Pellikka, Patricia A.

Abstract Aims The current guidelines recommend aortic valve intervention in patients with severe aortic regurgitation (AR) with the onset of symptoms, left ventricular enlargement, or systolic dysfunction. Recent studies have suggested that we might be missing the window of early intervention in a significant number of patients by following the guidelines. Methods and results The overarching goal was to determine if machine learning (ML)-based algorithms could be trained to identify patients at risk for death from AR independent of aortic valve replacement (AVR). Models were trained with five-fold cross-validation on a dataset of 1035 patients, and performance was reported on an independent dataset of 207 patients. Optimal predictive performance was observed with a conditional random survival forest model. A subset of 19/41 variables was selected for inclusion in the final model. Variable selection was performed with 10-fold cross-validation using random survival forest model. The top variables included were age, body surface area, body mass index, diastolic blood pressure, New York Heart Association class, AVR, comorbidities, ejection fraction, end-diastolic volume, and end-systolic dimension, and the relative variable importance averaged across five splits of cross-validation in each repeat were evaluated. The concordance index for predicting survival of the best-performing model was 0.84 at 1 year, 0.86 at 2 years, and 0.87 overall, respectively. Conclusion Using common echocardiographic parameters and patient characteristics, we successfully trained multiple ML models to predict survival in patients with severe AR. This technique could be applied to identify high-risk patients who would benefit from early intervention, thereby improving patient outcomes.

Background: Left ventricular global longitudinal strain (LVGLS) has been shown to improve risk stratification in patients with LV systolic dysfunction and subsequent recovery of LV ejection fraction (LVEF) in the acquired heart disease population. The purpose of this study was to assess the relationship between LVGLS and cardiovascular events (heart failure hospitalization, sustained ventricular tachycardia/appropriate shock, heart transplant, or cardiovascular death) and deterioration in LVEF (absolute decrease in LVEF ≥10% to LVEF <50%) in adults with congenital heart disease. Methods: Retrospective cohort study of congenital heart disease patients with previous diagnosis of LV systolic dysfunction (LVEF <50%) and subsequent recovery of LVEF (absolute increase in LVEF of ≥10% to LVEF ≥50%) on subsequent echocardiogram (index echocardiogram). Based on the index echocardiogram, patients were divided into normal LVGLS (absolute LVGLS >18%) versus abnormal LVGLS (absolute LVGLS ≤18%) groups. Results: Of 193 patients with recovered LVEF, 86 (45%) had normalization of LVGLS at index echocardiogram. A higher absolute LVGLS and use of renin angiotensin aldosterone system antagonist was associated with a lower risk of cardiovascular events and subsequent deterioration in LVEF, while hypertension was associated with higher risk of cardiovascular events and deterioration in LVEF. Conclusions: These results suggest that patients with congenital heart disease with recovered LVEF remained at risk for adverse outcomes, and LVGLS can be used to identify patients at risk for adverse outcomes. Medical therapy for heart failure and treatment of hypertension may reduce the risk of adverse outcome, but these findings require empirical validation, hence the need for a clinical trial.

Abstract Background Caseous calcification of the mitral annulus is an extremely rare variant of mitral annulus calcification occurring in &lt;1% of cases. The degeneration of caseous masses could act as a source of embolic strokes and a nidus for infective endocarditis (IE). Case summary A man in his sixties presented with transient left arm weakness. His history was pertinent for bioprosthetic aortic valve replacement secondary to endocarditis and recent pneumococcal pneumonia complicated by empyema and bacteraemia. He was still on intravenous antibiotics when he presented. Evaluation including magnetic resonance imaging of the brain, transoesophageal echocardiography, and computed tomography (CT) of the chest revealed multifocal embolic strokes, degenerative bioprosthetic aortic valve dysfunction, mitral annular calcification with mobile calcific masses, and persistent empyema. 18F-fluorodeoxyglucose–positron emission tomography–CT showed indeterminate activity across a portion of the posterior mitral leaflet and no activity on the bioprosthetic aortic valve. The patient was deemed high risk for surgery and was treated with 6-week course of antibiotics both for the empyema and the possible IE of the native mitral valve. Repeat echocardiography 40 days later showed stable mitral masses. At 4 months of follow up, the patient had no evidence of recurrent clinical strokes. Discussion Caseous calcification of the mitral annulus is a rare but an increasingly recognized predisposing factor for embolic strokes and IE. Treatment ideally involves surgical resection of the calcified masses in such cases.

