Pellikka, Patricia A.

Introduction: Bioprosthetic valve thrombosis (BPVT) is a well-recognized cause of prosthetic dysfunction. Anticoagulation restores prosthetic valve gradients, but long term outcomes and complications from therapy are unknown. Objectives: To define the complications and long-term outcomes of anticoagulant therapy for BPVT. Methods: Retrospective matched cohort study of patients treated with warfarin for presumed BPVT at a single center from 1999 to 2016. Controls with normal bioprostheses by echocardiography were matched 2:1 for age at implantation, gender, prosthetic valve position, and type of prosthesis (porcine / pericardial). Results: A total of 83 presumed BPVT patients (40 aortic, 21 mitral, 18 tricuspid, and 4 pulmonary) and 166 controls were included. Age at BPVT diagnosis was 60±19 yrs (41±41 months post implantation); 45 (54%) were male. Transvalvular gradients returned to baseline in 63 (76%) of the patients, after 5±4 months of warfarin; 60 (72%) patients were maintained on warfarin indefinitely. Recurrent BPVT was seen in 13 (16%) patients, 33±31 months after initial therapy. When compared to controls, warfarin-treated BPVT patients had similar incidence of stroke [4(5%) vs 5 (3%), p=0.49], peripheral embolic events [4(5%) vs 10 (6%), p=0.78)], and death [12 (14%) vs 28 (17%), p= 0.72] (Figure, left panel), but more bleeding requiring transfusion [18 (22%) vs 3 (2%), p<0.0001]. Presumed BPVT patients more often required surgical or percutaneous valve re-replacement (Figure, center panel); this difference persisted even when comparing only patients with confirmed BPVT (those who responded to anticoagulant therapy) vs. their matched controls (Figure, right panel). Conclusion: Warfarin anticoagulation for presumed BPVT is successful in the majority of patients, without increase in stroke, peripheral embolism or death, but at the cost of excess bleeding. Recurrent BPVT occured in 16% of patients. Importantly, patients with BPVT required more often valve re-replacement. This finding suggests that anticoagulant therapy does not fully restore prosthetic valve durability, and that BPVT patients should be closely monitored.

Background: CP/R-CP may be associated with subtle features of ventricular dysfunction which are not easily detectable with the use of conventional echocardiographic modalities. The aim of this study was to evaluate myocardial mechanics by 2D-STE (2 Dimensional speckle-tracking echocardiography) between CP and R-CP. We hypothesized that strain/ strain rate (S/SR) would be worse in the R-CP patients due to radiation-induced myocardial injury. Methods: We analyzed 180 patients (62% male, age 62±13 years, 127 CP and 53 R-CP) with suitable echocardiographic images and normal left ventricular ejection fraction (LVEF>55%). The two groups were similar in terms of age, cardiovascular symptoms, risk factor profile and LVEF (Table). Selected images were analyzed off-line using Velocity Vector Imaging technology. The diagnosis of CP was based on clinical parameters as well as echocardiography and/or hemodynamic cardiac catheterization. Patients in whom radiation therapy was the primary etiology of CP were classified as R-CP. Global and segmental circumferential, radial, longitudinal, systolic and early diastolic strain and strain rate were analyzed in all patients. Results: Global and segmental radial (GRadS), global longitudinal (GLS), global basal (GBS), global mid-segment (GMS), septal wall (SWS), and anterior wall (AWS) strain was significantly reduced in the R-CP patients compared with the CP patients (Table). Antero-septal and anterior wall diastolic strain and strain rates (AS + AW Sre, SR) were reduced in the R-CP group. The best differentiators between the two groups were antero-septal (SAS), basal anterior (BAS) and mid anterior (MAS) segmental strain, based on receiver operating characteristic (ROC) and area under the curve (AUC) analysis. ROC calculations were AUC: SAS 0.67, SBA 0.69, and SMA 0.71. Conclusion: The study showed that compared with CP, R-CP is associated more with myocardial dysfunction, likely due to radiation-induced myocardial injury.

