Pellikka, Patricia A.

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the “ABCDE protocol” of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study.

Introduction: Diastolic dysfunction has been characterized in relation to the relaxation and compliance properties of the left ventricle; limited information exists regarding its relationship to systolic function as assessed by deformation imaging. Objectives: To determine if there is left ventricular systolic dysfunction detected by global longitudinal strain (GLS) measured by two dimensional speckle tracking echocardiography in patients with immunoglobulin light chain (AL) amyloidosis with different degrees of diastolic dysfunction and normal ejection fraction (EF). Methods: Consecutive biopsy-proven AL patients with preserved EF (≥ 55%) who had a comprehensive echocardiogram performed and strain analysis were included. Cohort was divided into 5 groups according to the different grades of diastolic dysfunction: Group 0: normal filling pressures; Group 1: abnormal relaxation; Group 2: pseudo-normal pattern; Group 3: reversible restrictive; Group 4: fixed restrictive. Images were acquired and performed on a Vivid 9 from the 3 apical views, and analyzed on vendor-specific software (Echo-PAC, GE). GLS was averaged from the 16 segments, and their means compared by ANOVA and each pair with Student’s t test. Results: A total of 858 patients were included, mean age was 63.7 years ± 10.1, and 61.5% were male. From those, 205 (24%) were in group 0; 299 (35%) in group 1; 255 (30%) in group 2; 65 (7%) in group 3; and 34 in group 4 (4%). GLS means measurements were -18.95 ± 2.4, -16.86 ± 3.4, -15.60 ± 3.9, -12.31 ± 3.0, and -10.48 ± 3.3, respectively (P<0.0001). All individual GLS values were significantly different statistically when compared between each group (P<0.01 for all pairs; figure). Conclusions: Longitudinal systolic mechanical function is progressively impaired in AL amyloid patients as diastolic dysfunction progresses, despite normal EF. This systolic dysfunction provides insights into the intrinsic relationship between the components of the cardiac cycle.

Introduction: Transthoracic echocardiography (TTE) is a versatile tool for investigating cardiac function in hospitalized patients, but it was recently suggested that only a fraction of the studies result in an active change in management. The importance of early inpatient TTE to guide management and rule out important alternative pathology has not been previously investigated. The opinion of the referring provider has never been systematically surveyed. Hypothesis: Appropriate use (AU) of TTE in hospitalized patients has significant implications for patient care, even without resulting in direct alterations in management. Methods: We conducted a prospective review of 546 consecutive echocardiograms performed within 72 hours of hospital admission. An electronic survey consisting of 6 questions pertinent to rationale for TTE and consequences to patient care was sent to physicians. AU was independently determined by two investigators blinded to survey results and clinical outcomes, with differences adjudicated by a third independent investigator. Results: Of 546 TTEs included in this study, 526 (96%) were appropriate, 2% inappropriate, and 2% uncertain. Although only 48% of responders actively changed management after TTE results, 97% thought the TTE answered their clinical question. At least one new medication change occurred in 190 (35%) patients. Moreover, 95% of physicians would do another TTE in a similar situation, either to guide cardiac therapy, rule out contributing cardiac pathology, or support their current therapeutic plan. Only 5% of responders would not order another TTE if given a similar presentation in the future. Furthermore, our study uncovered a high incidence of unexpected findings (33% of TTEs), ranging from new decrease in LV systolic function, new valvular dysfunction, to pericardial effusion and new aortic aneurysm. These findings have significant clinical implications for the individual patient. Conclusions: Most early inpatient TTEs at our institution were appropriate and answered a specific clinical question important for management decisions. Even those not directly altering the acute therapeutic strategy impacted clinical course. A large number of significant incidental findings were recorded.

