Myocardial Stretch Research Articles

Abstract 13582: Biomarkers of Adverse Cardiovascular Events in Chronic Coronary Disease: Data From the ISCHEMIA Trial

Introduction: Circulating biomarkers may improve prediction of cardiovascular (CV) events in chronic coronary disease (CCD). The incremental value of biomarkers in CCD after adjustment for clinical factors, inducible ischemia and coronary artery disease (CAD) severity is uncertain. Methods: 756 ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) participants with site-determined moderate-severe ischemia and 9 assayed biomarkers (Figure) were included. Among participants with interpretable stress tests for ischemia and CAD by computed coronary tomography angiography (CCTA) (N=507), associations of biomarkers with the primary (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) or secondary endpoints (CV death or MI) were evaluated using sequentially adjusted multivariable Cox proportional hazards models (Model 1=unadjusted, Model 2=clinical features, Model 3=Model 2 + multivessel CAD by CCTA, and Model 4=Model 3 + severe ischemia). Results: Median (IQR) participant age was 64 (57-70) years, 19% were female, 81% white, and 5% Hispanic. Hypertension (85%), diabetes (46%) and obesity (45%) were common, 28% had an estimated glomerular filtration rate <60 ml/min/1.73m 2 . Severe ischemia was present in 44%, and 39% had multivessel CAD (≥70% stenosis) by CCTA. Over 3.5 (2.4-4.7) years of follow-up there were 146 (19%) primary and 128 (17%) secondary endpoints. Soluble CD40L, GDF-15, NT-proBNP, hsTnT were associated with the primary and secondary endpoints in univariable and multivariable (adjusting for clinical features, multivessel CAD and severe ischemia) models. Conclusion: Biomarkers of inflammation (GDF-15), thrombosis (sCD40L), myocardial stretch (NT-proBNP) and injury (hs-troponin) were associated with CV endpoints in the ISCHEMIA trial independent of clinical features, multivessel CAD and severe ischemia.

Abstract 12962: Circulating Biomarkers Are Associated With Left and Right Ventricular Strain Measured by Cardiac Magnetic Resonance Imaging in Repaired Tetralogy of Fallot Patients

Introduction: Circulating biomarkers thought to represent myocardial fibrosis and stretch are understudied in repaired tetralogy of Fallot (TOF) patients. We aim to identify associations between biomarkers and right ventricular (RV) and left ventricular (LV) function measured as strain by cardiac magnetic resonance (CMR) in repaired TOF patients. Methods: N-terminal-pro hormone BNP (NTproBNP), galectin-3 (Gal-3) and matrix metalloproteinase 1 (MMP1) were measured in serum obtained from TOF patients at the time of standard of care CMR. High and low biomarker groups were created using the median value. CMR strain analysis was performed using cvi42 (Circle Cardiovascular Imaging). CMR parameters were compared by biomarker group using two sample Student’s t tests (given normal distribution), and Pearson correlation coefficients were obtained. Results: Twenty patients were analyzed (45% male). Median age at TOF repair and CMR was 4.1 months (interquartile range [IQR] 1.6, 6.8) and 11.5 years (IQR 10, 15.5), respectively. Patients with higher Gal-3 had worse LV global longitudinal strain (Table) . Those with higher NTproBNP had worse RV global longitudinal and circumferential strain, and those with greater MMP1 values had worse LV global circumferential strain. Gal-3 was moderately inversely correlated with pulmonary regurgitant fraction and RV end-systolic volume (Table) . NTproBNP values were moderately directly correlated with RV mass. MMP1 values were moderately directly correlated with RV end-systolic volume and inversely correlated with RV ejection fraction. Conclusions: The three biomarkers investigated have associations with right and left ventricular strain. Gal-3 and MMP1 are potential biomarkers of LV function, while NTproBNP is a potential biomarker of RV function. Further, Gal-3 may inform more favorable RV remodeling. Future studies will determine if circulating biomarkers will identify early ventricular dysfunction after TOF repair.

Shark Fin Electrocardiogram in the Intensive Care Unit.

Shark Fin Electrocardiogram in the Intensive Care Unit.

