Pellikka, Patricia A

Abstract Aims Despite improvements in cardiac haemodynamics and symptoms, long-term mortality remains increased in some patients after aortic valve replacement (AVR). Limited data exist on the prognostic role of left ventricular (LV) chamber stiffening in these patients. Methods and results We performed a retrospective analysis in 1893 patients with severe aortic stenosis (AS) referred for AVR. LV end-diastolic pressure–volume relations (EDPVR, P = αV^β) were reconstructed from echocardiographic measurements of end-diastolic volumes and estimates of end-diastolic pressure (EDP). The impact of EDPVR-derived LV chamber stiffness (CS30, at 30 mmHg EDP) on all-cause mortality after AVR was evaluated. Mean age was 76 ± 10 years, 39% were females, and ejection fraction (EF) was 61 ± 12%. The mean LV chamber stiffness (CS30) was 2.2 ± 1.3 mmHg/mL. A total of 877 (46%) patients had high LV stiffness (CS30 >2 mmHg/mL). In these patients, the EDPVR curves were steeper and shifted leftwards, indicating higher stiffness at all pressure levels. These patients were slightly older, more often female, and had more prevalent comorbidities compared to patients with low stiffness. At follow-up [median 4.2 (interquartile range 2.8–6.3) years; 675 deaths], a higher CS30 was associated with lower survival (hazard ratio: 2.7 for severe vs. mild LV stiffening; P < 0.0001), both in patients with normal or reduced EF. At multivariate analysis, CS30 remained an independent predictor, even after adjusting for age, sex, comorbidities, EF, LV remodelling, and diastolic dysfunction. Conclusion Higher preoperative LV chamber stiffening in patients with severe AS is associated with poorer outcome despite successful AVR.

Objectives To test the relationship between increasing severity of obesity, calculated risk and observed outcomes. Methods Patients with symptoms suggestive of coronary artery disease (CAD) (n=10 003) were stratified according to body mass index (BMI). We compared risk factors, pooled risk scores and physicians’ perception of risk. Cox regression tested the association between BMI and (1) presence of obstructive CAD and (2) composite clinical endpoints (death, cardiovascular death, unstable angina hospitalisation and myocardial infarction). Results BMI was ≥30 kg/m2 in 48% of patients and ≥35 in 20%. Increasingly obese patients were younger, female and non-smoking but with higher prevalence of hypertension, diabetes, black race and sedentary lifestyle. Pooled risk estimates of CAD were highest in those with mid-range BMI. In contrast, physicians’ estimation of the likelihood of significant CAD based on clinical impression increased progressively with BMI. For a 10% increase in the Diamond-Forrester probability of CAD, the adjusted OR for obstructive CAD was 1.5 (95% CI 1.4 to 1.5) in patients with BMI <35, but only 1.2 (95% CI 1.1 to 1.3) in those with BMI ≥35 (interaction p<0.001). Framingham Risk Score increased across increasing BMI categories. However, there was a strong and consistent inverse relationship between degree of obesity and all three composite clinical endpoints over a median 25 months of follow-up. Conclusions Despite perceptions of higher risk and higher risk scores, increasingly obese patients had obstructive CAD less frequently than predicted and had fewer adverse clinical outcomes. There is a need for risk assessment tools and guidelines that account for obesity. Trial registration number NCT01174550.

Background: Mitral stenosis frequently coexists in patients with severe aortic stenosis. Mitral stenosis severity evaluation is challenging in the setting of combined aortic stenosis and mitral stenosis because of hemodynamic interactions between the 2 valve lesions. The impact of aortic valve replacement (AVR) for severe aortic stenosis on mitral stenosis is unknown. This study aimed to assess the effect of AVR on mitral stenosis hemodynamics and the clinical outcomes of patients with severe aortic stenosis with and without mitral stenosis. Methods: We retrospectively investigated patients who underwent surgical AVR or transcatheter AVR for severe aortic stenosis from 2008 to 2015. Mean transmitral gradient by Doppler echocardiography ≥4 mm Hg was identified as mitral stenosis; patients were then stratified according to mitral valve area (MVA, by continuity equation) as >2.0 cm 2 or ≤2.0 cm 2 . MVA before and after AVR in patients with mitral stenosis were evaluated. Clinical outcomes of patients with and without mitral stenosis were compared using 1:2 matching for age, sex, left ventricular ejection fraction, method of AVR (surgical AVR versus transcatheter AVR) and year of AVR. Results: Of 190 patients with severe aortic stenosis and mitral stenosis (age 76±9 years, 42% men), 184 were matched with 362 with severe aortic stenosis without mitral stenosis. Among all mitral stenosis patients, the mean MVA increased after AVR by 0.26±0.59 cm 2 (from 2.00±0.50 to 2.26±0.62 cm 2 , P <0.01). MVA increased in 105 (55%) and remained unchanged in 34 (18%). Indexed stroke volume ≤45 mL/m 2 (odds ratio [OR] 2.40; 95% CI, 1.15–5.01; P =0.020) and transcatheter AVR (OR, 2.36; 95% CI, 1.17–4.77; P =0.017) were independently associated with increase in MVA. Of 107 with significant mitral stenosis (MVA ≤2.0 cm 2 ), MVA increased to >2.0 cm 2 after AVR in 52 (49%, pseudo mitral stenosis) and remained ≤2.0 cm 2 in 55 (51%, true mitral stenosis). During follow-up of median 2.9 (0.7–4.9) years, true mitral stenosis was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.88; 95% CI, 1.20–2.94; P <0.01). Conclusions: MVA improved after AVR in nearly half of patients with severe aortic stenosis and mitral stenosis. MVA remained ≤2.0 cm 2 (true mitral stenosis) in nearly half of patients with severe aortic stenosis and significant mitral stenosis; this was associated with worse survival among patients undergoing AVR for severe aortic stenosis.

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.