Kane, Garvan C.

Background: In right heart failure, Doppler-derived indices such as RV performance index (RIMP) and tricuspid regurgitant duration (TRD) have been linked to clinical outcomes, but variably. We tested the hypothesis that this variability is based on varying timing and predictive value of the onset of diastolic phase, according to right atrial pressure (RAP) and to whether tissue or flow Doppler is used. Methods: We reviewed echocardiograms and catheter examinations for 151 consecutive patients with pulmonary arterial hypertension. Te’ and TE were defined as the time from QRS onset to the onset of early diastolic velocity on tissue Doppler imaging at the tricuspid valve annulus and to TRD terminal indicating the onset of tricuspid inflow. All measurements were corrected for heart rate. The patients were grouped into low (RAP < 10mmHg, n = 84) and high RAP groups (RAP ≧ 10mmHg, n = 67). Results: Over 3 years, there were 62 total deaths and 8 lung transplantations. In low RAP group, Te’ was prolonged in association with an increase in Tau (R = 0.51, p = 0.0001) and prolonged Te’ predicted higher mortality (HR = 1.20 / 10ms, p = 0.02). In high RAP group, Te’ was still prolonged as Tau increased (R = 0.43, p = 0.008) independently of RAP, while TE was reversely shortened as RAP rose (R = 0.41, p = 0.0006) and shortened TE predicted higher mortality (HR = 0.86 / 10ms, p = 0.008). An increase in RIMP using tissue Doppler only in low RAP group and shortened TRD only in high RAP group predicted higher mortality (HR = 2.09 / 0.1, p = 0.002 and HR = 0.89 / 10ms, p = 0.02, respectively), keeping in line with Te’ and TE, respectively. Conclusions: Both the onset of diastolic tricuspid annular movement and the onset of tricuspid inflow relate to relaxation disorder. As RAP elevates, only the tricuspid inflow onsets early. These observations should be considered when interpreting Doppler-derived indices: they predict clinical outcomes in a limited group of patients according to RAP and to whether tissue or flow is focused on.

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.

Background: Increased reflective wave from pulmonary artery (PA) causes mid-systolic deceleration (MSD) and notching in Doppler flow velocity envelope of RV ejection flow. Our aim is to test whether profile of MSD and notching provides insight into hemodynamics and patient outcomes in pulmonary artery hypertension (PAH), using quantitative measurements. We hypothesized that the deceleration time of the MSD slope (DTMSD), meaning the steepness of the slope, reflects interaction between RV ejection and reflective wave, and that peak velocity of post-notching flow (Vpost) reflects RV function. Methods: We reviewed RV ejection flow envelope recordings by pulsed wave Doppler for 157 consecutive patients with PAH between 1/2008 and 3/2013 (age 57 ± 14) with an estimated RV systolic pressure of 79 ± 23 mmHg. DTMSD was measured as the time between the first peak acceleration wave and MSD slope extrapolated to zero line. We also reviewed right heart catheterization performed within one month from echocardiography in 78 of the 157 patients. Results: We identified MSD and notching in 148 patients. On multivariate regression analyses, PA capacitance was the key determinant of DTMSD (beta = -0.49, p <0.0001). Vpost was determined by cardiac index (beta = -0.36, p = 0.0014). During a median follow-up period of 30 months, there were 47 deaths from all causes and 7 lung transplantations. On Cox hazard analyses, shorter DTMSD and smaller Vpost are significant predictors of higher mortality independently of each other (HR 0.92 / 10ms, p = 0.045 and HR 0.97, p = 0.028, respectively). Conclusion: Mid-systolic deceleration of RV ejection flow became steeper in the setting of lower PA compliance causing a greater reflectance wave. Reduced peak velocity of post-notching flow reflected impaired RV with reduced cardiac output. Quantitative assessment of profile of mid-systolic deceleration and notching in RV ejection flow envelope is useful in predicting hemodynamics and patient outcomes in PAH.

Abstract Hypertrophic cardiomyopathy (HCM) is a heritable, phenotypically diverse, and often asymptomatic heart muscle disease which is a major cause of sudden cardiac death (SCD) in young adults. The gold-standard for the diagnosis of HCM is echocardiography (echo), which is an ultrasound-based cardiac imaging modality. Across all sites of the Mayo Clinic enterprise, echo images and measurement data are reviewed, interpreted, and reported via the Echo Information Management System (EIMS). The objective of this paper is to develop a machine learning model for the identification of HCM from cardiac measurements obtained by the echo. We developed a novel machine learning model on patient demographic information and echo measurements that were retrieved from the EIMS digital data registry and selected by cardiologists. Random forest (RF) was utilized to investigate the predictive performance of these features on the identification of HCM patients. The HCM cohort consists of 3,548 patients with at least one HCM diagnostic billing code (ICD-9 or ICD-10), from 2014 to 2019. The class labels “HCM yes” and “HCM no” were assigned by manual review of medical records as well as the outcomes of the gold standard imaging tests for HCM diagnosis. The developed model performed well in finding HCM patients with an accuracy of 95%, recall of 99%, and precision of 97%. The F1 score was 98 %, while 4% of patients were misclassified. This model will be translated into clinical practice for a clinical decision support system in EIMS to assist providers in the accurate diagnosis of HCM from echo data automatically while ensuring high-quality echo interpretation.

