Left Ventricular Contractile Reserve Research Articles

CHANGES IN LEFT ATRIAL VOLUME DURING ECHOSTRESS IN PATIENTS UNDERGOING MITRAL VALVE PLASTIC CARDIAC SURGERY

Abstract Mitral Regurgitation (MR) is characterized by a high morbidity and mortality that often finds a solution only in the reparative surgical treatment, in particular in presence of myxomatous degeneration that cause the prolapse of one or both leaflets. This results in an increase in diastolic pressure that leads to a progressive dilation of the left atrium. The increase in Left Atrium Volume Index (LAVI) during stress test represents a negative prognostic factor in the clinical evolution of many pathologies, such as ischemic heart disease, hypertrophic cardiomyopathy, heart failure. An increase in peak/rest LAVI >6.8 ml/m2 correlates with a higher incidence of heart failure decompensation, reduced left ventricular contractile reserve (LVCR), pulmonary congestion. We evaluate the effect of MR reparative surgery on the changes of LAVI during stress–echo. We enrolled 19 patients, 11 females and 8 males, affected by MR candidate to cardiac surgery. We performed a physical stress–echo test by using the ABCDE protocol suggested by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), before and after 12 weeks from surgery. During each test, the changes in LAVI (ΔLAVI) expressed as peak/rest difference in ml/m2 was measured. In addition, the prognostic score deriving from the sum of the ABCDE criteria was calculated, such as the LVCR (C parameter of the score) that represents a parameter of the force deriving from the hemodynamic changes during the test. In all patients we observed a significant reduction in ΔLAVI (8.4+0.5 mL/m2 vs 9.7+0.7 mL/m2; p<0.0001). In addition, there was a significant reduction in the ABCDE prognostic score (from 4.19+0.43 to 3.48+0.37; p=0.002), secondary to the increase in the LVCR observed approximately 3 months after surgery (from 1.77 mmHg/ml to 2.44 mmHg/ml, p<0.0001), as well as a significant reduction in pulmonary congestion during stress (B parameter). There were no significant changes in ejection fraction, wall motion score index–WMSI (A parameter), coronary reserve (D parameter) and heart rate reserve (E parameter). These data demonstrate for the first time that mitral valve plastic surgery is able to reduce the ΔLAVI during stress echocardiography in patients with severe MR. The surgical procedure also resulted in both an improvement in the LVCR and a reduction in the degree of pulmonary congestion, that ultimately led to an improvement in the ABCDE prognostic score.

Stress Echocardiography by the ABCDE Protocol ln the Assessment of Prognosis of Stable Coronary Heart Disease.

To assess the role of clinical indicators and parameters of stress echocardiography performed according to an extended protocol as predictors for the occurrence of a composite cardiovascular endpoint (CCVEP) in IHD. The study included 186 patients (60.2% men, mean age 60.6±9.9 years) with an established (n=73; 39.2%) and suspected (60.8%) diagnosis of IHD. Stress EchoCG with adenosine triphosphate (38.2%), transesophageal pacing (15.1%), dobutamine (2.6%), and bicycle ergometry on a recumbent ergometer (44.1%) was performed. The stress EchoCG protocol included assessment of regional wall motion abnormalities (WMA), B-lines, LV contractile reserve (CTR), coronary reserve (CR), and heart rate reserve. The median follow-up period was 13 [9; 20] months. The composite CCVEP included death from cardiovascular diseases and their complications, acute coronary syndrome, and revascularization and was defined at the first of these events. Statistical analysis was performed with the Statistica 16.0 and SPSS Statistics 23.0 software packages. Differences were considered statistically significant at p<0.05. Invasive or noninvasive coronary angiography was performed in 90.3% of patients; obstructive coronary disease (stenosis ≥50%) was detected in 67.9% of cases. During the follow-up period, 58 (31.2%) patients had cardiovascular complications. The risk of developing CCVEP was associated with the pretest probability (PTP) of ischemic heart disease (odds ratio, OR, 1.05; 95% confidence interval, CI, 1.02-1.08), dyslipidemia (DLP) (OR 0.40; 95% CI 0.20-0.82), carotid atherosclerosis (OR 0.39; 95% CI 0.18-0.86), LV ejection fraction (OR 0.96; 95% CI 0.93-0.99), appearance at peak stress of new significant (2 LV segments or more) regional WMAs (OR 0.32; 95% CI 0.18-6.55), decreased LV CTR (OR 0.46; 95% CI 0.27-0.79) and CR (OR 0.33; 95% CI 0.18-0.61); p<0.05 for all. In a multivariate analysis with Cox regression, the model with clinical indicators included PTP of IHD (OR 1.04; 95% CI 1.01-1.07; p=0.01) and DLP (OR 0.14; 95% CI 0.02-1.01; p=0.05) as predictors. The model with stress EchoCG parameters included the appearance of new significant WMAs (OR 0.33, 95% CI 0.16-0.65; p=0.001) and reduced <2.0 CR (OR 0.44; 95% CI 0.24-0.82; p=0.01). A comparative analysis of Kaplan-Meier curves confirmed statistically significant differences in the dynamics of the CCVEP occurrence depending on the absence or presence of hemodynamically significant WMAs and/or reduced CR during stress EchoCG (p<0.01). Reduced LV CR and WMA during stress EchoCG in patients with suspected or confirmed IHD are significant independent predictors for the CCVEP occurrence. Among clinical indicators, PTP of IHD and DLP are of the greatest importance for prognosis.