Abstract Aims Aortic stenosis (AS) induces characteristic changes in left ventricular (LV) mechanics that can be reversed after aortic valve replacement (AVR). We aimed to comprehensively characterize LV mechanics before and after AVR in patients with severe AS and identify predictors of short-term functional recovery and long-term survival. Methods and results We prospectively performed comprehensive strain analysis by 2D speckle-tracking echocardiography in 88 patients with severe AS and LV ejection fraction ≥50% (mean age 71 ± 12 years, 42% female) prior to and within 7 days after AVR. Patients were followed for up to 5.2 years until death from any cause or last encounter. Within days after AVR, we observed an absolute increase in global longitudinal strain (GLS) (−16.0 ± 2.0% vs. −18.5 ± 2.1%, P&lt;0.0001) and a decrease in apical rotation (10.5 ± 4.0° vs. 8.3 ± 2.8°, P = 0.0002) and peak systolic twist (18.2 ± 5.0° vs. 15.5 ± 3.8°, P = 0.0008). A baseline GLS is less negative than −16.2% was 90% sensitive and 67% specific in predicting a ≥ 20% relative increase in GLS. During a median follow-up of 3.8 years, a global circumferential systolic strain rate (GCSRs) less negative than −1.9% independently predicted lower survival. Conclusion In patients with severe AS, a reversal in GLS, apical rotation, and peak systolic twist abnormalities towards normal occurs within days of AVR. Baseline GLS is the strongest predictor of GLS recovery but neither was associated with long-term survival. In contrast, abnormal baseline GCSRs are associated with worse outcomes.

Abstract Background Increased left ventricular (LV) stiffness (LVStiffn) was shown to be associated with mortality in patients with severe aortic stenosis (AS), despite aortic valve replacement (AVR), and may contribute to future heart failure (HF) symptoms. The aim was to assess whether preoperative LVStiffn is a risk factor of HF in these patients. Methods A retrospective analysis was done in patients with severe AS who underwent AVR (93% surgical). LV end-diastolic pressure-volume relations (P=aVb) were reconstructed from LV end-diastolic volumes and estimated end-diastolic pressures (from E/e'); LVStiffn at 30 mmHg (CS30) and capacitance (V30) were then derived. Primary endpoint was development of symptomatic HF at &gt;1 month post AVR. Results 1,837 patients were studied (age 76±10 years, 62% males, LVEF 61±12%; Table). Mean CS30 was 2.2±1.3 mmHg/mL and V30 64±17 mL/m2. Patients with higher CS30 ≥3 mmHg/mL were older, more frequently female, and had more comorbidities. During a median follow-up of 5.0 [3.0–7.9] years, 607 (33%) patients developed HF. A higher CS30 (≥3 mmHg/mL), but not V30 (P=0.32), was associated with higher risk of HF events (HR 1.86 [95% CI 1.52–2.27], P&lt;0.0001), along with other clinical and echo predictors (Table). In multivariate analysis, adjusting for age, sex, comorbidities, advanced NYHA class III–IV, creatinine &gt;1.5 mg/dL, medication use, severity of AS, reduced LVEF &lt;50%, diastolic dysfunction grade ≥2, right ventricular size and pulmonary hypertension, a higher CS30 ≥3 mmHg/mL remained independently associated with HF events (adjusted HR 1.61 [1.29–2.01], P&lt;0.0001; Figure). Conclusion Increased LVStiffn in patients with severe AS undergoing AVR is associated with HF at follow-up, despite the benefits brought by AVR, and can help identify patients with poorer outcomes who may need closer monitoring/more intensive treatment of comorbidities Funding Acknowledgement Type of funding sources: None.

