McCully, Robert B.

Background: Atrial fibrillation (AF) is a low-flow state and may underestimate aortic stenosis (AS) severity. Single-high Doppler signals (HS) consistent with severe AS (peak velocity ≥4 m/s or mean gradient ≥40 mm Hg) are averaged down in current practice. The objective for the study was to determine the significance of HS in AF low-gradient AS (LGAS). Methods: One thousand five hundred forty-one patients with aortic valve area ≤1 cm 2 and left ventricular ejection fraction ≥50% were identified and classified as high-gradient AS (HGAS) (≥40 mm Hg) and LGAS (<40 mm Hg), and AF versus sinus rhythm (SR). Available computed tomography aortic valve calcium scores (AVCS) were retrieved from the medical record. Outcomes were assessed. Results: Mean age was 76±11 years, female 47%. Mean gradient was 51±12 in SR-HGAS, 48±10 in AF-HGAS, 31±5 in SR-LGAS, and 29±7 mm Hg in AF-LGAS, all P ≤0.001 versus SR-HGAS; HS were present in 33% of AF-LGAS. AVCS were available in 34%. Compared with SR-HGAS (2409 arbitrary units; interquartile range, 1581–3462) AVCS were higher in AF-HGAS (2991 arbitrary units; IQR1978–4229, P =0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817–2810, P =0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945–1832, P <0.001); AVCS in AF-LGAS were higher when HS were present ( P =0.048). Compared with SR-HGAS, the age-, sex-, comorbidity index-, and time-dependent aortic valve replacement-adjusted mortality risk was higher in AF-HGAS (hazard ratio=1.82 [1.40–2.36], P <0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04–2.26], P =0.03) but not different in AF-LGAS without HS or SR-LGAS (both P =not significant). Conclusions: Severe AS was common in AF-LGAS. AVCS in AF-LGAS were not different from SR-HGAS. AVCS were higher and mortality worse in AF-LGAS when HS were present.

Limited information exists regarding the echocardiographic and clinical predictors of exercise capacity and their effects on exercise with advancing age or by sex. We hypothesized that LV diastolic function (DF) impacts exercise capacity to a greater degree with advancing age. This was a prospective cohort study of consecutive patients undergoing routine exercise echocardiography with the Bruce protocol (n=2955). DF assessments at rest and exercise were performed. Those with echocardiographic exercise-induced ischemia and significant valvular disease were excluded. Univariate and multivariate analyses were conducted to determine the strongest echocardiographic and clinical predictors of exercise capacity (METs). Results were reported as unstandardized β coefficient (Standard Error) as outlined beside each variable. Age and sex interactions of these predictors with exercise capacity were determined. The strongest independent multivariate predictors of exercise capacity were female vs. male sex [−1.98 (0.07), p<0.0001], body mass index >30 kg/m 2 [−1.24 (0.08), p<0.0001], age per 10 year increment [−0.85 (0.01), p<0.0001], mild resting diastolic dysfunction vs. normal [−0.70 (0.10), p<0.0001], and moderate/severe resting diastolic dysfunction vs. normal [−1.3 (0.13), p<0.0001]. LV filling pressures measured by a resting E/e’ ≥ 15 [−0.42 (0.14), p=0.004] or exercise E/e’≥ 15 [−0.31 (0.14), p<0.0001] similarly predicted a reduction in exercise capacity, each in separate multivariate analyses. The impact of impaired relaxation and left ventricular filling pressures on exercise capacity increased with advancing age (p<0.001 and p=0.02 respectively), and was most marked after age 50. These predictors had a similar negative effect on exercise capacity among men and women (p=NS). In conclusion, in this large population referred for exercise echocardiography and not limited by ischemia, resting DF and resting/exercise LV filling pressures independently predicted exercise capacity. The increasingly potent effect of impaired relaxation and exercise LV filling pressures with advancing age suggest that DF plays an important role in the development of exercise intolerance in the elderly.

