Stress Echocardiography Research Articles

Coronary and Extra-coronary Subclinical Atherosclerosis to Guide Lipid-Lowering Therapy.

To discuss and review the technical considerations, fundamentals, and guideline-based indications for coronary artery calcium scoring, and the use of other non-invasive imaging modalities, such as extra-coronary calcification in cardiovascular risk prediction. The most robust evidence for the use of CAC scoring is in select individuals, 40-75 years of age, at borderline to intermediate 10-year ASCVD risk. Recent US recommendations support the use of CAC scoring in varying clinical scenarios. First, in adults with very high CAC scores (CAC ≥ 1000), the use of high-intensity statin therapy and, if necessary, guideline-based add-on LDL-C lowering therapies (ezetimibe, PCSK9-inhibitors) to achieve a ≥ 50% reduction in LDL-C and optimally an LDL-C < 70 mg/dL is recommended. In patients with a CAC score ≥ 100 at low risk of bleeding, the benefits of aspirin use may outweigh the risk of bleeding. Other applications of CAC scoring include risk estimation on non-contrast CT scans of the chest, risk prediction in younger patients (< 40 years of age), its value as a gatekeeper for the decision to perform nuclear stress testing, and to aid in risk stratification in patients presenting with low-risk chest pain. There is a correlation between extra-coronary calcification (e.g., breast arterial calcification, aortic calcification, and aortic valve calcification) and incident ASCVD events. However, its role in informing lipid management remains unclear. Identification of coronary calcium in selected patients is the single best non-invasive imaging modality to identify future ASCVD risk and inform lipid-lowering therapy decision-making.

Completion of Recommended Tests and Referrals in Telehealth vs In-Person Visits

Use of telehealth has increased substantially in recent years. However, little is known about whether the likelihood of completing recommended tests and specialty referrals-termed diagnostic loop closure-is associated with visit modality. To examine the prevalence of diagnostic loop closure for tests and referrals ordered at telehealth visits vs in-person visits and identify associated factors. In a retrospective cohort study, all patient visits from March 1, 2020, to December 31, 2021, at 1 large urban hospital-based primary care practice and 1 affiliated community health center in Boston, Massachusetts, were evaluated. Prevalence of diagnostic loop closure for (1) colonoscopy referrals (screening and diagnostic), (2) dermatology referrals for suspicious skin lesions, and (3) cardiac stress tests. The study included test and referral orders for 4133 patients (mean [SD] age, 59.3 [11.7] years; 2163 [52.3%] women; 203 [4.9%] Asian, 1146 [27.7%] Black, 2362 [57.1%] White, and 422 [10.2%] unknown or other race). A total of 1151 of the 4133 orders (27.8%) were placed during a telehealth visit. Of the telehealth orders, 42.6% were completed within the designated time frame vs 58.4% of those ordered during in-person visits and 57.4% of those ordered without a visit. In an adjusted analysis, patients with telehealth visits were less likely to close the loop for all test types compared with those with in-person visits (odds ratio, 0.55; 95% CI, 0.47-0.64). The findings of this study suggest that rates of loop closure were low for all test types across all visit modalities but worse for telehealth. Failure to close diagnostic loops presents a patient safety challenge in primary care that may be of particular concern during telehealth encounters.

Comparing Costs of Noninvasive Cardiac Diagnostic Tests—a Population-Based Study

Noninvasive cardiac diagnostic tests (NITs) for the diagnosis of coronary artery disease have been estimated to cost >$3 billion annually in the United States alone and have recently undergone scrutiny over concerns of overuse. Consequently, comparing costs of different NIT testing strategies is of urgent importance to health care planning. We utilized population-based administrative and clinical data from Ontario, Canada, to compare downstream costs between 4 available NIT testing strategies (graded exercise stress testing [GXT], stress echocardiography, cardiac computed tomography angiography [CCTA], and myocardial perfusion imaging [MPI] as well as no testing), among patients evaluated for chest pain. To compare costs among the tested (overall and by testing strategy) and nontested groups, we used a log-gamma generalized linear model to account for the skewed distribution of health care cost data, adjusting for relevant clinical covariates. A total of 2,340,699 patients were included in our cohort, of whom 481,170 (21%) patients received 1 of the 4 NITs. Among patients who received a NIT, 254,492 (53%) received a GXT as their initial test, 154,137 (32%) received MPI, 69,160 (14%) received a stress echo, and 3,381 (<1%) received a CCTA. After adjustment for differences in baseline patient characteristics, receipt of any NIT was associated with an approximate 12% reduction in downstream 1-year mean costs (cost ratio= 0.88; 95% CI, 0.87, 0.89) compared with those without any testing. Comparing the different testing strategies with no testing, both GXT (cost ratio= 0.80; 95% CI, 0.79-0.81) and stress echocardiography (cost ratio= 0.82; 95% CI, 0.81-0.83) were associated with the lower downstream costs, while both MPI (cost ratio= 1.26; 95% CI, 1.25, 1.27) and CCTA (cost ratio= 1.29; 95% CI, 1.23, 1.35) were associated with higher downstream costs. In a large population-based cohort consisting of >2 million people evaluated for chest pain, we report that receipt of noninvasive testing was associated with a 12% reduction in downstream costs when compared with no testing. Graded exercise stress testing and stress echocardiography were associated with the least downstream costs, whereas CCTA and MPI were associated with higher costs when compared with no testing. These findings may help inform testing decisions in chest pain patients.

