Stress Echo 2030: the new ABCDE protocol defining the future of cardiac imaging.

Functional testing with stress echocardiography is based on the detection of regional wall motion abnormality with two-dimensional echocardiography and is embedded in clinical guidelines. Yet, it under-uses the unique versatility of the technique, ideally suited to describe the different functional abnormalities underlying the same wall motion response during stress. Five parameters converge conceptually and methodologically in the state-of-the-art ABCDE protocol, assessing multiple vulnerabilities of the ischemic patient. The five steps of the ABCDE protocol are (1) step A: regional wall motion; (2) step B: B-lines by lung ultrasound assessing extravascular lung water; (3) step C: left ventricular contractile reserve by volumetric two-dimensional echocardiography; (4) step D: coronary flow velocity reserve in mid-distal left anterior descending coronary with pulsed-wave Doppler; and (5) step E: assessment of heart rate reserve with a one-lead electrocardiogram. ABCDE stress echo offers insight into five functional reserves: epicardial flow (A); diastolic (B), contractile (C), coronary microcirculatory (D), and chronotropic reserve (E). The new format is more comprehensive and allows better functional characterization, risk stratification, and personalized tailoring of therapy. ABCDE protocol is an 'ecumenic' and 'omnivorous' functional test, suitable for all stresses and all patients also beyond coronary artery disease. It fits the need for sustainability of the current era in healthcare, since it requires universally available technology, and is low-cost, radiation-free, and nearly carbon-neutral.

Noninvasive echocardiographic cardiac power output predicts mortality in cardiac intensive care unit patients.

BACKGROUND: Low cardiac power output (CPO), measured invasively, can identify critically ill patients at increased risk of adverse outcomes, including mortality. We sought to determine whether non-invasive, echocardiographic CPO measurement was associated with mortality in cardiac intensive care unit (CICU) patients. METHODS: Patients admitted to CICU between 2007 and 2018 with echocardiography performed within one day (before or after) admission and who had available data necessary for calculation of CPO were evaluated. Multivariable logistic regression determined the relationship between CPO and adjusted hospital mortality. RESULTS: A total of 5,585 patients (age of 68.3 ± 14.8 years, 36.7% female) were evaluated with admission diagnoses including acute coronary syndrome (ACS) in 56.7%, heart failure (HF) in 50.1%, cardiac arrest (CA) in 12.2%, shock in 15.5%, and cardiogenic shock (CS) in 12.8%. The mean left ventricular ejection fraction (LVEF) was 47.3 ± 16.2%, and the mean CPO was 1.04 ± 0.37 W. There were 419 in-hospital deaths (7.5%). CPO was inversely associated with the risk of hospital mortality, an association that was consistent among patients with ACS, HF, and CS. On multivariable analysis, higher CPO was associated with reduced hospital mortality (OR 0.960 per 0.1 W, 95CI 0.0.926-0.996, P = .03). Hospital mortality was particularly high in patients with low CPO coupled with reduced LVEF, increased vasopressor requirements, or higher admission lactate. CONCLUSIONS: Echocardiographic CPO was inversely associated with hospital mortality in unselected CICU patients, particularly among patients with increased lactate and vasopressor requirements. Routine calculation and reporting of CPO should be considered for echocardiograms performed in CICU patients.

Prognostic value of peak stress cardiac power in patients with normal ejection fraction undergoing exercise stress echocardiography.

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 < 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P < 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.

Aetiology and outcomes of severe right ventricular dysfunction.

AIMS: Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. METHODS AND RESULTS: Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58-64%] and 35% (95% CI 31-38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57-65%) and 33% (95% CI 28-37%), respectively; vs. 76% (95% CI 68-82%) and 50% (95% CI 40-59%) in PAH, vs. 71% (95% CI 64-76%) and 49% (95% CI 41-58%) in thromboembolic diseases, vs. 42% (95% CI 35-49%) and 8% (95% CI 4-15%) in CLD (log-rank P < 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD. CONCLUSION: One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.

Noninvasive evaluation of pulmonary artery pressure during exercise: the importance of right atrial hypertension.