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.

Introduction: Patients with heart failure with preserved ejection fraction (HFpEF) may have elevated left ventricular filling pressure with exercise (LVFP-ex), despite normal LVFP at rest. We aimed to assess the diagnostic value of resting left atrial strain (LAS) in detecting elevated LVFP-ex in dyspneic patients evaluated by exercise stress echocardiography. Methods: We performed 2D-speckle tracking analysis for LAS in 669 consecutive patients (mean age 64 ± 14, men 53%) who underwent treadmill echocardiography evaluation and had LV ejection fraction ≥50%. Assessment of LVFP at rest was based on the 2016 ASE Guidelines for diastolic function assessment. We used the 2019 ESC HFA-PEEF diagnostic algorithm to define elevated LVFP-ex (early mitral inflow wave/septal early diastolic tissue velocity (E/e’) ≥ 15 after exercise) and calculate a continuous HFA-PEEF score. Results: LAS reservoir was lowest in patients with elevated LVFP at rest (n=81) and lower in those with normal resting FP who developed elevated LVFP-ex (n=108) compared to those who maintained normal LVFP-ex (29.0 ± 5.2% vs. 33.1 ± 5.0% vs.39.3 ± 4.8%, p < 0.001). In patients with normal or indeterminate LVFP at rest (n=587), LAS reservoir and pre-exercise HFA-PEEF score demonstrated an area-under-the-curve (AUC) of 0.82 and 0.7 respectively for elevated LVFP-ex. There was a 28% higher odds of developing elevated LVFP-ex per 1% decrease in LAS reservoir (odds ratio, 95%CI: 0.78, 0.74 - 0.82). In patients with the intermediate score (n=461), 123 patients developed elevation in LVFP with exercise and were classified as having HFpEF per the diagnostic algorithm. Addition of LAS reservoir improved the predictive value of HFA-PEEF score for HFpEF (AUC increased from 0.71 to 0.80, p for ΔAUC =0.01). Conclusions: LAS reservoir has a potential to identify patients at intermediate-risk for HFpEF who may develop elevated LVFP with exercise only, and therefore a promising parameter to aid in the diagnosis of HFpEF when exercise testing is not feasible.

Introduction: A low cardiac power output (CPO), measured invasively, identifies critically ill patients at increased risk of mortality. CPO can also be measured non-invasively with transthoracic echocardiography (TTE), although prognostic data in critically ill patients is not available. Hypothesis: Reduced CPO measured by TTE is associated with increased hospital mortality in cardiac intensive care unit (CICU) patients. Methods: Using a database of CICU patients admitted between 2007 and 2018, we identified patients with TTE within one day (before or after) of CICU admission who had data necessary for calculation of CPO. Multivariable logistic regression determined the relationship between CPO and adjusted hospital mortality. Results: We included 5,585 patients with a mean age of 68.3±14.8 years, including 36.7% females. Admission diagnoses included acute coronary syndrome (ACS) in 57%, heart failure (HF) in 50%, cardiac arrest (CA) in 12%, and cardiogenic shock (CS) in 13%. The mean left ventricular ejection fraction (LVEF) was 47±16%, and the mean CPO was 1.0±0.4 W. CPO was inversely associated with the risk of hospital mortality (Figure A), including among patients with ACS, HF, and CS (Figure B). On multivariable analysis, lower CPO was associated with higher hospital mortality (OR 0.96 per 0.1 W, 95% CI 0.0.93-0.99, p=0.03). Hospital mortality was highest in patients with low CPO coupled with reduced LVEF, increased vasopressor requirements, or higher admission lactate. Hospital mortality was higher among patients with a CPO <0.6 W (adjusted OR 1.57, 95% CI 1.13-2.19, p = 0.007), particularly in the presence of admission lactate level >4 mmol/L (50.9%). Conclusions: Echocardiographic CPO was inversely associated with hospital mortality in CICU patients, particularly among patients with increased lactate and vasopressor requirements. Routine measurement of CPO provides important information beyond LVEF and should be considered in CICU patients.

Echocardiography (Echo), a widely available, noninvasive, and portable bedside imaging tool, is the most frequently used imaging modality in assessing cardiac anatomy and function in clinical practice. On the other hand, its operator dependability introduces variability in image acquisition, measurements, and interpretation. To reduce these variabilities, there is an increasing demand for an operator- and interpreter-independent Echo system empowered with artificial intelligence (AI), which has been incorporated into diverse areas of clinical medicine. Recent advances in AI applications in computer vision have enabled us to identify conceptual and complex imaging features with the self-learning ability of AI models and efficient parallel computing power. This has resulted in vast opportunities such as providing AI models that are robust to variations with generalizability for instantaneous image quality control, aiding in the acquisition of optimal images and diagnosis of complex diseases, and improving the clinical workflow of cardiac ultrasound. In this review, we provide a state-of-the art overview of AI-empowered Echo applications in cardiology and future trends for AI-powered Echo technology that standardize measurements, aid physicians in diagnosing cardiac diseases, optimize Echo workflow in clinics, and ultimately, reduce healthcare costs.

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.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( p < 0.001), predominantly female ( p = 0.01) and had higher mean Charlson scores ( p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.