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Abstract Introduction Echocardiography is the recommended modality for non-invasive assessment of pulmonary pressures. However, in patients with severe tricuspid regurgitation (TR), the reliability of echocardiographically derived systolic pulmonary artery pressure (sPAP) is questioned. Limited data exists on the correlation between echocardiography and right heart catheterization (RHC) in selected group of patients with severe TR. Purpose To evaluate the correlation between echocardiographic and RHC measurements for sPAP in patients with varying TR severity. Method Patients who underwent echocardiography and RHC within three days at a large single referral center were retrospectively included. Exclusion criteria included incomplete echocardiographic and RHC data, ≥moderate pulmonary stenosis, low-quality images, and pregnancy. Echocardiographic sPAP was calculated using simplified Bernoulli equation. Echocardiographic right atrial pressure (RAP) was assessed by evaluating inferior vena cava (IVC) dimension and collapsibility. A difference of ≥10 mmHg between the two modalities for sPAP was considered clinically significant. Results Of 3696 patients included, mean age was 64±14 years, 1689 (46%) were females, 1659 (45%) had systemic hypertension, and 582 (16%) had atrial fibrillation. TR was <moderate in 2475 (67%) patients, moderate in 499 (14%), moderate-severe in 277 (7%), and severe in 445 (12%). Pulmonary hypertension (PH) was diagnosed in 3079 subjects (83%). A good correlation was found between sPAP derived by echocardiographic and RHC in the whole cohort (correlation coefficient (LCC) 0.79, CI 0.78-0.80), in severe TR subgroup (LCC 0.78, CI 0.75-0.82), and in severe TR with PH subgroup (LCC 0.76, CI 0.71-0.79). The mean echocardiographic misestimation for sPAP in severe TR was 3.97 mmHg (CI -5.24 to -2.71). The correlation between the two modalities for RAP was moderate in the whole cohort (LCC 0.59, CI 0.57-0.61) and fair in severe TR (LCC 0.35, CI 0.27-0.42). A clinically significant difference between the two modalities for sPAP was found in 1504 patients (41%), predominantly due to the right ventricle-right atrium gradient misestimation, rather than RAP misestimation, in patients with no PH (67% vs 33%), patients with mild-moderate PH (mean Pulmonary Artery Pressure (mPAP) 21-34 mmHg) (67% vs 33%) and severe PH (mPAP ≥35 mmHg) (76% vs 24%). Conclusion The correlation between echocardiographic and RHC measurements is good for sPAP, even in severe TR patients, while it is only fair to moderate for RAP. A clinically significant difference between echocardiographic and RHC sPAP is more commonly observed in patients with PH, with right ventricle-right atrium gradient misestimation being the most common cause.

Abstract Introduction Secondary tricuspid regurgitation (STR) is a highly prevalent valve disease. STR and Heart Failure with preserved Ejection Fraction (HFpEF) share common features including exertional intolerance and high burden of atrial fibrillation (AF) and pulmonary hypertension (PH), making it challenging to disentangle HFpEF from TR. The incidence of clinically-recognized HFpEF in STR and its impact on mortality are not well established. Purposes To define the incidence of newly diagnosed HFpEF and its impact on mortality in a cohort of patients with significant STR and to evaluate the likelihood of a larger hidden burden of HFpEF. Methods Patients with a first diagnosis of ≥moderate-severe STR between 2004-2019 at our institution were retrospectively included. Patients with left ventricle ejection fraction <50%, left-sided valve diseases, and intracardiac device leads were excluded. HFpEF was identified by manual chart review as well as by use of ICD codes. The estimated prevalence of HFpEF was evaluated using an H2FPEF score ≥6, which corresponds to a ≥90% probability of having HFpEF. Results Of 2118 patients (mean age 70 ± 14, 36% females), 1057 (50%) had systemic hypertension (HTN) and 1091 (51%) had AF, with median 2.3 years of follow-up. From this cohort, 536 (25%) patients were diagnosed with HFpEF based upon chart review during the follow up period, while ICD diagnosis was only present in fewer than 50% of these patients (254). High H2FPEF score was present in 880 patients (41.5%), of whom 383 received a chart diagnosis of HFpEF, while 153 patients with H2FPEF score <6 received a chart HFpEF diagnosis. The cumulative incidence of chart-based diagnosis of HFpEF was 20.8% (N=158) at 1-year and 38.6% (N=273) at 5-years in patients with an H2FPEF score ≥6 and 5.5%(N=60) at 1-year and 11.1%(N=111) at 5-years in those with a score <6 (Figure). In Cox regression analyses, the diagnosis of HFpEF during follow-up was associated with increased mortality (HR 2.14, CI 1.86-2.46, p < 0.001) after adjusting for age, sex, body mass index, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, diuretics, HTN, pulmonary hypertension, chronic kidney disease and AF. Conclusions The incidence of clinically documented HFpEF in a cohort of patients with significant STR at index evaluation is high (25%). Use of ICD code underestimates clinical recognition, with the actual burden of HFpEF probably being even greater, as indicated by an H2FPEF score ≥ 6. Among those with significant STR, HFpEF diagnosis is an independent risk factor for mortality.

