Citations

Abstract Backgrounds Transthoracic echocardiography (TTE) identifies a peculiar hypercontractile phenotype (HP) in patients with heart failure and preserved ejection fraction (HFpEF) with high resting left ventricular (LV) elastance (also called force). Objectives To assess the functional response and its prognosis associated with HP in HFpEF by stress echocardiography (SE). Methods In a prospective, observational, multicenter study, 1213 patients with HFpEF were divided into two groups based on the highest quartile of rest force: non-hypercontractile phenotype group (non-HP, < 5.64 mmHg/mL, Group 1, n= 910), and HP group (≥5.64 mmHg/mL, Group 2, n= 303). All patients underwent SE with at least 4 of the following stress parameters assessed: wall motion score index (WMSI), B-lines (4-site score), force-based LV contractile reserve, coronary flow velocity reserve (CFVR), and heart rate reserve (HRR). The employed stress was exercise (n=687), dobutamine (n=195), or vasodilators (n=331). SE score ranged from 0 (all steps normal) to 1-5, according to the number of abnormal steps. Follow-up was completed in a subset of 260 patients. Results The 2 groups showed similar values of peak stress WMSI but the global functional burden was higher in Group 2 patients: see table. In a subset of 260 patients who finished follow-up, there were 212 non-HP patients and 48 HP patients. During a median follow-up of 15 months (interquartile range: 10-20), 26 deaths, 20 heart failure (HF) rehospitalizations, and 64 major adverse cardiovascular events (MACEs) occurred. The cumulative HF rehospitalization rate and MACEs rate were higher in HP group (log-rank p<0.01): see figure. Rest force (HR, 1.17; 95% CI: 1.06-1.29; P: 0.040), rest SPAP (HR, 1.08; 95% CI: 1.02-1.14; P: 0.007) and ABCDE score (HR, 1.15; 95% CI: 1.01-1.66; P: 0.032) were independently associated with MACEs. Conclusions HFpEF patients with HP are functionally weaker with multiple vulnerabilities during stress and at higher risk of subsequent events compared to non-HP patients.Relation between resting values of force

Abstract Aims Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. The aim of the study is to assess the risk stratification value of CI during exercise or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods and results In a prospective, multicenter, international, observational study, we enrolled 13 445 patients with known or suspected chronic coronary syndromes who underwent stress echocardiography in 19 clinical sites from 10 countries using either exercise (n = 2594), dobutamine (n = 2440), or dipyridamole (n = 8411). Heart rate was automatically measured from the 1-lead ECG in the echocardiography monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) ≤ 1.22 (≤1.17 if in permanent atrial fibrillation) for dipyridamole stress. The primary outcome was all-cause death. CI was observed in 5045 patients (38%) and stress-induced regional wall motion abnormalities in 1648 (13%). Over a median follow-up time of 3.4 years (interquartile range, 1.6–9.1 years), there were 2426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (P < 0.0001). CI was associated with a significant increase in 10-year mortality in all age groups ranging from ≤54 years to ≥75 years (P < 0.0001). In addition, it was associated with increased mortality (P < 0.0001) irrespective of β-blocker use. Cox multivariable analysis revealed that CI was an independent predictor of mortality (HR: 1.60, 95% confidence interval: 1.47–1.74; P < 0.0001) together with age, male sex, diabetes mellitus, left ventricular ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during exercise or pharmacological stress is a simple and objective predictor of survival.