INTRODUCTION: Identification of elevated pulmonary artery pressures during exercise has important diagnostic, prognostic and therapeutic implications. Stress echocardiography is frequently used to estimate pulmonary artery pressures during exercise testing, but data supporting this practice are limited. This study examined the accuracy of Doppler echocardiography for the estimation of pulmonary artery pressures at rest and during exercise. METHODS: Simultaneous cardiac catheterisation-echocardiographic studies were performed at rest and during exercise in 97 subjects with dyspnoea. Echocardiography-estimated pulmonary artery systolic pressure (ePASP) was calculated from the right ventricular (RV) to right atrial (RA) pressure gradient and estimated RA pressure (eRAP), and then compared with directly measured PASP and RAP. RESULTS: Estimated PASP was obtainable in 57% of subjects at rest, but feasibility decreased to 15-16% during exercise, due mainly to an inability to obtain eRAP during stress. Estimated PASP correlated well with direct PASP at rest (r=0.76, p<0.0001; bias -1 mmHg) and during exercise (r=0.76, p=0.001; bias +3 mmHg). When assuming eRAP of 10 mmHg, ePASP correlated with direct PASP (r=0.70, p<0.0001), but substantially underestimated true values (bias +9 mmHg), with the greatest underestimation among patients with severe exercise-induced pulmonary hypertension (EIPH). Estimation of eRAP during exercise from resting eRAP improved discrimination of patients with or without EIPH (area under the curve 0.81), with minimal bias (5 mmHg), but wide limits of agreement (-14-25 mmHg). CONCLUSIONS: The RV-RA pressure gradient can be estimated with reasonable accuracy during exercise when measurable. However, RA hypertension frequently develops in patients with EIPH, and the inability to noninvasively account for this leads to substantial underestimation of exercise pulmonary artery pressures.

Outcomes After Noncardiac Surgery for Patients with Pulmonary Hypertension: A Historical Cohort Study.

OBJECTIVE: Pulmonary hypertension (PH) is a substantial preoperative risk factor. For this study, morbidity and mortality were examined after noncardiac surgery in patients with precapillary PH. DESIGN: A retrospective cohort study. SETTING: Quaternary medical center in Rochester, MN. PARTICIPANTS: Adults with PH undergoing noncardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The PH and surgical databases were reviewed from 2010 to 2017. Patients were excluded if PH was attributable to left-sided heart disease or they had undergone cardiac or transplantation surgeries. To assess whether PH-specific diagnostic or cardiopulmonary testing parameters were predictive of perioperative complications, generalized estimating equations were used. Of 196 patients with PH, 53 (27%) experienced 1 or more complications, including 5 deaths (3%) within 30 days. After adjustment for age and PH type, there were more complications in those undergoing moderate- to high-risk versus low-risk procedures (odds ratio [OR] 4.17 [95% confidence interval {CI} 2.07-8.40]; p < 0.001). After adjustment for age, surgical risk, and PH type, the complication risk was greater for patients with worse functional status (OR 2.39 [95% CI 1.19-4.78]; p = 0.01 for classes III/IV v classes I/II) and elevated serum N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) (OR 2.28 [95% CI 1.05-4.96]; p = 0.04 for ≥300 v <300 pg/mL). After adjusting for age, surgical risk, and functional status, elevated NT-proBNP remained associated with increased risk (OR 2.23 [95% CI 1.05-4.76]; p = 0.04). CONCLUSION: PH patients undergoing noncardiac surgery have a high frequency of complications. Worse functional status, elevated serum NT-proBNP, and higher-risk surgery are predictive of worse outcome.

Overview of Optimal Techniques for Pericardiocentesis in Contemporary Practice.

PURPOSE OF REVIEW: This review summarizes the optimal techniques for the performance of pericardiocentesis in contemporary practice, highlighting the indications, contraindications, and techniques used. Routine pericardial catheter management and the diagnostic role of pericardial fluid analysis are described. RECENT FINDINGS: Echocardiographic-guided pericardiocentesis should be considered the therapy of choice in current clinical practice and may be performed safely despite the presence of coagulopathy and thrombocytopenia in the hands of expert operators. Computed tomography (CT)-guided techniques may provide a useful adjunctive tool in patients with poor acoustic windows or complex loculated effusions. Conservative management utilizing pericardiocentesis may be considered in select patients with device lead and interventional-related pericardial effusions. Echocardiographic-guided pericardiocentesis with extended pericardial drainage (goal output < 50 mL/24 h) should be considered the standard of care in contemporary practice. Pericardial fluid analysis should be tailored based on the clinical history and appearances of the pericardial fluid.