Abstract Background/Introduction Close monitoring of aortic stenosis (AS) by follow-up echocardiography is recommended by all Cardiology and Imaging Societies’ guidelines. Whether these guidelines are strictly followed is unknown. Purpose We aimed to describe our institution’s practice patterns for echocardiographic monitoring in patients with aortic sclerosis (AScl) and AS of any severity. Methods Adult patients residing in our institution’s county with an echocardiographic diagnosis of AScl or AS between 01/2005-01/2022 were identified and classified into 4 groups: AScl, mild AS, moderate AS, or severe AS, at each echocardiogram during the study timeframe. Kaplan Meier analyses were used to evaluate the composite outcome, the occurrence of follow-up echocardiogram or death. Patients were censored at the time of aortic valve replacement/repair, heart transplant, or last clinical follow-up. Guideline follow-up was considered appropriate when the primary outcome occurred by 5 years (AScl/mild AS), 2 years (moderate AS), and 1 year (severe AS). Results A total of 23,726 echocardiograms from 9,578 unique patients were included. At index echocardiogram, median patient age was 74 years (IQR 65-82) and 4,806 (50.2%) were women. AScl was observed in 7,358 (76.8%) cases, mild AS in 1,442 (15.1%) cases, moderate AS in 479 (5%), and severe AS in 301 (3.1%) cases. Rates of composite outcome achievement by the end of the guideline-recommended interval were 81%, 90%, 80%, and 72% in AScl, mild, moderate, and severe AS, respectively. Rates for men were 83%, 92%, 82%, and 75% in these groups, while rates for women were 78%, 88%, 78%, and 68%, respectively (Figure 1). Follow-up rates were similar before and after 2012 (when transcatheter aortic valve replacement was approved for treatment of severe AS in high-risk surgical patients in the USA). Follow-up rates were higher in patients managed by cardiovascular providers compared to non-cardiovascular providers (Figure 2). Conclusion Depending on disease severity, between one fourth and one tenth of patients remained alive and unfollowed at the end of their guideline-recommended surveillance interval. There is significant variability in echocardiogram monitoring based on sex and referring provider specialty. Figure 1 Figure 2

Abstract Background Transthoracic echocardiography is the primary modality used for the assessment of the pericardial space. Guidelines recommend semi-qualitative assessment of the size of a pericardial effusion with characterization as trace, small, moderate or large. The reproducibility and association of this characterization is variable. Whether simple 2D-based quantitative measures of effusion size better associate with pericardial volumes is unclear. An accurate measure of pericardial volume would be helpful for tracking patients over time. Purpose To test whether 2D-based measures of the pericardial space could accurately predict pericardial volumes. Methods We retrospectively assessed a series of echos performed immediately prior to pericardiocentesis. 2D-based area tracings from the parasternal long and short axis at the papillary muscle level as well as 2D volumetric tracings from the apical 4 chamber view using the Simpson's method were tested with the operator blinded to the true pericardial volume (recorded at pericardiocentesis). Patients who underwent pericardiocentesis in setting of acute perforation were excluded as were patients where pericardiocentesis was unsuccessful or incomplete. Pericardial fluid area or volume was calculated by taking the difference between the measures