Background: Non-cardiac surgery (NCS) in patients with severe aortic stenosis has traditionally been associated with high perioperative mortality. Aortic valve replacement is recommended prior to elective NCS, but the impact of this strategy has not been systematically assessed. Methods: A retrospective review was performed of all patients with severe aortic stenosis undergoing major NCS at Mayo Clinic between 2000 and 2013. Patients undergoing aortic valve intervention (AVI) prior to NCS were compared to those undergoing surgery without prior AVI (control). Patients undergoing emergency surgery were excluded. Primary endpoint was occurrence of major adverse cardiac events (MACE; combination of death, stroke, myocardial infarction, new/worsening heart failure, ventricular arrhythmia) within 30 days of NCS; secondary endpoints were mortality at 30 days and 1 year after NCS. Results: 180 patients (age 74.5 ± 10.5 years, 64% male) who underwent NCS within 12 months after AVI, were compared to 232 patients (age 76.6 ± 10.7 years, 56% male) in the control group. Patients undergoing AVI were more often symptomatic than controls (41% vs 26%, p = 0.002). MACE was significantly higher in the control group (21.6% vs 5.6%, p < 0.001), mainly due to the increased risk of heart failure in the postoperative period in this group (18.5% vs 2.2%, p < 0.001). There was no significant difference in the rate of myocardial infarction (1.7% vs 0.6%, p = 0.39), ventricular arrhythmia (0.9 % vs 0 %, p = 0.51) or stroke (0.9 % vs 0 %, p = 0.51). Kaplan-Meier assessment demonstrated no significant difference at 30 days but a reduction in 1 year mortality in the AVI group compared to the control group (Figure). Conclusions: Pre-operative AVI for severe aortic stenosis results in reduced heart failure and improved 1 year survival. However, other MACE and 30 day mortality appears unchanged. Pre-operative AVI should be considered in symptomatic patients, where the benefit of AVI is demonstrated to be greatest.

Background: Evaluation of obese patients with suspected CAD is challenging because obesity is a CV risk factor, but adiposity itself may mimic symptoms of CAD and reduce the accuracy of diagnostic testing. Optimal testing strategies in obese patients are not known. Methods: Patients with stable symptoms suggestive of cardiac ischemia from the PROMISE trial (n=9230) were classified according to BMI. Providers specified a functional test modality prior to stratified randomization to functional (stress testing) or anatomical (CTA) testing. We assessed relationships between BMI, physician’s preference of functional test, test positivity and results of catheter angiography (cath) using logistic regression. Results: Providers were more likely to choose SPECT over other functional tests as BMI increased (OR 1.04 per unit increase in BMI above 27, p<0.001). In patients with BMI ≥ 35 vs. < 35, the rate of positivity with CTA was similar (10% vs. 12%; see Table). The same was true for stress echo and stress ECG (positivity 8-13%, p>0.8 for both). In contrast, SPECT was significantly more likely to be positive in those with BMI ≥ 35 vs. <35 (18% vs. 13%; p=0.001). The likelihood of finding obstructive CAD at cath did not differ with BMI ≥ 35 vs. <35 in patients having CTA (59% vs. 52%, p=0.22), but among SPECT patients, positivity was only 29% with BMI ≥ 35 compared to 52% with BMI < 35 (p=0.005; Table). Conclusions: Increasing levels of obesity were associated with stronger physician preference for SPECT over other noninvasive tests. In patients receiving SPECT, higher levels of obesity were associated with a higher rate of positive results, but a lower cath yield for obstructive CAD. In contrast, in patients receiving CTA, positivity rates and cath yield did not vary by BMI. Obesity appears to significantly influence provider decision-making with regard to noninvasive test choice, probability of abnormal test results and probability of finding obstructive disease at cath.