Abstract Aims Our aim was to assess the clinical and prognostic significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM), which until now remains unclear. Methods and results We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥ 50%, referred for rest transthoracic echocardiography (TTE) in 27 laboratories from 13 countries. Two-dimensional volumetric TTE assessment included LV outflow tract gradient (LVOTG), LV EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). HP was defined as the highest quartile of the force (> 7.32 mmHg/mL). Survival analysis was performed in a subset of 1200 patients with follow-up information. Compared with non-HP patients, HP showed higher heart rate (72 ± 14 vs. 67 ± 14 beats per minute, P < 0.001), lower stroke volume (50 ± 22 vs. 67 ± 22 mL, P < 0.001), larger left atrial volume index (44 ± 16 vs. 40 ± 16 mL/m2, P = 0.011) and higher coronary flow velocity in the mid-distal left anterior descending artery (n = 325, 41 ± 12 vs. 37 ± 14 cm/s, P = 0.021). Force was moderately related to LV EF (r = 0.48, P < 0.001) and weakly to LVOTG (r = 0.36, P < 0.001). During a median follow-up of 87 months (interquartile range 45–143 months), 131 all-cause deaths occurred. At multivariable Cox analysis, a force > 7.32 mmHg (the fourth quartile for analyzed patients) was associated with a hazard ratio of 1.44 (95% Confidence intervals 1.00–2.07) for all-cause death, independently of LVOTG and LV EF. Conclusion HP in HCM is associated with a disadvantageous systemic, cardiac and coronary hemodynamic profile as well as lower survival in the long-term.

Introduction Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, with a high 5-year survival rate of approximately 98%. Despite advances in diagnosis and treatment, up to 20% of patients experience recurrence, adversely affecting their quality of life. Predictive models have been developed to assess recurrence risk and guide clinical decision-making, but these models often face limitations such as retrospective design, lack of diversity in study populations and absence of external validation. The primary aim is to externally validate existing predictive models for DTC recurrence using prospective data from a diverse Latin American cohort. The secondary aim is to explore opportunities for model recalibration to improve their performance in our population. Methods and analysis The CaTaLiNA study is a multicentre prospective observational study conducted across 10 hospitals in five Latin American countries, including Ecuador, Peru, Uruguay and Mexico. Patients aged 18 years or older receiving treatment for DTC, such as the first thyroid surgery, active surveillance or radiofrequency ablation will be included. Recruitment will occur from November 2023 to June 2025, with follow-up extending until June 2028. Data collection will include baseline clinical, surgical and histological characteristics, treatment details and follow-up outcomes. Statistical analysis will follow the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis guidelines, using imputation strategies for missing data and evaluating calibration and discrimination of the prediction models. Calibration measures include the ratio of expected and observed events, calibration slope and calibration plot, while discrimination will be assessed using the C-index and area under the receiver operating characteristic curve. Ethics and dissemination This study protocol was approved by Comité de Ética de Investigación en Seres Humanos de la Universidad San Francisco de Quito USFQ ‘CEISH-USFQ’ APO-010–2023-CEIHS-USFQ Oficio No. 161-2023-CA-23030M-CEISH-USFQ. Results will be disseminated via peer-reviewed publications.

Over the past decade, stress echocardiography has evolved from a test for assessing epicardial artery stenosis to a comprehensive functional test, targeting multiple cardiovascular parameters. The new approach includes several structured steps: (a) evaluating regional wall motion abnormalities to detect epicardial artery stenosis or vasospasm; (b) assessing pulmonary congestion and diastolic function via B-lines with lung ultrasound; (c) gauging preload and contractile reserve with volumetric echocardiography; (d) measuring coronary microvascular reserve using Doppler-based coronary flow velocity in the middistal left anterior descending artery; and (e) determining cardiac sympathetic reserve by tracking heart rate reserve on an ECG. This evolution was supported extensively by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), which played a key role in five areas: (1) developing the initial, curiosity-driven project; (2) disseminating protocols and results at national and international conferences, supporting logistic infrastructure and publication expenses; (3) establishing a digital platform (customized Redcap) for data entry and storage; (4) facilitating patient recruitment across 19 Italian centers; and (5) offering formal endorsement through six presidencies, adding credibility and reach beyond any single institution. The protocol quickly advanced from concept to high-impact publications, earning inclusion in 2024 specialty guidelines. Initially Italian-led, the study now includes 50 centers across 20 countries (e.g. USA and China). Beyond the 50 peer-reviewed papers published in 2016–2024, this study offers a novel, sustainable approach to cardiac stress testing, providing more information at lower costs, with zero radiation and minimal environmental impact. SIECVI’s endorsement was instrumental in amplifying the study’s rigor and outreach.