Multiple Phenotypes of Chronic Coronary Syndromes Identified by ABCDE Stress Echocardiography

Regional wall motion abnormality is considered a sensitive and specific marker of ischemia during stress echocardiography (SE). However, ischemia is a multifaceted entity associated with either coronary artery disease (CAD) or angina with normal coronary arteries, a distinction difficult to make using a single sign. The aim of this study was to evaluate the diagnostic potential of the five-step ABCDE SE protocol for CAD detection. From the 2016-2022 Stress Echo 2030 study data bank, 3,229 patients were selected (mean age, 66±12years; 2,089 men [65%]) with known CAD (n=1,792) or angina with normal coronary arteries (n=1,437). All patients were studied using both the ABCDE SE protocol and coronary angiography, within 3months. In step A, regional wall motion abnormality is assessed; in step B, B-lines and diastolic function; in step C, left ventricular contractile reserve; in step D, coronary flow velocity reserve in the left anterior descending coronary artery; and in step E, heart rate reserve. SE response ranged from a score of 0 (all steps normal) to a score of 5 (all steps abnormal). For CAD, rates of abnormal results were 347 for step A (19.4%), 547 (30.5%) for step B, 720 (40.2%) for step C, 615 (34.3%) for step D, and 633 (35.3%) for step E. For angina with normal coronary arteries, rates of abnormal results were 81 (5.6%) for step A, 429 (29.9%) for step B, 432 (30.1%) for step C, 354 (24.6%) for step D, and 445 (31.0%) for step E. The dominant "solitary phenotype" was step B in 109 patients (9.1%). Stress-induced ischemia presents with a wide range of diagnostic phenotypes, highlighting its complex nature. Using a comprehensive approach such as the advanced ABCDE score, which combines multiple markers, proves to be more valuable than relying on a single marker in isolation.

Echocardiographic functional determinants of survival in heart failure with abnormal ejection fraction

Background and AimsPatients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion and EF.Methods and resultsIn a prospective multicenter study design, we enrolled 1,408 HF patients (age 66 ± 12 years, 1,035 men), with EF <50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004–2022) involved 8 accredited laboratories, with inter-observer variability <10% for CFV measurement. Baseline CFV (abnormal value >31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. CFVR (abnormal value ≤2.0) was assessed with exercise (n = 99), dobutamine (n = 100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress > rest (cut-off Δ ≥ 0.12). LV contractile reserve (CR) was identified with WMSI stress < rest (cutoff Δ ≥ 0.25). Test response ranged from score 0 (EF > 30%, CFV ≥ 32 cm/s, CFVR > 2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only endpoint. Results. During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943–0.968, p < 0.0001), CFV (HR: 2.407, 95% CI: 1.871–3.096, p < 0.001), CFVR (HR: 3.908, 95% CI: 2.903–5.260, p < 0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642–3.009, p < 0.001), and LVCR (HR: 0.524, 95% CI: 0.324–.647, p = 0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (n = 61) and highest (31.9%) in patients with a score of 5 (n = 15, p < 0.001).ConclusionHigh resting CFV is associated with worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.

