Comparison of Myocardial Layer-Specific Strain and Global Myocardial Work Efficiency During Treadmill Exercise Stress in Detecting Significant Coronary Artery Disease

BackgroundMyocardial layer-specific strain can identify myocardial ischemia. Global myocardial work efficiency (GWE) based on non-invasive left ventricular (LV) pressure-strain loops is a novel parameter to determine LV function considering afterload. The study aimed to compare the diagnostic value of GWE and myocardial layer-specific strain during treadmill exercise stress testing to detect significant coronary artery disease (CAD) with normal baseline wall motion.MethodsEighty-nine patients who referred for coronary angiography due to suspected of CAD were included. Forty patients with severe coronary artery stenosis were diagnosed with significant CAD, and 49 were defined as non-significant CAD. Stress echocardiography was performed 24 h before angiography. Layer-specific longitudinal strains were assessed from the endocardium, mid-myocardium, and epicardium by 2D speckle-tracking echocardiography. Binary logistic regression analyses were performed to evaluate the association between significant CAD and echocardiographic parameters. A receiver operating characteristic curve was used to assess the capability of layer-specific strain and GWE to diagnose significant CAD.ResultsPatients with significant CAD had the worse function in all three myocardial layers at peak exercise compared with those with non-significant CAD when assessed with global longitudinal strain (GLS). At the peak exercise and recovery periods, GWE was lower in patients with significant CAD than in patients with non-significant CAD. In multivariable binary logistic regression analysis, peak endocardial GLS (OR: 1.35, p = 0.006) and peak GWE (OR: 0.76, p = 0.001) were associated with significant CAD. Receiver operating characteristic curves showed peak GWE to be superior to mid-myocardial, epicardial, and endocardial GLS in identifying significant CAD. Further, adding peak GWE to endocardial GLS could improve diagnostic capabilities.ConclusionsBoth GWE and endocardial GLS contribute to improving the diagnostic performance of exercise stress echocardiography. Furthermore, adding peak GWE to peak endocardial GLS provides incremental diagnostic value during a non-invasive screening of significant CAD before radioactive or invasive examinations.

The H2FPEF and HFA-PEFF algorithms for predicting exercise intolerance and abnormal hemodynamics in heart failure with preserved ejection fraction

Exercise intolerance is a primary manifestation in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with abnormal hemodynamics and a poor quality of life. Two multiparametric scoring systems have been proposed to diagnose HFpEF. This study sought to determine the performance of the H2FPEF and HFA-PEFF scores for predicting exercise capacity and echocardiographic findings of intracardiac pressures during exercise in subjects with dyspnea on exertion referred for bicycle stress echocardiography. In a subset, simultaneous expired gas analysis was performed to measure the peak oxygen consumption (VO2). Patients with HFpEF (n = 83) and controls without HF (n = 104) were enrolled. The H2FPEF score was obtainable for all patients while the HFA-PEFF score could not be calculated for 23 patients (feasibility 88%). Both H2FPEF and HFA-PEFF scores correlated with a higher E/e′ ratio (r = 0.49 and r = 0.46), lower systolic tricuspid annular velocity (r = − 0.44 and = − 0.24), and lower cardiac output (r = − 0.28 and r = − 0.24) during peak exercise. Peak VO2 and exercise duration decreased with an increase in H2FPEF scores (r = − 0.40 and r = − 0.32). The H2FPEF score predicted a reduced aerobic capacity (AUC 0.71, p = 0.0005), but the HFA-PEFF score did not (p = 0.07). These data provide insights into the role of the H2FPEF and HFA-PEFF scores for predicting exercise intolerance and abnormal hemodynamics in patients presenting with exertional dyspnea.

Hypertensive response to exercise in adult patients with repaired aortic coarctation

