Prognostic value of stress echocardiography assessed by the ABCDE protocol.

AIM: The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. METHODS AND RESULTS: From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13-36), 73 deaths occurred. Global X2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B-E steps (P < 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. CONCLUSION: ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

Ivabradine in Cardiovascular Disease Management Revisited: a Review.

Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or vascular tone. Ivabradine is a use-dependent inhibitor targeting the sinoatrial node. It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction. In this scenario, ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions. However, there has been conflicting evidence from prospective studies and randomized controlled trials for its use in stable ischemic heart disease regarding efficacy in symptom reduction and mortality benefit. Ivabradine may also play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers. In this review, we highlight the evidence for the nuances of using ivabradine in heart failure, stable ischemic heart disease, and inappropriate sinus tachycardia to raise awareness for its vital role in the treatment of select populations.

Echocardiographic assessment of coronary microvascular dysfunction: Basic concepts, technical aspects, and clinical settings.

Coronary flow reserve is the capacity of the coronary circulation to augment the blood flow in response an increase in myocardial metabolic demands and has a powerful prognostic significance in different clinical situations. It might assess with invasive and noninvasive technique. Transthoracic echocardiography Doppler is an emerging diagnostic technique, noninvasive, highly feasible, safe for patient and physician, without radiation, and able to detect macrovascular and microvascular anomalies in the coronary circulation. This review aims to describe the benefit and limits of echocardiographic assessment of coronary flow reserve.

Endothelial Progenitor Cells: An Appraisal of Relevant Data from Bench to Bedside.

The mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow is well known to be present in several clinical settings, including acute coronary syndrome, heart failure, diabetes and peripheral vascular disease. The aim of this review was to explore the current literature focusing on the great opportunity that EPCs can have in terms of regenerative medicine.

Myocardial 123I-metaiodobenzylguanidine imaging in hypertension and left ventricular hypertrophy.

Sympathetic nervous system plays a pivotal role in essential hypertension and in the development of left ventricular hypertrophy. Moreover, cardiac sympathetic dys-regulation has been demonstrated as a key con-causal factor in the genesis and progression of pathologic conditions such as congestive heart failure and ischemic heart disease to which hypertension predisposes as a risk factor. However, despite its fundamental role in cardiac pathophysiology, the evaluation of cardiac sympathetic nervous system has never gained a wide clinical application, remaining mostly a research tool. In this context, nuclear imaging techniques are the only modalities to allow the direct evaluation of cardiac sympathetic nervous integrity, giving the chance to obtain objective measures of the sympathetic tone. This review, while summarizing the general profile of currently available tests for autonomic evaluation, focuses on 123I-metaiodobenzylguanidine nuclear imaging as a preferential tool to assess cardiac sympathetic status. Specifically, the review discusses the available evidence on cardiac 123I-metaiodobenzylguanidine scintigraphy in arterial hypertension and left ventricular hypertrophy and its diagnostic and prognostic potential in congestive heart failure and ischemic heart disease.

The new clinical standard of integrated quadruple stress echocardiography with ABCD protocol.

BACKGROUND: The detection of regional wall motion abnormalities is the cornerstone of stress echocardiography. Today, stress echo shows increasing trends of utilization due to growing concerns for radiation risk, higher cost and stronger environmental impact of competing techniques. However, it has also limitations: underused ability to identify factors of clinical vulnerability outside coronary artery stenosis; operator-dependence; low positivity rate in contemporary populations; intermediate risk associated with a negative test; limited value of wall motion beyond coronary artery disease. Nevertheless, stress echo has potential to adapt to a changing environment and overcome its current limitations. INTEGRATED-QUADRUPLE STRESS-ECHO: Four parameters now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-stress echo. They are: 1- regional wall motion abnormalities; 2-B-lines measured by lung ultrasound; 3-left ventricular contractile reserve assessed as the stress/rest ratio of force (systolic arterial pressure by cuff sphygmomanometer/end-systolic volume from 2D); 4- coronary flow velocity reserve on left anterior descending coronary artery (with color-Doppler guided pulsed wave Doppler). IQ-Stress echo allows a synoptic functional assessment of epicardial coronary artery stenosis (wall motion), lung water (B-lines), myocardial function (left ventricular contractile reserve) and coronary small vessels (coronary flow velocity reserve in mid or distal left anterior descending artery). In "ABCD" protocol, A stands for Asynergy (ischemic vs non-ischemic heart); B for B-lines (wet vs dry lung); C for Contractile reserve (weak vs strong heart); D for Doppler flowmetry (warm vs cold heart, since the hyperemic blood flow increases the local temperature of the myocardium). From the technical (acquisition/analysis) viewpoint and required training, B-lines are the kindergarten, left ventricular contractile reserve the primary (for acquisition) and secondary (for analysis) school, wall motion the university, and coronary flow velocity reserve the PhD program of stress echo. CONCLUSION: Stress echo is changing. As an old landline telephone with only one function, yesterday stress echo used one sign (regional wall motion abnormalities) for one patient with coronary artery disease. As a versatile smart-phone with multiple applications, stress echo today uses many signs for different pathophysiological and clinical targets. Large scale effectiveness studies are now in progress in the Stress Echo2020 project with the omnivorous "ABCD" protocol.