Stress echocardiography: application of the ABCDE protocol in patients with permanent atrial fibrillation

Abstract Objectives A new standard of practice in stress echocardiography (SE) was founded with the development of the ABCDE protocol, which added functional information to conventional ischemia diagnosis. Each step showed to provide incremental prognostic information: 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 the left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. However, the utility of SE and ABCDE protocol in patients with atrial fibrillation (AF) has never been tested. Background A growing body of evidence suggests that AF patients have a significant residual risk of myocardial infarction despite anticoagulant treatment; furthermore, they have an increased risk of heart failure and all-cause death. However, ABCDE-SE has never been applied in this population. Methods Of the 3965 patients who completed clinically indicated ABCDE-SE and with available information on rhythm stored in the shared data bank and enrolled from 13 certified centers, 3891 were in sinus rhythm (SR, Group 1) and 50 in permanent AF (Group 2) at the time of the test. ABCDE-SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). The employed stress was an exercise in 1626 (41%), vasodilator in 1864 (47%), and dobutamine in 475 (12%). Results Group 2 pts were older than Group 1 patients, more frequently hypertensives and diabetics, with lower ejection fraction, and with more signs of pulmonary congestion at rest. During stress, differences were magnified, and Group 2 patients showed more peak stress B-lines and higher values of peak WMSI compared with Group 1 (see Table). In addition, patients with AF had higher ABCDE scores (Group 1= 1.5 ±1.4 vs. Group 2= 2.6±1.6, p<0.0001). The distribution of the score in patients in SR and AF is shown in Figure. Conclusions Patients with AF are scarcely represented among patients undergoing SE. Patients with AF showed a higher prevalence of positivity in each step and a higher ABCDE score. More specifically, AF patients are more vulnerable than patients in SR to coronary microvascular dysfunction and chronotropic incompetence during stress.TableFigure

Independent prognostic value of ejection fraction, resting coronary flow, coronary flow reserve, myocardial viability, and inducible ischemia in heart failure with a reduced ejection fraction

Abstract Background and Aims Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion. Methods and results In a prospective multicenter study design, we enrolled 1,408 HF patients (age 66±12 years, 1,035 men), with EF <50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004-2022) involved 8 accredited laboratories, with inter-observer variability <10% for CFV measurement. Baseline CFV (abnormal value >31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. Coronary flow velocity reserve (CFVR, abnormal value ≤2.0) was assessed with exercise (n=99), dobutamine (n=100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress> rest (cut-off ∆≥0.12). LV contractile reserve (CR) was identified with WMSI stress< rest (cutoff ∆≥0.25). Test response ranged from score 0 (EF>30%, CFV ≤31 cm/s, CFVR >2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only end-point. Results During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943-0.968, p<0.0001), CFV (HR: 2.407, 95% CI: 1.871-3.096, p<0.001), CFVR (HR: 3.908, 95% CI: 2.903-5.260, p<0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642-3.009, p<0.001), and LVCR (HR: 0.524, 95% CI: 0.324-.647, p=0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (n=61) and highest (31.9%) in patients with a score of 5 (n=15, p<0.001). Conclusion High resting CFV predicts worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.

Functional and transcriptional sequelae of cardiomyocyte telomere shortening and their pathologic relevance in dilated cardiomyopathy and ischemic heart failure

Abstract Background Heart failure (HF) is associated with cardiomyocyte (CM) telomere shortening. Sequelae have been described with the telomere-p53-mitochondrion model. P53 deficiency only partially ameliorates mitochondrial defects in telomerase deficient mice hinting at additional pathways. Purpose We assessed the cardiac phenotype and transcriptome of early/advanced telomere shortening and evaluated the pathological relevance by correlation to published HF datasets. Methods Male (6-8w) telomerase RNA-component deficient mice, early (generation 2, mTRG2) and advanced (mTRG5) were phenotyped vs age-matched C57BL/6 mice (B6). Adult CMs from mTRG2/G5 vs B6 mice were characterized (live imaging, quantitative fluorescence in situ hybridization (Q-FISH) and transcriptome analysis (microarray Mouse MTA 1.0)). Gene expression analysis was performed (Ingenuity Pathway Analysis, Qiagen) and correlated to comparable datasets from > 120 000 curated datasets. Results CMs exhibited significant telomere shortening in mTR(-/-) mice increasing with every generation (mTRG2/G5 p<0.0001 vs B6). In parallel, echocardiography revealed increasing defects of left ventricular (LV) systolic function (LVEF, mTRG5 <0.01 vs B6), LV global longitudinal strain mTRG2/G5 p<0.001 vs B6) and LV contractile reserve (mTRG2/G5 p<0.05 vs B6). Live imaging showed increasing impairment of mitochondrial polarization with all energy substrates (mTRG2/G5 p<0.0001 vs B6). Transcriptome analysis revealed 357/2906 differentially expressed genes (DEGs) in mTRG2/G5-CMs vs B6-CMs (fold change <-1.5 or >1.5 and p-value <0.05). Upstream Regulator (UR) analysis revealed significant overrepresentation of numerous regulators including angiotensinogen (z-score 7.5, p-value 1.1E-32), transforming growth factor (TGF)-b1 (z-score 7.5, p-value 2.2E-60), interleukin (IL)-1 (z-score 5.6, p-value 1.1E-26), IL-6 (expression fold change 11.3, z-score 6.9 p-value 2.65E-32), IL-17A (z-score 4.8, p-value 4.4E-27) and NFkB (z-score 6.0 p-value 4.9E-19). Activation of TP53 (z-score 5.8, p-value 5.3E-31) and inhibition of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) (z-score -4.4, p-value 6.3E-19) confirmed the relevance of the p53-mitochondrion-axis. Analysis matching revealed a significant overlap of gene expression patterns in the same direction (positive z-score) between mTR-/--mice and all comparable datasets of dilated (DCM) and ischemic cardiomyopathy (ICM) (human/mouse), the overlap increasing with increasing telomere shortening (e.g. DCM vs mTRG2: z-score 17.7, UR p-value 1.5E-16; DCM vs mTRG5: z-score 56.8, UR-value 1.5E-62). Matching to datasets after cardiac regeneration (e.g. after left ventricular assist device implantation) revealed a reversal of gene expression patterns (negative z-score). Conclusions Our results reveal the large extent of transcriptional alterations upon cardiac telomere shortening and support their central role in the pathogenesis of HF.

