Quality control of B-lines analysis in stress Echo 2020.

BACKGROUND: The effectiveness trial "Stress echo (SE) 2020" evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. PURPOSE: To provide web-based upstream quality control and harmonization of B-lines reading criteria. METHODS: 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. RESULTS: All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). CONCLUSIONS: Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.

Stress echo 2020: the international stress echo study in ischemic and non-ischemic heart disease.

BACKGROUND: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. METHODS: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). RESULTS: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. CONCLUSIONS: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls.

The potential value of integrated natriuretic peptide and echo-guided heart failure management.

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach.

Effect of concomitant oral chronic dipyridamole therapy on inflammatory cytokines in heart failure patients.

BACKGROUND: To assess whether dipyridamole therapy exerts a significant anti-inflammatory effect in heart failure patients. METHODS: We performed a retrospective analysis of the stored bio-samples of 3 groups of patients: 1) 25 normal healthy controls (N); 2) 25 heart failure patients (HF) under standard optimal therapy, including aspirin; 3) 17 HF patients with previous stroke and under clinically-driven therapy with A (Aggrenox, long-acting dipyridamole 200 mg + aspirin 25 mg, twice daily) for at least 1 month (HF-A). In all, we evaluated interleukin (IL)-6, adiponectin and C-reactive protein (CRP) as well as NT-proBNP. The same laboratory measurements were performed in the 17 HF patients with recent or previous stroke, both before and 1-month after clinically driven administration of A. RESULTS: All laboratory inflammatory indices were significantly higher in HF patients compared to N: IL-6 (N = 0.68 (0.3 - 12.7) vs. HF = 3.10 (0.5 - 16.7) vs. HF-A = 1.24 (0.3 - 3.3) pg/mL; p < 0.001 N vs. HF, p < 0.01 N vs. HF-A, p = ns HF vs. HF-A); CRP (N = 0.12 (0.01 - 0.45) vs. HF = 0.58 (0.04 - 2.7) vs. HF-A = 0.72 (0.02 - 4.8) mg/dL; p = ns N vs. HF, p = 0.05 N vs. HF-A, p = ns HF vs. HF-A); Adiponectin (N = 8.8 (3.0 - 31.4) vs. HF = 12.16 (4.9 - 27.3) vs. HF-A = 10.0 (4.8 - 15.6) pg/mL; p < 0.05 N vs. HF, p = ns N vs. HF-A p = ns HF vs. HF-A). NT-proBNP was also increased (N = 42.2 (13 - 93) vs. HF = 1907 (18.1 - 8038) vs. HF-A = 497.9 (7.8 - 3686) pg/mL; p < 0.001 N vs. HF, p = 0.01 N vs. HF-A, p = ns HF vs. HF-A). In 17 subjects, the intra-patient assessment (before and 1-month after starting of Aggrenox therapy) did not show a decrease in inflammation markers. CONCLUSIONS: HF patients show an increase in inflammatory indices independently of underlying A therapy.

Real time 3D echocardiography (RT3D) for assessment of ventricular and vascular function in hypertensive and heart failure patients.

BACKGROUND: Cardiac and systemic hemodynamics have been historically in the domain of invasive cardiology, but recent advances in real-time 3-Dimensional echocardiography (RT3D echo) provide a reliable measurement of ventricular volumes, allowing to measure a set of hemodynamic parameters previously difficult or impossible to obtain with standard 2D echo. AIM: To assess the feasibility of a comprehensive hemodynamic study with RT-3D echo. METHODS: We enrolled 136 patients referred for routine echocardiography: 44 normal (N), 57 hypertensive (HYP), and 35 systolic heart failure patients (HF). All patients underwent standard 2D echo examination followed by RT3D echo examination, including measurement of left ventricular (LV) end-diastolic and end-systolic volumes and derived assessment of LV elastance (an index of LV contractility), arterial elastance (characterizing the distal impedance of the arterial system downstream of the aortic valve); ventricular-arterial coupling (a central determinant of net cardiovascular performance); systemic vascular resistances. Blood pressure was derived from cuff sphygmomanometer and heart rate from ECG. RESULTS: A complete 2D echo was performed in all 136 patients. 3D echo examination was obtained in 130 patients (feasibility = 95 %). Standard 2D echo examination was completed in 14.8 ± 2.2 min. Acquisition of 3D images required an average time of 5 ± 0.9 min (range 3.5-7.5 min) and image analysis was completed in 10.1 ± 2.8 min (range 6-12 min) per patient. Compared to N and HYP, HF patients showed reduced LV elastance (1.7 ± 1.5 mmHg mL(-1) m(-2), p < 0.001 vs N = 3.8 ± 1.3 and HYP = 3.8 ± 1.3) and ventricular-arterial coupling (0.6 ± 0.5, p < 0.01 vs N = 1.4 ± 0.4 and HYP = 1.2 ± 0.4). Systemic vascular resistances were highest in HYP (2736 ± 720, p < .01 vs N = 1980 ± 432 and vs HF = 1855 ± 636 dyne*s/cm5). The LV elastance was related to EF (r = 0.73, p < 0.01) and arterial pressure was moderately related to vascular elastance (r = 0.54, p < 0.01). The ventricular-arterial coupling was unrelated to systemic vascular resistances (r = -0.04, p NS). CONCLUSION: RT-3D echo allows a non invasive, comprehensive assessment of cardiac and systemic hemodynamics, offering insight access to key variables--such as increased systemic vascular resistances in hypertensives and reduced ventricular-arterial coupling in heart failure patients.