Abstract Background Atrial fibrillation (AF) is the most prevalent atrial tachyarrhythmia, affecting an estimated 2-4% of adults worldwide. AF is a well-recognized and treatable risk factor for stroke, but it often remains asymptomatic or subclinical, leading to underdiagnosis. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF). Methods An international prospective cohort comprising 1035 consecutive patients was initially considered from 12 cardiology institutions. These patients were referred for clinically-driven ESE as part of the Stress Echo 2020-2030 study network. All patients underwent comprehensive ESE with the ABCDE protocol, which included assessment of B-lines, left ventricle contractile reserve (LVCR), ECG-based heart rate reserve (HRR), LV ejection fraction (EF), LV end-diastolic volume, E/e’, pulmonary artery systolic pressure estimation, tricuspid annular plane sytolic excursion (TAPSE), left atrium volume index (LAVi) and left atrium reservoir phase strain (LASr) at rest and with exercise. Results After excluding 89 patients who were in AF during the ESE, 946 patients in SR were included as the main study cohort (101 with and 845 without a history of PAF). A scoring system was then constructed using all independent variables that differentiate the two groups (those with and without history of PAF). Presence of systemic hypertension, rest LAVI>31ml/m2, rest |LASr|< 21%, stress LAVI >29 ml/m2, stress |LASr| <24%, stress E/e’ >7, ∆TAPSE <4.5 mm, HRR<1.87, and LVCR<1.6 were identified as the discriminators between patients with and without PAF. The composite score, summing all 9 items (with a total score range from 0 to 9), yielded a score of >4 as the best balance between sensitivity (87%) and specificity (60%) in predicting those with PAF. The receiver operating characteristic curve analysis of the scoring model showed an AUC of 0.79 (p-value <0.0001), Figure. Conclusion ESE evaluation can be a valuable adjunct for identifying patients in SR with history of PAF. This multifaceted approach enhances the potential for more accurate detection and clinical management of individuals in SR at risk for AF, who could be considered for aggressive monitoring programs to prevent the development of new onset AF and subsequent increase in cardiovascular risk.

Abstract Background Abnormal (<50%) ejection fraction (EF) is a cornerstone of risk stratification and therapy, but also an imperfect proxy of left ventricular (LV) cardiac pump function, better assessed with stroke volume (SV). Aim To assess the value of SV in stratifying risk of patients with abnormal EF. Methods In a prospective, observational, multicenter study, we recruited 746 patients (age 66± 11 years, 536 males, 72%, 359 with previous myocardial infarction, 48%) with chronic coronary syndromes (CCS) and EF <50% referred for resting transthoracic echocardiography with technically successful 2-dimensional volumetric echocardiography in 17 accredited laboratories. We quantitatively assessed LV end-diastolic volume (EDV) and end-systolic volume (ESV) by Simpson’s biplane method. EF (EDV-ESV/EDV) and SV (EDV-ESV) were calculated from LV volumes. The outcome end-point was all-cause death. Results EF was 39±9%, SV 48±20 ml. There were 100 all-cause deaths during a median follow-up of 796 days (interquartile range 420-1286 days). Receiver-operating curve analysis identified SV≤31.4 ml/b as the best cut-off for predicting mortality. At multivariable analysis, after adjustment for age and prior myocardial infarction, EF <40% and SV ≤31.4 ml/b were significantly associated with decreased survival (HR 2.09, 95%, confidence intervals 1.09-4.01, p=0.024). The annual mortality was lowest (3.19%) in the group with mildly reduced (40-49%) EF and normal (>31.4 ml) SV, and highest (8.30%) in patients with both reduced EF and abnormal SV: see figure. Conclusion Patients with CCS and abnormal EF are a prognostically heterogeneous group, and the mortality rate is almost 3-times worse in patients with reduced EF and abnormal SV compared to patients with mildly reduced EF and normal SV. A simple resting volumetric two-dimensional echocardiography can offer an efficient risk stratification, beyond EF, with no extra imaging or analysis time.Figure