Biomarkers in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing from multiple aetiologies with overlapping pathophysiological mechanisms. HFpEF diagnosis may be challenging, as neither cardiac imaging nor physical examination are sensitive in this situation. Here, we review biomarkers of HFpEF, of which the best supported are related to myocardial stretch and injury, including natriuretic peptides and cardiac troponins. An overview of biomarkers of inflammation, extracellular matrix derangements and fibrosis, senescence, vascular dysfunction, anaemia/iron deficiency and obesity is also provided. Finally, novel biomarkers from -omics technologies, including plasma metabolites and circulating microRNAs, are outlined briefly. A cardiac-centred approach to HFpEF diagnosis using natriuretic peptides seems reasonable at present in clinical practice. A holistic approach including biomarkers that provide information on the non-cardiac components of the HFpEF syndrome may enrich our understanding of the disease and may be useful in classifying HFpEF phenotypes or endotypes that may guide patient selection in HFpEF trials.

Brain Natriuretic Peptide Biomarkers in Current Clinical and Therapeutic Scenarios of Heart Failure.

Brain natriuretic peptide (BNP) and its inactive N-terminal fragment, NT-proBNP, are serum biomarkers with key roles in the management of heart failure (HF). An increase in the serum levels of these peptides is closely associated with the pathophysiological mechanisms underlying HF such as the presence of structural and functional cardiac abnormalities, myocardial stretch associated with a high filling pressure and neuro-hormonal activation. As BNP and NT-proBNP measurements are possible, several studies have investigated their clinical utility in the diagnosis, prognostic stratification, monitoring and guiding therapy of patients with HF. BNP and NT-proBNP have also been used as criteria for enrollment in randomized trials evaluating the efficacy of new therapeutic strategies for HF. Nevertheless, the use of natriuretic peptides is still limited in clinical practice due to the controversial aspect of their use in different clinical settings. The purpose of this review is to discuss the main issues associated with using BNP and NT-proBNP serum levels in the management of patients with HF under current clinical and therapeutic scenarios.

Atrial fibrillation in pregnancy

Developing countries with higher prevalence of RHD encounter cases of AF in pregnancy. Szekely et al reported new onset of AF in 8% of pregnant patients with RHD.1 Dilatation of LA, elevated LA pressure and myocardial stretch due to mitral valve disease results in slow conduction velocities, increased dispersion of refractoriness and automaticity leading to AF. Occurrence is common in third trimester due to Increased HR, cardiac output, heart size, plasma volume, wall tension and decreased SVR. AF intensifies hemodynamic changes and predisposes to heart failure.2

Novel Biomarkers of Heart Failure in Pediatrics.

Novel biomarkers of heart failure are the subject of numerous studies. Biomarkers of heart failure can be determined in the blood and in the urine. Seven groups of biomarkers of heart failure based on pathophysiological mechanisms are presented in this review, namely biomarkers of myocardial stretch, myocyte injury, myocardial remodeling, biomarkers of inflammation, renal dysfunction, neurohumoral activation, and oxidative stress. Studies of biomarkers in the pediatric population are scarce, therefore, further investigation is needed for reliable prognostic and therapeutic implications. The future of biomarker use is in multimarker panels that include a combination of biomarkers with different pathophysiological mechanisms in order to improve their diagnostic and prognostic predictive value.

PO-614-02 MICROTUBULE DETYROSINATION AND TRPA1 DRIVE STRETCH-INDUCED ARRHYTHMIAS IN THE ISOLATED RABBIT HEART

In hypertension, acute fluctuations in ventricular load can trigger arrhythmias due to myocardial stretch. In single rabbit ventricular myocytes, the incidence of stretch-induced arrhythmias (SIA) is increased by microtubule (MT) densification or detyrosination and transient receptor potential ankyrin 1 channel (TRPA1) activation, as occurs in hypertension.

Association of Plasma Methylglyoxal Increase after Myocardial Infarction and the Left Ventricular Ejection Fraction.

