Ventricular Contractile Reserve Research Articles

Feasibility and value of two-dimensional volumetric stress echocardiography

Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Clinical application of stress echocardiography in valvular heart disease: an expert consensus of the Working Group on Valvular Heart Disease of the Polish Cardiac Society.

Valvular heart diseases (VHDs) constitute an increasing problem both as a consequence of population aging and as the sequelae of other heart diseases. Accurate diagnosis is essential for correct clinical decision‑making; however, in many patients, transthoracic and transesophageal echocardiography is insufficient. Stress echocardiography (SE) proved to be a useful tool allowing for simultaneous assessment of left ventricular contractile reserve and HVD hemodynamics under conditions of physiological or pharmacological stress. It is recommended for assessing the severity of VHD, guiding the choice of treatment, as well as for surgical risk stratification. It can be applied both in asymptomatic patients with severe VHD and in symptomatic individuals with moderate disease. In patients with VHD, SE can be performed either as exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE). The first modality is recommended to unmask symptoms or abnormal blood pressure response in patients with aortic stenosis (AS) who report to be asymptomatic or in those with mitral stenosis with discordance between clinical symptoms and the severity of valve disease on transthoracic echocardiography. In asymptomatic patients with paradoxical low‑flow, low‑gradient (LFLG) AS, ESE can be used to assess the severity of stenosis. On the other hand, low‑dose DSE can be a useful diagnostic tool in classical LFLG AS, providing information on stenosis severity and contractile reserve. Moreover, SE is indicated in patients with prosthetic valve when there is discordance between symptoms and echocardiographic findings. It is also recommended in high‑risk surgical patients with VHD with poor functional capacity and more than 2 clinical risk factors. The present paper discusses in detail the use of SE in VHD.

Speckle tracking evaluation in endurance athletes: the "optimal" myocardial work.

To analyze left ventricular myocardial deformation and contractile reserve in endurance athletes at rest and during exercise, and their possible correlations with functional capacity. The athlete's heart in endurance training is characterized by physiologic eccentric remodeling, with left ventricle adaptation at rest and echocardiographic parameters at low end of normality. Assessment of left ventricle systolic function and contractile reserve has an important role in the decision-making and in differential diagnosis with cardiomyopathies. Standard echo, lung ultrasound, left ventricle 2D speckle-tracking strain and myocardial work were performed at rest and during exercise in endurance athletes and in age- and sex-comparable healthy controls. 350 endurance athletes (male sex 58.5%; 31.6 ± 4.2years) and 150 healthy controls were enrolled. Left ventricular ejection fraction at baseline was comparable between the two groups. Resting left ventricular global longitudinal strain was reduced in endurance athletes (-18.4 ± 2.6% vs. -22.4 ± 3.3% in controls; p < 0.01). Myocardial work efficiency did not show significative difference between the two groups. At peak exertion during exercise stress echocardiography, endurance athletes showed better exercise capacity and peak VO2 consumption (58.6 ± 10.2ml/kg/min vs 38.6 ± 3.3ml/kg/min in controls, p < 0.0001), associated with a preserved contractile reserve and augmented pulmonary artery systolic pressure. By multivariable analysis myocardial work efficiency at rest was closely related to maximal watts (p < 0.0001), peak VO2, (p < 0.0001), left ventricular E/e' (p < 0.001) and number of B-lines (p < 0.001), all measured at peak effort. Myocardial work efficiency shows less load-dependency than global longitudinal strain. Normal resting values of myocardial work efficiency in endurance athletes suggest a physiological remodeling, associated with a better exercise capacity and preserved contractile reserve during physical effort.

Heart rate reserve during dipyridamole stress test applied to potential heart donors in brain death

A blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (DSE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. Short-term adjustments of heart rate (HR) are thought to rise from changes in neural input to the heart. DSE is applied in potential heart donors to rule out underlying coronary artery disease and left ventricular dysfunction. The aim of this study is to assess HRR during DSE in brain death. We enrolled two groups: group 1 (N.=49, 22 men, 54.6±8.8 years) with patients in brain death enrolled in the nationwide marginal donor heart recruiting program; group 2 (N.=49, 18 men, 66.4±12.0 years) referred to DSE for suspected or known coronary artery disease. All underwent DSE (0.84 mg/kg in 6') by quality-controlled readers certified via web-based training (1487/CE Lazio-1). We assessed left ventricular contractile reserve (LVCR) as stress/rest ratio of force (systolic blood pressure/end-systolic volume). HRR was calculated as the peak/rest HR ratio from 12-lead EKG. The two study groups were similar for prevalence of inducible ischemia (4/49 vs. 9/49, P=NS). Group 1 showed higher resting HR (group 1: 88.1±15.5 bpm vs. group 2: 66.5±11.5 bpm, P<0.01) and similar peak HR (group 1: 94.7±15.3 bpm vs. group 2: 89.5±19.3 bpm, P=0.144), with blunted HRR (group 1: 1.08±0.10 bpm vs. group 2: 1.36±0.31 bpm, P<0.01). HRR was unrelated to LVCR. HRR is almost abolished and unrelated to LVCR in brain-dead patients during DSE. The modulation of neural input to the heart is essential to determine HRR, and plays no significant role in determining the inotropic response during DSE.