Abstract Background Hypercontractile phenotype (HP) of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS) or heart failure (HF), but its clinical recognition remains difficult. Objectives To assess the clinical variables associated with the HP. Methods In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65 ± 11 years, 2974 males, 58%) with CCS and/or HF with preserved ejection fraction (EF). Systolic blood pressure (SBP) was measured. We assessed wall motion score index (WMSI), LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), and ventricular-arterial coupling (VAC, as SV/ESV). Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Results For all the studied patients, force was 4.51 ± 2.11 mmHg/ml, with the highest sextile (Group 6) > 6.36 mmHg/ml. By multivariable logistic regression model, the highest sextile of force was associated with age > 65 years (OR 1.62, 95% CI 1.36–1.93, p < 0.001), hypertension (OR 1.76, 95% CI 1.40–2.21, p < 0.001), female sex (OR 4.52, 95% CI 3.77–5.42, p < 0.001), absence of beta-blocker therapy (OR 1.41, 95% CI 1.16–1.68), rest SBP ≥ 160 mmHg (OR 2.81, 95% CI 2.21–3.56, p < 0.001), high heart rate (OR 2.08, 95% CI 1.61–2.67, p < 0.001), and absence of prior myocardial infarction (OR 1.34, 95% CI 1.07–1.68, p = 0.012). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC. Conclusions HP of the LV with high force was clinically associated with advanced age, female sex, high resting SBP, and the absence of 𝛽-blocker therapy. By transthoracic echocardiography, HP was associated with a small heart with reduced EDV, reduced SV despite high EF, and higher arterial elastance.

Background Resting coronary flow velocity (CFV) in the mid‐distal left anterior descending coronary artery can be easily assessed with transthoracic echocardiography. In this observational study, the authors sought to assess the relationship between resting CFV, CFV reserve (CFVR), and outcome in patients with chronic coronary syndromes. Methods and Results In a prospective multicenter study design, the authors retrospectively analyzed 7576 patients (age, 66±11 years; 4312 men) with chronic coronary syndromes and left ventricular ejection fraction ≥50% referred for dipyridamole stress echocardiography. Recruitment (years 2003–2021) involved 7 accredited laboratories, with interobserver variability <10% for CFV measurement at study entry. Baseline peak diastolic CFV was obtained by pulsed‐wave Doppler in the mid‐distal left anterior descending coronary artery. CFVR (abnormal value ≤2.0) was assessed with dipyridamole. All‐cause death was the only end point. The mean CFV of the left anterior descending coronary artery was 31±12 cm/s. The mean CFVR was 2.32±0.60. During a median follow‐up of 5.9±4.3 years, 1121 (15%) patients died. At multivariable analysis, resting CFV ≥32 cm/s was identified by a receiver operating curve as the best cutoff and was independently associated with mortality (hazard ratio [HR], 1.24 [95% CI, 1.10–1.40]; P <0.0001) together with CFVR ≤2.0 (HR, 1.78 [95% CI, 1.57–2.02]; P <0.0001), age, diabetes, history of coronary surgery, and left ventricular ejection fraction. When both CFV and CFVR were considered, the mortality rate was highest in patients with resting CFV ≥32 cm/s and CFVR ≤2.0 and lowest in patients with resting CFV <32 cm/s and CFVR >2.0. Conclusions High resting CFV is associated with worse survival in patients with chronic coronary syndromes and left ventricular ejection fraction ≥50%. The value is independent and additive to CFVR. The combination of high resting CFV and low CFVR is associated with the worst survival.

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&lt;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