Nonischemic Causes Research Articles

Long-term outcomes among out-of-hospital cardiac arrest survivors with reversible vs. non-reversible causes.

A reversible cause of out-of-hospital cardiac arrest (OHCA) is vaguely defined in international guidelines as an identifiable transient or potentially correctable condition. However, studies evaluating long-term outcomes of patients experiencing OHCA due to reversible and non-reversible causes are lacking. We aimed to determine differences in long-term outcomes in OHCA survivors according to different aetiology. From the British Columbia Cardiac Arrest registry, adults with non-traumatic OHCA (2009-2016) surviving to hospital discharge were identified. Patients were categorized by OHCA aetiology combining reversibility and underlying ischaemic aetiology. The primary outcome was a composite of all-cause mortality, recurrent OHCA, or re-hospitalization for sudden cardiac arrest or ventricular arrhythmias. Using the Kaplan-Meier method and multivariable Cox regression models, we compared the risk of the composite outcome according to different OHCA aetiology. Of 1325 OHCA hospital-discharge survivors (median age 62.8 years, 77.9% male), 431 (32.5%) had reversible ischaemic, 415 (31.3%), non-reversible ischaemic, 99 (7.5%), reversible non-ischaemic, and 380 (28.7%), non-reversible non-ischaemic aetiologies. At 3 years post discharge, the Kaplan-Meier event-free rate was highest in patients with a reversible ischaemic aetiology [91%, 95% confidence interval (CI) 87-94%], and lowest in those with a reversible non-ischaemic aetiology (62%, 95% CI 51-72%). In multivariate analyses, compared with non-reversible non-ischaemic cause, reversible ischaemic cause was associated with a significantly lower hazard ratio (HR; 0.52, 95% CI 0.33-0.81), reversible non-ischaemic cause with a significantly higher HR (1.53, 95% CI 1.03-2.32), and non-reversible ischaemic cause with a non-significant HR (0.92, 95% CI 0.64-1.33) for the composite outcome. Compared to other aetiologies, the presence of a reversible ischaemic cause is associated with improved long-term OHCA outcomes.

The role of coronary CT angiography in athletes.

The sudden death of a young or high-level athlete or adolescent during recreational sports is one of the events with the greatest impact on public opinion in modern society. Sudden cardiac death (SCD) is the principal medical cause of death in athletes and can be the first and last clinical presentation of underlying disease. To prevent such episodes, pre-participation screening has been introduced in many countries to guarantee cardiovascular safety during sports and has become a common target among medical sports/governing organizations. Different cardiac conditions may cause SCD, with incidence depending on definition, evaluation methods, and studied populations, and a prevalence and etiology changing according to the age of athletes, with CAD most frequent in master athletes, while coronary anomalies and non-ischemic causes prevalent in young. To detect silent underlying causes early would be of considerable clinical value. This review summarizes the pre-participation screening in athletes, the specialist agonistic suitability visit performed in Italy, the anatomical characteristics of malignant coronary anomalies, and finally, the role of coronary CT angiography in such arena. In particular, the anatomical conditions suggesting potential disqualification from sport, the post-treatment follow-up to reintegrate young athletes, the diagnostic workflow to rule-out CAD in master athletes, and their clinical management are analyzed.

How to Use Cardiac Magnetic Resonance Imaging in Myocardial Infarction With Nonobstructive Coronary Arteries.

The working diagnosis Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA) is being increasingly recognized with the common use of high-sensitivity troponins and coronary angiography, accounting for 5% to 10% of all acute myocardial infarction presentations. Cardiac magnetic resonance (CMR) imaging is pivotal in patients presenting with suspected MINOCA, mainly to delineate those with a nonischemic cause, for example, myocarditis and Takotsubo syndrome, from those with true ischemic myocardial infarction, that is, MINOCA. The optimal timing for CMR imaging in patients with suspected MINOCA has been uncertain and, until recently, not been examined prospectively. Previous retrospective studies have indicated that the diagnostic yield decreases with time from the acute event. The SMINC studies (Stockholm Myocardial Infarction with Normal Coronaries) show that CMR should be performed early in all patients with the working diagnosis of MINOCA, with the possible exception of patients who are clearly identified as having Takotsubo syndrome as determined by echocardiography. In addition to CMR imaging, other investigations of importance in selected patients may be pulmonary artery computed tomography to exclude pulmonary embolism, optical coherence tomography to identify plaque disruption, and acetylcholine provocation to identify coronary artery spasm. Imaging of patients with the working diagnosis MINOCA, which is centered on CMR together with supplemental investigations, results in a clear diagnosis in approximately three-quarters of the patients. This is a good example of personalized medicine, because a correct diagnosis will not only increase the satisfaction of the individual patient but also result in optimizing treatment without harming the patient.