Primary mitral regurgitation: Toward a better quantification on left ventricular consequences.

Left ventricular end-systolic diameter (LVESD) and ejection fraction (LVEF) are the parameters to look for when discussing repair in asymptomatic patients with a primary mitral regurgitation (PMR). Loading conditions are altering LV-function quantification. LV-myocardial work (LVMW) is a method based on pressure-strain loops. We sought to evaluate the additive value of the LVMW for predicting clinical events in patients with PMR. 103 patients (66% men, median age 57 years) with asymptomatic severe PMR were explored at rest and during an exercise stress echocardiography. LV myocardial global work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were measured with speckle-tracking echocardiography at rest and low workload. The indication for surgery was based on the heart teams' decision. The median follow-up was 670 days. Clinical events occurred for 50 patients (48.5%) with a median of event-free survival distribution of 289 days. Systolic pulmonary artery pressure (sPAP) at rest was 32.61 ± 8.56 mmHg and did not predict the risk of event like LVEF and LVESD. Changes in, GLS (hazard ratio [HR] 0.55; 95% confidence interval (Cl): 0.36-0.83; p = .005), GWI (HR 1.01; 95% Cl: 1.00-1.02; p = .002) and GCW (HR 1.85; 95% Cl: 1.28-2.68; p = .001) in addition to Left Atrial Volume Index (HR 1.73; 95% CI: 1.28 - 2.33; p < 0,001) were independent predictors of events. Changes in myocardial work indices related to low-dose exercise are relevant to best predict PMR patient prognosis It might help to better select patient's candidate for "early-surgery."

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&amp;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

Typical and atypical chest pain: an equivocal and dangerous definition

Abstract Background The traditional classification of stable chest pain into typical, atypical and non anginal1 is equivocal and can lead to doctor's decisions and patient's perception that do not correspond to the real importance of the clinical picture. Methods In the last 15 years, 3,588 outpatients, aged &amp;gt;35 years (mean 64±9, female 55%) were evaluated for stable chest pain reported for more than 48 hours. We excluded 290 patients with a history of myocardial infarction or angina pectoris, heart failure, valve diseases or any other major cardiovascular event, or ECG signs of recent ischemia. In the other 3,298 cases we applied the traditional classification of chest pain. All patients were evaluated for the presence of HEART score risk factors² (smoking, obesity, family history of cardiovascular events, hypertension, diabetes, hypercholesterolemia) as well as age. All patients with typical or atypical angina and those with non-anginal pain according to the physician's judgment were evaluated with one or more functional cardiovascular tests (exertion test, nuclear stress tests, stress echo).A follow-up was performed at 6 months and 1 year, for the detection of major cardiovascular events (cardiovascular death, non-fatal heart attack, revascularization, stroke) and non-cardiovascular mortality. Results Table 1 shows the results of chest pain classification and positive functional test. Table 2 shows major events at one year of follow-up stratified according to the initial assessment of chest pain. Table 3 stratifies the events according to the extent of the risk factors and age. It is evident that a positive functional test is also present in 10% of patients with atypical pain and in 4% of those with non-anginal pain. Patients with typical pain undergo revascularization more frequently (39%). The peculiarity of our study is that the prognosis and rate of events do not differ in terms of clinical and ischemic burden among the 3 groups at 1 year of follow-up, except when patients are stratified by risk burden and for age (Table 4). About 1% of patients had a clinical event regardless of the type of pain and the presence of ischemia and 87% of the events involved patients with ≥ 3 risk factors or heavy smokers. Nine percent of all heavy smokers aged &amp;lt;65 years had a major event and are the highest risk group with a peak of 12.5% in those with atypical pain. Conclusions The traditional classification of stable chest pain should be abandoned, as it does not correlate with actual disease burden and prognosis, that appears to be linked to the burden of cardiovascular risk and above all to smoking in patients &amp;lt; 65 years of age, rather than to the clinical and ischemic burden. It will be necessary to evaluate whether the anatomical burden for the search of high-risk coronary lesions improves the prognosis with added value with respect to the treatment of risk factors³.Picture 1Picture 2

Even the presence of minimal changes in regional wall motion abnormalities with exercise stress echocardiography predicts MACE and all-cause mortality in patients with previous chest radiotherapy