Transcatheter-edge-to-edge-repair of functional mitral regurgitation in advanced HFrEF: the impact of intrinsic left ventricular performance on the degree of MR reduction and clinical outcome

Abstract Background Transcatheter-edge-to-edge-repair (TEER) of functional mitral regurgitation (FMR) reduces rehospitalisation and all-cause mortality in patients with HFrEF/HFmrEF. Not conclusively clarified is the interaction of pre-interventional intrinsic left ventricular (LV) function with TEER success and clinical outcome. By using the gold standard of LV contractility analysis, the invasive pressure-volume loop technique, we examined the interaction of pre-and post-interventional intrinsic LV performance with the degree of MR reduction and all-cause mortality after TEER in patients with advanced HFrEF. Methods In a prospective study of 71 patients with advanced HFrEF (median EF 26%, 22-31%) and severe FMR, we quantified different intrinsic parameters of LV performance by PV-loop analysis (single beat analysis) pre-and post-interventionally. Results In 83% of the patients a MR reduction to grad < 2 could be achieved (hospital discharge). In the ROC analysis, the best cut-off to separate medium-term survival from all-cause mortality (median FU 2.9 years) was a post-interventional regurgitation fraction (RF) < 20% (AUC 0.72, p<0.001, sensitivity 83%, specificity 60%) and a R-volume (RV) < 18ml (AUC 0,7, p=0.002, sensitivity 67%, specificity 72%). The PV-loop-derived intrinsic LV contractility (LV-endsystolic elastance, Ees), LV afterload (arterial elastance, Ea), LV-Ao-coupling (Ees/Ea), LV-mechanical efficacy (ME), PV-loop area (PVA), stroke work, Tau; end-diastolic elastance (Eed), LVEF, LVEDV, and LVESV, pre- and post-TEER, were not predictive for the extent of MR reduction acutely, after 6 months FU, and for all-cause mortality. In multivariate cox-regression analysis, only a post-interventional RF<20% (HR 0.36, p=0.017) or RV<18ml (HR 0.32, p=0.005) and the pre-interventional LV-contractile reserve (LV-CR: post-extra-systolic augmentation of LV-Ees) remained independent predictors of all-cause mortality. In a second model, we included the degree of LV-remodeling (LV-R: LVESV reduction from hospital discharge to 6 months) in the model. In addition to pre-interventional LV-CR, and RF<20%, the LV-R remains independent predictive for all-cause mortality. Conclusion In our peri-mitral-TEER LV-PV-loop study, only the extent of MR reduction and the pre-interventional LV-CR, but not the intrinsic LV performance at rest, determine the medium-term survival of patients with advanced HFrEF and FMR. TEER-mediated MR reduction itself seems not be determined by the LV performance.

The clinical use of stress echocardiography in chronic coronary syndromes and beyond coronary artery disease: a clinical consensus statement from the European Association of Cardiovascular Imaging of the ESC.