obtained by tracing the epicardial border of the heart and pericardium (figure 1). Results The median pericardiocentesis (n=118) fluid volume was 500 mL (IQR 350 – 750 mL) with a range, 95–2300 mL. The pericardial fluid was serous (22%), sero-sanguineous (37%) and sanguineous in 41%. The effusion was malignant in 24 cases and due to inflammation in 42 cases. Pericardial area traces from either the parasternal short (r=0.56, p<.0001) or long axis (r=0.62, p<.0001) correlated modestly with measured pericardial volume. The average volume estimated echocardiographically by the Simpson’s method was 580 ± 359 mL (range, 85.8–2419 mL). There was stronger linear correlation between echocardiographic (apical 4-chamber measurement) and pericardiocentesis-derived volumes (r=0.92, p < 0.0001; figure 2A). Etiology of the pericardial effusion was not associated with estimates of pericardial volumes. There was a large overlap in pericardial volume amongst the reading physician qualitative grading of effusion size (figure 2B). Categorization of pericardial effusion size was improved when based on volumetric estimates (Kappa 0.65) rather than physician estimates (Kappa 0.32; Figure 2B). Variation between measured pericardial volume and actual pericardial volume was most related to the quality of the image and the likely extent to which the pericardial fluid was not entirely captured in the image window. Conclusion Two-dimensional transthoracic echocardiography using biplane Simpson’s method of disks can simply and reasonably accurately estimate the pericardial effusion volume. This technique may add value in the serial assessment of pericardial effusions. Figure 2

Abstract Background Heart failure and preserved ejection fraction (HFpEF) is a heterogeneous entity including patients with different phenotypes of reduced, normal, and supernormal left ventricular (LV) function. Objectives To assess the value of resting LV elastance with transthoracic echocardiography (TTE) to identify HFpEF phenotypes. Methods In a prospective, observational, multicenter study, 2380 HFpEF patients were recruited from July 2016 to May 2024 by 35 certified laboratories of 15 countries. HFpEF was diagnosed according to the European Society of Cardiology (ESC) guidelines. Systolic blood pressure (SBP) was measured. We assessed wall motion score index (WMSI), LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (AE, SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and left atrial volume index (LAVI). Global longitudinal strain (GLS) was available in 1164 (48.9%) patients. In 271 (11.4%) patients, N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed. Patients were divided into three groups based on rest force: low rest force group (< 25% percentile, Group 1), median rest force group (≥ 25% percentile & ≤ 75% percentile, Group 2), and high rest force group (> 75% percentile, Group 3). Results 330 (13.9%) patients presented with ischemic RWMA. The 3 groups showed a gradient with descending values (Group 3>2>1) for SBP, EF, GLS, AE, and VAC, with the opposite gradient (Group 1> 2> 3) for EDV, EDVi, ESV, ESVi, SV, SVi, and LAVI values (all P<0.01). Patients in Group 3 have higher NTproBNP level and higher percentage of B-line compared to groups 1 and 2 (P<0.05). The 3 groups were similar for values of coronary flow velocity, systolic pulmonary artery pressure, and E/e’ (see table). Univariable linear regression analysis showed that NTproBNP was correlated with force (r = 0.271, p < 0.001), VAC (r = 0.194, p = 0.001), LAVI (r = 0.327, p < 0.001), LVEDV (r = -0.245, p < 0.001), LVEDVi (r = -0.261, p < 0.001), LVESVi (r = -0.190, p = 0.002) and LVESV (r = -0.187, p = 0.002) (see figure). However, multivariable linear regression analysis showed that NTproBNP was independently associated with LAVI (β= 0.211, p < 0.001) and force (β= 1.804, p = 0.002). Conclusions HFpEF patients present with different LV contractile phenotypes, easily identified with resting LV force and volumetric TTE. LV force is linearly correlated with cardiac natriuretic peptide levels. The dominant hemodynamic feature of hypocontractile phenotype is a preload recruitment with dilation of LV EDV and normal SV, while the hypercontractile phenotype is characterized by a small LV with reduced SV. heat map

Abstract Background Catheter ablation for atrial fibrillation (AF) improves quality of life and lowers cardiovascular adverse events. However, AF recurrence rates remain high - thus the need for better or improved predictors of AF recurrence. The role of left atrial (LA) stiffness remains unclear, as prior findings were controversial. Purpose To explore the relationship between a noninvasive LA stiffness index (LAstiffn) and AF recurrence after catheter ablation. Methods We analyzed a prospectively recruited cohort of patients who underwent catheter ablation for AF, were in sinus rhythm at 3 months post-ablation, had no significant (< moderate) valvular disease, and had LA volumes and LA diastolic function prospectively measured. LAStiffn was calculated as (E/e’)/LA emptying fraction (LAEF) ratio (abnormal defined as >15/45≈0.3). Outcome endpoint was the first documented AF/atrial flutter episode, lasting >30s, beyond 3 months post ablation (end of blanking period). Results A total of 589 patients were studied (mean age 60±10 years; 75% men; 50% with persistent AF; Table 1). At 3 months post-ablation, mean LAVI(Left atrial volume index) was 36±10 mL/m2 and LAstiffn 0.32±0.22. LAstiffn tended to be higher in older patients, in females, and patients with persistent AF and comorbidities (hypertension, congestive heart failure, coronary artery disease, CHA2DS2-VASc score ≥2, etc). At multivariable regression analysis, LAstiffn correlated with LV size and mass, degree of mitral/tricuspid regurgitation, and right ventricular systolic pressure. At 1 year, 3 years, and 8 years follow up, AF recurred in 118, 191, and 347 patients, respectively. At univariate Cox proportional hazards regression analysis, LAstiffn index >0.3 was significantly associated with AF recurrence at 1 year (log-rank P=.0005), 3 years (P=.0002), and 8 years follow up (P<.0001; Figure). In multivariate analysis including all clinical and laboratory factors with P<.10 in univariate analysis, LAstiffn >0.3 remained an independent factor for AF recurrence only at 3-years (adjusted HR 1.40 [1.03-1.91], P=.03) and 8 years follow up (adjusted HR 1.65 [1.29-2.13], P<.0001) after adjustment for age, sex, type of AF (persistent/paroxysmal), LA volume index (LAVi), obstructive sleep apnea, and prior pacemaker/ICD implantation (best independent factors); P=.14 at 1 year follow up. In ROC analysis, LAstiffn (AUC 0.61, P=.001) performed slightly better than LA deformation LAEF (AUC 0.59, P=.002) or E/e’ (AUC 0.58, P=.03), though with modest sensitivity/specificity (58%/62%). Conclusions LAstiffn may reflect LA myopathy that is likely due to the cumulative effects of comorbidities, diastolic dysfunction, and intrinsic LA tissue remodeling. LA stiffening may be a substrate facilitating redevelopment of AF, thus patients with increased LAstiffn may need more frequent monitoring to prevent/treat AF recurrence earlier.