The neurohormonal basis of pulmonary hypertension in heart failure with preserved ejection fraction.

AIMS: Pulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve. METHODS AND RESULTS: Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = -0.52 and -0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s' and e' tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e', r = -0.59 and -0.67, both P < 0.001), reduced cardiac output responses to exercise (r = -0.59 and -0.61, both P < 0.0001), and more severely impaired peak VO2 (r = -0.60 and -0.67, both P < 0.0001). CONCLUSION: Subjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype. CLINICAL TRIAL REGISTRATION: NCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search.

Changes in Right Ventricle Function After Mitral Valve Repair Surgery.

BACKGROUND: Right ventricular (RV) dysfunction can occur after cardiac surgery and persist for years. We assessed perioperative RV systolic function in patients undergoing mitral valve (MV) repair and further compared minimally invasive robotic-assisted mitral valve repair (MIMVr) vs standard 'open' MV repair (MVr). Speckle tracking (RV free wall strain [RVS]) was used as a sensitive echocardiography method to assess RV function. METHODS: Retrospective analysis, over 3 years, of consecutive patients (n = 158) referred to Mayo Clinic (Rochester, MN, USA). Preoperative, pre-discharge and 1 year transthoracic echocardiograms were reviewed. A prospective pilot study was performed for sample size estimation. Primary outcome was RV free wall strain (RVS). RESULTS: Right ventricular free wall strain declined after MV repair surgery (-22.6 ± 7% vs -15 ± 6%, p < 0.001). There were smaller reductions in RVS in MIMVr vs MVr group (-6.0 ± 9% vs -10.3 ± 8%, p < 0.01), which persisted after adjusting for baseline values (RVS treatment effect 1.5%, p = 0.007). There was greater recovery in MIMVr vs MVr group at 1 year follow-up vs pre-surgery values (-3.4 ± 9% vs -8.1 ± 8% respectively, p < 0.001, RVS treatment effect 1.7%, p = 0.001). Bypass time was higher in the MIMVr group (80min ± 22 vs 40min ± 20, p < 0.0001). The echo findings remained significant correcting for age, pulmonary pressures and change in ejection fraction. CONCLUSIONS: Right ventricular systolic dysfunction is common after MV repair surgery. Deterioration in RV contraction is less pronounced following MIMVr vs MVr and is associated with enhanced RV functional recovery at 1 year, albeit not to preoperative levels. This may potentially be associated with clinical functional improvement but further studies are warranted to investigate this.

Echocardiographic Diastolic Stress Testing: What Does It Add?

PURPOSE OF REVIEW: Diastolic stress echocardiography may help facilitate the attribution of exertional dyspnea to cardiac and non-cardiac disease. It represents a non-invasive hemodynamic test to assess the patients with unexplained dyspnea. It can improve the diagnosis of heart failure with preserved ejection fraction (HFpEF) or diastolic heart failure. RECENT FINDINGS: A number of studies have validated exercise E/e' as a measure of left ventricular (LV) filling pressure against invasively measured LV filling pressure using simultaneous exercise echocardiography-catheterization studies. Addition of E/e' during exercise echocardiography improved sensitivity for diagnosis of HFpEF compared with resting assessment alone, and its specificity can be improved if tricuspid regurgitation velocity also increases above the normal range with exercise. The independent prognostic value of exercise E/e' has also been well delineated in a number of studies. Diastolic stress exercise echocardiography should be considered for all patients with unexplained or exertional dyspnea and normal diastolic filling pressure or grade 1 diastolic dysfunction on resting echocardiography. Addition of diastolic assessment with exercise echocardiography improves the sensitivity of the test in patients with dyspnea and there are sufficient data to integrate diastolic exercise test into our clinical practice.

