Pellikka, Patricia A.

Abstract Background: Aortic valve stenosis (AS) commonly causes left ventricular (LV) pressure overload; thus, identifying patients with adverse remodeling/early LV dysfunction is critical. We compared 2-dimensional (2D) to 3-dimensional (3D) echocardiographic measures of LV myocardial deformation in patients with severe AS and studied the relation of LV preload and afterload (Zva) to myocardial deformation. Methods: We prospectively included 168 symptomatic patients (72±12 years) with severe AS and ejection fractions ≥50%. Strain parameters from those patients were compared with normal values found in the literature. 3D full-volume and 2D images were analyzed for global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), systolic strain rate (SRs), basal rotation (Rotmax-B), apical rotation (Rotmax-A), and peak systolic twist (Twistmax). Results: 2D–GLS and 2D–GCS decreased significantly compared with normal values (P˂.001 and P=.02, respectively); 2D Rotmax-B and Twistmax increased (P˂.001 vs normal values). Agreement between 2D–GLS and 3D–GLS by concordance correlation coefficient was 0.49 (95% CI, 0.39-0.57) in patients with AS. Both 2D– and 3D–GLS correlated with valvulo-arterial impedance (Zva) (r=0.34, P<.001; and r=0.23, P=.003, respectively). Conclusion: In patients with severe AS, GLS and GCS decreased, and basal rotation and twist increased to maintain LV ejection fraction. 2D– and 3D–GLS had a relatively fair agreement. Both 2D– and 3D–GLS correlated modestly with Zva.

Background: Sex and age have long been known to affect the ECG. Several biologic variables and anatomic factors may contribute to sex and age-related differences on the ECG. We hypothesized that a convolutional neural network (CNN) could be trained through a process called deep learning to predict a person’s age and self-reported sex using only 12-lead ECG signals. We further hypothesized that discrepancies between CNN-predicted age and chronological age may serve as a physiological measure of health. Methods: We trained CNNs using 10-second samples of 12-lead ECG signals from 499 727 patients to predict sex and age. The networks were tested on a separate cohort of 275 056 patients. Subsequently, 100 randomly selected patients with multiple ECGs over the course of decades were identified to assess within-individual accuracy of CNN age estimation. Results: Of 275 056 patients tested, 52% were males and mean age was 58.6±16.2 years. For sex classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97 in the independent test data. Age was estimated as a continuous variable with an average error of 6.9±5.6 years (R-squared =0.7). Among 100 patients with multiple ECGs over the course of at least 2 decades of life, most patients (51%) had an average error between real age and CNN-predicted age of <7 years. Major factors seen among patients with a CNN-predicted age that exceeded chronologic age by >7 years included: low ejection fraction, hypertension, and coronary disease ( P <0.01). In the 27% of patients where correlation was >0.8 between CNN-predicted and chronologic age, no incident events occurred over follow-up (33±12 years). Conclusions: Applying artificial intelligence to the ECG allows prediction of patient sex and estimation of age. The ability of an artificial intelligence algorithm to determine physiological age, with further validation, may serve as a measure of overall health.

ObjectiveTo evaluate whether global peak systolic strain (PSS) and peak systolic strain rate (PSSR) derived from velocity vector imaging (VVI) allow early recognition of regional and global right ventricular (RV) dysfunction and the impact of this on left ventricular (LV) function in patients with pulmonary hypertension (PHT).BackgroundRV function is an important determinant of prognosis in patients with heart failure, pulmonary hypertension, heart transplant, and congenital heart diseases. However, evaluation of the right ventricle is often limited by its complex geometry and inadequate visualization of RV free wall. Furthermore, the impact of RV dysfunction on the LV function is not well elucidated.MethodsNinety‐nine participants, 35 control patients with normal RV systolic pressure (RVSP) (<30 mm Hg) and 64 patients with PHT (25 with mild‐to‐moderate increase in RVSP [≥36 and <60 mm Hg] and 39 with severe increase in RVSP [≥60 mm Hg]), underwent comprehensive echo‐Doppler assessment and velocity vector imaging (VVI) for strain rate analysis. RV regional peak systolic and diastolic tangential velocity, strain, and strain rate were obtained from the basal, mid and apical segments of the RV free wall and interventricular septum (IVS) from apical 4‐chamber view at end‐expiration. Similar data were obtained from eighteen LV segments from apical 4‐chamber, 2‐chamber, and long‐axis views.ResultsPeak systolic strain, strain rate, and tangential velocity at all segments in the RV free wall and IVS were decreased compared to controls in patients with PHT (P < 0.001). Significant correlation (r > 0.60; P < 0.001) was noted between RVSP and systolic and diastolic strain and strain rate at basal segment in IVS and global RV function. Peak early diastolic strain rate at all segments was also decreased in PHT patients compared with control patients (P < 0.01). Furthermore, RV systolic and diastolic strain and strain rate were lower in group 2 with mild‐to‐moderate hypertension while the conventional echo parameters were normal. Except for IVS segments, other LV segments had no statistical differences in systolic and diastolic velocity, strain, and strain rate compared to controls. However, they were lower than the published normal range.ConclusionsStrain and strain rate derived from VVI demonstrates early recognition of systolic and diastolic RV dysfunction in patients with PHT compared to controls. PHT is associated with global and regional RV systolic and diastolic dysfunction. Systolic and diastolic strain and strain rate from LV was lower compared to controls but were not statistically significant. This may indicate subclinical LV dysfunction in these patients, suggesting that conventional LV function parameters may not be sensitive to recognize subclinical LV dysfunction.