Abstract Background Exercise stress echocardiography (ESE) is a non-invasive, radiation-free, and widely available technique that has demonstrated a reliable accuracy for the detection of coronary artery disease (CAD). Chest radiotherapy (RT) is associated with accelerated age-related atherosclerosis and fibrosis in a dose-dependent manner. ESE plays a role as a screening tool of RT induced heart disease, however, the prognostic value of changes in regional wall motion abnormalities in this population during ESE has not been evaluated. Methods This is a retrospective cohort study of breast cancer survivors treated with adjuvant RT that underwent ESE from 2000-2020 after treatment completion. Outcomes evaluated were: major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, revascularization and stroke); and all-cause mortality. A univariate analysis was performed to characterize the population. Continuous variables were presented as means ± standard deviation (SD) or median with quartile 1 and 3 (Q1, Q3), and categorical variables as numbers and percentages. A Cox regression model adjusted by age and cardiovascular risk factors was used to evaluate variables associated with outcomes, and a time to first event approach was used. A p-value of &amp;lt;0.05 was considered statistically significant. Results From 2000-2020, 507 patients, with a mean age 66 ± 10 years, underwent ESE at a median of 5.8 years after RT completion. The most prevalent comorbidities were dyslipidemia (59%), HTN (55%) and obesity (37%). 55% underwent RT for left-sided breast cancer and 45% for right-sided, and median RT dose was 6000 cGy. Baseline characteristics are presented in Table 1. Most patients underwent Bruce Protocol (92%). Patients exercised a mean time of 6.6 minutes achieving 7.3 METS and 109% of functional aerobic capacity (Table 2). At a median follow up of 7.8 years, 61 MACE events occurred. Predictors of MACE were double product, baseline and stress EF, baseline and peak regional wall motion abnormalities (RWMA), development of new ischemic RWMA, inability to reach 85% of maximum HR, and an abnormal EF response with stress after adjusting for age, HTN, DM, smoking history, dyslipidemia, obesity, prior MI and cancer staging (Fig 1). Predictors of all-cause mortality were METS, LV mass index, baseline and peak RWMA, development of new ischemic RWMA and an abnormal EF change with stress even after adjusting for variables described previously (Fig 2). Conclusions The development of new or worsening RWMA of just 2 segments with stress, was a significant predictor of MACE and all-cause mortality in a large cohort of breast cancer survivors undergoing multidisciplinary management including adjuvant RT. Special emphasis on management of cardiovascular comorbidities and closer surveillance are recommended for these patients.

Is dobutamine stress echocardiography a good screening tool for coronary artery disease in breast cancer patients that underwent treatment with radiotherapy?

Abstract INTRODUCTION Accelerated atherosclerosis has been described in breast cancer patients receiving cardiac exposure from adjuvant radiotherapy (RT). As a result of multidisciplinary care, breast cancer cure rates have improved in recent decades. Therefore, evaluating radiation-induced heart disease (RIHD), especially coronary artery disease (CAD), is essential. The 2022 cardio-oncology European Society of Cardiology (ESC) guidelines recommend screening patients 5 to 10 years after RT for CAD according to cardiovascular risk factors. This screening is generally recommended with exercise stress echocardiography since it can assess the physiological functional performance. Until now, it is unknown if dobutamine stress echocardiography (DSE) is an equal screening tool and if it can predict major adverse cardiovascular events (MACE) (myocardial infarction, stroke, cardiac death, revascularization). PURPOSE Evaluate if DSE is an adequate tool to stratify and predict MACE in post-radiotherapy patients. Methods A retrospective, descriptive cohort study was conducted. Patients who had chest RT for breast cancer and underwent DSE from 2000 to 2022 were included. A bivariate analysis, including Kruskal Wallis and Pearson Chi-Squared test, was done to identify variables associated with a positive DSE. A multivariable Cox Model for MACE and a time-to-event curve for MACE were also performed. Results We identified 163 patients that underwent DSE after a median time of 5.8 years from the end of RT. The median age was 74 years, 98.2% were female, 50% had left and 45% right breast cancer, 81% had hypertension, 41% diabetes mellitus, 71% dyslipidemia, 34% were smokers, and 19% had a prior myocardial infarction. The average dose of photon RT to the chest was 55Gy in the cohort, and 40% received chemotherapy before RT. Patients were divided into two groups: positive and negative DSE. A positive DSE was seen in 19.6%. The median (Q1, Q3) regional wall motion abnormalities (RWMA) of patients with a positive DSE was 1 (1, 1.015) at baseline and 1.280 (1.190, 1.520) at peak stress, and for a negative DSE, was 1 (1, 1) at baseline and peak stress. 88.2% of negative DSE and 87.5% of positive DSE achieved the target heart rate of 85%. HTN, dyslipidemia, and prior MI were significantly associated with a positive DSE (p &amp;lt;0.023). The cumulative incidence of MACE was higher in the group of positive DSE (p&amp;lt;0.001), even after adjusting for hypertension, diabetes mellitus, dyslipidemia, smoking, and prior myocardial infarction, with a hazard ratio of 2.500 (1.51 – 4.13) and a p&amp;lt; 0.001. Similar results were observed regardless of RT laterality. Conclusions In breast cancer survivors that received adjuvant radiotherapy as part of multidisciplinary care, a positive DSE was an independent predictor of MACE compared to a negative result. These results support the usefulness of dobutamine stress echocardiography as a screening tool in breast cancer survivors.Kaplan-Meier Curve for MACE