Predictors of left ventricular remodelling in patients with dilated cardiomyopathy - a cardiovascular magnetic resonance study.

There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling. Prospective study of patients with recent-onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P=0.02). Baseline myocardial strain (P=0.39 global longitudinal strain), interstitial myocardial fibrosis (P=0.41), replacement myocardial fibrosis (P=0.25), and right ventricular contractile reserve (P=0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r=-0.22, P=0.23) or baseline LVEF (r=0.07, P=0.62). Men were more likely to experience adverse LV remodelling (P=0.01) but age (P=0.88) and disease-modifying heart failure medication (beta-blocker, P=0.28; angiotensin-converting enzyme inhibitor, P=0.92) did not predict follow-up LVEF. Substantial recovery of LV function occurs within 12 months in most patients with recent-onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.

P941 Evaluation of right ventricular contractile reserve with exercise stress echocardiography

Abstract INTRODUCTION Right ventricular (RV) contractile reserve reflects the ability of the RV to adapt to elevated afterload. RV functional response to exercise is challenging but could represent an important prognostic factor, especially in pulmonary arterial hypertension (PAH) patients. We aimed, using exercise stress echocardiography (ESE), to assess different RV contractile reserve evaluation methods in a cohort of PAH patients and controls. METHODS We prospectively included 12 patients with PAH and 12 healthy volunteers. An ESE (using tilt-table ergometer) was performed in all patients to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. 3D RV function as well as peak systolic strain, pulmonary pressures, TAPSE, pulmonary TVI and pulmonary output (using the right ventricular outflow tract diameter) were assessed in all patients. RESULTS Our patient group was composed by PAH patients, 61.5 ± 14.8 years; mean age of our control group was 29.33 ± 5.5 years. PAH patients achieved an exercise with a mean workload of 69.17 ± 26.4 Watts. There was no complication after the exercise test in all patients. Change in TAPSE was not significantly different between patients and controls (p = 0.17), whereas change in pulmonary TVI, pulmonary output and RV peak systolic strain was highly discriminant (respectively p = 0.03, p = 0.009 and p = 0.0009). Regarding RV contractile reserve parameters, RV end-systolic pressure area ratio (peak/rest) was not statistically different between controls and patients (p = 0.14) whereas change in TAPSE/sPAP, RV peak strain/sPAP, 3D RV EF/sPAP were significantly different (p = 0.005, p= 0.0008, p = 0004). CONCLUSION Changes in pulmonary output, RV peak systolic strain as well as changes in TAPSE/sPAP but mainly RV peak strain/sPAP, 3D RV EF/sPAP represent consistent and feasible tools to assess RV contractile reserve. echocardiographic parameters PAH (n = 12) Healthy Controls (n = 12) p value sPAP at rest (mmHg) 40.91 ± 10.7 15.42 ± 4.1 &amp;lt;0.001 sPAP at peak (mmHg) 82.50 ± 21.7 42.50 ± 17.8 &amp;lt;0.001 TAPSE at rest/sPAP at rest (mm/mmHg) 0.62 ± 0.2 1.72 ± 0.6 &amp;lt;0.001 TAPSE at peak /sPAP at peak 0.36 ± 0.1 0.80 ± 0.2 &amp;lt;0.001 ΔStrain (%) 3.43 ± 3.1 8.08 ± 2.8 &amp;lt;0.001 Δ(peak Strain/sPAP) -0.17 ± 0.2 -0.77 ± 0.4 &amp;lt;0.001 Δpulmonary TVI (cm) 3.88 ± 4.0 7.46 ± 3.5 0.03 Δ(RVEF/sPAP) -0.34 ± 0.4 -2.06 ± 1.7 &amp;lt;0.001 Abstract P941 Figure. echography (rest/peak) PAH patient

Evaluation of right ventricular contractile reserve with exercise stress echocardiography