Abstract Background AI-enhanced electrocardiogram (AI-ECG) is a cost-effective tool for left ventricular dysfunction screening. However, its cost-effectiveness for other forms of structural heart disease (SHD) is unknown. While AI-ECG is inexpensive, the relatively low positive predictive value (PPV) of many models can lead to high costs from unnecessary follow-up tests like transthoracic echocardiography (TTE). Therefore, strategies to improve the yield of AI-ECG-based screening are needed. Purpose To evaluate the cost savings of a stepwise approach to SHD screening using AI-ECG followed by point-of-care ultrasound (POCUS) compared to AI-ECG alone. Methods 286 adult outpatients undergoing AI-ECG were randomly selected to undergo same-day POCUS. All participants were required to have a recent TTE, our gold standard for SHD diagnosis, for comparison purposes. We evaluated four SHDs: aortic stenosis, cardiac amyloidosis, hypertrophic cardiomyopathy, and left ventricular dysfunction (defined as left ventricular ejection fraction <50%). The costs of AI-ECG ($75/test) and TTE ($1,305/test) were sourced from Healthcare Bluebook, while the cost of POCUS ($100/test) was independently estimated. We compared the costs of screening with AI-ECG alone to stepwise screening with AI-ECG followed by POCUS. Costs were analyzed for two paradigms: screening for all forms of SHD in parallel and screening for each SHD individually. Results AI-ECG alone identified potential SHD in 125 out of 286 patients. When compared to TTE, only 39 out of 125 were true positives (31% PPV). Among the AI-ECG-positive patients, POCUS demonstrated findings of SHD in 52 out of 125 cases. When compared to TTE, this stepwise approach yielded 32 true positives and 20 false positives (62% PPV). In the parallel screening paradigm, the cost per patient diagnosed with SHD was $4,733 with AI-ECG alone, which decreased to $3,182 with stepwise screening (33% cost savings). For the individual SHD screening paradigm, cost reductions were as follows: aortic stenosis ($18,724 to $6,315, 66% savings), cardiac amyloidosis ($21,023 to $12,230, 42% savings), hypertrophic cardiomyopathy ($9,883 to $6,175, 38% savings), and left ventricular dysfunction ($4,019 to $3,582, 11% savings). Conclusions Stepwise SDH screening with AI-ECG followed by POCUS markedly reduces costs compared to AI-ECG alone. The greatest cost savings for individual SHD screening were observed for aortic stenosis and cardiac amyloidosis, conditions where AI-ECG models have lower PPVs. Parallel screening for multiple SHDs is also less costly than screening for any individual SHD alone. Therefore, a parallel screening approach may maximize SHD detection while minimizing screening costs. Stepwise Screening Approach for SHD SDH Screening Costs

Abstract Background The left ventricular (LV) hypercontractile phenotype (HP) plays a critical role in hypertrophic cardiomyopathy (HCM) and is usually identified with the left ventricular outflow tract gradient (LVOTG). Purpose To assess the systemic and coronary hemodynamic profile associated with HP identified with increased LV elastance (also known as force) at rest in patients with HCM. Methods We enrolled 1248 HCM patients (age 50 ± 15 years, 798 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 14 quality-controlled sites from 7 countries TTE assessment included LVOTG, EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume, mmHg/mL). Volumetric echocardiography with Simpson’s method was used to measure EF from end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), arterial elastance (AE) and ventricular-arterial coupling (VAC). We also assessed resting peak diastolic coronary flow velocity (D-CFV) in the mid-distal left anterior descending artery in a subset of 275 patients. Results EF equaled 68 ± 7%, force = 6.8 ± 5.3 mmHg/ml and LVOTG = 22 ± 28 mmHg. HP was identified as the highest quartile of force (> 7.85 mmHg/ml, mean value= 13.3 ± 7.0). HP showed the lowest SV (46 ± 18 ml) and EDV (61 ± 20 ml), with the highest AE (3.19 ± 1.35 mmHg/ml) and VAC (3.46 ± 1.59) compared to other quartiles (p<0.001) ( see Picture) . D-CFV was not higher in patients with HP (n = 65) compared to those (n = 210) without HP (41± 11 vs 38 ± 14 cm/s, p=ns, but higher in comparison to joint first and second Force quartile (n=122) vs 37 ±14 p =0.0472). Table displays the demografic, clinical and TTE parameters related to HP (Table). In multivariate logistic analysis 4 independent predictors of HP were identified: SBP >130 mmHg with OR 2.5, female sex with OR 5.4, LV EF >70% with OR 6.1 and LVOTG >30 mmHg with the highest OR = 6.3. Conclusion: HCM patients with HP exhibit a distinctive systemic hemodynamic and coronary physiology profile, characterized by low SV, high VAC, and supranormal baseline D-CFV compared to non-HP patients. These findings suggest reduced cardiovascular efficiency and increased myocardial oxygen demand, possibly detrimental over time.