Objective: In patients with aortic stenosis (AS), the development of left ventricular (LV) systolic dysfunction adversely affects the natural history and is associated with poor outcomes following aortic valve replacement. However, the timing and possible reasons for transition from preserved to impaired LV ejection fraction (LVEF) in patients with AS have not been described. The aim of this study was to describe the time course of development of LV dysfunction and associated conditions in patients with severe AS. Methods & Results: Between 1/1/2009 and 12/31/2012, 667 (19%) of 3528 patients with severe AS (aortic valve area (AVA) ≤1 cm2) identified from the Mayo Clinic, Rochester, MN Echocardiographic Laboratory database; had LVEF ≤50%. Of those 667 patients, 263 (39%) had previous echocardiograms (median: 71.6 months, 25 IQR: 36.3, 75:118.2) before the development of severe AS, allowing an assessment of change in LVEF over time. Among these 263 patients, 8 (3%) had dilated cardiomyopathy (DCM), 225 (86%) had ischemic heart disease (IHD), 5 (2%) had other significant valve disease, and 25 (10%) had no concomitant heart disease before the development of severe AS. The evolution of development of reduced LVEF at several time points is shown in the Figure. The initial LVEF was 34±12 % in DCM patients, 51±13% in IHD patients and 61±9 % in AS patients without other heart diseases (p<0.001, ANOVA). Patients with AS alone or AS+DCM/IHD showed a gradual decline in LVEF before AS became severe, and a more rapid decline in LVEF once the AVA reached ≤ 1 cm2. Conclusion: In patients with severe AS, a majority of the patients (86%) with reduced EF had ischemic heart disease. Although there was a gradual decline in LVEF before development of severe AS, the decline was more rapid after AS became severe in almost all patients regardless of associated cardiac condition. More frequent monitoring may be indicated in AS patients especially when AVA reaches 1cm2 and concomitant IHD.

Background: Transthoracic echocardiography is the mainstay of cardiac imaging and is highly dependent upon cardiac sonographers for whom image acquisition can be physically demanding and associated with musculoskeletal pain. Prior studies are limited by the absence of adequate control groups and a lack of adjustment for potential confounders. Objectives: The purpose of this study was to determine the prevalence and impact of work-related musculoskeletal pain in cardiac sonographers as compared to a large control group of non-invasive healthcare professionals with similar demographics. Methods: An electronic survey was administered to Mayo Clinic employees identified by human resources at six major patient care facilities in four different states. Results: There were 2682 employees within the departments of cardiology and radiology who were contacted and 1532 (57%) completed the survey. After exclusion of those who wear protective lead aprons, 517 employees comprised the control group and 66 cardiac sonographers made up the study group. Cardiac sonographers and the control group were similar in age, sex, BMI, length of employment and history of prior musculoskeletal pain. Cardiac sonographers reported work-related musculoskeletal pain more frequently than the control group (88% vs 40%; p<0.001). This association persisted after multivariable adjustment for age, sex, body mass index, length of current employment and history of pre-existing musculoskeletal pain (OR 11.6; (95% CI 5.32, 25.5); p<0.001). Cardiac sonographers were more likely to seek medical care for their work-related pain (55% vs 21%; p<0.001) and to have missed work due to pain (35% vs 12%, p<0.001). Conclusions: In this multi-site case control study, cardiac sonographers experienced significantly more work-related pain and missed more work due to pain than a large control group of non-invasive healthcare professionals with similar demographics.

Background Carcinoid involvement of left-sided heart valves has been reported in patients with a patent foramen ovale, carcinoid tumor of the lung, and active carcinoid syndrome with high levels of serotonin. The present study details the clinical features and surgical management of patients with carcinoid heart disease affecting both left- and right-sided valves. Methods and Results Eleven patients (7 men, 4 women) with symptomatic carcinoid heart disease underwent surgery for left- and right-sided valve disease between 1989 and 1999. Mean age was 57±9 years, and median preoperative NYHA class was 3. All patients had metastatic carcinoid tumors and were on somatostatin analog. Of 11 patients, 5 (45%) had a patent foramen ovale; 1 of these also had a primary lung carcinoid tumor. Surgery included tricuspid valve replacement in all patients, pulmonary valve replacement in 3 and valvectomy in 7, mitral valve replacement in 6 and repair in 1, aortic valve replacement in 4 and repair in 2, CABG in 2, and patent foramen ovale closure in 5. One myocardial metastatic carcinoid tumor was removed. There were 2 perioperative deaths. At a mean follow-up of 41 months, 4 additional patients were dead. All but 1 surgical survivor initially improved ≥1 functional class. No patient required reoperation. Conclusions Carcinoid heart disease may affect left- and right-sided valves and occurred without intracardiac shunting in 55% of this surgical series. Despite metastatic disease that limits longevity, operative survivors had improvement in functional capacity. Cardiac surgery should be considered for select patients with carcinoid heart disease affecting left- and right-sided valves.