Right ventricular (RV) contractile reserve reflects the ability of RV to adapt to elevated afterload. RV functional response to exercise is challenging but could represent an important prognostic factor, especially in pulmonary arterial hypertension (PAH) patients. To assess different RV contractile reserve evaluation methods in a cohort of PAH patients and controls, using exercise stress echocardiography (ESE). We prospectively included 12 patients with PAH and 12 healthy volunteers. An ESE (using tilt-table ergometer) was performed in all patients to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. 3D RV function as well as peak systolic strain, pulmonary pressures, TAPSE, pulmonary VTI and pulmonary output (using the right ventricular outflow tract diameter) were assessed in all patients. Our patient group was composed by PAH patients, 52 ± 11 years; mean age of our control group was 31 ± 6 years. PAH patients achieved an exercise with a mean workload of 70 ± 26.4 Watts. There was no complication after the exercise test in all patients. Change in TAPSE was not significantly different between patients and controls ( P = 0.17), whereas change in pulmonary VTI, pulmonary output and RV peak systolic strain was highly discriminant (respectively P = 0.03, P = 0.009 and P = 0.0009). Regarding RV contractile reserve parameters, RV end-systolic pressure area ratio (peak/rest) was not statistically different between controls and patients ( P = 0.14) whereas change in TAPSE/sPAP, RV peak strain/sPAP, 3D RV EF/sPAP were significantly different ( P = 0.005, P = 0.0008, P = 0004). Changes in pulmonary output, RV peak systolic strain as well as changes in TAPSE/sPAP but mainly RV peak strain/sPAP, 3D RV EF/sPAP represent consistent and feasible tools to assess RV contractile reserve.

P1711 Exploring the full spectrum of right ventricular exercise contractile reserve among health and disease: a prospective clinical and echocardiography observational multicenter study

Abstract Funding Acknowledgements None OnBehalf RIGHT-NET Background Exercise Doppler echocardiography (EDE) has been implemented for applications beyond coronary artery disease detection, but its role in assessing subclinical pulmonary vascular disease and right ventricle (RV) impairment is less clear. The RIGHT heart international NETwork (RIGHT-NET) is a prospective clinical and echocardiography observational multicenter study designed to explore the full spectrum of RV function and non-invasive pulmonary circulation hemodynamics during exercise in a large cohort of subjects, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). Right ventricular (RV) exercise contractile reserve (RVECR) can be assessed through the ratio between tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) and has proved to provide prognostic value in patients with left heart disease (LHD) and pulmonary arterial hypertension (PAH). Methods We enrolled 1424 patients (age 55.4 ± 15 years old, 44.4% males): 353 healthy controls, 40 athletes, 369 patients with cardiovascular risk factors (CVRF: arterial hypertension and/or diabetes mellitus), 46 with PAH (confirmed by right heart catheterization), 487 with systemic sclerosis (SSc) without overt PH, and 129 with LHD (including coronary artery disease and heart failure with reduced or preserved ejection fraction). All enrolled subjects underwent resting and EDE examinations on a semirecumbent cycle ergometer with an incremental workload of 25 Watts every 2 minutes up to the symptom-limited maximal tolerated workload, according to standardised protocols. Key echocardiographic measurements have been acquired at baseline, at 50 Watts, at peak exercise, and after 5-minutes recovery, including but not limited to RV function (TAPSE) and sPAP. Results In all six groups the ratio TAPSE/sPAP was significantly different at peak exercise compared to rest values (all p &amp;lt; 0.01). At rest, TAPSE/sPAP values were not significantly different among controls, athletes and CVRF patients, whereas during exercise TAPSE/sPAP values were significantly different, with CVRF showing the lowest values (p &amp;lt; 0.0001 vs controls and athletes). Patients with PAH and LHD had the worst RVECR both at rest and at peak exercise (all p &amp;lt; 0.0001 vs the other groups), while SSc groups reported intermediate values, which were lower than controls (p &amp;lt; 0.0001) and athletes (p &amp;lt; 0.0001), but higher than CVRF subjects (p = 0.003). (Figure) Conclusions EDE can non-invasively characterise different dynamic behaviours of the RVECR among healthy subjects, athletes and patients with various pathologic conditions. Whether a thorough EDE assessment of non-invasive hemodynamics, RVECR and coupling may predict later development of manifest PH, clinical deterioration or decreased survival will be further investigated during the ongoing follow-up. Abstract P1711 Figure

P1401 The prognostic value of the reduction of coronary flow velocity reserve in non-ischemic heart failure patients