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.

Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography.

BACKGROUND: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. PURPOSE: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. METHODS: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. RESULTS: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. CONCLUSIONS: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Feasibility and functional correlates of left atrial volume changes during stress echocardiography in chronic coronary syndromes.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

Myocardial ischemia: From disease to syndrome.

Although current guidelines on the management of stable coronary artery disease acknowledge that multiple mechanisms may precipitate myocardial ischemia, recommended diagnostic, prognostic and therapeutic algorithms are still focused on obstructive epicardial atherosclerotic lesions, and little progress has been made in identifying management strategies for non-atherosclerotic causes of myocardial ischemia. The purpose of this consensus paper is three-fold: 1) to marshal scientific evidence that obstructive atherosclerosis can co-exist with other mechanisms of ischemic heart disease (IHD); 2) to explore how the awareness of multiple precipitating mechanisms could impact on pre-test probability, provocative test results and treatment strategies; and 3) to stimulate a more comprehensive approach to chronic myocardial ischemic syndromes, consistent with the new understanding of this condition.

Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography.

OBJECTIVES: The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE). BACKGROUND: B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE. METHODS: The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up. RESULTS: According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction. CONCLUSIONS: Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020-The International Stress Echo Study [SE2020]; NCT03049995).

Functional, Anatomical, and Prognostic Correlates of Coronary Flow Velocity Reserve During Stress Echocardiography.

BACKGROUND: The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA). OBJECTIVES: The purpose of this study was to assess the feasibility and functional correlates of CFVR. METHODS: This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. A subset of 1,867 patients was followed up. RESULTS: The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome. CONCLUSIONS: CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome.

Lung Ultrasound for the Cardiologist.

For a cardiologist, lung ultrasound is an add-on to transthoracic echocardiography, just as lung auscultation is part of a cardiac physical examination. A cardiac 3.5- to 5.0-MHz transducer is generally suitable because the small footprint makes it ideal for scanning intercostal spaces. The image quality is often adequate, and the lung acoustic window is always patent. The cumulative increase in imaging time is <1 min for the 2 main applications targeted on pleural water (pleural effusion) and lung water (pulmonary congestion as multiple B-lines). In these settings, lung ultrasound outperforms the diagnostic accuracy of the chest radiograph, with a low-cost, portable, real-time, radiation-free method. A "wet lung" detected by lung ultrasound predicts impending acute heart failure decompensation and may trigger lung decongestion therapy. The doctors of tomorrow may still listen with a stethoscope to their patient's lung, but they will certainly be seeing it with ultrasound.

Exercise-induced B-lines identify worse functional and prognostic stage in heart failure patients with depressed left ventricular ejection fraction.

AIMS: Exercise stress echocardiography (ESE) is recommended by the European Society of Cardiology guidelines for the evaluation of heart failure (HF) patients. Recently, lung ultrasound (LUS) has been proposed for the assessment of extravascular lung water through B-lines. The aim of this study was to assess B-lines during ESE in HF. METHODS AND RESULTS: Standard transthoracic and LUS evaluation was performed during semi-supine ESE in 103 NYHA class I-III HF patients (76 male; mean age 64 ± 12 years) with depressed left ventricular ejection fraction (35 ± 8%). B-lines were measured by scanning 28 intercostal spaces on antero-lateral chest, both at rest and at peak stress. Resting plasma B-type natriuretic peptide (BNP) levels and exercise capacity during cardiopulmonary testing with peak oxygen uptake (peak VO2 ) were assessed in all patients. All patients were followed up for a median of 8 months (first quartile, 6; third quartile, 11). LUS was feasible and interpretable in all subjects. The overall number of B-lines increased from rest (median 5, interquartile range 0-10) to peak stress (median 12, interquartile range 0-45) (P < 0.0001). The number of stress B-lines was closely correlated with resting log-BNP (r = 0.88, P < 0.0001) and peak VO2 (r = -0.90, P < 0.0001). During follow-up, 37 events occurred: 10 deaths, 23 re-hospitalizations for acute HF, and 4 non-fatal myocardial infarctions. Twelve-month event-free survival was 95% in the 36 patients with stress B-lines <30 (best cut-off identified by receiver operating characteristic curve analysis) vs. 7% in patients with ≥30 B-lines (P < 0.0001). CONCLUSION: B-lines are easy to obtain, frequent in HF patients, and often increase during ESE. Adverse events were more frequent in patients with more B-lines during ESE.