Abstract Background/Introduction Patients with multiple myeloma (MM) are at increased risk of developing AL amyloidosis. It was determined by screening fat pad and bone marrow biopsy that 38% MM patients had amyloidosis at time of diagnosis and the majority were asymptomatic (1). However, whether amyloidosis-related echo features in MM affect survival remains unknown (1, 2). Purpose The goals of our study are to: 1) characterize prevalence of amyloidosis-related echo features in patients with multiple myeloma, 2) investigate whether decrease in longitudinal strain affect survival outcomes. Methods Patients diagnosed with MM between Jan 1, 2000 and Dec 31, 2017 at our institution were identified through Clinical Looking Glass. Those with echo within 1 year after myeloma diagnosis and left ventricular ejection fraction (LVEF) greater than 40% were included. Global longitudinal strain (GLS) and LVEF measurements were done using EchoGo (Ultromics, Oxford, UK). The average of GLS obtained from apical 4-chamber and apical 2-chamber views was used for analysis, with decreased GLS defined as absolute value less than 18%. Statistical analysis was conducted with STATA13, using Chi square test and Kruskal-Wallis for univariable analysis and Cox regression model for survival analysis. Results From a total cohort of 909 patients, 252 met inclusion criteria, of which 59 (23.4%) patients had decreased average GLS (see Table 1). Patients' mean age was 63±11 years, 44.8% were male and most were Black (42.7%) and the rest Hispanic (33.3%) and White (7.9%). Median follow up time was 4.25 years. The group with decreased GLS had lower percentage of females (22% vs 51.8%, p&lt;0.01), higher percentage of previous MI (11.9% vs 1.6%, p&lt;0.01) and more prior diagnosis of heart failure (20.3% vs 1.6%, p&lt;0.01). Among patients with decreased GLS, five-year mortality rate was 63.3% compared to 46.0% in those with preserved GLS (p&lt;0.036). Median survival time was 3.9 years among those with reduced GLS and 4.3 years in those without (see Figure 1; p&lt;0.01). Reduced GLS correlated with decreased survival (HR 1.6, p=0.03) even after adjusting for demographic variables (age, gender, race), history of MI, history of CHF, Charlson comorbidity index, myeloma RISS stage, and LVEF (≥50% vs 40–50%). Forty-seven (18.6%) patients had end diastolic inter-ventricular septum (IVSd) thickness ≥1.2cm. Median GLS in patients with increased IVSd thickness was 19% compared to 21% in those without (p=0.01). Nine patients had the apical sparing strain pattern for amyloidosis. Total of 158 patients had bone marrow specimen stained with Congo-red with 7 (4.4%) testing positive. Median GLS was 19% in the group staining positive for Congo-red compared 21% in the group with negative stain (p=0.03). Conclusions Decrease in GLS on baseline echo correlates with increased mortality in patients with MM and may be due to subclinical cardiac amyloidosis. Funding Acknowledgement Type of funding sources: None.

Abstract Adverse cardiac remodelling is the main determinant of patient prognosis in degenerative valvular heart disease (VHD). However, to give an indication for valvular intervention, current guidelines include parameters of cardiac chamber dilatation or function which are subject to variability, do not directly reflect myocardial structural changes, and, more importantly, seem to be not sensitive enough in depicting early signs of myocardial dysfunction before irreversible myocardial damage has occurred. To avoid irreversible myocardial dysfunction, novel biomarkers are advocated to help refining indications for intervention and risk stratification. Advanced echocardiographic modalities, including strain analysis, and magnetic resonance imaging have shown to be promising in providing new tools to depict the important switch from adaptive to maladaptive myocardial changes in response to severe VHD. This review, therefore, summarizes the current available evidence on the role of these new imaging biomarkers in degenerative VHD, aiming at shifting the clinical perspective from a valve-centred to a myocardium-focused approach for patient management and therapeutic decision-making.

Background: Inferior vena cava (IVC) size and collapsibility (IVC dynamics) are used for estimating right atrial pressure (RAP). However, the diagnostic performance of the American Society of Echocardiography IVC criteria for estimating RAP in patients with congenital heart disease are unknown. The purpose of this study was to assess the role of IVC dynamics for estimating RAP in adults with congenital heart disease. Methods: We conducted a retrospective study of adults with congenital heart disease that underwent cardiac catheterization and echocardiogram at Mayo Clinic (2003–2019). IVC diameter was measured at inspiration (IVC min ) and end-expiration (IVC max ), and IVC collapsibility index (IVC CI ) was calculated. Results: Based on 918 patients, we observed a good correlation between IVC max and invasive RAP ( r =0.56, P <0.001); IVC min and RAP ( r =0.58, P <0.001); and IVC CI ( r =−0.72, P <0.001). There was excellent correlation between invasive RAP and estimated RAP using IVC CI ( r =0.80, P <0.001). We observed that IVC CI <60% had superior diagnostic performance as compared with American Society of Echocardiography criteria (IVC max >2.1 cm, area under the curve difference 0.15, P <0.001; IVC CI <50%, area under the curve difference 0.09, P =0.008; combination of IVC max >2.1 cm; and IVC CI <50%, area under the curve difference 0.06, P =0.02). Estimated RAP >10 mm Hg based on IVC CI had comparable prognostic performance as invasive RAP but superior prognostic performance as the American Society of Echocardiography criteria. Conclusions: IVC CI <60% was the best criterion to identify patients with elevated RAP. IVC CI was comparable to invasively measured RAP in its relation to prognosis. Further studies are required to determine whether the use of IVC CI in clinical decision-making will improve clinical outcomes in this population.