Left ventricular ejection fraction and myocardial fibrosis in survivors of ventricular fibrillation and ventricular tachycardia

Abstract Background Primary prevention implantable cardioverter defibrillator (ICD) therapy is indicated in patients with a LVEF<35%. Increasing evidence suggests that LVEF is a poor predictor or ventricular arrhythmias, such as ventricular tachycardia (VT) or fibrillation (VF). Methods Patients hospitalized for VF (55.4%) or VT with hemodynamic compromise underwent late gadolinium enhancement cardiovascular magnetic resonance (CMR). Patients with congenital heart disease, channelopathies, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and chemotherapy-induced cardiomyopathy were excluded. Results Among patients (n=111, aged 62.1 ± 14.6 years [mean ± SD]) hospitalized for VF (55.4%) or VT with hemodynamic compromise (44.5%) only 29/111 (43.6%) had a history of cardiac disease. At the index hospitalization, an ischemic cause was identified in 69.3%, a non-ischemic cause in 24.8% and no cause emerged in 5.9%. The LVEF (39.1 ± 17.2%) was ≤35% in 55.4% and >35% in 44.6%. Myocardial fibrosis was present in 85.1% (LVEF≤35%: 91.1%; LVEF>35%: 77.8%; p = 0.0619). Conclusions A large proportion of sustained VT or VF survivors would not have previously met LVEF primary prevention criteria for ICD therapy. In this 'ICD treatment gap', myocardial fibrosis was more prevalent than a LVEF≤35%. Further studies are needed to determine whether myocardial scar rather than LVEF≤35% should be used as an indication for primary prevention ICD therapy.

MINOCA and Coronary Ectasia: a rare combination of causes of infarction

to describe a patient with myocardial ischemia with multiple causes. This clinical case describes a 58-year-old man with a history of hypertension, dyslipidemia, COPD and previous myocardial infarction (AMI). He went to the emergency room with chest pain and dyspnea. Findings included bibasal crackles, electrocardiogram with old anterior fibrosis, elevated NT-ProBNP, and echocardiogram with septoapical akinesia. During hospitalization, he experienced tachyarrhythmia and hemodynamic deterioration, undergoing electrical cardioversion (CVE). Non-ST segment elevation acute coronary syndrome (NSTEACS) complicated with ventricular arrhythmia and acute pulmonary edema was diagnosed. Coronary angiography revealed coronary ectasias without obstructive lesions, but with mild stenosis in three vessels. The patient was successfully treated with non-invasive ventilation, diuretics, vasodilators and anticoagulation. The discharge was granted with the plan to further studies to optimize and guide treatment and finally the diagnosis of Myocardial Infarction with Non-Obstructive Arteries (MINOCA) and the presence of coronary ectasias was addressed. it is important to highlight the non-ischemic causes in MINOCA and the association between coronary ectasia and cardiovascular events, which is why we emphasize the need for more studies to better understand the relationship between these phenomena.

Sudden cardiac death in women: causes of death at premenopausal and postmenopausal age