Abstract Aims Augmenting echocardiography with artificial intelligence would allow for automated assessment of routine parameters and identification of disease patterns not easily recognized otherwise. View classification is an essential first step before deep learning can be applied to the echocardiogram. Methods and results We trained two- and three-dimensional convolutional neural networks (CNNs) using transthoracic echocardiographic (TTE) studies obtained from 909 patients to classify nine view categories (10 269 videos). Transthoracic echocardiographic studies from 229 patients were used in internal validation (2582 videos). Convolutional neural networks were tested on 100 patients with comprehensive TTE studies (where the two examples chosen by CNNs as most likely to represent a view were evaluated) and 408 patients with five view categories obtained via point-of-care ultrasound (POCUS). The overall accuracy of the two-dimensional CNN was 96.8%, and the averaged area under the curve (AUC) was 0.997 on the comprehensive TTE testing set; these numbers were 98.4% and 0.998, respectively, on the POCUS set. For the three-dimensional CNN, the accuracy and AUC were 96.3% and 0.998 for full TTE studies and 95.0% and 0.996 on POCUS videos, respectively. The positive predictive value, which defined correctly identified predicted views, was higher with two-dimensional rather than three-dimensional networks, exceeding 93% in apical, short-axis aortic valve, and parasternal long-axis left ventricle views. Conclusion An automated view classifier utilizing CNNs was able to classify cardiac views obtained using TTE and POCUS with high accuracy. The view classifier will facilitate the application of deep learning to echocardiography.

Background Resting coronary flow velocity (CFV) in the mid‐distal left anterior descending coronary artery can be easily assessed with transthoracic echocardiography. In this observational study, the authors sought to assess the relationship between resting CFV, CFV reserve (CFVR), and outcome in patients with chronic coronary syndromes. Methods and Results In a prospective multicenter study design, the authors retrospectively analyzed 7576 patients (age, 66±11 years; 4312 men) with chronic coronary syndromes and left ventricular ejection fraction ≥50% referred for dipyridamole stress echocardiography. Recruitment (years 2003–2021) involved 7 accredited laboratories, with interobserver variability <10% for CFV measurement at study entry. Baseline peak diastolic CFV was obtained by pulsed‐wave Doppler in the mid‐distal left anterior descending coronary artery. CFVR (abnormal value ≤2.0) was assessed with dipyridamole. All‐cause death was the only end point. The mean CFV of the left anterior descending coronary artery was 31±12 cm/s. The mean CFVR was 2.32±0.60. During a median follow‐up of 5.9±4.3 years, 1121 (15%) patients died. At multivariable analysis, resting CFV ≥32 cm/s was identified by a receiver operating curve as the best cutoff and was independently associated with mortality (hazard ratio [HR], 1.24 [95% CI, 1.10–1.40]; P <0.0001) together with CFVR ≤2.0 (HR, 1.78 [95% CI, 1.57–2.02]; P <0.0001), age, diabetes, history of coronary surgery, and left ventricular ejection fraction. When both CFV and CFVR were considered, the mortality rate was highest in patients with resting CFV ≥32 cm/s and CFVR ≤2.0 and lowest in patients with resting CFV <32 cm/s and CFVR >2.0. Conclusions High resting CFV is associated with worse survival in patients with chronic coronary syndromes and left ventricular ejection fraction ≥50%. The value is independent and additive to CFVR. The combination of high resting CFV and low CFVR is associated with the worst survival.

Background Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown. Methods and Results This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm 2 . Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation ( P =0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area ( r =0.07; P =0.6) or mitral valve gradient ( r =−0.03; P =0.8). Conclusions MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC‐related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.

Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging due to non-diagnostic imaging outputs and discordant clinical features. Using only a single videoclip from a standard transthoracic echocardiogram (TTE), we developed an artificial intelligence (AI) model to differentiate patients with HFpEF from those without HFpEF. In a separate test population, we assessed the model’s ability to predict cardiac mortality. Methods: A 3-dimensional convolutional neural network was developed and trained on apical 4-chamber videoclips to classify patients with HFpEF (cases) versus without HFpEF (controls). Overall and cardiac mortality were obtained from the National Death Index. Results: The model was independently tested in 646 cases and 638 controls from 8 centers in 4 states. Sensitivity (87.8%; 84.5-90.9%) and specificity (81.9%; 78.2-85.6%) were high and sustained in various subgroups, including increased left atrial volume index, average E/e’ ≥15, and pulmonary artery systolic pressure >35 mm Hg. During follow-up (median [IQR] 3.4 [1.7-6.5] years), 540 patients died. There were 135 cardiac deaths attributable to heart failure (47%), coronary artery disease (41%), valve disease (4%), arrhythmia (4%), and others (5%). Compared to a negative output, all-cause mortality was higher in patients with a positive (HR 2.9 [2.4-3.5]) or uncertain output (HR 1.8 [1.2-2.5]), and cardiac mortality (Figure) was also higher in patients with a positive (HR 7.7 [4.5-13.3]) or uncertain output (HR 3.4 [1.4-8.1]). Cardiac mortality differences according to AI model prediction remained after age adjustment (positive: HR 5.9 [3.3-10.4], p<0.001; uncertain: HR 2.8 [1.2-6.8], p=0.02). Conclusion: A novel AI model to detect HFpEF based on a single routinely acquired TTE videoclip also identifies those at increased risk of cardiac mortality.