Since the 2009 publication of the stress echocardiography expert consensus of the European Association of Echocardiography, and after the 2016 advice of the American Society of Echocardiography-European Association of Cardiovascular Imaging for applications beyond coronary artery disease, new information has become available regarding stress echo. Until recently, the assessment of regional wall motion abnormality was the only universally practiced step of stress echo. In the state-of-the-art ABCDE protocol, regional wall motion abnormality remains the main step A, but at the same time, regional perfusion using ultrasound-contrast agents may be assessed. Diastolic function and pulmonary B-lines are assessed in step B; left ventricular contractile and preload reserve with volumetric echocardiography in step C; Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and ECG-based heart rate reserve in non-imaging step E. These five biomarkers converge, conceptually and methodologically, in the ABCDE protocol allowing comprehensive risk stratification of the vulnerable patient with chronic coronary syndromes. The present document summarizes current practice guidelines recommendations and training requirements and harmonizes the clinical guidelines of the European Society of Cardiology in many diverse cardiac conditions, from chronic coronary syndromes to valvular heart disease. The continuous refinement of imaging technology and the diffusion of ultrasound-contrast agents improve image quality, feasibility, and reader accuracy in assessing wall motion and perfusion, left ventricular volumes, and coronary flow velocity. Carotid imaging detects pre-obstructive atherosclerosis and improves risk prediction similarly to coronary atherosclerosis. The revolutionary impact of artificial intelligence on echocardiographic image acquisition and analysis makes stress echo more operator-independent and objective. Stress echo has unique features of low cost, versatility, and universal availability. It does not need ionizing radiation exposure and has near-zero carbon dioxide emissions. Stress echo is a convenient and sustainable choice for functional testing within and beyond coronary artery disease.

Left Ventricular Physiology and Ventricular-Vascular Interactions in Young Patients After Heart Transplantation.

Background In patients after heart transplantation, systemic arterial hypertension and enhanced central aortic stiffness contribute to increased ventricular afterload, which might lead to graft dysfunction. The aim of our study was to characterize systemic arterial elastance and its impact on left ventricular function and ventriculo-arterial coupling in a cohort of children, adolescents, and young adults after heart transplantation using invasive conductance catheter technique. Methods and Results Thirty patients who had heart transplants (age, 20.0±6.5 years, 7 female) underwent invasive cardiac catheterization including pressure-volume loop analysis. Load-independent parameters of systolic (ventricular elastance [Ees]) and diastolic (ventricular compliance) function as well as systemic arterial elastance (Ea, end-systolic pressure/stroke volume) and ventriculo-arterial coupling (Ea/Ees) were assessed at baseline level and during dobutamine infusion (10 μg/kg/min). Ees showed an appropriate increase under inotropic stimulation from 0.43 (0.11-2.52) to 1.00 (0.20-5.10) mm Hg/mL/m2 (P<0.0001), whereas ventricular compliance remained rather unchanged (0.16±0.10 mm Hg/mL/m2 to 0.12±0.07 mm Hg/mL/m2; P=0.10). Ventriculo-arterial coupling Ea/Ees was abnormal at rest and did not improve significantly under dobutamine (1.7 [0.6-6.7] to 1.3 [0.5-4.9], P=0.70) due to a simultaneous rise in Ea from 0.71 (0.37-2.82) to 1.10 (0.52-4.03) mm Hg/mL/m2 (P<0.0001). Both Ees and ventricular compliance were significantly associated with Ea at baseline and under dobutamine infusion. Conclusions Patients who underwent heart transplantation show impaired ventriculo-arterial coupling at rest and under inotropic stimulation despite preserved left ventricular contractile reserve. An abnormal response in vascular function resulting in increased afterload seems to represent an important factor that may play a role for the development of late graft failure.