Abstract OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Coronary microvascular abnormalities determining a reduction of coronary flow velocity reserve (CFVR) have been described in patients (pts) with non-ischemic heart failure (HF). Aim To assess the prognostic value of CFVR in HF. Methods In a prospective, observational, multicenter study, we recruited 333 pts with angiographically normal coronary arteries: 105 patients with HF and preserved (&amp;gt;50%) ejection fraction (HFpEF); 71 with HF and mid-range (40-50%) ejection fraction (HFmrEF); 157 with HF and reduced (&amp;lt;40%) ejection fraction (HFrEF). All patients underwent vasodilator SE with dipyridamole (0.84 mg/kg) in 10 accredited laboratories of 5 countries (Argentina, Brazil, Italy, Mexico, Serbia). CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed wave-Doppler assessment of LAD flow. In all patients we also assessed left ventricular contractile reserve (LVCR) based on force (systolic blood pressure/end-systolic volume) Abnormal cutoff values were ≤2.0 for CFVR and ≤1.1 for LVCR. All pts were followed-up. Results After a median follow-up time of 15 months, 78 events occurred: 36 hospital admissions for acute decompensated heart failure, 23 deaths, 16 worsening in NYHA functional class, 2 stroke and 1 late revascularization. Event-free survival was best in patients with preserved CFVR and LVCR and worst in pts with reduced CFVR and impaired LVCR, with intermediate values for patients with either one (CFVR or LVCR) abnormal results: see figure. A preserved CFVR was associated with a better 24-month event-free survival than reduced CFVR in a subset analysis in pts with HFpEF (HR = 16.2, 95% CI, 1.8-145.1, p = 0.001) and in HFrEF (HR = 3.06, 95% CI, 1.6-5.6, p &amp;lt; 0.001). A multivariable analysis in the overall group of HF pts identified a reduced CFVR as the only independent predictor of event-free survival (HR = 3.455,95% CI 1.723-6.929). Conclusions A reduction in CFVR identifies a high risk subset in HF patients, outlining a shared role of coronary microvascular abnormalities as a marker and potential therapeutic target of HF, independently of underlying EF. Abstract P1401 Figure. Event-free survival based on CFVR-LVCR

1675 ABCDE vasodilator stress echocardiography in non-ischemic heart failure

Abstract OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background ABCDE-stress echocardiography (SE) may explore different aspects in the heterogeneous entity of known or suspected heart failure (HF). Aim To assess ABCDE-vasodilator SE in non-ischemic HF Methods In a prospective, observational, multicenter study, we recruited 428 patients with angiographically normal coronary arteries: 148 patients with HF and preserved (&amp;gt;50%) ejection fraction (HFpEF, Group 1); 100 with HF and mid-range (40-50%) ejection fraction (HFmrEF, Group 2); 180 with HF and reduced (&amp;lt;40%) ejection fraction (HFrEF, Group 3). A group of 75 healthy asymptomatic patients (30 male, 40%, age 57 ± 14 years) referred to testing for screening was also selected (Controls). All patients underwent vasodilator SE with dipyridamole (0.84 mg/kg) in 14 accredited laboratories of 5 countries (Argentina, Brasil, Russian Federation, Serbia and Italy). The ABCDE-SE protocol was adopted: A for regional wall motion abnormalities; B for B-lines (positivity criterion: stress ≥ rest for ≥ 2 points in a 4-site simplified scan available in 181 pts and 10 controls); C for left ventricular contractile reserve (LVCR) based on force (systolic blood pressure/end-systolic volume, positivity criterion: peak/ rest ≤1.1); D for pulsed wave Doppler-based assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (positivity criterion: peak/rest ≤2.0); E for EKG-based assessment of heart rate reserve (positivity criterion: peak/rest ≤1.22). Results All positivity criteria, except A, were more prevalent (p&amp;lt;.01) in Group 3 compared to Group 2, in Group 2 compared to Group 1, and Group 1 compared to controls: see figure. In particular, a blunted heart rate reserve was found in 4/75 controls (5%), 27/148 pts of Group 1 (18%), 28/100 of Group 2 (28%) and 98/180 of Group 3 (54%). Conclusions ABCDE-vasodilator SE can help to identify the profound pathophysiological heterogeneity underlying a similar clinical presentation in patients with known or suspected HF with angiographically normal coronary arteries. These patients rarely show stress-induced regional wall motion abnormalities (A), but may exhibit pulmonary congestion (B), reduced myocardial functional reserve (C), altered coronary microcirculation (D) and cardiac autonomic dysfunction (E). Abstract 1675 Figure. The positivity rate of ABCDE criteria

P208 Abnormal coronary flow reserve assessed with stress echocardiography induces a reduction in transmural strain gradient and an increase in heterogeneous myocardial electrical activation