Abstract Background Among women the incidence of sudden cardiac death (SCD) is lower than in men but still significant. On average menopause occurs at the age of 51.4 years. During the last decades the proportion of nonischemic SCD seems to have increased in both sexes. In postmenopausal women both the incidence and severity of the coronary artery disease (CAD) increase unpredictably 3-fold compared to premenopausal women of similar age. Purpose The aim of this study was to determine whether the causes of SCD differ among women at premenopausal and postmenopausal age. Methods The Fingesture study has systematically collected clinical and autopsy data from SCD victims in Northern Finland between 1998 and 2017. The cohort consists of 5,869 SCD victims of which 1,238 are women (21.1%). Women aged ≥52 years were considered as postmenopausal and ≤51 years old as premenopausal as the direct information of the menopause lacked due to the retrospective nature of this autopsy-based data. Results Approximately one fifth of the SCD victims were women (21.1%; P<0.001). The mean age of female subjects was 70.1±13.1 years (P<0.001). Only 7.9% of the women experienced SCD under the age of 52 years (P<0.001). Causes of death among women at premenopausal and postmenopausal age are represented in Table 1. Amongst all women 71.7% of the SCDs were ischemic (P<0.001). Majority of those women were at postmenopausal age but CAD caused still one third of the SCDs of the women at premenopausal age (33.7%, P<0.001). Overall nonischemic causes of death were more common at premenopausal age compared to postmenopausal women. Statistically significant nonischemic causes of death were primary myocardial fibrosis (PMF), obesity cardiomyopathy (CM), myocarditis, arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated CM. PMF was considerably more common cause of death among premenopausal women than in postmenopausal women (19.4 % vs. 3.9%, P<0.001), as was also the obesity CM (16.3% vs. 5.3%, P<0.001). Myocarditis caused the death of 5.1% of the premenopausal women but only 1.3% of the postmenopausal women (P=0.004). Both dilated CM (P=0.021) and ARVC (P=0.008) were the cause of death of 2.0% of the premenopausal women and 0.3-0.4% of the postmenopausal women. Subjects with anatomically and histologically normal finding at autopsy were mainly at premenopausal age (2.0% vs. 0.3%, P=0.008) even though the overall amount of cases remained low. Conclusions SCD at premenopausal age is rare. One third of the premenopausal SCDs are ischemic even though majority of the SCDs at premenopausal age are nonischemic etiology. Especially the prevalence of PMF and obesity CM were remarkably higher among premenopausal women compared to the postmenopausal age group emphasizing the role of genetics and lifestyle behind the SCD of premenopausal women.Table 1.

Abstract 12522: Non-Ischemic Papillary Muscle Rupture Due to MRSA Myocarditis

Case Presentation: A 46-year-old male with diabetes, ESRD, and recurrent MRSA bacteremia, presented with septic shock and suffered cardiac arrest. Following resuscitation EKG showed inferolateral ischemia. TTE revealed acute mitral valve regurgitation resulting from posteromedial papillary muscle rupture (PMR). An intra-aortic balloon pump was implanted for cardiogenic shock. Coronary angiography revealed right dominant circulation and thrombotic occlusion of a small caliber distal left circumflex artery (LCX). Emergent mitral valve replacement surgery was performed. Pathologic analysis of the excised muscle and leaflet showed marked acute inflammation, bacterial invasion, and myocyte necrosis, confirming non-ischemic rupture due to MRSA myocarditis. Discussion: PMR predominantly occurs after MI, complicating 0.03% of STEMI cases in the reperfusion era. Non-ischemic causes are rare. Coexistence of myocarditis, infective endocarditis (IE), and MI poses a challenge in determining etiology. Establishing causation guides whether to expedite emergent valve surgery or focus on cardiomyocyte salvage by revascularization. The posteromedial papillary muscle is most commonly involved in PMR due to single blood supply from the PDA (most commonly a branch of the RCA, and less commonly the LCX). Coronary angiography, postoperative histopathology, and culture results determined the etiology of PMR was fulminant MRSA bacteremia culminating in myocarditis. Bacterial colonization and resultant inflammation induced physical and mechanical strain leading to complete rupture. The occluded LCX was incidental, and may have been the result of septic embolization, which occurs in up to 65% of left-sided IE. Albeit rare, non-ischemic etiologies must be considered when the anatomic presentation of acute PMR on TTE is incongruent with angiography. Definitive treatment relies on surgical intervention and mechanical circulatory support is often necessary.

An Extensive Review on Imaging Diagnosis Methods in Takotsubo Syndrome.

Takotsubo Syndrome (TS) is an acute, reversible cardiac dysfunction, with complex, not entirely understood pathophysiology and heterogeneous clinical picture. Imaging methods each have a crucial role in the diagnosis, in-hospital management, short term and long term follow up. Coronary angiography needs to be performed, especially in the setting of a suspected acute coronary syndrome, in order to rule out coronary artery disease. Echocardiography plays a central role both in the acute and the chronic phase. It is the first imaging investigation performed in patients with TS, valuable to diagnose systolic dysfunction, the wall motion pattern and early complications. Cardiac magnetic resonance tissue characterization provides an essential role in the differential diagnosis of TS with other non-ischemic causes of systolic dysfunction. This review focuses on the imaging methods and the important part they play in the complex management of the disease.

Cardiac Magnetic Resonance Imaging (CMRI) Applications in Patients with Chest Pain in the Emergency Department: A Narrative Review.