P44 IMPROVEMENT OF THE LEFT VENTRICULAR CONTRACTILE RESERVE IN PATIENTS UNDERGOING MITRAL VALVE PLASTIC CARDIAC SURGERY

Abstract Mitral Regurgitation (MR) is a clinical condition characterized by a high morbidity and mortality in severe or moderate forms complicated by hemodynamic instability, that often finds a solution only in the reparative surgical treatment. MR is often caused the presence of myxomatous degeneration that affects one or more structures of the valve apparatus, causing the prolapse of one or both leaflets. Surgical treatment can improve the hemodynamic parameters and consequently the prognosis of the patients, even though there is not still data concerning the myocardial contractile reserve. The aim of the study was to evaluate the effect of MR reparative surgery on the left ventricular contractile reserve during physical stress echocardiography. We enrolled 12 patients, 8 females and 4 males, affected by MR candidate to cardiac surgery. We performed a physical stress–echo test by using the ABCDE protocol suggested by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), before and after approximately 12 weeks from cardiac surgery. After each test, the prognostic score deriving from the sum of the ABCDE criteria was calculated; in addition, we measured the left ventricular contractile reserve (C parameter of the score) that represents a parameter of the force deriving from the hemodynamic changes during the test. In all patients we observed a significant improvement in the ABCDE prognostic score after cardiac surgery (3.89 + 0.43 vs 3.18 + 0.37; p = 0.002). There were no significant changes in ejection fraction, indexed left atrial volume, wall motion score index–WMSI (A parameter), coronary reserve (D parameter), and heart rate reserve (E parameter). The most relevant data concerns the increase in the left ventricular contractile reserve at 3 months after cardiac surgery (1.77 mmHg/ml vs 2.44 mmHg/ml, p&amp;lt;0.0001). Furthermore, a significant reduction in pulmonary congestion during stress was observed (B parameter). These data demonstrate for the first time that mitral valve plastic surgery is able to improve the left ventricular contractile reserve in patients with severe MR. Furthermore, the surgical procedure determined both a reduction in the degree of pulmonary congestion and an improvement in the ABCDE prognostic score during physical stress echocardiography.

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination.

Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter-Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of -17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m2, and the right ventricular free wall longitudinal strain (LS) was impaired in some patients but not in all. There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group (32% vs. 62.5%, p = 0.04). In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy (-19.1 ± 3.1% vs. -16.5 ± 5.1%, p = 0.04). DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter-Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment.

ABCDEG Stress Echocardiography in Aortic Stenosis.

Rest and stress echocardiography (SE) plays a pivotal role in the evaluation of valvular heart disease. The use of SE is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms. In aortic stenosis (AS), rest echocardiographic analysis is a stepwise approach that begins with the evaluation of aortic valve morphology and proceeds to the measurement of the transvalvular aortic gradient and aortic valve area (AVA) using continuity equations or planimetry. The presence of the following three criteria suggests severe AS: AVA < 1.0 cm2, a peak velocity > 4.0 m/s, or a mean gradient > 40 mmHg. However, in approximately one in three cases, we can observe a discordant AVA < 1 cm2 with a peak velocity < 4.0 m/s or a mean gradient <40 mmHg. This is due to reduced transvalvular flow associated with LV systolic dysfunction (LVEF < 50%) defined as "classical" low-flow low-gradient (LFLG) AS or normal LVEF "paradoxical" LFLG AS. SE has an established role in evaluating LV contractile reserve (CR) patients with reduced LVEF. In classical LFLG AS, LV CR distinguished pseudo-severe AS from truly severe AS. Some observational data suggest that long-term prognosis in asymptomatic severe AS may not be as favorable as previously thought, offering a window of opportunity for intervention prior to the onset of symptoms. Therefore, guidelines recommend evaluating asymptomatic AS with exercise stress in physically active patients, particularly those younger than 70 years, and symptomatic classical LFLG severe AS with low-dose dobutamine SE. A comprehensive SE assessment includes evaluating valve function (gradients), the global systolic function of the LV, and pulmonary congestion. This assessment integrates considerations of blood pressure response, chronotropic reserve, and symptoms. StressEcho 2030 is a prospective, large-scale study that employs a comprehensive protocol (ABCDEG) to analyze the clinical and echocardiographic phenotypes of AS, capturing various vulnerability sources which support stress echo-driven treatment strategies.

Stress Echo 2030: the new ABCDE protocol defining the future of cardiac imaging.

Functional testing with stress echocardiography is based on the detection of regional wall motion abnormality with two-dimensional echocardiography and is embedded in clinical guidelines. Yet, it under-uses the unique versatility of the technique, ideally suited to describe the different functional abnormalities underlying the same wall motion response during stress. Five parameters converge conceptually and methodologically in the state-of-the-art ABCDE protocol, assessing multiple vulnerabilities of the ischemic patient. The five steps of the ABCDE protocol are (1) step A: regional wall motion; (2) step B: B-lines by lung ultrasound assessing extravascular lung water; (3) step C: left ventricular contractile reserve by volumetric two-dimensional echocardiography; (4) step D: coronary flow velocity reserve in mid-distal left anterior descending coronary with pulsed-wave Doppler; and (5) step E: assessment of heart rate reserve with a one-lead electrocardiogram. ABCDE stress echo offers insight into five functional reserves: epicardial flow (A); diastolic (B), contractile (C), coronary microcirculatory (D), and chronotropic reserve (E). The new format is more comprehensive and allows better functional characterization, risk stratification, and personalized tailoring of therapy. ABCDE protocol is an 'ecumenic' and 'omnivorous' functional test, suitable for all stresses and all patients also beyond coronary artery disease. It fits the need for sustainability of the current era in healthcare, since it requires universally available technology, and is low-cost, radiation-free, and nearly carbon-neutral.