Abstract OnBehalf Echo Lab INC Background The integrated quadruple stress echo (IQ-SE) is a state-of-the-art protocol that expands the risk stratification potential of SE. The coronary flow reserve (CFVR) has pronostic implication mainly in the absence of wall motion abnormalities. Longitudinal multilayer strain analysis assesses trasmural strain gradient. The prognostic value of multilayer strain analysis alongside the IQ-SE has not been established. We aim to determine the additive value of multilayer strain analysis during IQ-SE. Methods Prospective observational study. We evaluated one hundred twenty intermediate-high risk patients without obstructive coronary artery disease (mean age 61 ± 12 years, female 43%) with IQ-SE dipyridamole at our institution. Abnormal CFVR was defined as CFVR &amp;lt;2. Multilayer strain analysis and mechanical dispersion, were performed during rest and stress, with an automatic frame-by-frame with speckle tracking. Results The IQ-SE was feasible in all patients. At rest, mean three-dimensional left ventricular ejection fraction (3D LVEF) was 59% (53-62) without wall motion abnormalities. Abnormal CFVR was seen in 38 patients (32%) and reduced left ventricular contractile reserve (LVCR) in 56 patients (46%). Patients with abnormal CFVR, showed a reduction in EndoLS and transmural strain gradient, and an increase in mechanical dispersion and in lung B-lines during stress. No differences were observed in 3D LVEF and LVCR. Conclusions Endocardial ischemia due to microvascular dysfunction leads to a reduction in transmural strain gradient. Adding multilayer strain analysis to IQ-SE might detect myocardial subclinical dysfunction, arrhythmic risk and pulmonary congestion due to microvascular dysfunction. Left ventricular mechanics analysis CVFR &amp;lt;2 (38) CVFR &amp;gt;2 (81) P Rest EpiLS (%) -14.9 ±4.2 -18 ± 3.7 0.001 EndoLS (%) -20.2 ± 5.9 -23.5 ± 4.5 0.001 EndoLS- EpiLS 5.1 (3.8-6.3) 5.4 (4.2-6.3) 0.27 Mechanical Dispersion (ms) 57.7 (42.2-69) 44.2 (35-54) 0.006 Stress EpiLS (%) -17.2 ± 4.8 -20 ± 4.4 0.003 EndoLS (%) -23 ± 6 -26.6 ± 5.7 0.002 EndoLS- EpiLS 5.6 (4.5-6.7) 6.3 (5.4-7.9) 0.01 Mechanical Dispersion (ms) 47 (39.5 - 59) 39 (30-54.6) 0.007 CVFR: coronary flow reserve; EpiLS: Epicardium longitudinal strain; EndoLS: endocardial longitudinal strain; EndoLS- EpiLS: trasmural strain gradient. Abstract P208 Figure. IQ-SE and Multilayer Strain

P329 Outcome prediction with force-based left ventricular contractile reserve during stress echocardiography

Abstract OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Stress echo (SE) risk stratification is based on regional wall motion abnormalities (RWMA). The assessment of global left ventricular contractile reserve (LVCR) based on load-independent Force may refine prognosis. Aim To assess the value of LVCR during SE in predicting outcome Methods From September 2016 to December 2018, we prospectively enrolled 1848 patients (age 63 ± 11 years; 1121 males, 60%) with known or suspected coronary artery disease and/or heart failure evaluated with SE (exercise in 543, dipyridamole in 1184, adenosine in 10, dobutamine in 43) in 9 quality-controlled centers of 6 countries. Force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/end-systolic volume by 2D and biplane Simpson method of disks. When Simpson method was not feasible, apical single plane or linear parasternal methods were used to calculate volumes. Abnormal values of LVCR (peak/ rest) based on force were ≤1.10 for dipyridamole and adenosine; ≤1.61 for exercise or dobutamine. All patients were followed-up for a median of 16 months. Results RWMA and Force-based LVCR were obtained in all pts. Force was 4.24 ± 1.88 mmHg/ml at rest and increased during stress (7.07 ± 4.60 mmHg/ml, p&amp;lt;.001). At individual patient analysis, LVCR was abnormal in 495 (26%) and normal in 1373 (74%) patients. At follow-up, there were 218 events: 22 deaths, 22 non-fatal myocardial infarctions, 62 hospital admissions for acute heart failures, and 112 late (&amp;gt; 3 months from SE) myocardial revascularizations. At multivariable analysis, stress-induced RWMA (Hazard Ratio, HR, 2.899, 95% Confidence Intervals, CI: 2.032-4.137, p&amp;lt;.0.001), force-based LVCR (HR 1.747, 95% CI: 1.245-2.470, p=.002) were independent predictors. Kaplan-Meier curves showed worse event-free survival for pts with abnormal LVCR: see figure. Conclusion LVCR based on Force is a useful adjunct to RWMA for risk stratification with SE. Abstract P329 Figure. Survival curves and LVCR

Stress echocardiography of the righ heart-pulmonary circulation unit: rationale and possibilities of application in clinical practice

The right heart has been traditionally considered a passive conduit between the venous system and the lungs. Today, we know that a close hemodynamic interdependence exists between right ventricle, pulmonary circulation, and left ventricle, and that the right ventricle plays a key role in the ability to adapt to many super-physiological and pathological conditions. Dynamic exercise is a considerable stress for the "right heart-pulmonary circulation unit", which responds, in healthy subjects, with an increase of right ventricular contractility and cardiac output, a decrease of pulmonary vascular resistance, and a non-significant rise in pulmonary pressures. In patients affected by cardiac and/or pulmonary diseases (e.g. ischemic heart disease, heart failure, severe valvular stenosis or regurgitation, systemic sclerosis, chronic obstructive pulmonary disease, etc.) right ventricular contractile reserve may be impaired, and pulmonary artery systolic pressure may abnormally increase during exercise. From this perspective, stress echocardiography is a primary tool to evaluate right ventricle and pulmonary circulation during exercise, and can be useful in setting diagnosis, prognosis, and therapeutic timing of many cardiopulmonary diseases.