Background: Preclinical studies suggest that methylglyoxal (MG) increases within the myocardium upon acute myocardial infarction (AMI) and thereafter contributes to adverse postinfarct remodeling. The aims of this study were to test whether MG increases in plasma of humans after AMI and whether this increase is related to the left ventricular ejection fraction (LVEF). Methods: The plasma samples of 37 patients with ST elevation AMI undergoing primary percutaneous coronary intervention (pPCI) acquired in a previously conducted randomized controlled trial testing remote ischemic conditioning (RIC) were analyzed by means of high-performance liquid chromatography. Time courses of the variables were analyzed by means of mixed linear models. Multiple regression analyses served to explore the relationship between MG levels and the LVEF. Results: Compared to the MG levels upon admission due to AMI, the levels were increased 2.4-fold (95% CI, 1.6–3.6) 0.5 h after reperfusion facilitated by pPCI, 2.6-fold (1.7–4.0) after 24 h and largely returned to the baseline after 30 d (1.1-fold, 0.8–1.5). The magnitude of the MG increase was largely independent of that of cardiac necrosis markers. Overall, the highest MG values within 24 h after AMI were associated with the lowest LVEF after 4 d. While markers of myocardial necrosis and stretch quantified within the first 24 h explained 52% of the variance of the LVEF, MG explained additional 23% of the variance (p < 0.001). Conclusions: Considering these observational data, it is plausible that the preclinical finding of MG generation after AMI negatively affecting the LVEF also applies to humans. Inhibition of MG generation or MG scavenging might provide a novel therapeutic strategy to target post-AMI myocardial remodeling and dysfunction.

Abstract 058: Subclinical Myocardial Injury, Coagulopathy, And Inflammation In Covid-19: A Meta-analysis

Introduction: Infection with the SARS-CoV-2 virus can lead to myocardial injury, with cardiac biomarker elevations. Objective: To quantify the association between biomarkers of myocardial injury, coagulation, and severe COVID-19 and death in hospitalized patients. Methods: Studies were identified from PubMed, Embase, CINAHL, Cochrane, Web of Science, and Scopus, published between December 2019 to August 2021. Effect estimates for association between markers of myocardial injury (Troponin), myocardial stretch (N-terminal-pro hormone BNP, NT-proBNP), and coagulopathy (D-Dimer) and death or severe/critical COVID-19 were pooled using random-effects models. Odds Ratios (OR), Hazard Ratios (HR), and 95% Confidence Intervals (CI) were pooled separately and reported by outcomes of critical/severe COVID-19 and death. A meta-analysis of proportions summarized pooled prevalence of co-morbidities. Results: We included 62 articles, with 41,013 patients. Pooled proportion of patients with hypertension history was 39% (95% CI: 34-44%); diabetes, 21% (95% CI: 18%-24%); coronary artery disease, 13% (95% CI: 10-16%); chronic obstructive pulmonary disease, 7% (95% CI: 5-8%), and cancer, 5% (95% CI: 4-7%). Elevated troponin was associated with higher pooled odds of critical/severe COVID-19 and death [Odds Ratio (OR: 1.77, 95% CI: 1.42-2.18)] ( Figure ); also, separately for death (OR: 1.72, 95% CI: 1.32-2.25), and critical/severe COVID-19 (OR: 1.93, 95% CI: 1.45-2.40). Elevated NT-proBNP were associated with higher odds for severe COVID-19/death (OR: 3.00, 95% CI: 1.58-5.70). Elevated D-dimer levels was significantly associated with critical/severe COVID-19 and death (OR: 1.38, 95% CI: 1.07-1.79). Conclusions: This meta-analysis synthesizes evidence showing that myocardial injury, and coagulopathy are complications of COVID-19. Patients who have recovered from COVID-19 may benefit from minimally invasive assessment for markers of myocardial injury, stretch and coagulopathy for early risk stratification.

The Prognostic Potential of Growth Differentiation Factor-15 on Bleeding Events and Patient Outcome after Cardiac Surgery-A Prospective Cohort Study.