Pressure-volume Relationship in the Stress-echocardiography Laboratory: Does (Left Ventricular End-diastolic) Size Matter?

INTRODUCTION AND OBJECTIVES: The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function. METHODS: We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy. They were studied with exercise (n = 172), dipyridamole (n = 482) or dobutamine (n = 237) stress echocardiography. The end-systolic pressure-volume relation was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson rule 2-dimensional echocardiography. RESULTS: Absolute values of delta rest-stress end-systolic pressure-volume relation were higher for exercise and dobutamine than for dipyridamole. In the overall population, an inverse relationship between end-systolic pressure-volume relation and end-diastolic volume was present at rest (r2 = 0.69, P < .001) and peak stress (r2 = 0.56, P < .001), but was absent if the delta rest-stress end-systolic pressure-volume relation was considered (r2 = 0.13). CONCLUSIONS: Left ventricular end-diastolic volume does not affect the rest-stress changes in end-systolic pressure-volume relation in either normal or abnormal left ventricles during physical or pharmacological stress.

B-lines with Lung Ultrasound: The Optimal Scan Technique at Rest and During Stress.

Various lung ultrasound (LUS) scanning modalities have been proposed for the detection of B-lines, also referred to as ultrasound lung comets, which are an important indication of extravascular lung water at rest and after exercise stress echo (ESE). The aim of our study was to assess the lung water spatial distribution (comet map) at rest and after ESE. We performed LUS at rest and immediately after semi-supine ESE in 135 patients (45 women, 90 men; age 62 ± 12 y, resting left ventricular ejection fraction = 41 ± 13%) with known or suspected heart failure or coronary artery disease. B-lines were measured by scanning 28 intercostal spaces (ISs) on the antero-lateral chest, 2nd-5th IS, along with the midaxillary (MA), anterior axillary (AA), mid-clavicular (MC) and parasternal (PS) lines. Complete 28-region, 16-region (3rd and 4th IS), 8-region (3rd IS), 4-region (3rd IS, only AA and MA) and 1-region (left 3rd IS, MA) scans were analyzed. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. Interpretable images were obtained in all spaces (feasibility = 100 %). B-lines (>0 in at least 1 space) were present at ESE in 93 patients (69%) and absent in 42. More B-lines were found in the 3rd IS and along AA and MA lines. The B-line cumulative distribution was symmetric at rest (right/left = 1.10) and asymmetric with left lung predominance during stress (right/left = 0.67). The correlation of per-patient B-line number between 28-S and 16-S (R2 = 0.9478), 8-S (R2 = 0.9478) and 4-S scan (R2 = 0.9146) was excellent, but only good with 1-S (R2 = 0.8101). The average imaging and online analysis time were 5 s per space. In conclusion, during ESE, the comet map of lung water accumulation follows a predictable spatial pattern with wet spots preferentially aligned with the third IS and along the AA and MA lines. The time-saving 4-region scan is especially convenient during stress, simply dismissing dry regions and focusing on wet regions alone.

Prognostic value of cardiac power output to left ventricular mass in patients with left ventricular dysfunction and dobutamine stress echo negative by wall motion criteria.