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction.

AIM: Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. METHODS: The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. RESULTS: In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. CONCLUSION: Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies.

The Role of Nitrates in the Management of Stable Ischemic Heart Disease: A Review of the Current Evidence and Guidelines.

Coronary artery disease is the leading cause of mortality in the United States and can result in significant morbidity. In particular, stable ischemic heart disease (SIHD) is a condition that affects nearly 9 million individuals in the United States alone, with substantial annual health care costs related to recurrent medical visits and chronic disease management. Nitrates form a cornerstone of SIHD management by reducing myocardial oxygen consumption and increasing exercise capacity by several mechanisms, including increasing epicardial blood flow through vasodilation and decreased vascular resistance, blunting coronary steal, and reducing preload. Yet the role of nitrates may be underappreciated in clinical practice and their utilization may be limited due to concerns of tolerance to treatment, a lack of randomized data validating their ability to prevent adverse cardiovascular events, and the pervasive use of percutaneous interventions without robust attempts at implementing optimal medical therapy. In this review, we discuss both the recent ACC/AHA/ACP/AATS/PCNA/SCAI/STS and European Society of Cardiology guidelines, with a particular focus on indications, contraindications, and future directions of nitrate therapy in SIHD.

Pharmacological Agents Targeting Myocardial Metabolism for the Management of Chronic Stable Angina : an Update.

Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, CSA is interpreted as episodes of reversible myocardial ischemia related to the presence of stable coronary artery plaque causing myocardial demand/supply mismatch when myocardial oxygen consumption increases. Accordingly, revascularization procedures are performed with the aim to remove the flow limiting stenosis, whereas traditional medical therapy (hemodynamic agents) aims at reducing myocardial oxygen demands. However, although effective, none of these treatment strategies or their combination is either able to confer symptomatic relief in all patients, nor to reduce mortality. Failure to significantly improve QoL and prognosis may be attributed at least in part to this "restrictive" understanding of IHD. Despite for many years myocardial metabolic derangement has been overlooked, recently it has gained increased attention with the development of new pharmacological agents (metabolic modulators) able to influence myocardial substrate selection and utilization thus improving cardiac efficiency. Shifting cardiac metabolism from free fatty acids (FA) towards glucose is a promising approach for the treatment of patients with stable angina, independently of the underling disease (macrovascular and/or microvascular disease). In this sense cardiac metabolic modulators open the way to a "revolutionary" understanding of ischemic heart disease and its common clinical manifestations, where myocardial ischemia is no longer considered as the mere oxygen and metabolites demand/supply unbalance, but as an energetic disorder. Keeping in mind such an alternative approach to the disease, development of new pharmacological agents directed toward multiple metabolic targets is mandatory.

Influence of depression and anxiety on circulating endothelial progenitor cells in patients with acute coronary syndromes.

OBJECTIVES: Circulating endothelial progenitor cells (EPCs) are related to endothelial function and progression of coronary artery disease. There is evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression. We investigated the relationships between the level of circulating EPCs and depression and anxiety in patients with acute coronary syndrome (ACS). METHODS: Patients with ACS admitted to three Cardiology Intensive Care Units were evaluated by the SCID-I to determine the presence of lifetime and/or current mood and anxiety disorders according to DSM-IV criteria. The EPCs were defined as CD133(+) CD34(+) KDR(+) and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed where appropriate. RESULTS: Out of 111 ACS patients, 57 were found to have a DSM-IV lifetime or current mood or anxiety disorder at the time of the inclusion in the study. The ACS group with mood or anxiety disorders showed a significant decrease in circulating EPC number compared with ACS patients without affective disorders. In addition, EPC levels correlated negatively with severity of depression and anxiety at index ACS episode. CONCLUSIONS: The current study indicates that EPCs circulate in decreased numbers in ACS patients with depression or anxiety and, therefore, contribute to explore new perspectives in the pathophysiology of the association between cardiovascular disorders and affective disorders.