Introduction: Stress echocardiography (SE) has an established role in the evaluation of symptomatic patients, but its utility in asymptomatic patients is unclear. Current guidelines discourage the use of SE in most asymptomatic patients, citing lack of data to support its use. We therefore sought to describe the yield of SE in a group of asymptomatic individuals according to risk profile. Hypothesis: We hypothesized that SE would rarely be abnormal in asymptomatic individuals. Methods: We conducted a retrospective cohort study of all asymptomatic individuals who underwent exercise or pharmacologic SE between 2003 and 2013. Reasons for SE included screening for CAD, preoperative evaluation, abnormal ECG, coronary calcification, and assessment of established CAD (defined as prior myocardial infarction or coronary revascularization). We grouped subjects using both the 10-year Framingham risk equation and ATP3-suggested categories of low-risk (<10%), intermediate-risk (10-20%), and high-risk (>20%) for non-diabetic subjects without known CAD and by ACC/AHA Pooled Cohort risk estimates for subjects with and without diabetes. Subjects with established CAD were considered separately. Abnormal echocardiograms were defined as having ischemic, fixed, or mixed defects. Results: The study population comprised 19,170 subjects; 63% men, mean±SD age was 64±13 years, and 52% underwent pharmacologic SE. The likelihood of abnormal SE results was proportional to risk, with the highest yield in those with established CAD (59%). Those with diabetes had a yield similar to those with a 10 year risk of 10-20% by both ATP3/FRS and ACC/AHA. Conclusions: SE abnormalities are commonly seen in asymptomatic individuals; the likelihood of abnormal SE results was proportional to patients’ estimated risk. The frequency of SE abnormalities in diabetic patients is similar to that of intermediate-risk, but not high-risk patients.

Introduction: Diastolic dysfunction impairs exercise capacity and has prognostic value in exercise echocardiography. We aimed to assess whether left atrial strain (LAS), which is reduced with worsening in diastolic function, is associated with all-cause death or heart failure hospitalization in patients undergoing treadmill echocardiography. Methods: We performed 2D-speckle tracking analysis of LAS in 1636 consecutive patients (mean age 64±13 and 59% men) who underwent treadmill echocardiography between 1/2013 and 1/2014. We used the 2016 ASE recommendation to define diastolic function and elevated LV filling pressure. Results: Of 1636 study subjects, 95% had LV ejection fraction ≥ 50%. Diastolic function was normal in 44% of patients and abnormal in the remaining (23% grade I, 9% grade II, 1% grade III, and 23% indeterminate). During a mean follow-up of 5.5±1.8 years, 210 patients (12.8%) experienced the composite outcome (157 death and 88 heart failure hospitalization). Lower LASreseroivr, LASbooster and LA emptying fraction (LAEF) were all associated with increased risk for the adverse outcome independent of age, sex, clinical and echocardiographic parameters, and after further adjustment for diastolic function (abnormal vs. normal) (all p≤0.001). The association of LASbooster with the outcome attenuated in a model with LASreservoir or LAEF (both p>0.1). Adding LASreservoir to clinical and echocardiographic parameters provided incremental prognostic value (continuous net reclassification improvement=0.09, p=0.04), but not LAEF or LASbooster. Patients with LASreservoir <34.2% (lowest tertile) had more than doubled risk for death or heart failure hospitalization than those with LASreservoir ≥34.2% after multivariable adjustment in the entire cohort (adjusted hazard ratio 2.2, 95%CI: 1.53 - 3.23), as well as in those with normal stress test (n=1217, adjusted HR, 3.53, 95%CI: 2.29 - 5.53) or those without elevated resting LV filling pressure (n=1466, adjusted HR: 2.08, 95%CI: 1.46 - 2.96). Conclusions: LASreservoir provides independent prognostic information in patients undergoing exercise echocardiography.

Abstract Aims Cardiac power is a measure of cardiac performance that incorporates both pressure and flow components. Prior studies have shown that cardiac power predicts outcomes in patients with reduced left ventricular (LV) ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise cardiac power and power reserve in patients with normal EF. Methods and results We performed a retrospective analysis in 24 885 patients (age 59 ± 13 years, 45% females) with EF ≥50% and no significant valve disease or right ventricular dysfunction, undergoing exercise stress echocardiography between 2004 and 2018. Cardiac power and power reserve (developed power with stress) were normalized to LV mass and expressed in W/100 g of LV myocardium. Endpoints at follow-up were all-cause mortality and diagnosis of heart failure (HF). Patients in the higher quartiles of power/mass (rest, peak stress, and power reserve) were younger and had higher peak blood pressure and heart rate, lower LV mass, and lower prevalence of comorbidities. During follow-up [median 3.9 (0.6–8.3) years], 929 patients died. After adjusting for age, sex, metabolic equivalents (METs) achieved, ischaemia/infarction on stress test results, medication, and comorbidities, peak stress power/mass was independently associated with mortality [adjusted hazard ratio (HR), highest vs. lowest quartile, 0.5, 95% confidence interval (CI) 0.4–0.6, P &lt; 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P &lt; 0.001]. Power reserve showed similar results. Conclusion The assessment of cardiac power during exercise stress echocardiography in patients with normal EF provides valuable prognostic information, in addition to stress test findings on inducible myocardial ischaemia and exercise capacity.