Dobutamine stress echocardiography in low-gradient aortic stenosis

Abstract Background Dobutamine stress echocardiography (DSE) is recommended to distinguish between true-severe and pseudo-severe aortic stenosis (AS) in patients with low flow low-gradients and left ventricular ejection fraction (LVEF) &amp;lt;50%. However, DSE has mostly been tested in the setting of LVEF&amp;lt;35%. Purpose The purpose of this study was to examine the diagnostic accuracy of DSE according to aortic valve calcification (AVC) score, in patents with low-flow, low-gradient AS across a wide range of LVEF. Methods Patients with aortic mean gradient &amp;lt;40 mmHg, aortic valve area (AVA) &amp;lt;1.0 cm2, and stroke volume index (SVi) ≤35 mL/m2 undergoing DSE were identified from three prospectively collected patient cohorts, and stratified according to LVEF; &amp;lt;35%, 35-50% and &amp;gt;50%. Severe AS was defined as AVC score ≥2000 AU among men, and ≥1200 AU for women. Recommendation for severe AS according to DSE, are an AVA &amp;lt;1.0 cm2 combined with an aortic mean gradient ≥40 mmHg or peak velocity ≥4 m/s. Receiver operating characteristic curves for DSE-derived AVA, mean gradient and Vmax were used to identify optimal cut-off points for each LVEF subgroup. Results Of the 221 patients included in the study, 78 (35%) presented with LVEF &amp;lt;35%, 67 (30%) with LVEF 35-50%, and 76 (34%) with LVEF &amp;gt;50%. Baseline characteristics are presented in the table. Based on AVC, severe AS was present in 102 (46%) of patients. Using recommended thresholds for severe AS for AVC and DSE, led to a sensitivity of 49%, a specificity of 84% and an accuracy of 67% for DSE for all patients with LVEF &amp;lt;50%, but with significant heterogeneity between groups figure. AVA performed rather uniformly across LVEF subgroups; (AUC =0.68 vs 0.62 vs 0.54, p=0.36) LVEF&amp;lt;35%, LVEF 35-50%, LVEF&amp;gt;50% respectively and displayed a rather uniform optimal cut-off (1.0 cm2 vs 0.9 cm2 vs 0.8 cm2). However, mean gradient and Vmax during DSE, both showed significantly diagnostic heterogeneity across LVEF groups (AUC= 0.90 vs 0.67 vs 0.65, p=&amp;lt;0.001 and AUC= 0.90 vs 0.66 vs 0.60, p=&amp;lt;0.001) with different optimal thresholds (30 mmHg &amp; 3.8 m/s, 45 mmHg &amp; 4.3 m/s and 37mmHg &amp; 4 m/s, LVEF&amp;lt;35%, LVEF 35-50%, LVEF&amp;gt;50%, respectively). Conclusion Our study shows, that the association between DSE gradients and AS severity assessed by AVC demonstrates important heterogeneity depending on LVEF. While DSE had the highest accuracy in patients with LVEF&amp;lt;35% both patients with LVEF 35-50%, and patients with LVEF&amp;gt;50% showed significantly less concordance between DSE and AVC.

Left atrial dysfunction during stress in patients with atrial fibrillation

Abstract Background Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS). Objective This study sought to assess LA function at rest and during stress across the spectrum of AF. Methods In a prospective, multicentric, observational study design, we studied a cohort of 2391 patients (age=67±12 years; 1459, 61% male): 2142 (89.6%) were in sinus rhythm (SR, Group 1), 165 (6.9%) had a history of paroxysmal AF (Group 2) and 84 (3.5%) were in permanent AF (Group 3). All patients were referred for CCS and underwent stress echocardiography (SE) with exercise (n=1092, 45.3%), dobutamine (n=320, 13.4%) or vasodilators (n= 989, 40.3%: dipyridamole n=963 and adenosine n=26). Left atrial volume index (LAVI) and LA reservoir strain (LASr) were assessed at rest and peak stress. Analysis with different vendors was performed offline on anonymized cine-loops by observers unaware of the study hypothesis. Results The progressive increase in LA dysfunction from Group 1 to 3 was accompanied by greater signs of pulmonary congestion and LV dysfunction (see Table 1). In particular, LASr progressively decreased from Group 1 to 3, both at rest and during stress, regardless of the stress employed (see Figure 1). Conclusions LA reservoir function can be easily assessed with deformation imaging at rest and during exercise or pharmacological stress echocardiography. LA dysfunction progressively increases from SR to paroxysmal to permanent AF and is associated with more important LV systolic dysfunction, LV filling pressure, and pulmonary congestion in CCS.Table 1.Echocardiographic parametersFigure 1.LAVI and LASr at rest and peak

Exercise gas exchange and echo-derived analysis in HFpEF based on patterns of oxygen peripheral utilization

Abstract Background Exercise limitation is a key signature of heart failure with preserved ejection fraction (HFpEF) syndrome evolution with studies highlighting a significant cardiac reserve limitation and others identifying a predominant limit in the peripheral VO2 kinetics and utilization. Aims To clarify the cardiopulmonary and hemodynamic response in HFpEF according to the high or low peripheral O2 utilization patterns during maximal exercise. Materials and Method 38 patients with a HFpEF diagnosis based on the ESC HFpEFF criteria underwent cardiopulmonary exercise test (CPET) combined with stress echocardiography. Patients were divided in two groups according to the median peak c(A-V) O2 difference (Group 1: &amp;lt; 11 mL/dL and Group 2: &amp;gt; 11 mL/dL). Cardiac output (CO) was calculated by echocardiography according to the formula LVOT velocity integral x LVOT area. Data were obtained after a familiarization CPET session. Results Group 1 and 2 presented similar rest demographic, left and right hemodynamic data (table). The relationship between CO and c (A-V) O2 in terms of VO2 isopleths at peak exercise were not related to any difference in CO (figure) Conclusions In HFpEF, an impairment in O2 utilization during exercise appears independent of the cardiac reserve response (similar peak CO increase) but rather peripheral mechanisms implicated in O2 diffusion/release seem to play a dominant role, emerging as selective therapeutic targets for improving functional capacity and symptoms.