Cardiovascular multimodality imaging in women: a scientific statement of the European Association of Cardiovascular Imaging of the European Society of Cardiology.

Cardiovascular diseases (CVD) represent an important cause of mortality and morbidity in women. It is now recognized that there are sex differences regarding the prevalence and the clinical significance of the traditional cardiovascular (CV) risk factors as well as the pathology underlying a range of CVDs. Unfortunately, women have been under-represented in most CVD imaging studies and trials regarding diagnosis, prognosis, and therapeutics. There is therefore a clear need for further investigation of how CVD affects women along their life span. Multimodality CV imaging plays a key role in the diagnosis of CVD in women as well as in prognosis, decision-making, and monitoring of therapeutics and interventions. However, multimodality imaging in women requires specific consideration given the differences in CVD between the sexes. These differences relate to physiological changes that only women experience (e.g. pregnancy and menopause) as well as variation in the underlying pathophysiology of CVD and also differences in the prevalence of certain conditions such as connective tissue disorders, Takotsubo, and spontaneous coronary artery dissection, which are all more common in women. This scientific statement on CV multimodality in women, an initiative of the European Association of Cardiovascular Imaging of the European Society of Cardiology, reviews the role of multimodality CV imaging in the diagnosis, management, and risk stratification of CVD, as well as highlights important gaps in our knowledge that require further investigation.

In-stent restenosis after percutaneous coronary intervention: emerging knowledge on biological pathways.

Percutaneous coronary intervention (PCI) has evolved significantly over the past four decades. Since its inception, in-stent restenosis (ISR)-the progressive reduction in vessel lumen diameter after PCI-has emerged as the main complication of the procedure. Although the incidence of ISR has reduced from 30% at 6 months with bare-metal stents to 7% at 4 years with drug-eluting stents (DESs), its occurrence is relevant in absolute terms because of the dimensions of the population treated with PCI. The aim of this review is to summarize the emerging understanding of the biological pathways that underlie ISR. In-stent restenosis is associated with several factors, including patient-related, genetic, anatomic, stent, lesion, and procedural characteristics. Regardless of associated factors, there are common pathophysiological pathways involving molecular phenomena triggered by the mechanical trauma caused by PCI. Such biological pathways are responses to the denudation of the intima during balloon angioplasty and involve inflammation, hypersensitivity reactions, and stem cell mobilization particularly of endothelial progenitor cells (EPCs). The results of these processes are either vessel wall healing or neointimal hyperplasia and/or neo-atherosclerosis. Unravelling the key molecular and signal pathways involved in ISR is crucial to identify appropriate therapeutic strategies aimed at abolishing the 'Achille's heel' of PCI. In this regard, we discuss novel approaches to prevent DES restenosis. Indeed, available evidence suggests that EPC-capturing stents promote rapid stent re-endothelization, which, in turn, has the potential to decrease the risk of stent thrombosis and allow the use of a shorter-duration dual antiplatelet therapy.

Myocardial infarction with nonobstructive coronary arteries: from pathophysiology to therapeutic strategies.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by clinical evidence of acute myocardial infarction (AMI) with normal or near-normal coronary arteries on coronary angiography (stenosis < 50%) and without an over the alternative diagnosis for the acute presentation. Its prevalence ranges from 6% to 11% among all patients with AMI, with a predominance of young, nonwhite females with fewer traditional risks than those with an obstructive coronary artery disease (MI-CAD). MINOCA can be due to either epicardial causes such as rupture or fissuring of unstable nonobstructive atherosclerotic plaque, coronary artery spasm, spontaneous coronary dissection and cardioembolism in-situ or microvascular causes. Besides, also type-2 AMI due to supply-demand mismatch and Takotsubo syndrome must be considered as a possible MINOCA cause. Because of the complex etiology and a limited amount of evidence, there is still some confusion around the management and treatment of these patients. Therefore, the key focus of this condition is to identify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, echocardiography, and coronary angiography represent the first-level diagnostic investigations, but coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offer additional information to understand the underlying cause of MINOCA. Although the prognosis is slightly better compared with MI-CAD patients, MINOCA is not always benign and depends on the etiopathology. This review analyzes all possible pathophysiological mechanisms that could lead to MINOCA and provides the most specific and appropriate therapeutic approach in each scenario.