CMRI is the exclusive imaging technique capable of identifying myocardial edema, endomyocardial fibrosis, pericarditis accompanied by pericardial effusions, and apical thrombi within either the left or right ventricle. In this work, we examine the research literature on the use of CMRI in the diagnosis of chest discomfort, employing randomized controlled trials (RCTs) to evaluate its effectiveness. The research outlines the disorders of the chest and the machine learning approaches for detecting them. In conclusion, the study ends with an examination of a fundamental illustration of CMRI analysis. To find a comprehensive review, the Scopus scientific resource is analyzed. The issue, based on the findings, is to distinguish ischemia from non-ischemic cardiac causes of chest pain in individuals presenting with sudden chest pain or discomfort upon arrival at the emergency department (ED). Due to the failure of conventional methods in accurately diagnosing acute cardiac ischemia, individuals are still being inappropriately discharged from the ED, resulting in a heightened death rate.

Prognostic Value of Cardiac Magnetic Resonance Imaging in Patients With a Working Diagnosis of MINOCA-An Outcome Study With up to 10 Years of Follow-Up.

Patients with a working diagnosis of myocardial infarction with unobstructed coronary arteries (MINOCA) represent a heterogeneous cohort. The prognosis could vary substantially depending on the underlying cause. Although cardiac magnetic resonance (CMR) is considered a key diagnostic tool in these patients, there are limited data linking the CMR diagnosis with the outcome. This study is a prospective outcomes registry of consecutive patients presenting with a working diagnosis of MINOCA who were clinically referred for CMR at an academic hospital from October 2003 to February 2020. We assessed the relationships between the prespecified CMR diagnoses of acute myocardial infarction (AMI), myocarditis, nonischemic cardiomyopathy (NICM), normal CMR study, and major adverse cardiac events (MACEs). Of 252 patients, the CMR diagnosis was AMI in 63 (25%), myocarditis in 33 (13%), NICM in 111 (44%), normal CMR in 37 (15%), and other diagnoses in 8 (3%). A specific nonischemic cause was diagnosed allowing true MINOCA to be ruled-out in 57% of the cohort. During up to 10 years of follow-up (1595 patient-years), MACE occurred in 84 patients (33%), which included 64 deaths (25%). The unadjusted cumulative 10-year rate of MACE was 47% in AMI, 24% in myocarditis, 50% in NICM, and 3.5% in patients with a normal CMR (Log-rank P<0.001). The CMR diagnosis provided incremental prognostic value over clinical factors including age, gender, coronary artery disease risk factors, presentation with ST-elevation, and peak troponin (incremental χ² 17.9, P<0.001); and patients with diagnoses of AMI, myocarditis, and NICM had worse MACE-free survival than patients with a normal CMR. In patients with a working diagnosis of MINOCA, CMR allows ruling-out true MINOCA in over half of the patients. CMR diagnoses of AMI, myocarditis, and NICM are associated with worse MACE-free survival, whereas a normal CMR study portends a benign prognosis.

Cardiac magnetic resonance in suspected MINOCA patients, clinical and imaging profile, diagnostic performance and 1 year clinical follow up

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac magnetic resonance (CMR) is fundamental at the evaluation of patients with differential diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) due to its tissue characterization potential to exclude non-ischaemic causes such as myocarditis and Takotsubo syndrome and better stratify ischaemic disease in acute and chronic disease. Purpose To describe the clinical profile, cardiac magnetic resonance findings, final clinical and CMR diagnosis and clinical 1-year follow-up in patients with a working diagnosis of MINOCA evaluated with a CMR. Methods All patients who underwent a CMR for suspected MINOCA during a period of 1 year from June 2021 to June 2022 were retrospectively evaluated, past medical history, clinical characteristics, CMR reports and 1 year follow up were obtained. Myocarditis was defined by modified Lake Louise criteria. Patients were stratified following CMR diagnosis, accurate CMR diagnosis was considered when matched clinical final diagnosis. Results A total of 107 patients were evaluated with a CMR for a suspected MINOCA from June 2021 to June 2022, of whom CMR classified 51 (47.7%) as myocarditis, 11 (10.3%) as Takotsubo syndromes, 13 (12.2%) as acute ischaemic etiology, 3 (2.8%) as chronic ischaemic etiology, 24 (22.4%) as normal CMR and 5 (4.7%) had other diagnoses (cardiomyopathies and type II myocardial infarctions). Myocarditis patients were younger and more frequently males, ischaemic etiologies were older, had more comorbidities and were more frequently males, Takotsubo syndromes were more frequently females and were frequently hypertense. (Table 1) The final clinical diagnosis corresponded to the diagnosis provided by CMR in 92.2% of myocarditis, 100% of Takotsubo syndromes, 84.6% in acute ischaemic etiologies and 100% of chronic ischaemic etiologies. Patients with a normal CMR or other diagnosis had significantly lower correspondence between final and CMR diagnosis, in this setting CMR was still useful to rule out ischaemic etiology, myocarditis and Takotsubo syndrome. During follow-up there were no clinical differences between groups in terms of deaths, readmissions myocardial infarction and visits for recurrent chest pain. Patients with myocarditis CMR diagnosis were more likely to be followed up with CMR than other groups. (Table 2). Conclusions The final diagnosis of the patient studied for suspected MINOCA was given or facilitated by CMR in most cases, being of clinical use in the diagnostic and the follow up strategy of patients.