Background Many patients with symptomatic severe aortic stenosis do not undergo aortic valve replacement (AVR) despite clinical guidelines. This study analyzed the association of managing provider type with cardiac specialist follow‐up, AVR, and mortality for patients with newly diagnosed severe aortic stenosis (sAS). Methods and Results We identified adults with newly diagnosed sAS per echocardiography performed between January 2017 and March 2019 using Optum electronic health record data. We then selected from those meeting all eligibility criteria patients managed by a primary care provider (n=1707 [25%]) or cardiac specialist (n=5039 [75%]). We evaluated the association of managing provider type with cardiac specialist follow‐up, AVR, and mortality, as well as the independent association of cardiac specialist follow‐up and AVR with mortality, within 1 year of echocardiography detecting sAS. A subgroup analysis was limited to patients with symptomatic sAS. Patient characteristics and comorbidities at baseline were used for covariate‐adjusted cause‐specific and multivariable Cox proportional hazard models assessing group differences in outcomes by managing provider type. An adjusted Cox proportional hazard model with additional time‐dependent covariates for follow‐up and AVR was used to assess these practices' association with mortality. Within 1 year of echocardiography detecting sAS, data revealed that primary care provider management was associated with lower rates of cardiac specialist follow‐up (hazard ratio [HR], 0.47 [95% CI, 0.43–0.50], P <0.0001) and AVR (HR, 0.58 [95% CI, 0.53–0.64], P <0.0001) and with higher 1‐year mortality (HR, 1.45 [95% CI, 1.26–1.66], P <0.0001). Cardiac specialist follow‐up and AVR were independently associated with lower mortality (follow‐up: HR, 0.55 [95% CI, 0.48–0.63], P <0.0001; AVR: HR, 0.70 [95% CI, 0.60–0.83], P <0.0001). Results were similar for patients with symptomatic sAS. All analyses were adjusted for baseline patient characteristics and comorbidities. Conclusions For patients newly diagnosed with sAS, we observed differences in rates of cardiac specialist follow‐up and AVR and risk of mortality between primary care provider‐ versus cardiologist‐managed patients with sAS. In addition, a lower likelihood of receiving follow‐up and AVR was independently associated with higher mortality.

Abstract Aims Electrocardiogram (ECG)-enabled stethoscope (ECG-Scope) acquires a single-lead ECGs during cardiac auscultation and may facilitate real-time screening for pathologies not routinely identified by cardiac auscultation alone. We previously demonstrated an artificial intelligence (AI) algorithm can identify left ventricular dysfunction (LVSD) [defined as ejection fraction (EF) ≤ 40%] with an area under the curve (AUC) of 0.91 using a 12-lead ECG. Methods and results One hundred patients referred for clinically indicated echocardiography were prospectively recruited. ECG-Scope recordings with the patient supine and sitting were obtained in multiple electrode locations at the time of the echocardiogram. The AI algorithm for the detection of LVSD was retrained using single leads from ECG-12 and validated against ECG-Scope to determine accuracy for low EF detection (≤35%, &lt;40%, or &lt;50%). We evaluated the algorithm with respect to body position and lead location. Amongst 100 patients (aged 61.3 ± 13.8; 61% male, BMI: 30.0 ± 5.4), eight had EF≤40%, and six had EF 40–50%. The best single recording position was V2 with the patient supine [AUC: 0.88 (CI: 0.80–0.97) for EF≤35%, 0.85 (CI: 0.75–0.95) for EF≤40%, and 0.81 (CI: 0.71–0.90) for EF &lt; 50%]. When using an AI model to select the recording automatically, AUC was 0.91 (CI: 0.84–0.97) for EF≤35%, 0.89 (CI: 0.83–0.96) for EF≤40%, and 0.84 (CI: 0.73–0.94) for EF &lt; 50%. Conclusion An AI algorithm applied to an ECG-enabled stethoscope recording in standard auscultation positions reliably detected the presence of a low EF in this prospective study of patients referred for echocardiography. The ability to screen patients with a possible low EF during routine physical examination may facilitate rapid detection of LVSD.