Abstract Funding Acknowledgements None Background/Purpose: Anemia is a common condition in patients with cardiovascular disease. The effect of anemia in exercise stress testing has not been evaluated in a large cohort of patients. Methods We performed a retrospective review of patients undergoing exercise stress echocardiography over a 10 year period who had blood hemoglobin assessed within 48 hours of stress testing. World Health Organization cutoffs were used in defining the degree of anemia. The effect of anemia on exercise capacity and stress testing safety outcomes was assessed. Results In 15,652 patients, 90.3% were non-anemic, 7.6% mildly anemic, 2.1% moderately anemic, and 0.1% severely anemic. The incidence of serious supraventricular or ventricular arrhythmias and need to transfer to the hospital was low (0.1%) and did not correlate to anemia severity (p = 0.25). There was an increased incidence of non-sustained SVT or atrial fibrillation with moderate anemia and increased incidence of hypotension with stress testing with mild and moderate anemia. There was a significant reduction in duration of exercise (p &lt; 0.001) and METS (p &lt; 0.001) achieved with worsening anemia. Conclusion Our study demonstrates that exercise stress testing is safe in patients with mild and moderate anemia, albeit with reduced exercise capacity. Low numbers of severely anemic patients despite a large study population limit generalizability of these results in this group. Exercise Capacity Severe Anemia (N = 9) Moderate Anemia (N = 332) Mild Anemia (N = 1183) Non-anemic (N = 14128) P value Resting heart rate 81 ± 13 # 79 ± 14 # 72 ± 14 74 ± 13 &lt;0.001* Peak heart rate 148 ± 22 139 ± 24 # 138 ± 23 # 147 ±22 &lt;0.001* Exercise duration 5.3 ± 2.5 # 6.3 ± 2.1 # 7.2 ± 2.5 # 8.6 ± 2.7 &lt;0.001* METS 6.3 ± 2.5 # 7.1 ± 2.2 # 8.0 ± 2.5 # 9.5 ± 2.7 &lt;0.001* Safety Hypotension with stress 0 (0%) 31 (9.4%) # 94 (8.0%) # 437 (3.1%) &lt;0.001* Mild supraventricular arrhythmia 1 (11.1%) 15 (4.5%) # 20 (1.7%) # 237 (2.3%) 0.04* Severe supraventricular arrhythmia 0 (0%) 0 (0%) 0 (0%) 7 (0.1%) 0.99 Mild ventricular arrhythmia 0 (0%) 20 (6.0%) 74 (6.3%) 756 (5.4%) 0.94 Moderate ventricular arrhythmia 0 (0%) 3 (0.9%) 13 (1.1%) 182 (1.3%) 0.78 Severe ventricular arrhythmia 0 (0%) 1 (0.3%) 2 (0.2%) 1 (0.0%) 0.02 Transfer to hospital 0 (0%) 2 (0.6%) 1 (0.1%) 9 (0.1%) 0.29 Any severe arrhythmia or hospitalization 0 (0%) 2 (0.6%) 3 (0.3%) 17 (0.1%) 0.25 # Multi-comparison adjusted P-value &lt;0.05 compared to non-anemic when group P &lt; 0.05