Childhood Cancer Survivors Have Impaired Strain-Derived Myocardial Contractile Reserve by Dobutamine Stress Echocardiography.

Abnormal left ventricular contractile reserve (LVCR) is associated with adverse cardiac outcomes in different patient cohorts and might be useful in the detection of cardiomyopathy in childhood cancer survivors (CCS) after cardiotoxic treatment. The aim of this study was to evaluate LVCR by dobutamine stress echocardiography (DSE) combined with measures of myocardial strain in CCS previously treated with anthracyclines (AC). Fifty-three CCS (age 25.34 ± 2.44 years, 35 male) and 53 healthy controls (age 24.40 ± 2.40 years, 32 male) were included. Subjects were examined with echocardiography at rest, at low-dose (5 micrograms/kg/min), and at high-dose (40 micrograms/kg/min) dobutamine infusion. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), strain rate (GSR), and early diastolic strain rate (GEDSR) at different DSE phases were used as measures of LVCR. The mean follow-up time among CCS was 15.8 ± 5.8 years. GLS, GSR, and LVEF were lower at rest in CCS compared to controls (p ≤ 0.03). LVEF was within the normal range in CCS. ΔGLS, ΔGSR, and ΔGEDSR but not ΔLVEF were lower in CCS compared to controls after both low- (p ≤ 0.048) and high-dose dobutamine infusion (p ≤ 0.023). We conclude that strain measures during low-dose DSE detect impaired myocardial contractile reserve in young CCS treated with AC at 15-year follow-up. Thus, DSE may help identify asymptomatic CCS at risk for heart failure and allows for tailored follow-up accordingly.

(381) Left Ventricular Contractile Reserve is Associated with Optimal Exercise Hemodynamics in Cf-lvad Patients: A Pressure-Volume Loop Analysis

(381) Left Ventricular Contractile Reserve is Associated with Optimal Exercise Hemodynamics in Cf-lvad Patients: A Pressure-Volume Loop Analysis

Myocardial Work Efficiency in Physiologic Left Ventricular Hypertrophy of Power Athletes.

The athlete's heart in power training is characterized by physiologic concentric remodeling. Our aim was to analyze left ventricular (LV) myocardial deformation and contractile reserve (CR) in top-level power athletes (PA) at rest and during exercise and their possible correlations with functional capacity. Standard echo, lung ultrasound, and LV 2D speckle-tracking strain were performed at rest and during exercise in PA and in age- and sex-comparable healthy controls. 250 PA (male: 62%; 33.6 ± 4.8 years) and 180 age- and sex-comparable healthy controls were enrolled. LV ejection fraction (EF) at baseline was comparable between the two groups, while LV global longitudinal strain (GLS) was reduced in PA (GLS: -17.8 ± 2.4 in PA vs. -21.9 ± 3.8 in controls; P < 0.01). Conversely, myocardial work efficiency (MWE) did not show significant difference between the two groups (94.4 ± 3.2 in PA vs. 95.9 ± 4.6% in controls; P NS). At peak exertion during exercise stress echocardiography (ESE), PA showed better exercise capacity and peak VO2 consumption (51.6 ± 10.2 in EA vs. 39.8 ± 8.2 mL/Kg/min in controls, P < 0.0001), associated with augmented pulmonary artery systolic pressure (PASP). By multivariable analysis, MWE at rest was the most predictive factor of maximal watts (P < 0.0001), peak VO2, (P < 0.0001), PASP (P < 0.001), and number of B-lines (P < 0.001), all measured at peak effort. In power athletes, MWE showed less load dependency than GLS. Normal resting values of MWE in PA suggest a physiological LV remodeling, associated with a better exercise capacity and preserved CR during physical stress.

