Wierzbowska-Drabik, K

Abstract Background Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. Aim To assess the risk stratification value of CI during physical or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods In a prospective, multicenter, international, observational study design, we enrolled 13,445 patients with known or suspected chronic coronary syndromes who underwent stress echo in 19 sites from 10 countries using either exercise (n=2,594), dobutamine (n=2,440), or dipyridamole (n=8,411). Heart rate was automatically measured from the 1-lead ECG in the echo 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 in permanent atrial fibrillation) for dipyridamole. All-cause death was the outcome measure. Results Heart rate reserve was available in all patients; there was no extra imaging or analysis time, and no intra- and inter-observer variability. CI was observed in 5,045 patients (38%); abnormal regional wall motion abnormality in 1,648 (13%). Over a median follow-up time of 3.5 years, there were 2,426 (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 (p<0.0001) increase in 10-year mortality in all age groups ranging from <54 years to >75 years. In addition, it was associated with increased mortality (p<0.0001) irrespective of β-blocker use (Figure). Cox multivariable analysis revealed that CI was a significant predictor of mortality (HR 1.60, 95% confidence interval 1.47-1.74; p<0.0001) together with age, male sex, diabetes mellitus, ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during physical or pharmacological stress is a simple, inexpensive, quantitative, and objective predictor of survival.

Abstract Background The functional significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM) remains unclear. Purpose To assess the systemic and coronary hemodynamic correlates of HP in HCM. Methods 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), end-diastolic volume (EDV), end-systolic volume (ESV), EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). Coronary flow velocity in the mid-distal left anterior descending (LAD) coronary artery was assessed in 325 patients. HP was defined as the highest quartile of the force (> 7.32 mmHg/ml). Results Force was moderately related to EF (r = 0.48, p < 0.0001) and weakly to LVOTG (r = 0.36, p < 0.0001). Compared to non-HP patients, HP showed higher heart rate (72 ± 14 vs 67 ± 14 beats per minute, p <0.0001), lower stroke volume (50 ± 22 vs 67 ± 22 ml, p < 0.0001), larger left atrial volume index (44 ± 16 vs 40 ± 16 ml/m2, p = 0.011) and higher coronary flow velocity in the LAD (n = 325, 41 ± 12 vs 37 ± 14 cm/s, p = 0.021), see Figure. Abnormal B-lines (≥ 2) were present in 11 of the 39 HP compared to 39 of the 271 non-HP patients (28% vs 14 %, p = 0.05). E/e’ ratio was higher in HP (n = 59) vs. non-HP (n = 571) patients (11 ± 5.4 vs 9.6 ± 4.2, p = 0.018). Conclusion In patients with HCM, preserved EF, and no history of coronary artery disease, HP identified by resting TTE with supernormal LV force was associated with an unfavorable systemic hemodynamic and coronary flow profile. Compared to non-HP HCM patients, the HP was characterized by reduced stroke volume, impaired diastolic function, and increased resting coronary flow velocity. HP may reflect inefficient myocardial mechanics, with disproportionate energy expenditure mirrored by higher resting coronary flow despite reduced stroke volume generation, ultimately contributing to adverse remodeling and worse prognosisNon-HP vs HP LAVI and coronary LAD flow

Abstract Background Obese patients often exhibit a clustering of cardiovascular risk factors and are frequently referred for noninvasive cardiac imaging. Coronary microvascular dysfunction (CMD) represents an early indicator of cardiovascular disease that can be noninvasively diagnosed using coronary flow velocity reserve (CFVR) measurements obtained during stress echocardiography (SE) in patients without evidence of obstructive coronary artery disease (CAD). Purpose This study aimed to evaluate the prognostic significance of CFVR in overweight and obese patients within a prospective multicenter cohort. Methods 2273 patients (mean age 65 ± 11 years; 51% women) classified as overweight or obese (for definition see Table) were included in 27 sites from 11 countries. All patients had normal left ventricular ejection fraction (EF ≥ 50%), no prior history of CAD, and underwent exercise or pharmacological SE, which was negative for inducible ischemia. CFVR of the left anterior descending coronary artery was assessed, with CMD defined as CFVR >2.0. Patients were divided into two groups based on the presence (Group 1) or absence (Group 2) of CMD. The primary endpoint was overall mortality. Results CMD was identified in 492 patients (22%), with a mean CFVR of 2.3 ± 0.5 across the study population. Group 1 patients (CMD) were older, with a greater prevalence of diabetes and metabolic syndrome compared to group 2 (no CMD) (Table). During a median follow-up period of 2.1 years (IQR: 1.2-3.7 years), 103 patients (5%) died. Patients with CMD had significantly worse late survival compared to those without CMD (3-year survival: 96 ± 1% vs. 96 ± 1%, p=ns; 6-year survival: 79 ± 4% vs. 93 ± 1%, p < 0.0001): see Figure. Multivariate analysis adjusting for age, sex, EF, body mass index, smoking habits, diabetes, dyslipidemia, arterial hypertension, and type of stress confirmed CMD as an independent predictor of mortality (hazard ratio: 1.8 [95% CI: 1.1–2.8], p = 0.01). Conclusions CMD, assessed via CFVR during SE, was a robust and independent prognostic marker of long-term mortality in obese patients with preserved EF and no evidence of inducible ischemia. These findings underscore the pivotal role of noninvasive assessment of CMD in refining risk stratification and guiding clinical decision-making in this high-risk population.