AIMS: Cardiac power output to left ventricular mass (power/mass) is an index of myocardial efficiency reflecting the rate at which cardiac work is delivered with respect to the potential energy stored in the left ventricular mass. In the present study, we sought to investigate the capability of power/mass assessed at peak of dobutamine stress echocardiography to predict mortality in patients with ischaemic cardiomyopathy and no inducible ischaemia. METHODS AND RESULTS: One-hundred eleven patients (95 males; age 68 ± 10 years) with 35 ± 7% mean left ventricular ejection fraction and a dobutamine stress echocardiography (up to 40 µg/kg/min) negative by wall motion criteria formed the study population. Power/mass at peak stress was obtained as the product of a constant (K = 2.22 × 10-1) with cardiac output and the mean arterial pressure divided by left ventricular mass to convert the units to W/100 g. Patients were followed up for a median of 29 months (inter-quartile range 16-72 months). All-cause mortality was the only accepted clinical end point. Mean peak-stress power/mass was 0.70 ± 0.31 W/100 g. During follow-up, 29 deaths (26%) were registered. With a receiver operating characteristic analysis, a peak-stress power/mass ≤0.50 W/100 g [area under curve 0.72 (95% CI 0.63; 0.80), sensitivity 59%, specificity 80%] was the best value for predicting mortality. Univariate prognostic indicators were age, male sex, peak-stress ejection fraction, peak-stress stroke volume, peak-stress cardiac output, peak-stress cardiac power output ≤1.48 W, and peak-stress power/mass ≤0.50 W/100 g. At multivariate analysis, age (HR 1.08, 95% CI 1.04; 1.14; P = 0.004) and peak-stress power/mass ≤0.50 W/100 g (HR 4.05, 95% CI 1.36; 12.00; P = 0.01) provided independent prognostic information. Three-year mortality was 14% in patients with peak-stress power/mass >0.50 W/100 g and 47% in those with peak-stress power/mass ≤0.50 W/100 g (log-rank 20.4; P < 0.0001). CONCLUSION: Power/mass assessed at peak of dobutamine stress echocardiography allows effective prognostication in patients with ischaemic cardiomyopathy and test result negative by wall motion criteria. In particular, a peak-stress power/mass ≤50 W/100 g is a strong and multivariable predictor of mortality.

A computational approach for the estimation of heart failure patients status using saliva biomarkers.

The aim of this work is to present a computational approach for the estimation of the severity of heart failure (HF) in terms of New York Heart Association (NYHA) class and the characterization of the status of the HF patients, during hospitalization, as acute, progressive or stable. The proposed method employs feature selection and classification techniques. However, it is differentiated from the methods reported in the literature since it exploits information that biomarkers fetch. The method is evaluated on a dataset of 29 patients, through a 10-fold-cross-validation approach. The accuracy is 94 and 77% for the estimation of HF severity and the status of HF patients during hospitalization, respectively.

Stress echocardiography with smartphone: real-time remote reading for regional wall motion.

The diffusion of smart-phones offers access to the best remote expertise in stress echo (SE). To evaluate the reliability of SE based on smart-phone filming and reading. A set of 20 SE video-clips were read in random sequence with a multiple choice six-answer test by ten readers from five different countries (Italy, Brazil, Serbia, Bulgaria, Russia) of the "SE2020" study network. The gold standard to assess accuracy was a core-lab expert reader in agreement with angiographic verification (0 = wrong, 1 = right). The same set of 20 SE studies were read, in random order and >2 months apart, on desktop Workstation and via smartphones by ten remote readers. Image quality was graded from 1 = poor but readable, to 3 = excellent. Kappa (k) statistics was used to assess intra- and inter-observer agreement. The image quality was comparable in desktop workstation vs. smartphone (2.0 ± 0.5 vs. 2.4 ± 0.7, p = NS). The average reading time per case was similar for desktop versus smartphone (90 ± 39 vs. 82 ± 54 s, p = NS). The overall diagnostic accuracy of the ten readers was similar for desktop workstation vs. smartphone (84 vs. 91%, p = NS). Intra-observer agreement (desktop vs. smartphone) was good (k = 0.81 ± 0.14). Inter-observer agreement was good and similar via desktop or smartphone (k = 0.69 vs. k = 0.72, p = NS). The diagnostic accuracy and consistency of SE reading among certified readers was high and similar via desktop workstation or via smartphone.

Quality control of regional wall motion analysis in stress Echo 2020.

BACKGROUND: The trial "Stress Echo (SE) 2020" evaluates novel applications of SE beyond coronary artery disease. The aim of the study was control quality and harmonize reading criteria. METHODS: One reader from 78 centers of the SE 2020 network asked for credentials to read a set of 20 SE video-clips selected by the core lab. All aspiring centers met the pre-requisite of high-volume and the years of experience in SE ranged from 5 to 31years (mean value 18years). The diagnostic gold standard was a reading by the core lab. The a priori determined pass threshold was 18/20 (≥90%). RESULTS: Of the initial 78 who started, 57 completed the first attempt: individual readers' score on first attempt ranged from 07/20 to 20/20 (accuracy from 35% to 100%, mean 78.7±13%) and 44 readers passed it. There was a very poor correlation between years of experience and the reader's score on first attempt (r=-0.161, p=0.231). Of the 13 readers who failed the first attempt, 12 took it again after the web-based session and their accuracy improved (74% vs. 96%, p<0.001). The kappa inter-observer agreement before and after web-based training was 0.59 on first attempt and rose to 0.91 on the last attempt. CONCLUSIONS: In SE reading, the volume of activity or years of experience is not synonymous with diagnostic quality. Qualitative analysis and operator-dependence can become a limiting weakness in clinical practice, in the absence of strict pathways of learning, credentialing and audit.