AbstractObjectivesWe sought to validate a deep learning algorithm designed to predict an ejection fraction (EF) less than or equal to 35% based on the 12‐lead electrocardiogram (ECG) in a large prospective cohort.BackgroundPatients undergoing routine ECG may have undetected left ventricular (LV) dysfunction that warrants further echocardiographic assessment. However, identification of these patients can be challenging.MethodsWe applied the algorithm to all ECGs interpreted by the Mayo Clinic ECG laboratory in September 2018. The performance of the algorithm was tested among patients with recent echocardiographic assessments of LV function. We also applied the algorithm in patients with no recent echocardiographic assessments of LV function to determine the rate of new “positive screens.”ResultsAmong 16 056 adult patients who underwent routine ECG, 8600 (age 67.1 ± 15.2 years, 45.6% male), had a transthoracic echocardiogram (TTE) and 3874 patients had a TTE and ECG less than 1 month apart. Among these patients, the algorithm was able to detect an EF less than or equal to 35% with 86.8% specificity, 82.5% sensitivity, and 86.5% accuracy, (area under the curve, 0.918). Among 474 “false‐positives screens,” 189 (39.8%) had an EF of 36% to 50%. Among patients with no prior TTE, the algorithm identified 3.5% of the patients with suspected EF less than or equal to 35%. Exploratory analysis suggests false positives could be reduced by assessing NT‐pro‐BNP after the initial “positive screen.”ConclusionsA deep learning algorithm detected depressed LV function with good accuracy in routine practice. Further studies are needed to validate the algorithm in patients with no prior echocardiogram and to assess the impact on echocardiography utilization, cost, and clinical outcomes.

Background Optimal management of patients with severe mitral stenosis ( MS ) and low transmitral gradient is incompletely understood. Methods and Results We examined 101 consecutive patients with severe rheumatic MS (mitral valve area ≤1.5 cm 2 ) who underwent balloon valvuloplasty. Low gradient was defined as mean transmitral gradient <10 mm Hg and low flow as stroke volume index ≤35 mL/m 2 by echocardiography. Symptoms and mortality data were collected. Systolic, diastolic, and arterial function were characterized by measuring left ventricular (LV) end‐systolic elastance, LV stiffness constant (β), diastolic capacitance (predicted LV end‐diastolic volume at a common LV filling pressure of 30 mm Hg), and effective arterial elastance. Low gradient (<10 mm Hg) was present in 55 patients, including low flow/low gradient in 11 and normal flow/low gradient in 44 patients, and high gradient was present in 46 patients. Participants with low‐flow/low‐gradient (LG) MS were older with higher rates of atrial fibrillation (64%) and subvalvular thickening, higher afterload, and decreased LV compliance with lower ejection fraction (57±10% versus 65±4% versus 63±6%, P =0.002) but similar end‐systolic elastance compared with patients with normal‐flow/ LG and high‐gradient MS . The normal‐flow/ LG group had larger mitral valve area and lower left atrial pressure by catheterization, as well as favorable long‐term outcomes compared with the low‐flow/ LG and high‐gradient MS group. A total of 40% of patients with LG MS had no symptomatic benefit from valvuloplasty compared with 18% of patients with high‐gradient MS ( P =0.02). Conclusions Presence of low gradient in patients with severe MS was associated with lesser symptomatic benefit from valvuloplasty. In the subset with low stroke volume index, this may be related to independent ventricular‐vascular uncoupling, decreased LV compliance, and high prevalence of atrial fibrillation in addition to intrinsic MS .