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: Presence of subclinical left ventricle (LV) dysfunction may influence outcomes after percutaneous mitral balloon valvotomy (PMBV), but cannot be detected by conventional echocardiography. Hypothesis: Preprocedure LV global longitudinal strain (GLS) by speckle tracking TTE detects subclinical LV dysfunction and predicts long-term outcome after successful PMVB. Methods: Consecutive patients undergoing PMBV between 2003-2011 who had comprehensive baseline TTE were included. Patients with suboptimal immediate results (repeat PMBV or mitral surgery within first 6 months) and those with suboptimal TTE strain were excluded. LV strain was analyzed with commercial software (Syngo VVI), and GLS averaged from 18 segments. The primary end point was all-cause mortality. Secondary end point was the composite of death and mitral valve reintervention. Results: Of 110 patients screened, 29 (26%) had unsuitable strain imaging, and 8 (7%) had poor immediate results, leaving 73 in the final cohort. Median follow-up was 3.7 years (interquartile range 1.3-7.2). There were 10 deaths (14%) and 25 late mitral valve interventions (34%). Univariate predictors of death were GLS, age, EF, stroke volume, pulmonary artery pressure, mitral valve area and coronary artery disease. In a multivariate Cox model, GLS was the strongest predictor of death after adjustment for age [HR=1.40 (1.09-1.84), P=0.008]. For the composite endpoint, GLS, mitral valve gradient, and invasively mean left atrial pressure were univariate predictors of death or reintervention. At multivariate analysis, GLS was the sole predictor of events [HR=1.17 (1.01-1.34), P=0.03]. Event-free survival is shown in figure. Intra and inter observer intra-class correlation for strain analysis was 0.87 (0.66-0.96) and 0.84 (0.53-0.95), respectively. Conclusions: GLS is a powerful predictor of long-term outcome after PMVB and appears to have an incremental prognostic value over traditional parameters.

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: In asymptomatic patients with severe aortic stenosis (SAS), left ventricular (LV) ejection fraction (EF) <50% is generally considered to be the threshold for referral for aortic valve replacement (AVR). Hypothesis: We investigated the importance of LVEF on long-term outcome after AVR in symptomatic and asymptomatic SAS patients and studied whether LVEF < 50% is the optimal threshold for referral for AVR. Methods and Results: We retrospectively identified 2017 patients with SAS (aortic valve area (AVA)<1cm2, mean aortic valve gradient ≥40 mm Hg, or indexed AVA <0.6 cm2/m2) who underwent surgical AVR from January 1995 to June 2009 at our institution. Patients were divided into 4 groups depending on preoperative LVEF (<50% in 300 (15%) patients, 50-59% in 331 (17%), 60-69% in 908 (45%), and ≥70% in 478 (24%)). The primary end-point was all-cause mortality. During follow-up of 5.3±4.4 years, 1056 (52%) died. Five-year mortality rate increased with decreasing LVEF (41% (n=106), LVEF<50%); 35% (n=98), LVEF 50-59%; 26% (n=192), LVEF 60-69%; 22% (n=90), LVEF≥70%, p<0.0001). Compared to patients with LVEF≥60%, patients with LVEF 50-59% had increased mortality (HR 1.58, p<0.001), with a similar risk increase in both symptomatic (HR=1.56, p<0.001) and asymptomatic patients (HR 1.58, p=0.006, Figure). In a Cox regression analysis corrected for standard risk factors, LV mass index, AVA, and stroke volume index, LVEF was predictive of all-cause mortality (HR=0.89 per 10%, p<0.001). When this multivariable analysis was repeated in the subset of 1333 patients with no history of coronary artery disease, LVEF was still associated with all-cause mortality (HR=0.90 per 10%, p=0.009). Conclusion: In patients with SAS undergoing AVR, patients with LVEF 50-59% have also increased mortality compared to patients with LVEF>60%, suggesting that a different LVEF threshold should be used when referring for AVR.