High resting coronary flow velocity and reduced coronary flow velocity reserve independently predict worse survival in diabetic patients without inducible ischemia and normal left ventricular function

Abstract Background High resting coronary flow velocity (CFV) in the mid-distal left anterior descending coronary artery (LAD) can be easily assessed with transthoracic echocardiography (TTE) and is a predictor of worse survival. Purpose In this study, we sought to assess the relationship between resting CFV, coronary flow velocity reserve (CFVR), and outcome in patients without inducible regional wall motion abnormality during stress echo (SE). Methods In a prospective multicenter study design, we enrolled 6,887 patients (age 65±11 years, 3,838 men, 1,963 diabetics), with left ventricular ejection fraction (LVEF) ≥50% referred for SE. Recruitment (years 2004-2022) involved 7 accredited laboratories, with inter-observer variability &amp;lt;10% for CFV measurement at study entry. Baseline peak diastolic CFV (abnormal value &amp;gt;32 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. Coronary flow velocity reserve (CFVR, abnormal value ≤2.0) was assessed with dipyridamole. All-cause death was the only end-point. Results The mean CFV of LAD was 30±11 cm/s. The mean CFVR was 2.37±0.58. During a median follow-up of 6.0±4.2, 1,015 (15%) patients died. At Cox analysis, resting CFV &amp;gt;32 cm/s independently predicted mortality together with CFVR &amp;lt;2, age, diabetes, previous myocardial infarction, history of coronary surgery and LVEF. Resting CFV allowed effective risk stratification either in diabetics and nondiabetics although the difference in survival based on resting CFV was more marked in the former (Figure). In addition, it added significant (p&amp;lt;0.0001) prognostic information to CFVR result in the diabetic, but not in the non-diabetic population (Figure). Conclusion High resting CFV with TTE in mid-distal LAD predicts worse survival in patients without inducible ischemia. The value is independent and additive to CFVR in diabetic patients. The combination of high resting CFV-low CFVR is associated with worse survival.

Biventricular dysfunction and lung congestion in post-COVID patients: a speckle tracking and stress lung echocardiography analysis

Abstract Background Cardiovascular abnormalities have been observed in half of all COVID-19 patients in the acute phase of the infection. Additionally, 10-35% of these patients have various long-term symptoms diagnosed with post-acute sequelae of COVID-19 (PASC). Aim of this study was to evaluate the role of exercise stress echocardiography (ESE) with an integrated approach, inclusive of Speckle-Tracking Echocardiography (STE) with Myocardial Work (MW) analysis in the evaluation of patients after COVID infection. Methods We prospectively recruited a population of 370 post-COVID 19 patients (Group 1) (225 males; 55.8 ±8.3 years), and of 250 age- and sex-comparable healthy controls (Group 2). In Standard Doppler echocardiography, STE and MW analyses and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Results Left ventricular (LV) wall thickness, diameters and mass index were comparable between the two groups. Both LV ejection fraction (EF) and right ventricular (RV) functional indexes (TAPSE and Tissue Doppler S’ wave) at rest did not show differences between the two groups. Conversely, baseline LV GLS (-16.2±2.8 vs. –20.4±3.3 %; p&amp;lt;0.01), MW efficiency (88.8±3.2 vs. 93.2±3.3 %; p&amp;lt;0.001), and RV strain (-16.4±2.8 vs. –20.4±4.3 %; p&amp;lt;0.01), were significantly reduced in Group 1. Also pulmonary artery systolic pressures (PASP) (33.5±3.8 vs. 24.6±3.1 mmHg; p&amp;lt;0.001), and LV E/e’ ratio were significantly increased in COVID group, while B-lines ( ≥ 2) at rest were found in 25.3% of Group 1 and 5.1% of Group 2 (p &amp;lt; 0.001). During effort, COVID patients showed reduced exercise time and exercise capacity (&amp;lt;0.001). Values of LVEF, RV strain and LV GLS (all with p value &amp;lt;0.01) and MWE (p&amp;lt;0001) were much lower in COVID patients when compared to Group 2. Additionally, COVID patients showed at peak effort an increased LV E/e’ ratio, pulmonary pressures and B-lines by lung ultrasound (all p &amp;lt;0.001). Multivariable analysis detected independent associations of baseline GLS and MWE with maximal workload (watts reached), LV E/e’ ratio and B-lines during effort (p&amp;lt;0.001), stronger than the association of LVEF with the same functional parameters (p&amp;lt;0.01). What’s more, RV strain (p&amp;lt;0.001) was significantly associated with PASP levels at peak effort. Conclusions In post-COVID patients, biventricular involvement with impairment of LV and RV systolic function is frequent, missed by conventional indices such as EF or TAPSE, and detected by more sensitive STE indices such as LV-GLS, ME, and RV-strain. These alterations are functionally significant and associated with shorter exercise -time, more pulmonary hypertension, and greater pulmonary congestion during stress.