GDF-15 (growth/differentiation factor 15) is induced by myocardial stretch, volume overload, inflammation, and oxidative stress. Its expression is tightly linked with cardiovascular events as well as the risk for major bleeding and all-cause mortality. The present study aimed to elucidate the prognostic potential of GDF-15 in patients after cardiac surgery. A total of 504 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were prospectively enrolled. GDF-15 levels were measured prior to surgery to evaluate the impact on bleeding events, thromboembolic events, and mortality. Preoperative GDF-15 was associated with the primary endpoint of intra- and postoperative red blood cell transfusion (for bleeding risk factors adjusted [adj] OR [odds ratio] per 1-SD [standard deviation] of 1.62 [95% confidence interval [CI]: 1.31-2.00]; p < 0.001). Higher concentrations of GDF-15 were observed in patients reaching the secondary endpoint of major or clinically relevant minor bleeding (for bleeding risk factors adj. OR per 1-SD of 1.70 [95% CI: 1.05-2.75]; p = 0.030) during the first postoperative year, but not for thromboembolic events. GDF-15 was a predictor for cardiovascular mortality (for comorbidities adj. HR [hazard ratio] per 1-SD of 1.67 [95% CI: 1.23-2.27]; p = 0.001) and all-cause mortality (for comorbidities adj. HR per 1-SD of 1.55 [95% CI: 1.19-2.01]; p = 0.001). A combined risk model of GDF-15 and EuroSCORE II outperformed the EuroSCORE II alone for long-term survival (C-index: 0.75 [95% CI: 0.70-0.80], p = 0.046; net reclassification improvement: 33.6%, p < 0.001). Preoperative GDF-15 concentration is an independent predictor for intra- and postoperative major bleeding, major bleeding during the first year, and for long-term cardiovascular or all-cause mortality after cardiac surgery.

Subclinical myocardial injury, coagulopathy, and inflammation in COVID-19: A meta-analysis of 41,013 hospitalized patients.

Infection with the SARS-CoV-2 virus can lead to myocardial injury, evidenced by increases in specific biomarkers and imaging. To quantify the association between biomarkers of myocardial injury, coagulation, and severe COVID-19 and death in hospitalized patients. Studies were identified through a systematic search of indexed articles in PubMed, Embase, CINAHL, Cochrane, Web of Science, and Scopus, published between December 2019 to August 2021. Effect estimates from individual studies for association between markers of myocardial injury (Troponin), myocardial stretch (N-terminal-pro hormone BNP, NT-proBNP), and coagulopathy (D-Dimer) and death or severe/critical COVID-19 were pooled using inverse variance weighted random-effects model. Odds Ratios (OR), Hazard Ratios (HR), and 95% Confidence Intervals (CI) were pooled separately and reported by outcomes of critical/severe COVID-19 and death. A meta-analysis of proportions was also performed to summarize the pooled prevalence of co-morbidities in patients hospitalized with COVID-19. We included 62 articles, with a total of 41,013 patients. The pooled proportion of patients with history of hypertension was 39% (95% CI: 34-44%); diabetes, 21% (95% CI: 18%-24%); coronary artery disease, 13% (95% CI: 10-16%); chronic obstructive pulmonary disease, 7% (95% CI: 5-8%); and history of cancer, 5% (95% CI: 4-7%). Elevated troponin was associated with higher pooled odds of critical/severe COVID-19 and death [Odds Ratio (OR: 1.76, 95% CI: 1.42-2.16)]; and also separately for death (OR: 1.72, 95% CI: 1.32-2.25), and critical/severe COVID-1919 (OR: 1.93, 95% CI: 1.45-2.40). Elevations in NT-proBNP were also associated with higher severe COVID-19 and death (OR: 3.00, 95% CI: 1.58-5.70). Increases in D-dimer levels was also significantly associated with critical/severe COVID-19 and death (pooled OR: 1.38, 95% CI: 1.07-1.79). This meta-analysis synthesizes existing evidence showing that myocardial injury, and coagulopathy are complications of COVID-19. The durability of these complications and their contributions to long-term cardiac implications of the disease is still being investigated. Patients who have recovered from COVID-19 may benefit from minimally invasive assessment for markers of myocardial injury, stretch and coagulopathy for early risk stratification purposes.

NT Pro-BNP can be used as a risk predictor of clinical atrial fibrillation with or without left atrial enlargement.