Haemodynamics, dyspnoea, and pulmonary reserve in heart failure with preserved ejection fraction.

Aims: Increases in left ventricular filling pressure are a fundamental haemodynamic abnormality in heart failure with preserved ejection fraction (HFpEF). However, very little is known regarding how elevated filling pressures cause pulmonary abnormalities or symptoms of dyspnoea. We sought to determine the relationships between simultaneously measured central haemodynamics, symptoms, and lung ventilatory and gas exchange abnormalities during exercise in HFpEF. Methods and results: Subjects with invasively-proven HFpEF (n = 50) and non-cardiac causes of dyspnoea (controls, n = 24) underwent cardiac catheterization at rest and during exercise with simultaneous expired gas analysis. During submaximal (20 W) exercise, subjects with HFpEF displayed higher pulmonary capillary wedge pressures (PCWP) and pulmonary artery pressures, higher Borg perceived dyspnoea scores, and increased ventilatory drive and respiratory rate. At peak exercise, ventilation reserve was reduced in HFpEF compared with controls, with greater dead space ventilation (higher VD/VT). Increasing exercise PCWP was directly correlated with higher perceived dyspnoea scores, lower peak exercise capacity, greater ventilatory drive, worse New York Heart Association (NYHA) functional class, and impaired pulmonary ventilation reserve. Conclusion: This study provides the first evidence linking altered exercise haemodynamics to pulmonary abnormalities and symptoms of dyspnoea in patients with HFpEF. Further study is required to identify the mechanisms by which haemodynamic derangements affect lung function and symptoms and to test novel therapies targeting exercise haemodynamics in HFpEF.

Role of Diastolic Stress Testing in the Evaluation for Heart Failure With Preserved Ejection Fraction: A Simultaneous Invasive-Echocardiographic Study.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging and relies largely on demonstration of elevated cardiac filling pressures (pulmonary capillary wedge pressure). Current guidelines recommend use of natriuretic peptides (N-terminal pro-B type natriuretic peptide) and rest/exercise echocardiography (E/e' ratio) to make this determination. Data to support this practice are conflicting. METHODS: Simultaneous echocardiographic-catheterization studies were prospectively conducted at rest and during exercise in subjects with invasively proven HFpEF (n=50) and participants with dyspnea but no identifiable cardiac pathology (n=24). RESULTS: N-Terminal pro-B type natriuretic peptide levels were below the level considered to exclude disease (≤125 pg/mL) in 18% of subjects with HFpEF. E/e' ratio was correlated with directly measured pulmonary capillary wedge pressure at rest (r=0.63, P<0.0001) and during exercise (r=0.57, P<0.0001). Although specific, current guidelines were poorly sensitive, identifying only 34% to 60% of subjects with invasively proven HFpEF on the basis of resting echocardiographic data alone. Addition of exercise echocardiographic data (E/e' ratio>14) improved sensitivity (to 90%) and thus negative predictive value, but decreased specificity (71%). CONCLUSIONS: Currently proposed HFpEF diagnostic guidelines on the basis of resting data are poorly sensitive. Adding exercise E/e' data improves sensitivity and negative predictive value but compromises specificity, suggesting that exercise echocardiography may help rule out HFpEF. These results question the accuracy of current approaches to exclude HFpEF on the basis of resting data alone and reinforce the value of exercise testing using invasive and noninvasive hemodynamic assessments to definitively confirm or refute the diagnosis of HFpEF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01418248.

Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction.

