Mechanisms of angina in patients with biopsy-proven viral myocarditis: insights from intracoronary acetylcholine testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Seitz ◽  
V Martinez Pereyra ◽  
A Hubert ◽  
K Klingel ◽  
R Bekeredjian ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Coronary Spasm ◽  
Viral Myocarditis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Pathophysiological Mechanism ◽  
Ecg Changes ◽  
Ventricular Ejection Fraction ◽  
Microvascular Spasm

Abstract Background Patients with myocarditis often present with angina pectoris despite unobstructed coronary arteries. The underlying pathophysiological mechanism of angina in these patients remains to be elucidated. Coronary artery spasm is a well-known cause of angina in patients with unobstructed coronary arteries. In this study, we sought to assess the frequency of coronary vasomotor disorders in patients with biopsy-proven viral myocarditis. Methods In total, 700 consecutive patients who underwent endomyocardial biopsy for suspected myocarditis between 2008 and 2018 were retrospectively screened. Of these patients, viral myocarditis was confirmed in 303 patients defined as histological/immunohistological evidence of myocardial inflammation and presence of viral genome confirmed by PCR. Of these patients, 34 patients had angina despite unobstructed coronary arteries and underwent intracoronary acetylcholine (ACh) provocation testing in search of coronary spasm. Epicardial spasm was defined as acetylcholine-induced reproduction of the patient's symptoms associated with ischemic ECG changes and >90% epicardial vasoconstriction. Microvascular spasm was defined as symptom reproduction and ECG changes in the absence of significant epicardial vasoconstriction. Results Patients were 49±16 years old, 62% were male and left ventricular ejection fraction was 54±16%. Most frequent viruses were parvovirus B19 (PVB19, 59%) and human herpes virus 6 (HHV6, 26%), 2 patients had combined PVB19/HHV6 infection and 3 patients other herpesviruses (CMV, EBV, VZV). Epicardial spasm was observed in 10 patients (29%) during ACh testing and microvascular spasm was found in 11 patients (32%). The rate of coronary spasm (epicardial and microvascular) was higher in the PVB19 subgroup compared to HHV6 (80% vs. 33%, p=0.031). In particular, there was a higher prevalence of microvascular spasm in PVB19 compared to HHV6 (45% vs. 0%, p=0.018). Conclusion We observed a high prevalence of microvascular and epicardial spasm in patients with biopsy-proven viral myocarditis suggesting coronary spasm as a potential underlying mechanism for angina in these patients. Microvascular spasm was most often observed in patients with PVB19-associated myocarditis. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Robert-Bosch-Stiftung; Berthold-Leibinger-Stiftung

Randomized, double blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-MI: rationale, design and first interim analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Adverse Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Early Recovery ◽  
Ventricular Ejection Fraction ◽  
Combined Application

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF <45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect >3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor

Genetic polymorphisms and cardiovascular outcomes in Chinese patients undergoing PCI and treated with clopidogrel and aspirin

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Xu ◽  
L Ying ◽  
J Chen ◽  
L Xu ◽  
J Li ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Genetic Polymorphisms ◽  
Light Transmission ◽  
Left Ventricular ◽  
Cardiovascular Outcomes ◽  
Chinese Patients ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
One Year