BackgroundNT Pro‐BNP is a blood marker secreted by cardiomyocytes. Myocardial stretch is the main factor to stimulate NT Pro‐BNP secretion in cardiomyocytes. NT Pro‐BNP is an important risk factor for cardiac dysfunction, stroke, and pulmonary embolism. So does atrial myocyte stretching occur when patients have atrial fibrillation (AF)? Whether atrial muscle stretch induced by AF leads to increased NT Pro‐BNP remains unclear. The purpose of this study is to investigate the relationship between NT Pro‐BNP and AF.HypothesisAF can cause changes in myocardial tension. Changes in myocardial tension may lead to increased secretion of NT Pro‐BNP. We hypothesize that NT Pro‐BNP may increase in AF with or without LAD enlargement.MethodsThis clinical study is an observational study and has been approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University. Ethical approval documents is attached. The study retrospectively reviewed 1345 patients with and without AF. After excluding 102 patients who were not eligible, the final total sample size was 1243 cases: AF group 679 patients (378, 55.7% males) and non‐AF group 564 patients (287, 50.8% males). NT Pro‐BNP was observed in AF group and non‐AF group with or without LAD. After adjusting for age, gender, BMI, left atrial diameter, hypertension, diabetes, coronary heart disease, and cerebral infarction, NT Pro‐BNP remains statistically significant with AF.ConclusionNT Pro‐BNP can be used as a risk predictor of AF with or without left atrial enlargement.

MiR-208a in Cardiac Hypertrophy and Remodeling.

Various stresses, including pressure overload and myocardial stretch, can trigger cardiac remodeling and result in heart diseases. The disorders are associated with high risk of morbidity and mortality and are among the major health problems in the world. MicroRNAs, a class of ~22nt-long small non-coding RNAs, have been found to participate in regulating heart development and function. One of them, miR-208a, a cardiac-specific microRNA, plays key role(s) in modulating gene expression in the heart, and is involved in a broad array of processes in cardiac pathogenesis. Genetic deletion or pharmacological inhibition of miR-208a in rodents attenuated stress-induced cardiac hypertrophy and remodeling. Transgenic expression of miR-208a in the heart was sufficient to cause hypertrophic growth of cardiomyocytes. miR-208a is also a key regulator of cardiac conduction system, either deletion or transgenic expression of miR-208a disturbed heart electrophysiology and could induce arrhythmias. In addition, miR-208a appeared to assist in regulating the expression of fast- and slow-twitch myofiber genes in the heart. Notably, this heart-specific miRNA could also modulate the “endocrine” function of cardiac muscle and govern the systemic energy homeostasis in the whole body. Despite of the critical roles, the underlying regulatory networks involving miR-208a are still elusive. Here, we summarize the progress made in understanding the function and mechanisms of this important miRNA in the heart, and propose several topics to be resolved as well as the hypothetical answers. We speculate that miR-208a may play diverse and even opposite roles by being involved in distinct molecular networks depending on the contexts. A deeper understanding of the precise mechanisms of its action under the conditions of cardiac homeostasis and diseases is needed. The clinical implications of miR-208a are also discussed.

384 Morpho-functional analysis of subvalvular apparatus in mitral valve prolapse and response to dipyridamole stress echocardiography. A pilot study