Outcome of Out-of-Hospital Cardiac Arrest Patients Stratified by Pre-Clinical Loading with Aspirin and Heparin: A Retrospective Cohort Analysis.

Background: Out-of-hospital cardiac arrest (OHCA) has a high prevalence of obstructive coronary artery disease and total coronary occlusion. Consequently, these patients are frequently loaded with antiplatelets and anticoagulants before hospital arrival. However, OHCA patients have multiple non-cardiac causes and high susceptibility for bleeding. In brief, there is a gap in the evidence for loading in OHCA patients. Objective: The current analysis stratified the outcome of patients with OHCA according to pre-clinical loading. Material and Methods: In a retrospective analysis of an all-comer OHCA registry, patients were stratified by loading with aspirin (ASA) and unfractionated heparin (UFH). Bleeding rate, survival to hospital discharge and favorable neurological outcomes were measured. Results: Overall, 272 patients were included, of whom 142 were loaded. Acute coronary syndrome was diagnosed in 103 patients. One-third of STEMIs were not loaded. Conversely, 54% with OHCA from non-ischemic causes were pretreated. Loading was associated with increased survival to hospital discharge (56.3 vs. 40.3%, p = 0.008) and a more favorable neurological outcome (80.7 vs. 62.6% p = 0.003). Prevalence of bleeding was comparable (26.8 vs. 31.5%, p = 0.740). Conclusions: Pre-clinical loading did not increase bleeding rates and was associated with favorable survival. Overtreatment of OHCA with non-ischemic origin, but also undertreatment of STEMI-OHCA were documented. Loading without definite diagnosis of sustained ischemia is debatable in the absence of reliable randomized controlled data.

The role of left ventricular hypertrophy measured by echocardiography in screening patients with ischaemia with non-obstructive coronary arteries: a cross-sectional study.

Many patients with ischaemia with non-obstructive coronary arteries (INOCA) have a poor prognosis. This study aims to explore the diagnostic value of left ventricular hypertrophy (LVH)-related ultrasound parameters in INOCA patients. The study group consisted of 258 patients with INOCA in this retrospective cross-sectional study, and these patients were free of obstructive coronary artery disease, previous revascularization, atrial fibrillation, ejection fraction < 50%, major distortions of left ventricular geometry, suspected non-ischaemic causes. Control individuals were matched 1:1 with study group according to age, sex, cardiovascular risk factors, and time of hospital stay. According to left ventricular mass index (LVMI) and relative wall thickness, left ventricular geometry was composed of concentric hypertrophy, eccentric hypertrophy, concentric remodeling and normal geometry. LVH-related parameters, left ventricular geometry, demographic characteristics, laboratory parameters and other echocardiographic indicators were compared between the two groups. Subgroup analysis was performed based on sex. LVMI in the study group was higher than that in the control group (86.86 ± 18.83g/m2 vs 82.25 ± 14.29g/m2, P = 0.008). The ratio of LVH was higher in the study group (20.16% vs 10.85%, P = 0.006). After subgroup analysis based on sex, LVMI differences (85.77 ± 18.30g/m2 vs 81.59 ± 14.64g/m2, P = 0.014) and the ratio of LVH differences (25.00% vs 14.77%, P = 0.027) still existed in females between the two groups. There was no difference in the constituent ratio of left ventricular geometry between the two groups (P = 0.157). Sex-based subgroup analysis showed no difference in the constituent ratio of left ventricular geometry between the two groups in females (P = 0.242). The degree of LVH in the study group was higher than that in the control group, suggesting that LVH may play an important role in the occurrence and development of INOCA. Moreover, LVH-related ultrasound parameters may be of higher diagnostic value for female INOCA patients than for male INOCA patients.