Rest and Stress Left Atrial Dysfunction in Patients with Atrial Fibrillation.

BACKGROUND: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. AIM: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. METHODS: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. RESULTS: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). CONCLUSIONS: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Clinical outcomes of patients with coronary microvascular dysfunction in absence of obstructive coronary atherosclerosis.

Up to 50% of patients presenting with stable, mainly exercise-induced, chest pain and 10-20% of those admitted to hospital with chest pain suggesting an acute coronary syndrome show normal or near-normal coronary arteries at angiography. Coronary microvascular dysfunction (CMD) is a major cause of symptoms in these patients. However, controversial data exist about their prognosis. In this article, we critically review characteristics and results of the main studies that assessed clinical outcome of patients with angina chest pain and nonobstructive coronary artery disease presenting with either a stable angina pattern or an acute coronary syndrome. Published data indicate that the patients included in most studies are heterogeneous and a major determinant of clinical outcome is the presence of atherosclerotic, albeit not obstructive, coronary artery disease. Long-term prognosis seems instead excellent in patients with totally normal coronary arteries and a syndrome of CMD-related stable angina (microvascular angina). On the other hand, the prognostic impact of CMD in patients presenting with an acute coronary syndrome needs to be better assessed in future studies.

Diagnostic approach for coronary microvascular dysfunction in patients with chest pain and no obstructive coronary artery disease.

A large number of studies has demonstrated that abnormalities of coronary microcirculation may be responsible for both acute and chronic cardiac ischemic syndromes. In clinical practice the microvascular origin of myocardial ischemia and angina is usually considered in patients who are found to have normal or near-normal coronary arteries at angiography. In this article, we review the diagnostic approach to patients with suspected coronary microvascular dysfunction as a cause of ischemic syndromes and also suggest a classification of chronic and acute microvascular coronary ischemic syndrome, including myocardial infarction with normal coronary arteries.

Left atrial volume changes during exercise stress echocardiography in heart failure and hypertrophic cardiomyopathy.

OBJECTIVE: We aimed to assess feasibility and functional correlates of left atrial volume index (LAVI) changes during exercise stress echocardiography (ESE). METHODS: ESE on a bike or treadmill was performed in 363 patients with heart failure with preserved ejection fraction (HFpEF, n = 173), reduced ejection fraction (HFrEF, n = 59), or hypertrophic cardiomyopathy (HCM, n = 131). The LAVI stress-rest increase ≥6.8 ml/m2 was defined as dilation. RESULTS: LAVI measurements were feasible in 100%. LAVI did not change in HFrEF being at rest 32 (25-45) vs at stress 36 (24-54) ml/m2, P = NS and in HCM at rest 35 (26-48) vs at stress 38 (28-48) ml/m2, P = NS, whereas it decreased in HFpEF from 30 (24-40) to 29 (21-37) ml/m2 at stress, P = 0.007. LA dilation occurred in 107 (30%) patients (27% with treadmill vs 33% with bike ESE, P = NS): 26 with HFpEF (15%), 26 with HFrEF (44%), and 55 with HCM (42%) with P < 0.001 for HFrEF and HCM vs HFpEF. A multivariate analysis revealed as the predictors for LAVI dilation E/e' > 14 at rest with odds ratio (OR) 4.4, LVEF <50% with OR 2.9, and LAVI at rest <35 ml/m2 with OR 2.7. CONCLUSION: The LAVI assessment during ESE was highly feasible and dilation equally frequent with a treadmill or bike. LA dilation was three-fold more frequent in HCM and HFrEF and could be predicted by increased resting E/e' and impaired EF as well as smaller baseline LAVI.

Perspectives in noninvasive imaging for chronic coronary syndromes.

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.

Pulmonary Congestion During Exercise Stress Echocardiography in Ischemic and Heart Failure Patients.

BACKGROUND: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). METHODS: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. RESULTS: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015-4.680]; P=0.046) and ejection fraction <50% (hazard ratio, 2.942 [95% CI, 1.268-6.822]; P=0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). CONCLUSIONS: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03049995.