Abstract Aims Myocardial fibrosis has been found in papillary muscles (PM) and basal segment of left ventricular (LV) inferior-lateral wall in patients with mitral valve prolapse (MVP), which may be due to stretch from valve. Moreover, ST-segment depression is common in patients with MVP, despite low prevalence of epicardial coronary artery disease, and it is attributed to microvascular dysfunction or myocardial stretch. Longitudinal strain (LS) correlates with myocardial fibrosis, while dipyridamole stress echocardiography (DSE) identifies microvascular dysfunction. We aimed at assessing morphology and function of PM and left ventricular walls at rest and during DSE by LS, and at determining prevalence of microvascular dysfunction in patients with MVP. Methods and results Seven consecutive patients with MVP (age 55.4 ± 15.7 years, 57% female) and LV ejection fraction 64 ± 5% underwent DSE. Length and LS of PM were measured at rest and retrospectively compared with those of patients with ischaemic heart disease (n = 8, age 67.1 ± 10.1 years, 37% female) and healthy controls (n = 8, age 39.6 ± 13.3 years, 50% female). LS of PM and LV was also determined at rest and during stress in MVP. Length of PM did not differ among groups, but in MVP, posterior PM was longer than the anterior PM (24 ± 3.8 vs. 20.6 ± 3.6 mm, P = 0.028). Significant difference in resting PM LS was found among groups (overall P = 0.04), with PM LS value in MVP (16.7 ± 7.1%) intermediate between ischaemic (14.2 ± 3.2%) and controls (20.5 ± 2.7%). No difference was found between rest and stress LS of PM in MVP. Global LS tended to increase in MVP during DSE compared to rest (23.1 ± 3.8% vs. 21.1 ± 2.6%, respectively, P = 0.07), while no significant difference between rest and stress LS was found in every LV myocardial segments. Nevertheless, in MVP, LS of LV inferior-lateral wall tended to improve under DSE in patients with mild regurgitation (19.7 ± 4.6 vs. 14.2 ± 5 at rest), but to decrease (16 ± 6.1 vs. 20.3 ± 2.3 at rest) in patients with severe mitral regurgitation (P = 0.006 for interaction). ST-segment depression was elicited by DSE in 29% of MVP. No significant difference in echocardiographic parameters was found between patients with and without ST-segment depression. Conclusions In MVP, sub-valvular apparatus may have peculiar morpho-functional features. DSE does not alter LS of PM, neither of LV walls, except for inferior-lateral wall, which impairs in severe mitral regurgitation. Prevalence of microvascular dysfunction is comparable to that of the general population.

292 Mechanical stress, myocardial deformation abnormalities, and ventricular fibrosis: a fatal cascade in arrhythmic mitral valve prolapse patients

Abstract Aims Arrhythmic mitral valve prolapse (MVP) is characterized by left ventricular (LV) fibrosis in the basal inferolateral wall and papillary muscles. We hypothesized that LV fibrosis are driven by excessive mechanical forces acting on myocardial susceptible cells, representing the last step in the MVP-induced myocardial stretch process. We evaluated the LV myocardial deformation, using strain assessed with cardiac magnetic resonance (CMR), in arrhythmic MVP patients with normal LV ejection fraction (LVEF) and absent/trivial mitral regurgitation (MR) and its correlation with the presence of LV fibrosis, detected by late gadolinium enhancement (LGE) in post-contrast CMR images. Methods and results We enrolled consecutive arrhythmic MVP patients with normal LVEF and no/trivial MR. Sixty-nine (39 female; median age: 40 years) patients without MVP, arrhythmias or cardiovascular history served as control group. All patients underwent CMR for identification of LGE and evaluation of LV myocardial deformation. A total of 66 patients were enrolled (47 female; median age: 44 years). In the overall MVP population, LGE was present in 41 patients (62.1%). MVP patients without LGE (25 patients, 37.9%) presented a higher global radial (median: 42.19 vs. 33; P &amp;lt;0.0001) and higher global longitudinal strain (median: −21.61 vs. −18.10; P &amp;lt;0.0001), compared to the control group. A reduction of regional basal posterolateral radial (BPL median: 50.60 vs. 67.30; P = 0.0015) and longitudinal strain (BPL median: −23.50 vs. −26.70; P = 0.0186) were observed in the MVP patients as compared with controls (Figures A–D). Conversely to the basal region, mid anterolateral and posterolateral region presented a higher radial (MAL median: 52.60 vs. 31.10; P &amp;lt; 0.0001 and MPL median: 52.80 vs. 21.50; P &amp;lt; 0.0001) and longitudinal strain (MAL median: −24.80 vs. −18.30; P &amp;lt; 0.0001 and MPL median: −25.30 vs. −14.80; P &amp;lt; 0.0001), when compared to control group. MVP patients with LGE had a lower global radial (median: 36.48 vs. 42.19; P &amp;lt;0.0047), longitudinal (median: −19.18 vs. −21.61; P = 0.0013), and circumferential strain (median: −17.80 vs. −19.28; P = 0.0134) compared with those without fibrosis. According to MVP patients without LGE, the presence of fibrosis is associated with a lower regional radial (BAL median: 64.40 vs. 82.80; P = 0.0481; MAL median: 42.60 vs. 52.60; P = 0.0287) and circumferential strain (BAL median: −21.90 vs. −24.20; P = 0.0174; BPL median: −16.80 vs. −18.80; P = 0.0411; MPL median: −15.50 vs. −19.40; P = 0.0077) in the LV basal-mid lateral walls (Figures E–H). 292 Figures A–D and E-H Conclusions Arrhythmic MVP patients with normal LV systolic function and absent/trivial MR presented an abnormal myocardial deformation pattern. The reduced strain in BPL wall of MVP patients without LGE could be considered as an early marker of MVP-induced myocardial stress, that could promote, time by time, LV fibrosis and arrhythmias in MVP patients.