BACKGROUND: Exercise intolerance is common in people with heart failure and preserved ejection fraction (HFpEF). Right ventricular (RV) dysfunction has been shown at rest in HFpEF but little data are available regarding dynamic RV-pulmonary artery (PA) coupling during exercise. METHODS AND RESULTS: Subjects with HFpEF (n = 50) and controls (n = 24) prospectively underwent invasive cardiopulmonary exercise testing using high-fidelity micromanometer catheters along with simultaneous assessment of RV and left ventricular (LV) mechanics by echocardiography. Compared with controls at rest, subjects with HFpEF displayed preserved RV systolic and diastolic mechanics (RV s' and e'), impaired LV s' and e', higher biventricular filling pressures, and higher pulmonary artery pressures. On exercise, subjects with HFpEF displayed less increase in stroke volume, heart rate, and cardiac output (CO), with blunted increase in CO relative to O2 consumption (VO2). Enhancement in RV systolic and diastolic function on exercise was impaired in HFpEF compared with controls. Exercise-induced PA vasodilation was reduced in HFpEF in correlation with greater venous hypoxia. Elevations in biventricular filling pressures and limitations in CO reserve were strongly correlated with abnormal enhancement in ventricular mechanics in the RV and LV during stress. CONCLUSIONS: In addition to limited LV reserve, patients with HFpEF display impaired RV reserve during exercise that is associated with high filling pressures and inadequate CO responses. These findings highlight the importance of biventricular dysfunction in HFpEF and suggest that novel therapies targeting myocardial reserve in both the left and right heart may be effective to improve clinical status.

Effect of positive end-expiratory pressure on porcine right ventricle function assessed by speckle tracking echocardiography.

BACKGROUND: Right ventricle (RV) dysfunction and hypotension can be induced by high levels of positive end-expiratory pressure (PEEP). We sought to determine in an animal model if a novel ultrasound analysis technique: speckle tracking echocardiography (STE), could determine deterioration in RV function induced by PEEP and to compare this to a conventional method of RV analysis: fractional area change (FAC). STE is a sensitive, angle-independent method for describing cardiac deformation ('strain') and is particularly useful in analyzing RV function as has been shown in pulmonary hypertension cohorts. METHODS: Ten pigs, 40-90 kg, anaesthetized, fully mechanically ventilated at 6 ml/kg were subject to step-wise escalating levels of PEEP at two-minute intervals (0, 5, 10, 15, 20, 25 and 30 cmH20). Intracardiac echocardiography was used to image the RV as transthoracic and transesophageal echocardiography did not give sufficient image quality or flexibility. Off-line STE analysis was performed using Syngo Velocity Vector Imaging (Seimens Medical Solutions Inc., USA). STE systolic parameters are RV free wall strain (RVfwS) and strain rate (RVfwSR) and the diastolic parameter RV free wall strain rate early relaxation (RVfwSRe). RESULTS: With escalating levels of PEEP there was a clear trend of reduction in STE parameters (RVfwS, RVfwSR, RVfwSRe) and FAC. Significant hypotension (fall in mean arterial blood pressure of 20 mmHg) occurred at approximately PEEP 15 cmH2O. Comparing RVfwS, RVfwSR and RVfwSRe values at different PEEP levels showed a significant difference at PEEP 0 cmH2O vs PEEP 10 cmH2O and above. FAC only showed a significant difference at PEEP 0 cmH2O vs PEEP 20 cmH2O and above. 30% of pigs displayed dyssychronous RV free wall contraction at the highest PEEP level reached. CONCLUSIONS: STE is a sensitive method for determining RV dysfunction induced by PEEP and deteriorated ahead of a conventional assessment method: FAC. RVfwS decreased to greater extent compared to baseline than FAC, earlier in the PEEP escalation process and showed a significant decrease before there was a clinical relevant decrease in mean arterial blood pressure. Studies in ICU patients using transthoracic echocardiography are warranted to further investigate the most sensitive echocardiography method for detecting RV dysfunction induced by mechanical ventilation.

Reference Values for Right Ventricular Strain in Patients without Cardiopulmonary Disease: A Prospective Evaluation and Meta-Analysis.

BACKGROUND: Myocardial strain imaging is a sensitive echocardiographic technique for identifying ventricular dysfunction. The aim of this study was to describe a reference range for right ventricular (RV) strain in subjects without cardiopulmonary disease and to report these values from a systematic review and meta-analysis of the current literature. METHODS: Prospective online measurement of RV free wall longitudinal systolic strain using speckle tracking echocardiography (STE) was performed in 116 subjects with normal echocardiograms and without cardiopulmonary disease or risk factors. A systematic search of studies in EMBASE and Medline reporting RV strain values was performed through February 2014. RESULTS: The mean age was 48 ± 16 years and 58% were female. Mean RV strain was -26 ± 4%. Ten studies involving a total of 486 patients met our inclusion criteria. The mean age range was 43-57 years and 59% were female. All prior studies were performed with offline strain analysis, and 9 used a GE Healthcare strain analysis software system. The weighted estimate of RV free wall strain measured using tissue Doppler imaging (4 studies) was -27 ± 1% (95% confidence interval [CI] -30% to -25%) and with STE (8 studies, including the current study data) -27 ± 2% (95% CI -29% to -24%), respectively. CONCLUSIONS: A reference range for RV strain in subjects without cardiopulmonary disease is presented. These data may help facilitate the routine clinical measurement of RV strain in patients referred for right heart echocardiography assessment.