Abstract Background Genetic polymorphisms of key proteins involved in clopidogrel absorption, metabolism, and action may contribute to variability in platelet inhibition in patients undergoing percutaneous coronary intervention (PCI), but their impacts on cardiovascular outcomes remain unclear. Purpose To examine the associations between genetic polymorphisms and cardiovascular outcomes in Chinese patients undergoing PCI and treated with clopidogrel and aspirin. Methods This prospective cohort study consecutively enrolled 2,453 post-PCI patients treated with clopidogrel and aspirin. Adenosine diphosphate-induced platelet aggregation was measured by light transmission aggregometry. A total of 40 single nucleotide polymorphisms (SNPs) of 18 genes selected according to published studies were investigated using an improved multiplex ligation detection reaction technique. The primary outcome was major adverse cardiovascular event (MACE), the composite of cardiovascular death, non-fatal myocardial infarction (MI), and ischemic stroke within one year after PCI. Results We restricted the analyses to the first 1,452 patients who had finished one-year follow-up and complete data on genotyping and platelet aggregation. 44 (3.03%) patients suffered MACE. Among the 40 SNPs, only the A-allele carriers of CYP2C19*2 had a significant higher risk of MACE (adjusted HR 2.05; 95% CI, 1.01–4.19; p=0.048) and platelet aggregation than non-A-carriers after adjusting age, sex, MI presentation, and left ventricular ejection fraction. CYP2C19*3, CYP2B6 rs3745274, and PEAR1 rs12041331 variants were also significantly associated with platelet aggregation (all p<0.05) but not with MACE at 1 year. Conclusion About 54.2% of Chinese patients with PCI were A-allele carriers of CYP2C19*2, who face a two-fold higher risk of MACE than non-A-allele carriers in Chinese patients after PCI. It would help identify low clopidogrel responders and optimize antiplatelet therapy before drug administration. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Funding of China

scholarly journals Beta-blocker use is associated with prevention of left ventricular remodeling in recovered dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Enzan ◽  
S Matsushima ◽  
T Ide ◽  
H Kaku ◽  
T Higo ◽  
...  
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Beta Blocker ◽  
Primary Outcome ◽  
Protocol Analysis ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction

Abstract Background Withdrawal of optimal medical therapy has been reported to relapse cardiac dysfunction in patients with dilated cardiomyopathy (DCM) whose cardiac function had improved. However, it is unknown whether beta-blockers can prevent deterioration of cardiac function in those patients. Purpose We examined the effect of beta-blockers on left ventricular ejection fraction (LVEF) in recovered DCM. Methods We analyzed the clinical personal records of DCM, a national database of Japanese Ministry of Health, Labor and Welfare, between 2003 and 2014. Recovered DCM was defined as a previously documented LVEF <40% and a current LVEF ≥40%. Patients with recovered DCM were divided into two groups according to the use of beta-blockers. The primary outcome was defined as a decrease in LVEF >10% at two years of follow-up. A one to one propensity case-matched analysis was used. A per-protocol analysis was also performed. Considering intra- and inter-observer variability of echocardiographic evaluations, we also examined outcomes by multivariable logistic regression model after changing the inclusion criteria as follows; (1) previous LVEF <40% and current LVEF ≥40%; (2) previous LVEF <35% and current LVEF ≥40%; (3) previous LVEF <30% and current LVEF ≥40%; (4) previous LVEF <40% and current LVEF ≥50%. Outcomes were also changed as (1) decrease in LVEF ≥5% (2) decrease in LVEF ≥10% (3) decrease in LVEF ≥15%. The analysis of outcomes by using combination of multiple imputation and inverse probability of treatment weighting was also conducted to assess the effects of missing data and selection bias attributable to propensity score matching on outcomes. Results From 2003 to 2014, 40,794 consecutive patients with DCM were screened. Out of 5,338 eligible patients, 4,078 received beta-blockers. Propensity score matching yielded 998 pairs. Mean age was 61.7 years and 1,497 (75.0%) was male. Mean LVEF was 49.1±8.1%. The primary outcome was observed less frequently in beta-blocker group than in no beta-blocker group (18.0% vs. 23.5%; odds ratio [OR] 0.72; 95% confidence interval [CI] 0.58–0.89; P=0.003). The prevalence of increases in LVDd (11.5% vs. 15.8%; OR 0.70; 95% CI 0.54–0.91; P=0.007) and LVDs (23.1% vs. 27.2%; OR 0.80; 95% CI 0.65–0.99; P=0.041) was also lower in the beta-blocker group. Similar results were obtained in per-protocol analysis. These results were robust to several sensitivity analyses. As a result of preventing a decrease in LVEF, the deterioration to HFrEF was also prevented by the use of beta-blocker (23.6% vs. 30.6%). Subgroup analysis demonstrated that beta-blocker prevented decrease in LVEF regardless of atrial fibrillation. Conclusion Use of beta-blocker was associated with prevention of decrease in left ventricular ejection fraction in patients with recovered DCM. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Health Sciences Research Grants from the Japanese Ministry of Health, Labour and Welfare (Comprehensive Research on Cardiovascular Diseases)

scholarly journals Time saving, simple and reproducible method to quantify left ventricular function in patients with atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.V Bunting ◽  
S Gill ◽  
A Sitch ◽  
S Mehta ◽  
K O'Connor ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Controlled Trial ◽  
Global Longitudinal Strain ◽  
Intraclass Correlation ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction

Abstract Introduction Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility. Purpose To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference). Methods Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson's biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e'). Results 160 patients (median age 75 years (IQR 69–82); 46% female) were included, with median heart rate 100 beats/min (IQR 86–112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p<0.001). The index beat also had the lowest CV for GLS (26% versus 43% and 42%; p<0.001) and E/e' (25% versus 41% and 41%; p<0.001; see Figure for ICC comparison). Intra-operator reproducibility, assessed by the same operator from two different recordings in 50 patients, was superior for the index beat with GLS bias −0.5 and narrow limits of agreement (−3.6 to 2.6), compared to −1.0 for 10 consecutive beats (−4.0 to 2.0). For inter-operator variability, assessed in 18 random patients, the index beat also showed the smallest bias with narrow confidence intervals (CI). Using a single index beat did not impact on the validity of LVEF, GLS or E/e' measurement when correlated with natriuretic peptides. Index beat analysis substantially shortened analysis time; 35 seconds (95% CI 35 to 39 seconds) for measuring E/e' with the index beat versus 98 seconds (95% CI 92 to 104 seconds) for 10 consecutive beats (see Figure). Conclusion Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice. Comparison for measurement of E/e' Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research UK

scholarly journals The outcome of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and impaired kidney function: a 3-year observational study

2021 ◽  
Author(s):  
Malgorzata Zalewska-Adamiec ◽  
Jolanta Malyszko ◽  
Ewelina Grodzka ◽  
Lukasz Kuzma ◽  
Slawomir Dobrzycki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Incidence Rate ◽  
Kidney Function ◽  
Coronary Arteries ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Risk Of Death ◽  
Group 2 ◽  
Group 1

Abstract Background Myocardial infarction with nonobstructive coronary arteries (MINOCA) constitutes about 10% of the cases of acute coronary syndromes (ACS). It is a working diagnosis and requires further diagnostics to determine the cause of ACS. Methods In this study, 178 patients were initially diagnosed with MINOCA over a period of 3 years at the Department of Invasive Cardiology of the University Clinical Hospital in Białystok. The value of estimated glomerular filtration rate (eGFR) was calculated for all patients. The patients were divided into 2 groups depending on the value of eGFR: group 1—53 patients with impaired kidney function (eGFR < 60 mL/min/1.73 m2; 29.8%) and group 2—125 patients with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2; 70.2%). Results In group 1, the mean age of patients was significantly higher than that of group 2 patients (77.40 vs 59.27; p < 0.0001). Group had more women than group 2 (73.58% vs 49.60%; p = 0.003). Group 1 patients had higher incidence rate of arterial hypertension (92.45% vs 60.80%; p < 0.0001) and diabetes (32.08% vs 9.60%; p = 0.0002) and smoked cigarettes (22.64% vs 40.80%; p = 0.020). Group 1 patients had higher incidence rate of pulmonary edema, cardiogenic shock, sudden cardiac arrest (13.21% vs 4.00%; p = 0.025), and pneumonia (22.64% vs 6.40%; p = 0.001). After the 37-month observation, the mortality rate of the patients with MINOCA was 16.85%. Among group two patients, more of them became deceased during hospitalization (7.55% vs 0.80%; p = 0.012), followed by after 1 year (26.42% vs 7.20%; p = 0.0004) and after 3 years (33.96% vs 9.6%; p < 0.0001). Multivariate analysis revealed that the factors increasing the risk of death in MINOCA are as follows: older age, low eGFR, higher creatinine concentration, low left ventricular ejection fraction, and ST elevation in ECG. Conclusion Impaired kidney function is diagnosed in every third patient with MINOCA. Early and late prognosis of patents with MINOCA and renal dysfunction is poor, and their 3-year mortality is comparable to patients with myocardial infarction with significant stenosis of the coronary arteries and impaired kidney function.