Biomarkers in the clinical management of patients with atrial fibrillation and heart failure.

Atrial fibrillation (AF) and heart failure (HF) are two cardiovascular diseases with an increasing prevalence worldwide. These conditions share common pathophysiologiesand frequently co-exit. In fact, the occurrence of either condition can ‘cause’ the development of the other, creating a new patient group that demands different management strategies to that if they occur in isolation. Regardless of the temproral association of the two conditions, their presence is linked with adverse cardiovascular outcomes, increased rate of hospitalizations, and increased economic burden on healthcare systems. The use of low-cost, easily accessible and applicable biomarkers may hasten the correct diagnosis and the effective treatment of AF and HF. Both AF and HF effect multiple physiological pathways and thus a great number of biomarkers can be measured that potentially give the clinician important diagnostic and prognostic information. These will then guide patient centred therapeutic management. The current biomarkers that offer potential for guiding therapy, focus on the physiological pathways of miRNA, myocardial stretch and injury, oxidative stress, inflammation, fibrosis, coagulation and renal impairment. Each of these has different utility in current clinincal practice.

Abstract 12543: Limited Blood Biomarker Changes After Reverse Remodelling: A Markers and Response to CRT (Marc) Substudy

Objectives: Investigate if the amount of reverse remodelling after CRT coincides with blood biomarker changes. Background: Blood biomarkers are predictors of heart failure, but sparse data exist on the correlation between blood biomarkers changes and reverse remodelling. Methods: Fourteen blood biomarkers, reflecting collagen turnover (PIIINP, CICP, MMP-9, TIMP-1, ICTP), inflammation (hsCRP, IL-6), myocardial stretch and injury (NT-proBNP, hsTroponin-T), inflammatory-, fibrotic- and apoptotic pathways (Galectin-3, ST2, GDF-15) and renal function (creatinine, BUN), were assessed before and six months after CRT in 213 patients from the Markers and Response to CRT study. Additionally, baseline peripheral venous (PV) and coronary sinus (CS) samples were compared. Patients were divided in 4 groups based on indexed left ventricular end systolic volume change (LVESVi): no remodelling, lower, middle, and upper tertile. Results: Mean age was 66±10 years, 62% were men, 42% had ischemic aetiology. 169 patients experienced LVESVi reduction: lower tertile 12% (5-16%), middle tertile 32% (25-37%), upper tertile 53% (44-58%). Collagen markers increased in all groups. Inflammation markers remained in normal range. hsTroponin-T decreased in all groups. Renal markers showed no clinical significant change. GDF-15, ST2 and Galectin-3 remained elevated, showing no distinct pattern. Only NT-proBNP changes corresponded to LVESVi reduction (β -1.72, P&lt;0.001). Between all CS-PV samples was a positive correlation (R-range: 0.72-0.97, all P&lt;0.001). Conclusions: NT-proBNP changes are associated with amount of reverse remodelling 6 months after CRT. Thirteen other blood biomarkers, reflecting, among others, collagen turnover, fibrotic- and apoptotic pathways, are not. CS and PV samples correspond well, CS sampling does not seem to provide additional information in assessing reverse remodelling.