Coronary flow velocity reserve during exercise stress echocardiography in hypertrophic cardiomyopathy

Abstract Background Coronary flow velocity reserve (CFVR) can be assessed with transthoracic echocardiography (TTE) as the stress/rest ratio of coronary flow velocity (CFV). Reduced CFVR during vasodilator stress (adenosine or dipyridamole) is a powerful predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the feasibility and correlates of CFVR during the more physiological - and recommended - exercise stress echocardiography (ESE) is unresolved. Aim To assess the feasibility and functional correlates of CFVR during exercise in HCM. Methods We studied 56 HCM patients (age=49±13 years, 33 [59%] males) and 44 age- and sex-matched healthy subjects with symptom-limited semi-supine ESE. ESE assessment included CFVR (stress/rest diastolic CFV) in the mid-distal left anterior descending coronary artery, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate reserve (HRR, peak/rest heart rate). Results CFVR was feasible in 46/56 HCM patients and in 41/44 controls (82% vs 93%, p=0.138). Median CFVR was significantly lower in patients with HCM compared to controls (1.72 [1.48; 2.10] vs 2.57 [2.25; 3.30], p&amp;lt;0.001), see Figure 1. In HCM patients, among resting parameters, CFVR was inversely correlated with left ventricular maximal septal thickness (r= -0.308, p=0.038), end-systolic diameter (r= -0.393, p=0.007), resting DBP (r= -0.398, p=0.006) and resting SBP (r= -0.321, p=0.030), while in controls CFVR correlated only with resting DBP (r= -0.322, p=0.040). During exercise, HCM patients with lower CFVR (&amp;lt;1.72, i.e. 1.72) showed lower peak CFV (78±20 vs 96±24 cm/s, p=0.003) and lower HRR (1.55±0.29 vs 1.76±0.25, p=0.020), see Figure 2. Exercise duration, peak stress workload or metabolic equivalents were not related to CFVR. In multivariable analysis, resting CFV (b=-0.034, 95% CI -0.037 and -0.030, p&amp;lt;0.001), resting DBP (b=-0.003, 95% CI -0.005 and -0.001, p=0.020), peak stress CFV (b=0.019, 95% CI 0.017 and 0.021, p&amp;lt;0.001) and HRR (b=0.126, 95% CI 0.005 and 0.247, p=0.041) were independently associated with CFVR. Conclusion CFVR assessment by TTE in the left anterior descending coronary artery is feasible during semi-supine exercise in most HCM patients. CFVR is markedly reduced in HCM patients on effort, particularly in the presence of high resting CFV and low HRR.Figure 1Figure 2

Randomized study for the optimal treatment of symptomatic patients with low gradient severe aortic valve stenosis and preserved left ventricular ejection fraction (ROTAS trial)

Abstract Background the best management of symptomatic patients with low gradient (LG) severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) has not been established in randomized controlled trials. The ROTAS trial aimed to assess the superiority of aortic valve replacement (AVR) versus optimized medical therapy (OMT) in symptomatic patients with LG severe AS and preserved LVEF. Methods and Results Fifty-two patients (age 79±7 years; males 46%, mean aortic gradient: 31±5 mmHg; aortic surface: 0.8±0.1 cm², LVEF 61±8%) were randomized 1:1 to AVR or OMT. The stroke volume index (SVi, cut-off 35 ml/m²) was considered for randomisation so that the same percentage of patients with reduced SVi was present in the two groups. The follow-up lasted 14±7 months. An early interruption of the study occurred in 2021 because of the extremely low inclusion rate during the COVID-2019 pandemic and the large tendency to already implant TAVI in patients with severe LG AS with preserved LVEF. In all patients, a multimodality approach, including dobutamine stress echocardiography and/or aortic calcium score was applied to confirm AS severity. The primary end-point (a composite of overall death and heart failure hospitalisation) occurred in 13 (25%) patients. Patients receiving OMT did not experience worse survival compared to patients receiving AVR (HR=1.57, 95% CI:0.51-4.83, p=0.4275). Kaplan-Meier curves showed similar event-free survival (log-rank p=0.4236) among the 2 groups (Figure 1). Conclusions In the randomized ROTAS trial, AVR was not associated with a better prognosis in symptomatic patients with LG severe AS and preserved LVEF.Figure 1

Exercise-induced pulmonary congestion is a promising marker to diagnose early stage heart failure in patients referred to rule out myocardial ischemia

Abstract Backgrounds Pulmonary congestion assessed by B-lines using lung ultrasound (LUS) is a hallmark of heart failure (HF). Latent HF at rest can be unmasked during exercise but the diagnosis remains challenging. Exercise-induced B-lines could help diagnose HF with preserved left ventricular ejection fraction (LVEF) at an early stage. The patients in whom coronary artery disease is suspected are also at risk of HF. Objectives To assess exercise-induced pulmonary congestion in patients referred to rule out myocardial ischemia. Methods Data of stress echocardiography combined with LUS at rest and immediately after exercise in patients with LVEF≥50% referred for investigation of inducible myocardial ischemia in a tertiary center of cardiology, during a 3-years period of time, were retrospectively analyzed. Patients with induced myocardial ischemia, hypertrophic cardiomyopathy or moderate to severe valvular disease were excluded. B-lines were assessed by scanning 2 chest sites. Exercise-induced pulmonary congestion was defined as an increase of B-lines ≥ 2 between baseline and exercise. Results A total of 1114 patients were included. Mean age was 63±11 years, 54% of patients had hypertension and 27% diabetes. Exercise-induced pulmonary congestion was identified in 131 (12%) patients. Age, left atrial volume index (LAVi), resting and 20W septal E/e’&amp;gt;15 and peak tricuspid regurgitation velocity (TRV) were associated with exercise-induced B-lines. In a multivariate logistic regression analysis, LAVi (Odds ratio (OR) = 1.03; 95%confidence interval (CI): 1.01–1.06; p = 0.003) and peak TRV (OR = 3.8; 95%CI: 1.4–10.1; p = 0.009) were independent predictors of exercise-induced pulmonary congestion. Conclusion Exercise-induced pulmonary congestion could be diagnosed in patients with preserved LVEF referred to rule out inducible myocardial ischemia. Exercise B-lines are linked with left ventricular diastolic dysfunction indices.