IL-10 / IL-6 serum ratio as a prognosis marker of STEMI

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Leboube ◽  
T Bochaton ◽  
A Paccalet ◽  
C Crola Da Silva ◽  
P Jeantet ◽  
...  
Keyword(s):  
Acute Phase ◽  
Left Ventricular ◽  
Clinical Event ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Adverse Clinical Event ◽  
St Elevation ◽  
Prognosis Marker ◽  
Inflammatory Effect

Abstract Introduction IL-6 and IL-10 are two major cytokines secreted at the acute phase of myocardial infarction (MI). IL-6 has a pro-inflammatory effect whereas IL-10 has anti-inflammatory effect. Objective Our objective was to assess the prognosis value of IL-6, IL-10 and IL-10/IL-6 ratio serum level at the acute phase of ST elevation MI (STEMI). Methods We prospectively enrolled 247 patients admitted for acute STEMI from 2016 to 2019. Blood samples were collected at 5 time points: admission, 4, 24, 48 hours and 1 month (H4, H24, H48, M1). IL-6 and IL-10 were assessed using ELISA. Patients underwent cardiac magnetic resonance imaging at one month for infarct size (IS) and left ventricular ejection fraction (LVEF) assessment. Clinical outcomes were prospectively recorded over 18 months. Results Patient mean age was 59±12 years. IL-6 reached a peak at H24 at 5.4 pg/mL interquartile range (IQR) [2.1–11.0] and IL-10 peaked as early as admission at 5.6 pg/mL IQR [8.7–29.3] followed by a decrease within the first month. Median IL-10/IL-6 ratio at admission was 4.2 [1.4–8.6] with a strong decrease at H24 (0.5 [0.2–1.3]). IL-6 and IL-10 levels at H24 were correlated with IS (respectively r=0.44, p&lt;0.0001, and r=0.29, p=0.0001) and inversely correlated with LVEF (respectively r=−0.42, p&lt;0.0001 and r=−0.26, p=0.0003). Patients with IL-10/IL-6 ratio ≥1 had smaller IS compared to patients with IL-10/IL-6 ratio &lt;1 (respectively 9.0% IQR [2.4–15.4] of LV versus 17% IQR [8.7–29.3] of LV, p&lt;0.0001) and they had higher LVEF (58.0% IQR [52.0–62.3] versus 49.0% IQR [41.5–56.0], p&lt;0.0001). Patients with IL-10/IL-6 ratio &lt;1 were more likely to have an adverse clinical event (MI, stroke, hospitalization for heart failure and all-cause death) during the first 18 months after STEMI compared to patients with IL-10/IL-6 ratio ≥1 (HR=2.7, 95% CI [1.2–5.5], p=0.04). Conclusion Serum IL-10/IL-6 &gt;1 was associated with a poor outcome after STEMI and might be a valuable prognostic marker. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospices Civils de Lyon, Fédération Française de Cardiologie

Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adjuvant Therapy ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Systolic Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Coronary Reperfusion ◽  
Ventricular Ejection Fraction

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).

Right ventricular speckle tracking in patients with heart failure – a comparison of right ventricular measures

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.J Lundorff ◽  
M Sengeloev ◽  
S Pedersen ◽  
D Modin ◽  
N.E Bruun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
Risk Of Mortality ◽  
Patients With Heart Failure