AbstractBackgroundThe effect of utilizing transapical (TA) access for transcatheter aortic valve replacement (TAVR) on cardiac function has not been well studied.AimsThe aim of this retrospective study is to determine the direct effects of TA access for TAVR on myocardial function parameters and their correlation with 4‐year survival.MethodsThree hundred and thirty propensity matched patients, who underwent TAVR using Sapien valve (Edwards Lifesciences Corp, Irvine, CA) between February 15, 2012 and June 17, 2016 (115 TA and 115 transfemoral [TF] routes) were studied. The pre‐ and 1 month post‐TAVR echocardiographic features of both groups were compared. The 4‐year survival in both groups was analyzed.ResultsBaseline clinical characteristics, diastolic function parameters, left ventricular (LV) chamber size, and ejection fraction were similar between matched TA and TF groups. At 1 month following TAVR, there was a significant increase in stroke volume index (SVI) in both TA (mean increase 7 cm3/m2; P = 0.03) and TF groups (mean increase 7 cm3/m2; P < 0.001). Left ventricular ejection fraction (LVEF) significantly increased post TF TAVR (mean increase 2%; P = 0.008), but no significant increase was observed post TA TAVR (mean increase 1%; P = 0.27). Both groups had significant improvement in aortic valve (AV) hemodynamics post‐TAVR (P < 0.001). Overall, there were no significant differences in the mean change of SVI, LVEF, or left ventricular end diastolic dimensions (LVEDDs) post TA versus TF TAVR. There was no significant difference in 4‐year survival in the TF compared to TA group (49% vs 50%, P = 0.43).ConclusionBoth TA and TF TAVR were equally associated with favorable changes in LV SVI and AV hemodynamics in 30 days. TA TAVR patients had similar 4 year survival to propensity matched TF TAVR; therefore, TA TAVR remains an acceptable alternative access route in patients not amenable to TF TAVR.

Objective The presence of aortic paravalvular leak (PVL) is associated with lower survival, but a direct comparison of its impact after transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) has not been performed. This study sought to determine the differential influence of PVL on survival following TAVR versus SAVR and in patients with varying levels of risk as defined by the Society of Thoracic Surgeons (STS) risk score. Methods Patients with and without postprocedural PVL were identified from 2290 patients undergoing TAVR or SAVR at Mayo Clinic between 2008 and 2014. The primary endpoint was overall survival. Results There were 588 patients with PVL (374 TAVR, 214 SAVR): age 78±11 years, 63% male and mean follow-up of 3±2 years. PVL was trivial/mild in 442 (75%) patients. In propensity-matched analyses (n=86 per group), the overall survival at 1 and 4 years was 93% and 56% vs 89% and 61% in patients with PVL after TAVR versus SAVR, respectively (p=0.43). The presence or degree of PVL severity had no influence on survival of patients with high STS score (≥8%), while the presence of greater than mild PVL predicted worse survival in those with STS score <8%. During the first year after PVL diagnosis, while either improvement or stable PVL grade was seen in the majority of patients, worsening of PVL grade was more common in the TAVR group (19%) versus the SAVR group (4%) (p<0.0001). Conclusions At mid-term follow-up, the presence of PVL was associated with equally unfavourable outcomes following SAVR or TAVR. In patients with high STS risk score, the presence of PVL was not independently associated with increased mortality.

Introduction: Dobutamine stress echocardiography (DSE) is frequently used to screen for obstructive coronary artery disease in the pre-liver transplant evaluation. Although atropine is a commonly used adjunctive medication, no study has evaluated its side effect profile in patients with end-stage liver disease (ESLD). Research Question: What is the safety of atropine in candidates undergoing pre-liver transplant evaluation when atropine is used in stress testing? Design: This multicenter, prospective study enrolled patients over a 6-month period undergoing pre-liver transplant evaluation. Each patient completed a questionnaire assessing anticholinergic-related symptoms within 24 hours of testing and 48 hours following. Comparisons were made among patients receiving any atropine dose versus those who did not and among patients receiving at least 1 mg atropine and those receiving less/none. Results: Forty patients were evaluated, and 32 (80%) had adjunctive atropine administered. No differences in clinical characteristics were noted. In comparisons among patients receiving any dose of atropine with those who did not, questionnaire results indicated a higher rate of nausea prior to testing and higher overall symptom severity following testing in patients not receiving atropine. In comparisons among patients receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no difference in pre- or posttesting questionnaire responses was present. No patient in the study required reversal agents or hospitalization within 7 days of testing. Conclusions: Atropine, a hepatically metabolized medication, did not predispose patients with ESLD to an increased symptom burden, and clinical outcomes related to DSE were unaffected.