Background: Clinically significant tricuspid regurgitation (TR) is an important contributor to morbidity and mortality. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score based on 8 parameters (age, gender, chronic heart failure, chronic lung disease, heart rate, creatinine, aspartate transaminase level, and TR severity) is used for risk stratification. The performance of the TRIO score in patients with TR secondary to severe pulmonary hypertension (PH) is unknown. Research Questions: To evaluate whether the TRIO score can be applied in patients with TR and pulmonary hypertension (PH), and to identify other predictors of mortality. Methods: Retrospective study including patients with TR ≥ moderate. Severe PH was defined as right ventricular systolic pressure (RVSP) ≥50 mmHg. The impact of clinical, echocardiographic and laboratory variables on mortality was evaluated with the Cox proportional hazard method. Results: A total of 13,482 patients from the TRIO population were included; severe PH was present in 6,530 (48.4%); mean age 73.4 + 13.3, 55.7% females. TRIO score performance was modest (AUC 0.62) in risk stratification (Figure A). PH patients had significantly higher mortality than those without PH at all levels of TRIO score (Figure B); differences were progressively lower with increasing TRIO scores. At multivariate analysis, only TRIO score [HR = 1.54 (1.35-1.77) per unit change], presence of an elevated NT-proBNP [HR = 1.02 (1.02-1.03) per 1000 pg/ml change], RVSP (HR = 1.08 (1.02-1.16) per 10 mmHg change], presence of RV dysfunction [HR = 1.15, (1.05-1.26)] and pulmonary artery pulsatility index (PAPi) ≤ 4 [HR = 1.34 (1.07-1.67)] were significant predictors of mortality (model AUC 0.65). Conclusions: TRIO score allows risk stratification in PH patients, but performance is modest; incorporating additional factors marginally increased model performance. PH patients have higher mortality at all levels of TRIO score, more so at low scores.

Introduction: Isolated functional tricuspid regurgitation (FTR) in the absence of structural heart disease may develop secondary to elevation in left heart pressures caused by left ventricular diastolic dysfunction (DD), as in heart failure with preserved ejection fraction (HFpEF). FTR may also herald the presence of occult DD or indicate greater risk for new-onset DD. However, prevalence and incidence of diastolic dysfunction (DD) in isolated FTR have not been studied. Aims: Investigate the prevalence and incidence of DD across the different severities of FTR of unclear cause. Methods: Adults with normal EF and without structural heart disease undergoing echocardiography at a tertiary medical center with a repeat study ≥6 months from baseline were identified. Severe DD was defined by ≥3/4 abnormal DD parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, left atrial volume index) and moderate DD by ≥2. Results: Among 30,428 patients (median age 60; 50% women), FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. Severe DD was present in 2%, 5%, 11%, and 13% patients, respectively, (p<.001) and moderate DD in 9%, 19%, 31%, and 48%, respectively (p<.001). The association of DD with increasing FTR was independent of all clinical characteristics. Over median 3.0 (IQR 1.5-5.4) years, incident severe and moderate DD developed more frequently with increasing FTR severity ( Figure) . Findings were confirmed in a propensity-matched subset where patients were matched for age, sex, BMI, atrial fibrillation, and comorbidities and in patients without lung disease or ≥moderate right ventricular enlargement. Conclusions: Patients with FTR of undefined etiology commonly have DD suggesting the presence of underlying left heart disease. Patients without apparent DD or HF at baseline who have FTR remain at significantly increased risk of developing DD over follow-up and may be a target population for therapies to prevent progression to clinical HFpEF.