Abstract Background RV dysfunction is associated with increased mortality and morbidity in patients with heart failure. Due to the complex shape and position of the RV, assessing RV function from echocardiographic images remains a challenge. Purpose We have previously found that global longitudinal strain from 2DSTE is superior to left ventricular ejection fraction (LVEF) in identifying HFrEF patients with high risk of mortality. In this study we wanted to examine RV 2DSTE in patients with HFrEF and compare its prognostic value to conventional RV measures. Methods and results Echocardiographic examinations were retrieved from 701 patients with HFrEF. RV estimates were analysed offline, and end point was all-cause mortality. During follow-up (median 39 months) 118 patients (16.8%) died. RV GLS and RV FWS remained associated with mortality after multivariable adjustment, independent of TAPSE (RV GLS: HR 1.07, 95% CI 1.02–1.13, p=0.010, per 1% decrease) (RV FWS: HR 1.05, 95% CI 1.01–1.09, p=0.010, per 1% decrease). This seemed to be caused by significant associations in men as TAPSE remained as the only independent prognosticator in women. All RV estimates provided prognostic information incremental to established risk factors and significantly increased C-statistics (TAPSE: 0.74 to 0.75; RVFAC: 0.74 to 0.75; RVFWS: 0.74 to 0.77; RVGLS: 0.74 to 0.77). Conclusions RV strain from 2DSTE was associated with mortality in patients with HFrEF, independent of TAPSE and established risk factors. Our results indicate that RV strain is particularly valuable in male patients, whereas in women TAPSE remains a stronger prognosticator. RV GLS and the risk of mortality Funding Acknowledgement Type of funding source: Private company. Main funding source(s): PGJ reports receiving lecture fee from Novo Nordisk.

scholarly journals Cardiovascular phenotyping of the first mouse model of Sarcoidosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Bueno Beti ◽  
C Lim ◽  
A Protonotarios ◽  
A Kiss ◽  
M.N Sheppard ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Mechanisms ◽  
Left Ventricular ◽  
Cell Junctions ◽  
Left Ventricular Ejection ◽  
Unknown Etiology ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Arrhythmogenic Substrate ◽  
Inflammatory Infiltrates

Abstract Introduction Sarcoidosis is a potentially life-threatening, inflammatory, granulomatous disease that affects multiple organs including the heart. Heretofore, its unknown etiology had hindered the creation of experimental models and the understanding of the molecular mechanisms of pathogenesis behind it. Purpose To extensively phenotype the heart of the first mouse model of sarcoidosis created through deletion of the tuberous sclerosis 2 (Tsc2) gene in the CD11c-positive macrophage population. Methods Tsc2 fl/fl CD11c Cre+ (Tsc2-KO; n=7) and Tsc2 fl/fl CD11c Cre- (Tsc2-WT; n=7) mice were subjected to echocardiography at 25 weeks of age (woa) to assess myocardial dimensions and function. Hearts of 13 and 25woa animals were subjected to histological and immunological stains to assess tissue changes, subtype inflammatory infiltrates and examine the localization of key proteins shown to be re-distributed in patients. Results At 13 woa, Tsc2-KO animals show inflammatory infiltrates; subtyped mainly as macrophages as well as evidence of myocyte destruction. At 25 woa, the number of inflammatory cells is significantly higher and there is heavy fibrotic replacement primarily in the septum and trabeculae. Older animals also show giant cells and non-necrotizing granulomas. The hearts show heterogeneous gap junction remodeling known to constitute an arrhythmogenic substrate and lack of immunoreactive signal for the desmosomal protein plakoglobin from the cell-cell junctions just as described in patients. The left ventricular ejection fraction and LV morphology was not significantly different between the two groups (EF: 64±4% in Tsc2-KO vs 64±2% in Tsc2-WT; LV end-systolic diameter: 4.51±0.54 mm in Tsc2-KO vs 4.59±0.29 mm in Tsc2-WT). However, there was a strong trend towards increasing filling pressure (E/e'ratio; 14.24±4.01 vs 12.15±2.54) and mean pulmonary pressure (21±6 vs 18±3 mmHg) in Tsc2-KO mice compared to controls suggesting diastolic dysfunction. Conclusion Hearts of the Tsc2 fl/fl CD11c Cre+ animals show a phenotype highly reminiscent of cardiac sarcoidosis in patients. We anticipate that this model will be very useful in deciphering molecular mechanisms of pathogenesis as well as testing much-needed mechanism-based therapies. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation - PG/18/27/33616

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