ObjectiveThe clinical and prognostic implications of a hypertensive response to exercise after repair of coarctation of the aorta (CoA) remain controversial. We aimed to determine the prevalence of a hypertensive response to exercise, identify factors associated with peak exercise systolic blood pressure (SBP) and explore the association of peak exercise SBP with resting blood pressure and cardiovascular events during follow-up.MethodsFrom the Dutch national CONgenital CORvitia (CONCOR) registry, adults with repaired CoA who underwent exercise stress testing were included. A hypertensive response to exercise was defined as a peak exercise SBP ≥210 mm Hg in men and ≥190 mm Hg in women. Cardiovascular events consisted of coronary artery disease, stroke, aortic complications and cardiovascular death.ResultsOf the original cohort of 920 adults with repaired CoA, 675 patients (median age 24 years (range 16–72 years)) underwent exercise stress testing. Of these, 299 patients (44%) had a hypertensive response to exercise. Mean follow-up duration was 10.1 years. Male sex, absence of a bicuspid aortic valve and elevated resting SBP were independently associated with increased peak exercise SBP. Peak exercise SBP was positively predictive of office SBP (β=0.11, p<0.001) and 24-hour SBP (β=0.05, p=0.03) at follow-up, despite correction for baseline SBP. During follow-up, 100 patients (15%) developed at least 1 cardiovascular event. Peak exercise SBP was not significantly associated with the occurrence of cardiovascular events (HR 0.994 (95% CI 0.987 to 1.001), p=0.11).ConclusionsA hypertensive response to exercise was present in nearly half of the patients in this large, prospective cohort of adults with repaired CoA. Risk factors for increased peak exercise SBP were male sex, absence of a bicuspid aortic valve and elevated resting SBP. Increased peak exercise SBP independently predicted hypertension at follow-up. These results support close follow-up of patients with a hypertensive response to exercise to ensure timely diagnosis and treatment of future hypertension.

Sex and age interaction in fundamental circulatory volumetric variables at peak working capacity

Background Whether the fundamental hematological and cardiac variables determining cardiorespiratory fitness and their intrinsic relationships are modulated by major constitutional factors, such as sex and age remains unresolved. Methods Transthoracic echocardiography, central hemodynamics and pulmonary oxygen (O2) uptake were assessed in controlled conditions during submaximal and peak exercise (cycle ergometry) in 85 healthy young (20–44 year) and older (50–77) women and men matched by age-status and moderate-to-vigorous physical activity (MVPA) levels. Main outcomes such as peak left ventricular end-diastolic volume (LVEDVpeak), stroke volume (SVpeak), cardiac output (Qpeak) and O2 uptake (VO2peak), as well as blood volume (BV), BV–LVEDVpeak and LVEDVpeak–SVpeak relationships were determined with established methods. Results All individuals were non-smokers and non-obese, and MVPA levels were similar between sex and age groups (P ≥ 0.140). BV per kg of body weight did not differ between sexes (P ≥ 0.118), but was reduced with older age in men (P = 0.018). Key cardiac parameters normalized by body size (LVEDVpeak, SVpeak, Qpeak) were decreased in women compared with men irrespective of age (P ≤ 0.046). Older age per se curtailed Qpeak (P ≤ 0.022) due to lower heart rate (P < 0.001). In parallel, VO2peak was reduced with older age in both sexes (P < 0.001). The analysis of fundamental circulatory relationships revealed that older women require a higher BV for a given LVEDVpeak than older men (P = 0.024). Conclusions Sex and age interact on the crucial circulatory relationship between total circulating BV and peak cardiac filling, with older women necessitating more BV to fill the exercising heart than age- and physical activity-matched men.

Protective effect of BNT162b2 vaccination on aerobic capacity following mild to moderate SARS-CoV-2 infection: a cross sectional study, Israel, March-December 2021

There is increasing evidence that patients who were infected with SARS-CoV-2 may experience adverse health outcomes months after the acute infection has resolved including reduction in aerobic capacity and fatigue. In this study, we compared aerobic capacity and exercise performance of 28 unvaccinated participants to 15 vaccinated ones who performed a symptom limited cardio-pulmonary exercise test (CPET) after acute COVID-19. We identified a significant difference in aerobic capacity between vaccinated and unvaccinated individuals, with a lower V'O2 peak percentage of predicted in the unvaccinated group. In addition, the unvaccinated group had a reduction in the peak-exercise heart rate and lower ventilation values. Our results suggest objective limitations to exercise capacity in the months following acute COVID19 illness, mitigated by vaccination

Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have been shown to exhibit altered ventilatory characteristics on the second of two progressive maximal cardiopulmonary exercise tests (CPET) performed on consecutive days. However, maximal exercise can exacerbate symptoms for ME/CFS patients and cause significant post-exertional malaise. Assessment of heart rate (HR) parameters known to track post-exertional fatigue may represent more effective physiological markers of the condition and could potentially negate the need for maximal exercise testing. Sixteen ME/CFS patients and 10 healthy controls underwent a sub-maximal warm-up followed by CPET on two consecutive days. Ventilation, ratings of perceived exertion, work rate (WR) and HR parameters were assessed throughout on both days. During sub-maximal warm-up, a time effect was identified for the ratio of low frequency to high frequency power of HR variability (p=0.02) during sub-maximal warm-up, and for HR at ventilatory threshold (p=0.03), with both being higher on Day Two of testing. A significant group (p&lt;0.01) effect was identified for a lower post-exercise HR recovery (HRR) in ME/CFS patients. Receiver operator characteristic curve analysis of HRR revealed an area under the curve of 74.8% (p=0.02) on Day One of testing, with a HRR of 34.5bpm maximising sensitivity (63%) and specificity (40%) suggesting while HRR values are altered in ME/CFS patients, low sensitivity and specificity limit its potential usefulness as a biomarker of the condition.

Quantifying tidal expiratory flow limitation using a vector-based analysis technique

Objective: Tidal expiratory flow limitation (EFLT) is commonly identified by tidal breaths exceeding the forced vital capacity (FVC) loop. This technique, known as the Hyatt method, is limited by the difficulties in defining the FVC and tidal flow-volume (TV) loops. The vector-based analysis (VBA) technique described and piloted in this manuscript identifies and quantifies EFLT as tidal breaths that conform to the contour of the FVC loop. Approach: The FVC and TV loops are interpolated to generate uniformly spaced plots. VBA is performed to determine the smallest vector difference between each point on the FVC and TV curves, termed the flow reserve vector (FRV). From the FVC point yielding the lowest FRV, the tangential angles of the FVC and TV segments are recorded. If the TV and FVC loops become parallel, the difference between the tangential angles tends towards zero. We infer EFLT as parallel TV and FVC segments where the FRV is <0.1 and the tangential angle is within ±18 degrees for ≥5% of TV. EFLT is quantified by the percent of TV loop fulfilling these criteria. We compared the presence and degree of EFLT at rest and during peak exercise using the Hyatt method and our VBA technique in 25 healthy subjects and 20 subjects with moderate-severe airflow obstruction. Main results: Compared to the Hyatt method, our VBA technique reported a significantly lower degree of EFLT in healthy subjects during peak exercise, and in obstructed subjects at rest and during peak exercise. In contrast to the Hyatt method, our VBA technique re-classified five subjects (one in the healthy group and four in the obstructed group) as demonstrating EFLT. Significance: Our VBA technique provides an alternative approach to determine and quantify EFLT which may reduce the overestimation of the degree EFLT and more accurately identify subjects experiencing EFLT.

587 Exercise induced pulmonary hypertension in hypertrophic cardiomyopathy: a combined cardiopulmonary exercise test-echocardiographic study

Aims Pulmonary arterial hypertension (PAH) has been described in patients with hypertrophic cardiomyopathy (HCM) and it was associated with a worse prognosis. Nevertheless in most HCM patients, despite normal pulmonary pressures at rest, congestive symptoms are elicited by exercise. In the present study, combining cardiopulmonary exercise test (CPET) with echocardiography, we aimed to evaluate the presence of exercise-induced pulmonary hypertension (EiPAH) its role in functional limitation and its prognostic significance in a cohort of patients with obstructive and non-obstructive HCM. Methods and results 182 HCM patients (35% females, mean age 47.5 ± 15.9) undergoing CPET. During CPET, LVOT velocities and trans-tricuspid gradient were measured. Thirty-seven patients (20%) developed sPAP &gt; 40 mmHg at peak exercise (EiPAH). EiPAH was associated with an lower exercise performance, larger left atrial volumes, higher left ventricular gradient and higher VE/VCO2 slope .At multivariable model baseline sPAP (P &lt; 0.0001) and baseline left ventricular obstruction (LVOT) (P = 0.028) were significantly associated with EiPAH .Kaplan-Meier curve analysis showed EiPAH was a significant predictor of HCM –related morbidity (hazards ratio: 6.21, 95% CI: 1.47–26.19; P = 0.05; 4.21, 95% CI: 1.94–9.12; P &lt; 0.001) for the primary and the secondary endpoint respectively. Conclusions EiPAH was present in about one fifth of HCM patients without evidence of elevated pulmonary pressures at rest, and was associated with adverse clinical outcome. Diagnosing EiPAH by exercise echo/CPET may help physicians to detect early stage of PAH requiring a closer clinical monitoring and individualized treatment strategies.