Outcome prediction in sepsis: speckle tracking echocardiography based assessment of myocardial function.

INTRODUCTION: Speckle tracking echocardiography (STE) is a relatively novel and sensitive method for assessing ventricular function and may unmask myocardial dysfunction not appreciated with conventional echocardiography. The association of ventricular dysfunction and prognosis in sepsis is unclear. We sought to evaluate frequency and prognostic value of biventricular function, assessed by STE in patients with severe sepsis or septic shock. METHODS: Over an eighteen-month period, sixty patients were prospectively imaged by transthoracic echocardiography within 24 hours of meeting severe sepsis criteria. Myocardial function assessment included conventional measures and STE. Association with mortality was assessed over 12 months. RESULTS: Mortality was 33% at 30 days (n = 20) and 48% at 6 months (n = 29). 32% of patients had right ventricle (RV) dysfunction based on conventional assessment compared to 72% assessed with STE. 33% of patients had left ventricle (LV) dysfunction based on ejection fraction compared to 69% assessed with STE. RV free wall longitudinal strain was moderately associated with six-month mortality (OR 1.1, 95% confidence interval, CI, 1.02-1.26, p = 0.02, area under the curve, AUC, 0.68). No other conventional echocardiography or STE method was associated with survival. After adjustment (for example, for mechanical ventilation) severe RV free wall longitudinal strain impairment remained associated with six-month mortality. CONCLUSION: STE may unmask systolic dysfunction not seen with conventional echocardiography. RV dysfunction unmasked by STE, especially when severe, was associated with high mortality in patients with severe sepsis or septic shock. LV dysfunction was not associated with survival outcomes.

Machine Learning for Diagnosis of Pulmonary Hypertension by Echocardiography.

OBJECTIVE: To evaluate a machine learning (ML)-based model for pulmonary hypertension (PH) prediction using measurements and impressions made during echocardiography. METHODS: A total of 7853 consecutive patients with right-sided heart catheterization and transthoracic echocardiography performed within 1 week from January 1, 2012, through December 31, 2019, were included. The data were split into training (n=5024 [64%]), validation (n=1275 [16%]), and testing (n=1554 [20%]). A gradient boosting machine with enumerated grid search for optimization was selected to allow missing data in the boosted trees without imputation. The training target was PH, defined by right-sided heart catheterization as mean pulmonary artery pressure above 20 mm Hg; model performance was maximized relative to area under the receiver operating characteristic curve using 5-fold cross-validation. RESULTS: Cohort age was 64±14 years; 3467 (44%) were female, and 81% (6323/7853) had PH. The final trained model included 19 characteristics, measurements, or impressions derived from the echocardiogram. In the testing data, the model had high discrimination for the detection of PH (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.80 to 0.85). The model's accuracy, sensitivity, positive predictive value, and negative predictive value were 82% (1267/1554), 88% (1098/1242), 89% (1098/1241), and 54% (169/313), respectively. CONCLUSION: By use of ML, PH could be predicted on the basis of clinical and echocardiographic variables, without tricuspid regurgitation velocity. Machine learning methods appear promising for identifying patients with low likelihood of PH.

Prevalence and Prognostic Implications of Pulmonary Hypertension in Patients With Severe Aortic Regurgitation.