Submaximal in addition to peak stress echocardiogram differentiates pathological LV dilatation from physiological dilatation and could help facilitate early heart failure diagnosis

Abstract Background Left ventricular dimensions in athletes overlap with those observed in patients with dilated cardiomyopathy (DCM). Among athletes with concomitant baseline low left ventricular ejection fraction (LVEF), the differentiation between the two entities may be difficult. Purpose We compared the role of changes in left ventricular ejection fraction (LVEF) during submaximal and maximal stress exercise echocardiography to facilitate the differentiation between athlete’s heart and DCM individuals with asymptomatic exercising individuals with a dilated left ventricle (LV) and borderline/low LVEF (48-54%). Methods 47 highly active asymptomatic individuals with DCM and mildly impaired LVEF, 52 athletes with borderline/low LVEF (grey zone athletes) and 44 athletes with a normal EF (healthy athletes) underwent a stress echocardiography on a semi-recumbent bike with an incremental ramp protocol of 25watt/min.Echocardiographic images were obtained at rest, submaximal (80% of predicted heart rate) and maximal exercise. Maximal exercise was classified as a heart rate 90-100% of the calculated maximum heart rate for their age. Results Both grey zone and healthy athletes achieved a greater increase in peak LVEF compared with DCM individuals (20.4% and 20.2% vs 4.6% respectively). The mean increase in LVEF from submaximal exercise to maximal exercise in healthy athletes and grey zone athletes was 7.0% and 3.4% (p&amp;lt;0.001) respectively whereas individuals with DCM showed a mean reduction in LVEF of -4.3% during this period. 8 (17%) of DCM individuals were able to increase LVEF ≥10% from rest to peak exercise, however most (96%) revealed a drop in LVEF as effort progressed from submaximal to maximal exercise.97.7% of control athletes were able to augment an EF ≥10% from rest to maximum exercise and continued to show an increase in LVEF from submaximal to maximal exercise. Whereas 47 (90.4%) grey zone athletes also showed an increase in LVEF &amp;gt;10% from rest to peak exercise, the remaining 5 (9.6%) were unable to augment this response and revealed a drop in contractile reserve from submaximal to maximal exercise, suggesting the possibility of an underlying diagnosis of DCM. Conclusion Healthy athletes and grey zone athletes show a greater contractile reserve compared to DCM athletes during exercise.Over 90% athletes and 10% DCM patients reveal an increase in LVEF &amp;gt;10% from baseline to peak exercise.Comparison of changes in LVEF between submaximal and maximal exercise reveals that 96% DCM patients and 9.6% grey zone athletes show a drop in in LVEF during this period. Failure to augment LVEF between submaximal and maximal exercise may identify grey zone athletes with DCM.

The importance of vasodilator stress echocardiography in predicting all-cause mortality and acute heart failure in hypertrophic cardiomyopathy

Abstract Background Reduced coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) during vasodilator stress echocardiography (VSE) is a marker of poor outcome and is associated with higher baseline coronary flow velocity (CFV) in hypertrophic cardiomyopathy (HCM). However, whether resting CFV has additive predictive value to CFVR during VSE in HCM is unknown. Aim To assess the prognostic value of baseline CFV and CFVR during VSE in HCM. Methods 325 adult HCM patients (age=52+15 years, 147 [45%] females) with preserved left ventricular function and no known coronary artery disease who underwent VSE in 6 certified centers between 1999 and 2021 were prospectively analyzed. VSE modality was adenosine (0.14 mg/kg/min in 2', n=232) or dipyridamole (0.84 mg/kg in 6', n=93). CFVR in the LAD was assessed by transthoracic (n=306) or transoesophageal (n=19) echocardiography. Patients were followed for a median of 67 months (IQ range 31-103 months), the primary endpoint was a composite of all-cause mortality and acute heart failure (HF). Results Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (&amp;gt;31 cm/s, elevated) and CFVR (≤2.0, reduced) to predict the primary endpoint. Patients with reduced CFVR had more frequently elevated baseline CFV (75% vs 49%, p&amp;lt;0.001). Elevated resting CFV was a predictor of composite endpoint at univariable (HR 2.04, 95% CI 11.05-3.97, p=0.035) but not at multivariable analysis. A reduced CFVR was an independent predictor of all-cause mortality (HR 5.50, 95% CI 1.94-15.59, p=0.001), acute HF (HR 5.80, 95% CI 1.60-21.00, p=0.007), and the composite end-point (HR 4.95, 95% CI 2.39-10.25, p&amp;lt;0.001). The 5-year event rate was 6-fold higher in patients with reduced CFVR compared to patients with preserved CFVR (19% vs 3%, p&amp;lt;0.001), with no additional impact of resting CFV (see Figure). Conclusion LAD CFVR ≤2.0 during VSE is a strong and independent predictor of all-cause mortality and acute HF in HCM. Elevated resting CFV is more frequent in patients with reduced CFVR, but has no independent prognostic value when CFVR is considered.Kaplan-Meier event-free survival curves