138 Exercise haemodynamics in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Aims Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods and results We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise), and the PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-eight studies were identified, providing data for 2230 HFpEF patients and 706 controls. At peak exercise, patients with HFpEF achieved higher PAWP [30 (29–31) vs. 16 (15–17) mmHg, P &lt; 0.001] and mean right atrial pressure (P &lt; 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, body position. However, peak PAWP values were highly heterogeneous among the cohorts, with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls [3.81 (3.24–4.38) vs. 0.91 (0.24–1.58) mmHg/l/min, P &lt; 0.001], even after adjustment for covariates (P = 0.020) (Figure). Conclusions The haemodynamic profile of HFpEF patients is consistent across studies and characterized by a higher left and right filling pressure at rest, magnified by physical exercise. Our analysis strongly suggests that PAWP/CO slope might allow for a more consistent identification of HFpEF, irrespective of body position. This variable likely overcomes the shortcomings of an isolated peak PAWP measurement, allowing for a more univocal identification of HFpEF in patients with unexplained dyspnoea.

678 Safety and clinical role of the exercise testing during pregnancy

Aims The prevalence of arterial hypertension (AH) during pregnancy is ranging from 2% to 10%. Diagnostic criteria are based on rest blood pressure measurements. Exercise testing (ET) is a useful approach to detect latent hypertensive condition and may allow early diagnosis. Despite physical activity is encouraged during pregnancy in order to prevent systemic disorders, ET is not commonly performed during pregnancy due to limited data of safety. The aim of the study is to test the safety of ET during pregnancy and to explore its role in predicting the development of AH. Methods Pregnant women were tested through submaximal ET at Dyspnoea Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milano. The exercise was performed on a stationary cycle on which the power was increased of 15 W every 2 min starting from 5 W (first step). Subjects were continuously monitored during exercise through EKG, non-invasive blood pressure measurements every 2 min and peripheral oxygen saturation. 3 months clinical follow-up was made in order to assess the presence of AH or other pregnancy disorders. U-test analysis was performed in order to verify statistical difference between hypertensive and non-hypertensive women. Heart rate, systolic and diastolic blood pressure (SBP and DBP) were measured at rest, at the first step and at peak of ET and have been considered in analysis. U-test (Mann–Whitney analysis) was adopted to test difference between hypertensive and non-hypertensive group. Women were followed-up at second trimester (22nd–25th week of pregnancy) in order to monitor the clinical condition, the development of AH or any gestational disorders (e.g. diabetes and pre-eclampsia). Results All 73 women (mean age 32 years, gestational age 12–14 weeks) consecutively enrolled have completed the ET. The mean maximum load achieved was 65 W, no abrupt interruption of ET was needed because of symptoms or intolerance. Mean HR at rest, at the first step and at the peak was 80 b.p.m., 91 b.p.m. and 128 b.p.m., respectively. Mean arterial pressure reached values of 97/62 mmHg at rest, 107/66 mmHg at the first step and 140/73 mmHg at peak exercise. At follow-up 9 of 73 showed clinical disorders (12%) of which 5 patients had hypertension (6.8%), 3 patients had diabetes (4.1%) and 1 had pre-eclampsia (1.4%). Comparing the group with AH (n 5) with the group without AH (n 68), SBP at the first step (median values 127 mmHg vs 104 mmHg, P = 0.009), the DBP at rest (median values 72 mmHg vs 60 mmHg, P = 0.039) and the DBP at the peak (median values 90 mmHg vs 69.5 mmHg, P = 0.038) were significantly higher in the group with AH. Among these parameters a logistic regression selected the SBP as best predictor for developing AH (OR 1.139, 95% IC 029–1.261, P = 0.012). Conclusions Our results showed that submaximal ET is safe in pregnancy. Although limited, our data seem to support the validity of ET, even submaximal, in order to stratify the risk of developing AH in pregnancy. Moreover, even SBP response at first step could be considered in a normal and expected range, we can speculate that a relatively excessive increase of BP in the early phase of exercise could reflect a pre-clinical impairment of vascular compliance predisposing AH during the second gestational trimester. Further data are needed to validate our results.