Pressure/Volume Ratio as a Simple Parameter for Assessment of left Ventricular Contractile Reserve during Stress Echocardiography

Pressure/Volume Ratio as a Simple Parameter for Assessment of left Ventricular Contractile Reserve during Stress Echocardiography

PS-C14-2: QUANTITATIVE METHODS FOR ASSESSING CONTRACTILE RESERVE IN PATIENTS WITH DIASTOLIC HEART FAILURE

Aim: The effectiveness of isometric handgrip exercise on changes of cardiovascular hemodynamical parameter in patients with diastolic heart failure is unknown. We assessed the effect of several hemodynamic parameters and it changes during handgrip maneuvers in patients with different stages of diastolic heart failure during chemotherapy and their improvements after 4 months follow up (4mFU) treatment with single pill combination of ACE inhibitor ACE) and beta blocker(BB). Methods: The study population included 65 patients female / mean age of 45 ± 12 years/ 55 with breast cancer and undergoing chemotherapy / 30 pts with HFpEF and 25 pts with HFmrEF / and 10 pts with HFnEF and without chemotherapy. The effect of handgrip maneuver on hemodynamic parameters were studied by speckle tracking echocardiography. Following maximal squeeze by 100%, during the next 3 minutes patients were instructed to apply pressure at 50%. The global longitudinal strain were extracted by 3, 4 and 2 chamber apical view images on 70 fr/s and MAP and HR were performed at basal level, 1st, 2nd and 3rd minutes during handgrip stress test. The contractility /force/ of LV were also calculate as ratio SBP / ESV. Patients with HFmrEF and HFpEF received for 4 months treatment with single pill combination ACE (perindorpril)/ BB (bisoprolol) 5/5 mg. Results: Heart rate(HR) and mean arterial pressure(MAP) increased significantly after handgrip maneuver / from 75 ± 6 beats /min to 101 ± 12 beats/ min, 109 ± 15 mmHg to 118 ± 19mmHg, p &lt; 0,05 /. Pulmonary artery systolic(s) and diastolic (d) pressure(PAP),pulmonary capillary wedge pressure (PCWP), cardiac index(CI), LVEF did not change significantly(p &gt; 0,5) after handgrip maneuvers. On the other hand, LV force (SBP/ ESV ratio),MAP and HR decreases significantly (p &lt; 0,01) in group with HFmrEF. In same group were found significantly decreased GLVLS at 2nd and 3rd minutes during stress- test comparable with other 2 groups with HFpEF and HFnEF. After 4mFU and treatment with 5/5 mg doses combination of ACE / BB were found improvement in parameters: HR /p &lt; 0,001/, MAP /p &lt; 0.01/ and contractile reserve as well as LV force /p &lt; 0, 01/ and GLVLS /p &lt; 0,001/. Conclusion: Cardiovascular response to handgrip maneuver may be a marker of failure to respond to compensatory mechanisms. Patients with good LV reserve had a rise in stroke work with little or no change in LVEDP. Patients with poor contractile reserve had a fall in stroke work reserve together with a substantial rise in LVEDP. It is concluded that the stress imposed by sustained handgrip provides a simple test for evaluation of LV contractile reserve in patients, who will develop cardiotoxicity during chemotherapy treatment. The treatment with combination with small doses ACE/BB is a big challenge in patients with HFmrEF and HFpEF to improve the contractile reserve.

Impaired Left Ventricular Contractile Reserve in Patients With Hypertrophic Cardiomyopathy and Abnormal Blood Pressure Response: A Stress Echocardiographic Study.

Abnormal blood pressure response (ABPR) has been reported to be a risk factor for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). We aimed to elucidate the relationship between ABPR during exercise stress echocardiography (ESE) and impaired left ventricular (LV) contractile reserve based on two-dimensional strain in patients with HCM. Patients with HCM underwent ESE with treadmill exercise. Patients whose blood pressure elevation at maximum workload was lower than 20 mmHg from baseline were classified as having ABPR. Echocardiographic parameters were compared between patients with and without ABPR. Results: Of 26 patients with HCM, nine patients were diagnosed with ABPR. Significant LV outflow tract obstruction (>50 mmHg) was provoked only in one patient with ABPR (baseline to the conclusion of the exercise, 15.2 mmHg to 63.0 mmHg). Change in cardiac output (CO) and the ratio of early diastolic velocity to early annular velocity (E/e') from baseline to just after the conclusion of exercise did not differ between patients with and without ABPR (CO, 102±40% vs. 122±45%, P = 0.19; E/e', 4±22% vs. 2±20%, P = 0.86). Change in systemic vascular resistance change was not significant (patients with vs. without ABPR, -52±10% vs. -46±13%, P = 0.24). Percent change in LV global longitudinal strain was lower in patients with ABPR than patients without ABPR (12±17% vs. 27±15%, P = 0.02). In conclusion, impaired LV contractile reserve during exercise might contribute to ABPR in patients with HCM.