Dobutamine stress echocardiography remains indispensable for the diagnosis of low-flow low-gradient severe aortic stenosis

Abstract Background In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, current guidelines recommend dobutamine stress echocardiography (DSE) to determine valve stenosis severity. Additionally, aortic valve calcification (AVC) scores are also used with this intent. Previous studies have determined cut-off values of ≥2000AU for men and ≥1200AU for women to distinguish between true severe AS and pseudosevere AS. Purpose To assess the relationship between AVC and DSE in low-flow low-gradient aortic stenosis. Methods We performed a multicenter international registry study including patients that underwent DSE to determine AS severity and multi-slice computed tomography (MSCT) of sufficient quality to determine AVC scores. Severe AS was diagnosed when resting peak aortic valve velocity was ≥4.0 m/s, or stress aortic valve area (AVA) remained &amp;lt;1.0cm2 at peak dobutamine stress levels; moderate AS was diagnosed when resting AVA was ≥1.0cm2 and peak velocity was &amp;lt; 4.0m/s or stress AVA exceeded 1.0cm² at peak stress. Using the previous cut-off values, MSCT-AVC scores were compared to DSE-derived AS diagnoses to determine sensitivity and specificity of AVC, and the positive and negative predictive values of high and low scores. Subsequently, we performed a receiver-operating characteristics (ROC)-curve analysis for men and women separately. Results We included 271 patients from 8 centers, of which 231 patients had sufficiently interpretable DSE and MSCT. Median age was 79 years (Interquartile range (IQR): 71-84), median BMI was 26.4 kg/m2 (IQR: 24.1-30.0) and median BSA was 1.9 m2(IQR: 1.8-2.1). Left ventricular ejection fraction was reduced (&amp;lt;50%) in 209 (90.5%) patients. Bicuspid valve morphology was present in 20 patients (8.7%). DSE confirmed severe AS in 103 patients, 4 of whom already had resting peak aortic valve velocity ≥4.0m/s. Moderate AS was diagnosed in 128 patients, of which 76 had a resting AVA ≥ 1.0cm2. Characteristics of these patients are summarized the table. Of the patients with severe AS, 49 (47.6%) had a high AVC score (≥2000 for men or ≥1200 for women) and of patients with moderate AS, 75 (58.6%) had an AVC score below those cut-off values. This corresponds to a sensitivity of 47.6%, a specificity of 58.4% and positive and negative predictive values of 53.5% and 51.6%, respectively. The ROC-curves are shown in the figure; the area under the curve was 0.55 for men and 0.52 for women, signifying poor discriminative performance. Conclusion In this multicenter international registry we found that aortic valve calcification scores correlated poorly with AS severity and therefore DSE remains the preferred technique to assess borderline AS severity.Table.Patient characteristicsFigure.ROC curve

Abnormal workload-indexed blood pressure response to exercise in patients at risk of or with overt heart failure

Abstract Background Conflicting evidence exists regarding the functional and prognostic significance of hypertensive response to exercise (HRE), commonly defined as peak systolic blood pressure (SBP) &amp;gt;210 mmHg in males and &amp;gt;190 mmHg in females. No study yet has explored the impact of sex-specific, workload-indexed HRE in patients at different stages of the heart failure (HF) spectrum, as defined by the American College of Cardiology/American Heart Association HF staging system. Purpose We evaluated the SBP/Workload slope during exercise across the HF spectrum and investigated the hemodynamic, functional and prognostic correlates of HRE. Methods Fifty-eight healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) were enrolled; among the latter, 143 had preserved (HFpEF) and 226 reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. For each patient, we recorded at least two BP measurements during exercise: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each ACC/AHA HF Stage, we divided patients according to SBP/Workload slope tertiles; HRE was defined as the highest sex-specific SBP/Workload slope tertile. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome. Results The median SBP/Workload slope was 0.53 (interquartile range 0.36-0.72) mmHg/W and was steeper in women than in men in all subgroups (p&amp;lt;0.0001). After adjusting for age and sex, SBP/Workload slope was significantly higher in Stages A-B (0.61, 0.47-0.75 mmHg/W) and HFpEF (0.63, 0.42-0.86 mmHg/W) compared to controls (0.43, 0.35-0.57 mmHg/W) and HFrEF (0.47, 0.30-0.63 mmHg/W, Figure 1). In all subgroups, patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction (Table). After a median follow-up of 16 months, HRE was an independent predictor of adverse outcomes (Hazard Ratio 2.05, 95% confidence interval 1.81-5.18), while rest and peak absolute SBP values did not. Kaplan-Meier analysis confirmed a worse survival probability for patients with HRE in Stages A-B and HFpEF but not in HFrEF. After adjusting for confounding factors, the patients with the highest SBP/Workload slope had a 47% higher risk of the primary outcome than subjects in the lowest tertile (Figure 2). Conclusions Across the HF spectrum, patients with HRE, as evaluated by the SBP/Workload slope, present with peculiar pathophysiological features and impaired functional capacity. This is especially true for those in Stages A-B and patients with HFpEF. In these subgroups, HRE may portend an increased risk of adverse cardiovascular outcomes.SBP/workload slopesKaplan-Meier curves and Hazard Ratios