Background: Pulmonary hypertension (PH) has been shown to be associated with worse outcomes in patients with aortic regurgitation (AR) in small older studies. Objectives: The authors sought to evaluate the prevalence of PH in patients with severe AR, its impact on mortality and symptoms, and regression after aortic valve replacement (AVR). Methods: A total of 821 consecutive patients with chronic ≥ moderate-severe AR on echocardiography from 2004 to 2019 were retrospectively analyzed. PH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg on transthoracic echocardiogram (mild-moderate PH: RVSP 40-59 mm Hg, severe PH: RVSP > 60 mm Hg). Clinical and echocardiographic data were extracted from the electronic medical record and echocardiographic reports. The diastolic function and filling pressures were manually assessed and checked, and the left ventricular (LV) volumes were traced by a level 3-trained echocardiographer. The primary objectives were prevalence of PH in patients with ≥ moderate-severe AR, its risk associations and impact on all-cause mortality as the primary outcome. Secondary outcomes were impact of PH on symptoms and change in RVSP at discharge post-AVR. Logistic and Cox proportional hazards regression were used to analyze these outcomes. Results: The mean age was 61.2 ± 17 years, and 162 (20%) were women. Mild-moderate PH was present in 91 (11%) patients and severe PH in 27 (3%). Larger LV size, elevated LV filling pressures, and ≥ moderate tricuspid regurgitation were associated with PH. During follow-up of 7.3 (6.3-7.9) years, 188 patients died. Compared to those without PH, risk of mortality was higher in mild-moderate PH (adjusted HR: 1.59 (95% CI: 1.07-2.36) (P = 0.021)) and severe PH (adjusted HR: 2.90 (95% CI: 1.63-5.15) (P < 0.001)). Symptoms were also more prevalent in those with PH (P = 0.004). Of 396 patients who underwent AVR during the study period, 57 had PH. AVR similarly improved survival in patients without and with PH (P for interaction = 0.23), and there was regression in RVSP (≥8 mm Hg drop) at discharge post-AVR in 35/57 (61%) patients with PH. Conclusions: PH was present in 14% of patients with AR and was associated with higher mortality and symptoms. The survival benefit of AVR was similar in patients without and with PH.

Echocardiography-Based Deep Learning Model to Differentiate Constrictive Pericarditis and Restrictive Cardiomyopathy.

BACKGROUND: Constrictive pericarditis (CP) is an uncommon but reversible cause of diastolic heart failure if appropriately identified and treated. However, its diagnosis remains a challenge for clinicians. Artificial intelligence may enhance the identification of CP. OBJECTIVES: The authors proposed a deep learning approach based on transthoracic echocardiography to differentiate CP from restrictive cardiomyopathy. METHODS: Patients with a confirmed diagnosis of CP and cardiac amyloidosis (CA) (as the representative disease of restrictive cardiomyopathy) at Mayo Clinic Rochester from January 2003 to December 2021 were identified to extract baseline demographics. The apical 4-chamber view from transthoracic echocardiography studies was used as input data. The patients were split into a 60:20:20 ratio for training, validation, and held-out test sets of the ResNet50 deep learning model. The model performance (differentiating CP and CA) was evaluated in the test set with the area under the curve. GradCAM was used for model interpretation. RESULTS: A total of 381 patients were identified, including 184 (48.3%) CP, and 197 (51.7%) CA cases. The mean age was 68.7 ± 11.4 years, and 72.8% were male. ResNet50 had a performance with an area under the curve of 0.97 to differentiate the 2-class classification task (CP vs CA). The GradCAM heatmap showed activation around the ventricular septal area. CONCLUSIONS: With a standard apical 4-chamber view, our artificial intelligence model provides a platform to facilitate the detection of CP, allowing for improved workflow efficiency and prompt referral for more advanced evaluation and intervention of CP.

Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients.

BACKGROUND: Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. METHODS: We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. RESULTS: Over a mean follow-up of 3.3 ± 3.4 years, patients with E/e' ≥15 with exercise (n = 1,323; 9.2%) had lower exercise capacity (7.3 ± 2.1 vs 9.1 ± 2.4 metabolic equivalents, P < .0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P < .0001). Approximately 6% (n = 837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P < .0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR] = 0.58 [0.48-0.69]; P < .0001), had higher risk than if E/e' ≤8 (HR = 1.56 [1.37-1.78], P < .0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P < .0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR = 8.99 [4.7-17.3], P < .0001). CONCLUSION: Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.