Admission heart failure and coronary perfusion in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Studies demonstrated a link between the presence of HF on the admission of ACS patients and increased in-hospital morbidity and mortality. However, the literature did not establish the connection between the admission HF and the angiographic burden and the coronary vessel perfusion post-PPCI. Purpose To establish the correlation between acute HF on admission of STEMI patients, the coronary thrombus burden and the final coronary perfusion post PPCI. Methods We retrospectively studied 210 STEMI patients who presented to a single PPCI centre. We excluded post-fibrinolysis patients, patients with old stents and those who presented more than 24 hours after the onset of pain. We divided the studied cohort into two subgroups based on the presence of HF on presentation to the emergency department. We obtained Informed consent from all patients, and all procedures were done in compliance with the Helsinki declaration for research on human beings. Two blinded interventional cardiology consultants assessed the thrombus burden and coronary flow using TIMI grades of both variables. Results 20 patients (10%) of the studied group had HF on admission. There was no significant difference between the two subgroups regarding other cardiovascular risk factors (figure 1). The coronary thrombus burden did not differ significantly between the HF and no HF subgroups (50% vs 43.16%, respectively, p=0.557). However, the incidence of impaired coronary flow post-PPCI was significantly higher in the HF group (25% vs 8.4%, p=0.019) (figure 2). Multivariate logistic regression analysis showed that admission HF is an independent predictor of impaired perfusion post-PPCI ( OR= 5.49, 95% CI=1.54-19.49, p=0.01). Our study demonstrates the association between admission HF in STEMI patients undergoing PPCI and increased incidence of impaired coronary flow after PPCI. This finding was independent of the heavy coronary thrombus burden on angiography. Animal studies have demonstrated impaired coronary flow even in HF secondary to non-ischaemic causes.1,2 Possible mechanisms include impaired nitric oxide-mediated endothelium-dependent vasodilatation and enhanced vasoconstriction to mediators of neurohumoral activation.3 These mechanisms can explain our study's impaired coronary flow in HF patients. Conclusion Admission HF is an independent predictor of reduced coronary blood flow after PPCI. Timely treatment of STEMI patients can prevent HF development and improve their prognosis.

Circulating DPP3 is an early predictor of mortality and organ support in patients with cardiogenic shock: Post-hoc analyses of the ACCOST-HH trial

Dipeptidyl Peptidase 3 (DPP3) is a protease which has recently been shown to have an increased importance in the cardiovascular system. Previous studies demonstrated that elevated circulating DPP3 concentration (cDPP3) is an early predictor of short-term outcome in cardiogenic shock, mostly of ischemic origin. Whether cDPP3 is related to outcome in a more diverse cohort of cardiogenic shock remains unknown. To evaluate the association between cDPP3 levels and 30-days mortality in a mixed cardiogenic shock population. Post-hoc analysis of the ACCOST-HH cohort, a prospective, double-blind, multicentre, randomized, placebo-controlled trial on safety and efficacy of Adrecizumab, an adrenomedullin-modulating antibody, in cardiogenic shock patients, was performed. Values of cDPP3 under 40 ng/mL were considered low concentrations, and above defined as high. In all, 48% of the patient's cohort with high cDPP3 at admission died within 30 days after inclusion, whereas mortality was only 31% in the low cDPP3 group (HR = 1.8 (95% CI = 1.1–3.1), P < 0.05). Mortality in patients with non-ischemic cause of CS was much higher in the high cDPP3 group (HR 2.6, 95% CI = 1.2–5.6). The median number of days without need of cardiovascular support in the low cDPP3 group was 20.5 whereas the median in the high cDPP3 group was 3 days (P = 0.0005). There was a significant increase in need for renal replacement therapy when cDPP3 was high compared to when it was low at admission (56% vs. 22%, P < 0.05). In addition, elevated cDPP3 was associated with a higher need for invasive mechanical ventilation (90% in the high cDPP3 group vs. 74% in the low cDPP3 group, P < 0.05). Furthermore, kinetics of cDPP3 from 0 to 72 hours after admission for CS had a significant impact on outcome: when cDPP3 levels were low at both timepoints (LL-group) or when cDPP3 was initially high but low at 72 h (HL group), 30 day-mortality was significantly decreased when compared to the group with constantly high cDPP3 levels (HH). Sex- and age-adjusted HR for LL vs. HH was 0.2 (95% CI 0.1–0.4), and HR for HL vs. HH was 0.2 (95% CI 0.1–0.3). In cardiogenic shock, cDPP3 is an early predictor of mortality where low concentrations are correlated with improved survival. Moreover, monitoring cDPP3 kinetics is relevant for further assessment of patient care and therapy.

Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause.

Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90-1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72-1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68-0.99] for ischemic and HR, 0.67 [95% CI, 0.55-0.82] for nonischemic cause; P interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. Conclusions Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.

1025 PROGNOSTIC IMPACT OF STATINS AND DUAL ANTIPLATELET THERAPY ON LONG-TERM PROGNOSIS IN MINOCA PATIENTS

Abstract Background Myocardial Infarction with Non-Obstructive Coronary Artery disease (MINOCA) is a heterogeneous entity with relevant long-term major adverse cardiovascular events (MACE). There is solid evidence that secondary prevention strategies improve prognosis of patients with obstructive myocardial infarction. However, evidence-based treatments for MINOCA are lacking as no published randomized clinical trials have ever exclusively enrolled this population. In fact, treatment recommendations in current guidelines are mainly based on expert opinions and MINOCA patients are frequently discharged with statins and dual antiplatelet therapy (DAPT). Purpose To evaluate the effects of statins and DAPT as secondary prevention treatments on long-term outcomes in MINOCA patients. Methods We enrolled all consecutive MINOCA patients admitted to our Centre from 2016 to 2021. The diagnosis of MINOCA was made according to the current European Society of Cardiology diagnostic criteria (angiographic conventional cut-off of &amp;lt; 50% coronary stenosis without a clinically apparent alternative diagnosis). Second-level diagnostic work-up including cardiac magnetic resonance was performed to exclude non-ischemic troponin elevation cause. All-cause mortality and MACE (a composite of all-cause mortality, hospitalization for heart failure, myocardial re-infarction and stroke) were collected during follow-up. The prognostic impact of statins and DAPT at discharge was assessed. The relationship between treatments and outcomes was evaluated by using Kaplan-Meier survival analysis. Results 278 MINOCA patients were enrolled, of whom 203 (73%) were discharged on statins and 123 (44.2%) on DAPT. After a median follow-up of 36 ± 14.8 months, the overall all-cause mortality was 11.8% and the composite endpoint (MACE) was achieved in 28.4% of the entire population. Kaplan-Meier curves showed that patients treated with statins had a significantly lower rate of all-cause mortality (9.3% vs 18.2%, p=0.04) and MACE (24.6% vs 39.2%, p=0.02). On the other hand, rates of death (9.8% vs 13.2%, p=0.4) and MACE (23.6% vs 31.6%, p=0.1) were similar in MINOCA patients treated with DAPT or single antiplatelet therapy. Conclusions Among MINOCA patients, DAPT at discharge neither reduced long-term all-cause mortality nor MACE. In contrast, statin treatment provided beneficial effects on long-term outcomes. These results should be considered preliminary and require confirmation from randomized clinical trials.

Machine learning approach in diagnosing Takotsubo cardiomyopathy: The role of the combined evaluation of atrial and ventricular strain, and parametric mapping

BackgroundCardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a key diagnostic tool in the differential diagnosis between non-ischemic cause of cardiac chest pain. Some patients are not eligible for a gadolinium contrast-enhanced CMR; in this scenario, the diagnosis remains challenging without invasive examination. Our purpose was to derive a machine learning model integrating some non-contrast CMR parameters and demographic factors to identify Takotsubo cardiomyopathy (TTC) in subjects with cardiac chest pain. Material and methodsThree groups of patients were retrospectively studied: TTC, acute myocarditis, and healthy controls. Global and regional left ventricular longitudinal, circumferential, and radial strain (RS) analysis included were assessed. Reservoir, conduit, and booster bi-atrial functions were evaluated by tissue-tracking. Parametric mapping values were also assessed in all the patients. Five different tree-based ensemble learning algorithms were tested concerning their ability in recognizing TTC in a fully cross-validated framework. ResultsThe CMR-based machine learning (ML) ensemble model, by using the Extremely Randomized Trees algorithm with Elastic Net feature selection, showed a sensitivity of 92% (95% CI 78–100), specificity of 86% (95% CI 80–92) and area under the ROC of 0.94 (95% CI 0.90–0.99) in diagnosing TTC. Among non-contrast CMR parameters, the Shapley additive explanations analysis revealed that left atrial (LA) strain and strain rate were the top imaging markers in identifying TTC patients. ConclusionsOur study demonstrated that using a tree-based ensemble learning algorithm on non-contrast CMR parameters and demographic factors enables the identification of subjects with TTC with good diagnostic accuracy. Translational outlookOur results suggest that non-contrast CMR features can be implemented in a ML model to accurately identify TTC subjects. This model could be a valuable tool for aiding in the diagnosis of subjects with a contraindication to the contrast media. Furthermore, the left atrial conduit strain and strain rate were imaging markers that had a strong impact on TTC identification. Further prospective and longitudinal studies are needed to validate these findings and assess predictive performance in different cohorts, such as those with different ethnicities, and social backgrounds and undergoing different treatments.

