diastolic function. Secondary outcomes included transmitral E and A waves, e' lateral/septal, left atrial (LA) volume index and systolic pulmonary artery pressure.

Results

Of 217 randomized Swiss participants of the TRUST trial, 185 (mean age 74.1 years, 47% women, mean TSH at baseline 6.35 ± SD 1.95 mIU/L) underwent echocardiography. After a median treatment duration of 18.4 months, the mean TSH among participants randomized to levothyroxine (n=95) decreased to 3.55 mIU/L, whereas it remained elevated in the placebo group (n=89; 5.29 mIU/L). The mean LVEF was similar in both arms (adjusted between-group difference 0.4%, 95% CI −1.8% to 2.5%, P=0.72) and no significant differences were found for the E/e' ratio (adjusted between-group difference 0.4, 95% CI −0.7 to 1.4, P=0.47). In intention-to-treat and per-protocol analyses, no clinically significant differences were found for secondary diastolic function parameters: e' lateral 8 vs. 8 cm/s, P=0.54; e' septal 6 vs. 6 cm/s, P=0.75; LA volume index 34 vs. 33 ml/m2, P=0.57; E/A ratio 0.8 vs. 0.8, P=0.94; E deceleration time 225 vs. 216 ms, P=0.27, except for systolic pulmonary artery pressure (37 mm Hg in the levothyoxine group vs. 33 mm Hg in the placebo group, P=0.02 intention-to-treat and P=0.06 per protocol)

Conclusion

Treatment of subclinical hypothyroidism with levothyroxine was not associated with benefits regarding systolic and diastolic heart function in older adults with subclinical hypothyroidism.
P760Clinical profile of African-American and non-Hispanic caucasian patients with Takotsubo cardiomyopathy syndrome in a large urban hospital in the United States of America
Authors: Westman P , Ravindra K , Chiabrando J , Kadariya D , Maehara G , Dell M , Van Wezenbeek J , Moeller G , Keyser-Marcus L , Gal T S , Ma L , Abbate A
Published: October 2019

Background

Takotsubo (stress) cardiomyopathy is an acute reversible heart failure syndrome initially described in Japanese patients, but now well characterized in Caucasians patients in Europe or of European descent. An initial observation has suggested a lower incidence of Takotsubo in non-Caucasian subjects, particularly in the African-American (AA) population in the United States of America. The purpose of this study was to assess whether epidemiologic and clinical differences were present in Takotsubo in a large urban hospital in Virginia, USA.

Methods

We used an informatics-based system to query electronic health records (TriNetX, Cambridge, MA, USA) to search for cases of Takotsubo between 2010 and 2018 and a corresponding cohort of patients with non-ST segment elevation acute myocardial infarction (NSTEMI). We then performed a chart-level review of 160 cases and obtained additional clinical information including symptoms, risk factors, co-morbidities, and in-hospital outcomes. This retrospective study was approved by the Institutional Review Board of our institution.

Results

We identified 260 cases of Takotsubo and 6,270 of NSTEMI in the same time period (1:24, 4.2%). Being AA was associated with an odds ratio of Takotsubo versus NSTEMI of 0.38 [0.29–0.50] (P=0.0001). With further evaluation of patients with Takotsubo (N=160), AA (N=44, 27.2%) and Non-Hispanic Caucasian (C) (N=110, 67.9%) had no differences in age and sex. AA patients with Takotsubo however were more likely than C patients to be affected by type II diabetes mellitus (38.6% versus 14.5%, P=0.002, OR 3.70 [1.65–8.28]), have history of drug abuse (27.3% versus 9.1%, P=0.009, OR 3.75 [1.48–9.49]) and of cocaine use in particular (9.1% versus 0.9%, P=0.024, OR 11.0 [1.19–101.4]). The pattern of wall motion abnormality was not different between the 2 groups. AA patients presented with a lower ratio of brain natriuretic peptide (BNP) to troponin I (41.9 [12.7–258] pg./ml versus 281 [42–890] pg/ml, P=0.022). There was no significant difference of in-hospital mortality between the AA and C groups (9.1% versus 25%, respectively, OR 0.40 [0.13–1.24], P=0.11).

Conclusions

The incidence and clinical characteristics of Takotsubo (stress) cardiomyopathy appear to be different between African-American and Non-Hispanic Caucasian patients. African-American patients are more likely to have diabetes and illicit drug usage, but have a lower BNP/troponin I ratio. Both AA and Non-Hispanic Caucasian patients have similar in-hospital mortality.
P774Transcoronary transfer of Wharton's jelly mesenchymal pluripotent stem cells in patients with chronic ischaemic heart failure shows safety and unprecedented high-grade myocardial uptake
Authors: Kozynacka A , Kwiecien E , Mazurek A , Drabik L , Skubera M , Czyz L , Szot W , Urbanczyk M , Banys P , Duplicka M , Kostkiewicz M , Kijowski J , Majka M , Podolec P , Musialek P
Published: October 2019

Background

Chronic ischaemic heart failure (CIHF) remains an important health problem on the patient/family- and society level. In animal models, Wharton's jelly (umbilical cord matrix) multipotent stem cells (WJMSCs) effectively promote angiogenesis, can differentiate to cardiomyocytes, and drive functional myocardial regeneration. Effective uptake of regenerative cells in ischaemic-impaired tissue is fundamental for any therapeutic effect.