The prognostic potential of growth differentiation factor-15 on bleeding events and patient outcome after cardiac surgery

Abstract Background GDF-15 (growth/differentiation factor 15) is induced by myocardial stretch, volume overload, inflammation and oxidative stress. Its expression is tightly linked with cardiovascular events as well as the risk for major bleeding and all-cause mortality. Objective The objective of the present study was to elucidate the prognostic potential of GDF-15 in patients after cardiac surgery. Methods 504 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were prospectively enrolled. GDF-15 levels were measured prior surgery to evaluate the impact on bleeding events, thromboembolic events and mortality. Results Preoperative GDF-15 was associated with the primary endpoint of intra- and postoperative red blood cell transfusion (for bleeding risk factors adjusted [adj] OR [odds ratio] per 1-SD [standard deviation] of 1.62 [95% CI: 1.31–2.00]; p&amp;lt;0.001) and postoperative atrial fibrillation (for atrial fibrillation risk factors adj. OR per 1-SD of 1.49 [95% CI: 1.22–1.81]; p&amp;lt;0.001). Higher concentrations of GDF-15 were observed in patients reaching the secondary endpoint of major or clinically relevant minor bleeding (for bleeding risk factors adj. OR per 1-SD of 1.70 [95% CI: 1.05–2.75]; p=0.030) during the 1stpostoperative year, but not for thromboembolic events. GDF-15 was a predictor for cardiovascular mortality (for comorbidities adj. HR [hazard ratio] per 1-SD of 1.67 [95% CI: 1.23–2.27]; p=0.001) and all-cause mortality (for comorbidities adj. HR per 1-SD of 1.55 [95% CI: 1.19–2.01]; p=0.001). A combined risk model of GDF-15 and EuroSCORE II outperformed the EuroSCORE II alone for long-term survival (c-index: 0.75 [95% CI: 0.70–0.80], p=0.046; net reclassification improvement: 33.6%, p&amp;lt;0.001). Conclusion Preoperative GDF-15 concentration is an independent predictor for intra- and postoperative major bleeding, major bleeding during the first year and for long-term cardiovascular or all-cause mortality after cardiac surgery. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Vienna Central illustration

Liver stiffness as measured by transient elastography is a predictor of outcomes in patients with chronic heart failure with reduced, mid-range, and recovered left-ventricular ejection fraction

BackgroundTransient elastography is a noninvasive method for assessing liver stiffness (LS), which can reflect right-sided filling pressure associated with passive liver congestion in patients with HF. MethodsA prospective, single-center observational study in which LS was measured in consecutive ambulatory patients with heart failure with reduced, mid-range, and recovered left ventricular ejection fraction, between March 2018 and June 2019. Mean follow up was 219 ± 86 days. The primary endpoint was time to first event, which was defined as a composite of cardiovascular death or HF hospitalization. ResultsEighty-five patients were included in the final analysis. Mean age was 62 ± 10 and 68% were male. Mean ejection fraction and median NT-proBNP were, respectively, 38.7 ± 14.3% and 1140 pg/mL (interquartile range 224.3–2810.3). The median LS for the entire population was 6.3 (2.5-41.2) kPa. LS correlated with NT-proBNP (r = 0.46; p < 0.0001), total bilirubin (r = 0.47; p < 0.001), direct bilirubin (r = 0.43; p = 0.0001), gama-glutamyl-transpeptidase (r = 0.54; p < 0.0001), and alkaline phosphatase (r = 0.39; p = 0.0004). A Receiver Operating Characteristic (ROC) curve was performed and a cut point of 5.9 kPa showed sensitivity of 80% and specificity of 64.1% with area under the curve of 0.73. Using Cox proportional hazard model (independent variables: LS as a continuous variable, age, gender, NT-proBNP, LVEF, and creatinine), only LS was independently associated with the primary endpoint (hazard ratio 1.05, 95% confidence interval 1.01-1.09; for each increment of one unit of LS). ConclusionLS correlates with biomarkers of myocardial stretch and several liver function tests and is an independent predictor of outcomes in ambulatory patients with HF.