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

BackgroundThe 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). ObjectivesThe purpose of this study was to assess the feasibility and functional correlates of CFVR. MethodsThis 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. ResultsThe 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. ConclusionsCFVR 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.

Assessment of Left Ventricular Function and Contractile Reserve in Patients with Hypertension

Background: Hypertension is a prevalent and well-recognized cardiovascular risk factor, which may lead to left ventricular (LV) systolic impairment through chronic pressure overload. Aim of the work: An impaired contractile reserve (CR) may be an early manifestation of left ventricular (LV) systolic dysfunction in hypertensive patients. Using normotensive patients as controls, we examined LV CR and its correlates in hypertensive patients. Material and methods: The study was conducted prospectively on fifty cases. 30 cases (24 males and 6 females aged 55.57 ± 10.07) had hypertension. All patients were subjected to complete history taking including comorbidities, risk factors and full clinical examination. Patients with significant coronary or valvular disease, previous myocardial infarction or revascularization and diabetes were excluded. LV ejection fraction (LVEF) & global longitudinal strain (GLS) were measured at rest and at low-dose dobutamine. Results: Hypertensive patients, compared to control had significantly impaired GLS at rest (-19.00 ± 2.34% vs. -20.50 ± 1.52%, P <0.015) and at low dobutamine dose (-19.90 ± 2.33% vs. -22.60 ± 1.88 %, P <0.001). Absolute and relative GLS CR were significantly lower in hypertensive patients (-0.88 ± 0.45% vs.-2.12 ± 0.77% and 4.70 ± 2.76% vs. 10.33 ± 3.78 %, respectively, both P < 0.001). Absolute and relative LVEF CR were significantly lower in hypertensive patients (3.31 ± 0.97 % vs. 7.09 ± 1.67% and 5.37 ± 1.64% vs. 11.61 ± 3.19%, respectively, both P < 0.001). Conclusion: Compared to control, hypertensive patients with no other co-morbidities had impaired LV GLS at rest and impaired CR despite normal LVEF.

P4984The functional and coronary anatomic correlates of coronary flow velocity reserve during stress echocardiography

Abstract Background The assessment of coronary flow velocity reserve (CFVR) on left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on regional wall motion abnormalities (RWMA). Aim To assess the feasibility and functional correlates of CFVR. Methods In a prospective, observational, multicenter study, we initially screened 3,410 patients (2061, 60%, male; age 63±11 years; ejection fraction, EF=61±9%) with known or suspected coronary artery disease (CAD) and/or heart failure (HF). All patients underwent SE (exercise, n=1288; vasodilator, n=1860; dobutamine, n=262) based on 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. We also assessed B-lines (a sign of pulmonary congestion) with lung ultrasound and left ventricular contractile reserve (LVCR) based on Force (systolic blood pressure/end-systolic volume). Results The success rate for CFVR on LAD was 3,002/3,410 (feasibility=88%): 1,025/1,288 for exercise (80%), 1,766/1,860 (95%) for vasodilator (dipyridamole, n=1,841 and adenosine= 18) and 211/262 (81%) for dobutamine (p&lt;0.001 vs vasodilator, p=NS vs exercise). Imaging time was &lt;3 min and analysis time &lt;1 min per patient. Reduced (≤2.0) CFVR was found in 896/3,002 (30%) patients. At multivariate logistic regression analysis, age (odds ratio, OR: 1.025, 95% Confidence intervals, CI: 1.015–1.036, p&lt;0.001), diabetes (OR: 2.271, 95% CI: 1.218–4.235, p=0.10), RWMA (OR: 6.550, 95% CI: 4.989–8.599, p&lt;0.01), abnormal LVCR (OR: 3.446, 95% CI: 2.774–4.281, p&lt;0.01) and stress-rest B-lines change (OR: 1.519, 95% CI: 1.174–1.99, p=0.01) were associated with reduced CFVR. In the 1149 patients with coronary angiographic information, a reduced CFVR was present in 103/455 patients (23%) with no CAD, 119/432 (27%) with 1-, 72/167 (43%) with 2-, and 62/95 (65%) with 3-vessel disease (p&lt;0.001 by ANOVA for trend). Figure 1 Conclusions CFVR is feasible with all SE protocols. The reduced CFVR is often accompanied by RWMA, abnormal LVCR and pulmonary congestion during stress.