Abstract 154: Limitation of Troponin T In Identifying the Cause of Out-of-hospital Cardiac Arrest

Introduction: High Sense-Troponin T (HS-TnT) is a key determinant for presence or absence of acute MI in chest pain patients (pts). Its value for acute MI diagnosis in pts with out-of-hospital cardiac arrest (OHCA) needs assessment because myocardial ischemia may be the cause but also a consequence of cardiac arrest causing global ischemia during no and low flow periods. Methods: Data were prospectively collected. From pts included in the ARREST registry who survived OHCA to discharge with VF as initial rhythm, the cause of OHCA and peak HS-TnT were analyzed. Cause of OHCA was determined independently by researchers, from history, admission and serial ECG, coronary angiography (CAG), cardiac imaging and genetics as available and indicated, without using HS-TnT information. MI diagnosis was made according to the 4 th universal definition of MI: type 1 MI (thrombotic STEMI/NSTEMI), type 2 MI (supply/demand imbalance) and no MI (short transient ECG changes and all non-ischemic causes). Results: From 2012 till 2018 in the study region 373 OHCA pts met the inclusion criteria and had a known peak HS-TnT. Of these, Type 1 MI was present in 109 STEMI and 39 NSTEMI pts, type 2 MI in 116 pts and no MI in 109 pts. No significant coronary stenosis or normal CAG was present in 81 pts: 11/106 (10%) with type 2 MI and 70/109 (64%) without MI. HS-TnT exceeded the conventional diagnostic threshold of 4 times upper limit of normal (4x14ng/L = 56 ng/L) in 99%, 95%, 95% and 89% of pts, respectively. Median peak HS-TnT levels in STEMI, NSTEMI, Type 2 and no AMI pts was 1890 ng/L, 480 ng/L, 300 ng/L and 261 ng/L, respectively. (Figure) Area Under the ROC-Curve of HS-TnT values to differentiate between type 1 NSTEMI and type 2 AMI was 0.649, between type 1 NSTEMI and no MI 0.684 and between type 2 MI and no AMI 0.555. Conclusion: Exclusion of diagnosis of MI in OHCA pts cannot be made with HS-TnT, nor a distinction between NSTEMI, type 2 MI and no AMI. Based on HS-TnT many OHCA pts without ischemic cause would classify as NSTEMI.

Multi-modality cardiac imaging in the management of diabetic heart disease.

Diabetic heart disease is a major healthcare problem. Patients with diabetes show an excess of death from cardiovascular causes, twice as high as the general population and those with diabetes type 1 and longer duration of the disease present with more severe cardiovascular complications. Premature coronary artery disease and heart failure are leading causes of morbidity and reduced life expectancy. Multimodality cardiac imaging, including echocardiography, cardiac computed tomography, nuclear medicine, and cardiac magnetic resonance play crucial role in the diagnosis and management of different pathologies included in the definition of diabetic heart disease. In this review we summarise the utility of multi-modality cardiac imaging in characterising ischaemic and non-ischaemic causes of diabetic heart disease and give an overview of the current clinical practice. We also describe emerging imaging techniques enabling early detection of coronary artery inflammation and the non-invasive characterisation of the atherosclerotic plaque disease. Furthermore, we discuss the role of MRI-derived techniques in studying altered myocardial metabolism linking diabetes with the development of diabetic cardiomyopathy. Finally, we discuss recent data regarding the use of artificial intelligence applied to large imaging databases and how those efforts can be utilised in the future in screening of patients with diabetes for early signs of disease.