Abstract Background Noninvasive parameters of LV filling pressure (E/e’) and pulmonary pressures (RVSP) by Doppler echocardiography correlate with functional capacity and outcome in sinus rhythm (SR). Their role in AF is less clear. Elevated left ventricular filling pressures (E/e’) and pulmonary artery systolic pressures (PASP) by Doppler stress echocardiography correlate with impaired functional capacity in patients in sinus rhythm (SR). However, there is limited data in atrial fibrillation (AF). Purpose The aim of this study was to delineate the characteristics of patients with AF referred for exercise stress echocardiography and determine the prevalence and significance of E/e’ and PASP elevations in AF. Methods Subjects were patients referred for exercise treadmill stress echocardiography (n= 14,937) and underwent regional wall motion assessment, Doppler assessment of mitral inflow (E) and early tissue relaxation (e’) velocities and PASP at rest and immediately following maximum symptom limited exercise. Exclusion criteria included significant valvular heart disease (moderate or greater stenosis and/or regurgitation of any cardiac valve or previous valve repair or replacement) (1%), congenital heart disease (&lt;1%) or refusal to participate in research (&lt;1%). Results Patients with AF (n = 310, 2%) were older (71 ± 10 vs 59 ± 13 years, p &lt; 0.001). While resting blood pressure was similar, resting heart rates were higher in AF (80 ± 17 bpm vs 73 ± 13 bpm, p &lt; 0.0001). AF patients achieved lower workloads (6.4 ± 2.4 METS vs 9 ± 2.4 METS, p &lt; 0.001) with lower peak double products (22336 ± 6677 vs 25148 ± 5438, p &lt; 0.001). Rates of resting (27% vs 10%, p &lt; 0.0001) and exercise-induced (37% vs 20%, p &lt; 0.0001) regional wall motion abnormalities were higher in AF. Mean E/e’ was higher in AF at rest (12 ± 5 vs 9 ± 3, p &lt; 0.001) and with exercise (12 ± 5 vs 10 ± 4, p &lt; 0.001), with a higher percentage of patients in AF having E/e’ ≥15 at rest (20% vs 6% in SR, p= &lt;0.001) and with exercise in (23% vs 8%, p &lt; 0.001). PASP was higher in AF at rest (33 ± 8 mm Hg vs 28 ± 6 mm Hg, p &lt; 0.001) and with exercise (48 ± 12 vs 42 ± 11, p &lt; 0.001) compared to SR. E/e’ correlated with exercise capacity in AF and in SR, with an E/e’ cutoff of 11.7 that was best predictive of impaired functional capacity (&lt; 5 METS in women and &lt; 7 METS in men). Conclusions Abnormalities of E/e’ and PASP are more prevalent in patients with AF and correlate with impaired functional capacity. In patients with AF, a medial E/e’ ratio of ≥ 12 immediately following exercise is best associated with impaired functional capacity.

Abstract Background Cardiac power output-to-mass (CPOM) ratio is a measure of myocardial performance that incorporates both pressure and flow output, normalized to left ventricular (LV) mass generating that cardiac work. Prior small studies have shown that CPOM predicts outcomes in patients with ischemic cardiomyopathy and reduced LV ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise CPOM and power reserve (increase from rest to peak exercise) in patients with normal EF. Methods and results Retrospective study in 24,783 patients (age 59±13 years, 45% females) with EF≥50% and no significant valve disease or right ventricular (RV) dysfunction, undergoing exercise stress echocardiography between 2004–2018. CPOM was calculated as previously described (0.222 x cardiac output x mean blood pressure / LV mass) and expressed in Watts/100g myocardium. Power reserve was calculated as difference in CPOM between peak stress and rest. All-cause mortality was the primary endpoint. Patients were divided into quartiles of power reserve. Patients with higher power reserve were younger, had higher blood pressure and heart rate, lower LV mass, and lower prevalence of prior myocardial infarction. (Table). During follow-up (median (IQR) 3.9 (0.6–8.3) years), 931 (3.8%) patients died. Progressively lower power reserve was associated with increasing mortality (Figure A). Compared to patients with abnormal stress test, patients with the lowest power reserve but otherwise normal stress test had the same survival as those with infarction/cardiomyopathy or ischemia on stress test (Figure B). Resting CPOM had lower predictive value. After adjusting for age, sex, METs achieved, ischemia/infarction on stress test results, and diastolic function grade, both peak exercise CPOM and power reserve were independent predictors of mortality (p<0.0001), incremental to conventional measures. Conclusion Cardiac power output and reserve measured during exercise stress echo provides independent prognostic information in patients with normal resting EF and no significant valve disease or RV dysfunction. The survival of patients with low power reserve but normal stress test was similar to patients with prior infarction/ cardiomyopathy or ischemia on stress test.