P1506Pulmonary decongestion pattern during stress lung ultrasound

Abstract Background B-profile detected by lung ultrasound (LUS) during stress echocardiography (SE) consists in B-lines with lung sliding and mirrors extra-vascular lung water accumulation (“wet lung”), more often found with ischemic regional wall motion abnormalities (RWMA) and/or diastolic dysfunction. B-lines present at rest may also decrease during stress. Aim To assess the frequency and functional correlates of decreasing B-profile (“drying lung” pattern) during SE. Methods We prospectively performed transthoracic echocardiography (TTE) and LUS evaluation at rest and peak stress in 780 patients with B-lines at rest referred for exercise (n=387), vasodilator (n=324) or dobutamine (n=69) SE for known/suspected coronary artery disease (CAD) and/or heart failure (HF). Recruitment occurred in 17 certified labs of 8 countries with the ABCD protocol, including regional wall motion abnormalities with wall motion score index (WMSI), B-lines, left ventricular contractile reserve (LVCR based on force, systolic blood pressure/end-systolic volume) and Doppler-based coronary flow velocity reserve (CFVR, available in 473 patients). By LUS, we adopted the 4-site simplified scan, each site scored from 0=normal A-lines, to 10=coalescing B-lines. By selection, all patients had resting B-lines score ≥2. Invasive or noninvasive coronary angiography was available in 208 patients. Results Two B-lines stress patterns were identified: Group 1, increase or unchanged pattern (B-line stress score ≥ rest, n=698, 89%); Group 2, decrease-disappearance pattern (B-line stress score &lt; rest for ≤2 points, n=82, 11%). Group 1 showed higher prevalence of inducible ischemia (Group 1 = 74/698 vs. Group 2 = 5/82, 11% vs. 6%, p&lt;0.001), abnormal LVCR (Group 1 = 403/698 vs. Group 2 = 36/82, 58% vs. 42%, p=0.012) and impaired CFVR (Group 1 = 173/433 vs. Group 2 = 5/40, 40 vs. 12%, p&lt;0.001): see figure. Two- or three-vessel coronary artery disease was also more frequent in fixed-worsening pattern (Group 1 = 88/191 vs. Group 2 = 3/17, 46 vs. 17%, p=0.024). Multivariate logistic regression analysis identified peak Force (Odds Ratio, OR, 1.039, 95% Confidence Intervals, CI: 1.006–1.074, P=0.022), stress-rest Δ-WMSI (OR 0.190, 95% CI 0.086–0.419, P&lt;0.001) and normal CFVR (OR=1.754, 95% CI: 1.147–2.682, P=0.010) as significant predictors of drying lung pattern. Disappearing BLines Conclusion About one out of 10 patients with resting B-lines exhibit a decrease-disappearance pattern during stress. They show a more benign coronary anatomic, myocardial functional and coronary physiological profile compared to patients with the fixed-worsening pattern. The drying lung pattern is more often accompanied by a strong (higher peak force), non-ischemic and warm heart (with normal CFVR).

P4981The reduction of coronary flow velocity reserve in heart failure with reduced, mid-range or preserved ejection fraction

Abstract Background Coronary microvascular disease has been described in heart failure (HF) in presence of angiographically normal epicardial coronary arteries. The prevalence of a reduction of coronary flow velocity reserve (CFVR) in different types of HF and its link with left ventricular contractile reserve (LVCR) is unclear. Aim To assess CFVR and LVCR in HF. Methods In a prospective, observational, multicenter study, we recruited 380 patients (234 male, 61%, age 66±11 years): 143 (38%) with HF and reduced (&lt;40%) ejection fraction (HFrEF); 98 (26%) with HF and mid-range (40–50%) ejection fraction (HFmrEF); 139 (36%) patients with HF and preserved (&gt;50%) ejection fraction (HFpEF). A control group of 52 asymptomatic patients (23 male, 44%, age 61±14 years) referred to testing for screening was also selected (Controls). All patients underwent dipyridamole (0.84 mg/kg) stress echocardiography in 12 accredited laboratories of 3 countries (Argentina, Brazil and Italy). CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of left anterior descending (LAD) artery flow. We assessed left ventricular contractile reserve (LVCR) based on global LV Force (systolic blood pressure/end-systolic volume). Results Reduced (≤2.0) CFVR was observed in 0/52 controls (0%); 25/139 HFpEF (18%); 28/98 HFmrEF (29%); 78/143 HFrEF (54%, p&lt;0.001 vs all other groups). CFVR was highest in controls (2.80±0.57), lower in HFpEF (2.51±0.57) and HFmrEF (2.26±0.44), lowest in HFrEF (2.04±0.48, p&lt;0.001 vs all other groups). The correlation with LVCR was absent in controls (r=0.098, p=0.491) and HFmrEF (r=0.032, p=0.756), present in HFrEF (r=0.375, p&lt;0.001) and HFpEF (r=0.314, p&lt;0.001). LVCR vs CFVR Conclusions CFVR is frequently abnormal in all types of HF, although more frequently and more profoundly in HFrEF. CFVR mirrors contractile reserve in HFrEF and - less tightly - in HFpEF.