Abstract Background The presence of the significant left ventricular outflow tract gradient (LVOTG) changes clinical symptoms, prognosis and treatment in hypertrophic cardiomyopathy enabling the classification into its obstructive (HOCM) and non-obstructive form (non-HOCM). However, the more detailed functional characteristics and comparison of these forms remains poorly known. Purpose To compare the demographic, clinical and echocardiographic features between non-HOCM (defined as LVOTG < 30 mmHg) and HOCM patients enrolled into multi-centred study in years 1996-2024 as well as to analyse their long –term prognosis in relation to registered LVOTG. Methods 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 centers, nevertheless quantitative assessment of LVOTG was available in 1252 patients. Survival analysis was performed in a subset of 1200 patients with follow-up information. Beyond standard TTE, the number of B-lines, the maximal diastolic velocity of coronary flow in left anterior descending artery (LAD) as well as left ventricular force defined as the ratio of systolic blood pressure plus LVOTG divided by left ventricular end-systolic volume was assessed with specification of hypercontractile phenotype (HP) as the highest force quartile. Additionally age and sex matched control group was included. Results Compared to non-HOCM patients, HOCM showed a bit higher body mass index (27 ± 4 vs 26 ± 4 kg/m2, p = 0.001), were often burdened with diabetes and hypertension, presented more advanced NYHA class and higher risk of SCD, see Table. In the echocardiographic assessment HOCM presented lower end-systolic left ventricular volume (LV ESV: 27 ± 14 vs 29 ± 13 ml, p = 0.014) although maintained equal stroke volume and even higher ejection fraction (EF: 69 ± 8% vs 67 ± 7%, p < 0.001), cardiac output (CO: 4.3 ± 1.7 vs 4.0 ± 1.4 l/min, p < 0.001) and force in comparison to counterparts without LVOTG. This high-contractility performance was however sustained at the cost of larger left atrium volume index (LAVI: 49 ± 19 vs 40 ± 15 ml/m2, p < 0.001), higher coronary flow velocity (43 ± 12 vs 27 ± 13 cm/s, p < 0.001) as well as more frequent B-lines in the lung assessment. During a median follow-up of 87 months (interquartile range 45 – 143 months), 131 all-cause deaths occurred and not only patients with HOCM but also those with HP showed the worse long-term survival, see Figure. Conclusion HOCM remains the form of HCM burdened with more overt clinical symptoms, signs and prognosis. On the other hand LVOTG seems to be important but not always necessary element of this presentation, which seems to be related even more tightly to general hypercontractility phenotype reflected by higher force and resting coronary flow.Table.Non-HOCM vs HOCM comparison Figure.Force and LVOTG prognostic value

Abstract Background Hypercontractile phenotype of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS), but its clinical recognition remains elusive. Purpose To assess the clinical variables associated with the hypercontractile phenotype of the LV, identified with supernormal values of an index of LV contractility such as LV force, also known as ventricular elastance. Methods In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65± 11.1 years, 2974 males, 58%) with CCS referred for resting transthoracic echocardiography with technically successful volumetric echocardiography in 17 accredited laboratories. We measured systolic blood pressure (SBP) with a cuff sphygmomanometer. We assessed semi-quantitatively wall motion score index (WMSI), and quantitatively LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and cardiac output (CO = SV*heart rate).Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Odds ratios (ORs) with the corresponding 95% confidence interval (CI) were estimated. Results For all the studied patients, EF was 59±11%. Force was 4.51±2.11 mmHg/ml, with reference sextile = 3.50-4.26 mmHg/ml, lowest sextile (Group 1) <2.60 mmHg/ml and highest sextile (Group 6) > 6.36 mmHg/ml. The correlation between the log of EF and the log of Force was significant with linear regression (r = 0.73, p < 0.001). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC (Table). By multivariable logistic regression model, the highest sextile of force was associated with age > 71 years (OR 4.35, 95% CI 3.06-6.18, p < 0.001), female sex (OR 4.48, 95% CI 3.62-5.54, p < 0.001), absence of beta-blocker therapy (OR 1.56, 95% CI 1.27-1.91), rest SBP> 159 mmHg (OR 6.86, 95% CI 5.03-9.35, p < 0.001), high heart rate (OR 1.03, 95% CI 1.02-1.04, p < 0.001), absence of prior MI (OR 1.31, 95% CI 1-1.72, p = 0.049), and higher LV EF at rest (OR 1.24, 95% CI 1.22-1.26, p < 0.001). Conclusions A hypercontractile phenotype of the LV with high force is associated with a small heart, reduced SV, and higher arterial elastance. It was clinically associated with advanced age, female sex, history of hypertension, absence of beta-blocker therapy, and high resting SBP.

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 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