Purpose

To evaluate safety and myocardial uptake of WJMSCs transcoronary transfer in CIHF applied as a novel myocardial regeneration strategy employing allogenic yet hypo-immunogenic, off-the-shelf “unlimited” source of therapeutic cells (NCT03418233 pilot cohort).

Material and methods

In ten consecutive patients (age 62.6±2.5), with stable CIHF and no current need for revascularization (LVEF 29.3±3% by echo and 26.3±6% by SPECT; NT-proBNP 1746±329pg/mL; myocardial scar tissue 39.9±3.9% by SPECT) and patency of at least two major native coronary arteries or by-pass graft(s), the CardioCell Investigational Medical Product, based on 30x106 WJMSCs, was administered to viable yet hypokinetic segments using a novel algorithm including a dedicated catheter for transcoronary delivery of cellular therapies. The cells were labeled with 99mTc-extametazime to routinely evaluate their myocardial uptake magnitude.

Results

No symptoms or signs of novel myocardial ischaemia occurred with cell delivery and no patient showed any adverse periprocedural events. One hour after administration, myocardial WJMSCs uptake (SPECT) was 40.3±6%; see Fig for a typical raw data image. By 6 months there were no adverse events in the study cohort.

Figure 1

Conclusions

This work indicates safety and unprecedented high-grade myocardial uptake of WJMSCs in CIHF patients. Together with animal data, this provides basis for continued assessment of this strategy in an endpoint-powered randomized controlled clinical trial employing CardioCell as an “unlimited” off-the-shelf cellular therapy strategy.

Acknowledgement/Funding

K/ZDS/005644 and 265761 (National Centre for Research and Development STRATEGMED)
P796Intensive blood pressure treatment significantly increases visit-to-visit systolic blood pressure variability. A randomized clinical trial
Authors: Rueda-Ochoa O L , Rojas Sanchez L Z , Ikram M A , Deckers J W , Franco O H , Rizopoulos D , Kavousi M
Published: October 2019

Background

Intensive blood pressure lowering is increasingly gaining attention. Besides higher baseline blood pressure, visit-to-visit variability has showed association with target organ damage and major adverse cardiovascular outcomes in multiple medical reports.

Purpose

Our aim was to assess the effect of intensive treatment on systolic blood pressure (SBP) visit-to-visit variability in the SPRINT trial population during follow-up.

Methods

We included 9068 SPRINT participants with 128139 repeated SBP measurements. Participants were randomly assigned to intensive (SBP <120 mmHg) vs standard treatment (SBP between 135–139 mmHg). The primary outcome was a composite outcome of myocardial infarction, other acute coronary syndromes, acute decompensated heart failure, stroke, and cardiovascular mortality. We calculated the coefficient of variation (CV) and standard deviation (SD), taking into account all SBP measurements prior to the SPRINT primary outcome. Comparison of CV between intensive and standard treatment in the total SPRINT population and among different subgroups was made.

Results

CVs in intensive treatment groups were higher in total population and in all groups under study (See table). While second and third CV quartile showed a larger tendency to increase the risk for the primary SPRINT outcome in the intensive treatment compared to the standard treatment group, fourth CV quartiles were significantly associated with increase in primary SPRINT outcome in both intensive and standard treatment groups.

Coefficient of variation in SPRINT trial Group Intensive treatment Standard treatment Total population 9.80 (3.22)* 8.52 (2.96) Females 10.46 (3.29)* 9.18 (3.15) Black person 9.99 (3.38)* 8.82 (3.15) Prevalence CKD 10.14 (3.22)* 9.12 (3.06) Prevalence CVD 10.28 (3.32)* 8.93 (3.23) ≥75 year 10.40 (3.18)* 9.01 (3.07) SAEs 10.30 (3.39)* 9.08 (3.13) (CKD: chronic kidney disease; CVD: cardiovascular disease; SAEs: serious adverse events. *P<0.05).

Conclusions

Intensive blood pressure treatment significantly increases SBP visit-to-visit variability in total SPRINT population and in all subgroups under study. Additional longitudinal studies with long-term follow-up are warranted to evaluate the impact of increases in SBP visit-to-visit variability due to intensive treatment on risk of major cardiovascular events.