3151The prognostic meaning of a reduced reserve of left ventricular force during exercise in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) patients with blunted force-frequency relationship assessed with pacing during cardiac catheterization are at greater risk of adverse events. Left ventricular contractile reserve (LVCR) based on force can be obtained noninvasively during exercise stress echocardiography (ESE). Purpose To evaluate the prognostic correlates of force-based LVCR during ESE in HCM. Methods We enrolled 332 HCM patients (age 51±15 years, 193 males, New York Heart Association, NYHA, Class I-III, EF 68±9%, maximal wall thickness 20±5 mm, left ventricular outflow tract gradient, LVOTG, present at rest in 34 pts, 10%) referred for ESE in 7 quality-controlled labs. SE assessment included LVOTG (mm Hg), LV Force (systolic blood pressure by cuff sphygmomanometer + LVOTG/LV end-systolic volume assessed with 2-D, mmHg/ml) and LVCR (peak/rest ratio of LV Force). LV volumes were measured from apical biplane (4- and 2-chamber) views with Simpson method when feasible (n=290) or with linear Teichholz (T) method from parasternal (long- or short-axis) view (n=42). All patients were followed-up. Results Force values were 8.5±6.7 at rest and 15.0±13.7 mmHg/mL at peak stress (P&lt;0.001). During a median follow-up time of 58 months, 50 patients experienced at least one event: 19 deaths (10 cardiac), 9 hospitalizations for acute heart failure, 16 myotomy/myectomy and 22 atrial fibrillations. The event-free survival was lower in the 195 patients with LVCR &lt;1.77 (identified with Receiver-Operator Characteristic analysis) compared to the 137 with LVCR ≥1.77: see figure. Multivariate analysis identified LVCR (Hazard ratio, HR, 2.032, 95% confidence intervals, CI, 1.042–3.964, P=0.037), age (HR, 1.033, 95% CI 1.009–1.058, P=0.007) and NYHA class (HR 2.204, 95% CI 1.161–4.185, P&lt;0.016) as independent predictors of events. Figure 1. HCM-LVCR Conclusion A non-invasive evaluation of LVOTG, systolic blood pressure and LV end-systolic volume during ESE allows to assess force-based LVCR in HCM. Lower LVCR is associated with greater risk of events at follow-up.

P4985Blunted heart rate reserve as an imaging-independent predictor of abnormal left ventricular contractile reserve

Abstract Background Stress echocardiography (SE) relies on regional wall motion and left ventricular contractile reserve (LVCR) based on force (systolic blood pressure/end-systolic volume). An additional non-imaging parameter based on EKG is the blunted heart rate reserve (HRR) which is a simple marker of altered autonomic balance and is associated with worse prognosis independently of ischemia. Aim To assess the relationship between HRR and LVCR in patients undergoing SE. Methods We enrolled 4707 patients (age 63.6±11.3 yrs, 2800 males) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. The employed stress was exercise (n=2062), dipyridamole (n=2007) or dobutamine (n=638). We assessed LVCR (stress/rest ratio of force=systolic blood pressure/end-systolic volume, ESV). Stress-specific abnormal cutoff value of LVCR were &lt;2.0 for exercise and dobutamine and &lt;1.1 for dipyridamole. All readers had passed the upstream quality control reading for wall motion abnormalities and ESV. HR (with 12-lead ECG) was obtained each minute and recorded at rest and peak stress. HR reserve (HRR) was calculated as the peak/rest HR ratio. Results HRR was related to LVCR at cumulative (n=4707; r=0.351; p&lt;0.001: see figure) and stress-specific analysis for exercise (r=0.351; p&lt;0.001), dipyridamole (r=0.241; p&lt;0.001) and dobutamine (r=0.214; p&lt;0.001). At multivariate logistic regression analysis, blunted HRR (optimal cutoff: 1.73 for exercise, 1.306 for dipyridamole, 1.932 for dobutamine) was a significant predictor of abnormal LVCR at stress-specific analysis for exercise (Odds ratio = 0.285, 95% Confidence Intervals: 0.149–0.546, p=0.0001), dobutamine (Odds ratio = 0.187, 95% Confidence Intervals: 0.057–0.617, p=0.0001) and dipyridamole (Odds ratio = 0.263, 95% Confidence Intervals: 0.115–0.602, p=0.002). Conclusion A blunted HRR is a useful non-imaging predictor of abnormal LVCR response during exercise or pharmacological SE. HRR is a simple biomarker of autonomic unbalance of physiologic and potentially prognostic meaning. A “slow heart” during stress (with blunted HRR) is more often a “weak heart”, with blunted increase in force.