Pellikka, Patricia A.

Background Tricuspid valve surgery is recommended for severe isolated tricuspid regurgitation (TR) if symptoms persist despite optimal medical therapy. The definition of optimal therapy for TR is unclear beyond managing underlying conditions. Diuretics are the primary treatment for volume retention in TR, but it is unknown whether a “safe diuretic dose” exists for conservative management. We sought to evaluate the association between diuretic dose and outcomes. Methods Adult patients with ≥moderate–severe isolated TR were retrospectively identified from echocardiographic reports. Clinical and echocardiographic data were extracted from electronic medical records and manually reviewed. The primary end point was all‐cause mortality. Loop diuretic doses were converted to furosemide equivalent and categorized into 4 groups: <40 mg, 40 to 79 mg, 80 to 159 mg, and ≥160 mg daily. Results Of 1302 patients (age 72±13 years, 60% female), 565 (43%) had moderate–severe TR and 737 (57%) had severe TR. Median follow‐up was 8.7 (1.4, 14.0) years. Comorbidities increased with higher diuretic doses. A linear relationship between diuretic dose and mortality was observed in spline‐curve analysis. Hazard ratios (and CIs) for mortality adjusted for age, sex, coronary disease, chronic kidney disease, mild pulmonary hypertension, and New York Heart Association III/IV symptoms were 1.21 (0.96–1.53) ( P =0.12) for <40 mg, 1.50 (1.23–1.82) ( P <0.001) for 40 to 79 mg, 1.86 (1.46–2.37) ( P <0.001) for 80 to 159 mg, and 2.90 (2.18–3.88) ( P <0.001) for ≥160 mg furosemide equivalent. Any diuretic dose was associated with significant symptoms (New York Heart Association III–IV), with more patients experiencing symptoms at higher doses. Conclusion A daily loop diuretic dose ≥40 mg furosemide equivalent is associated with increased mortality and greater symptom severity in patients with TR.

Abstract Background and Aims Accurate differentiation of cardiac amyloidosis (CA) from phenotypic mimics remains challenging using current clinical and echocardiographic techniques. The accuracy of a novel artificial intelligence (AI) screening algorithm for echocardiography-based CA detection was assessed. Methods Utilizing a multisite, multiethnic dataset (n = 2612, 52% CA), a convolutional neural network was trained to differentiate CA from phenotypic controls using transthoracic apical four-chamber video clips. External validation was conducted globally across 18 sites including 597 CA cases and 2122 controls. Classification accuracy was assessed on the entire external validation dataset, and subgroup analyses were performed both on technetium pyrophosphate scintigraphy referrals, and individuals matched for age, sex, and wall thickness. Model accuracy was also compared with the transthyretin CA score and the increased wall thickness score within a subset of older heart failure with preserved ejection fraction patients with increased wall thickness. Results Cardiac amyloidosis patients and controls displayed similar age, sex, race, and comorbidities. After the removal of uncertain AI predictions (13%), model discrimination and classification were excellent for the entire external validation dataset [area under the receiver operating characteristic curve (AUROC) 0.93, sensitivity 85%, specificity 93%], irrespective of CA subtype (sensitivity: light-chain = 84%, wild-type transthyretin = 85%, and hereditary transthyretin = 86%). Performance was maintained in subgroup analysis in patients clinically referred for technetium pyrophosphate scintigraphy imaging (AUROC 0.86, sensitivity 77%, specificity 86%) and matched patients (AUROC 0.92, sensitivity 84%, specificity 91%). The AI model (AUROC 0.93) also outperformed transthyretin CA score (AUROC 0.73) and increased wall thickness (AUROC 0.80) scores. Conclusions This AI screening model—using only an apical four-chamber view—effectively differentiated CA from other causes of increased left ventricular wall thickness.

Abstract Aims In aortic stenosis (AS), estimation of left ventricular (LV) contractility is difficult as most markers of systolic LV function are load-dependent. The ratio of LV ejection fraction (LVEF) to end-systolic wall stress (ESWS), has been widely accepted as a marker of contractility. However, no studies have evaluated if this ratio is affected by loading conditions. The study describes changes in ESWS and ESWS corrected LVEF after transcatheter aortic valve replacement (TAVR). Methods and results In this prospective study, 41 patients with severe AS underwent echocardiography, LV catheterisation, and computed tomography (CT) before and immediately after TAVR. ESWS was estimated from echocardiography alone (ESWSEcho), combining CT LV dimensions and echocardiographic gradients (ESWSCT + echo) and combining CT LV dimensions and invasively measured LV end-systolic pressure (ESWSCT + Invasive). ESWSecho, ESWSCT + echo and ESWSCT + Invasive all decreased significantly after TAVR (89 ± 48 vs. 57 ± 37 Kdynes/cm2, P &lt; 0.01; 69 ± 8 vs. 51 ± 8 Kdynes/cm2, P &lt; 0.01, and 197 ± 69 vs. 137 ± 48 Kpa/cm2, P &lt; 0.01, respectively). We observed weak to moderate associations between the methods. After TAVR, LVEF corrected to ESWSecho, ESWSCT + echo and ESWSCT + Invasive increased (0.93 ± 0.07 vs. 1.91 ± 2.1, P = 0.013; 0.36 ± 0.19 vs. 0.58 ± 0.33, P &lt; 0.01, and 0.3 ± 0.02 vs. 2.5 ± 1.5, P &lt; 0.01, respectively). Conclusion ESWSecho, ESWSCT + echo and ESWSCT + Invasive decreased significantly after TAVR suggesting they reflect afterload, but independent of method, ESWS corrected LVEF increased slightly post-TAVR, indicating load dependency.

ABSTRACT Background Incident atrial functional mitral regurgitation (AFMR) is associated with mortality. Transcatheter edge‐to‐edge repair (TEER) has shown effectiveness in improving MR and symptoms in AFMR, but previous studies lacked comparison to conservative management. We aimed to study the association of AFMR severity and mitral TEER with symptoms, heart failure hospitalizations (HFH) and all‐cause mortality in moderate/severe AFMR. Methods Consecutive adults with moderate/severe AFMR managed conservatively or with TEER 2010−2023 were identified retrospectively. To ensure similar technique in evaluation in the two groups, variables were obtained from the closest transthoracic echocardiogram before TEER in the TEER group. In addition to multivariable analysis, the association of TEER (vs. conservative management) with HFH and mortality was assessed using propensity‐score matched analyses; the propensity score was based on age, sex, EuroSCORE II, effective regurgitant orifice area, integrative MR severity, and NYHA class III/IV (vs. I/II). Results Among 230 patients with moderate/severe AFMR [mean age 77; 56% females], 46 were managed with TEER. Severe (vs. moderate) AFMR was independently associated with baseline NYHA class III/IV (multivariable OR 2.18 [95% CI 1.13−4.26]) and HFH [multivariable HR 2.75 (95% CI 1.25−6.03)] but not mortality ( p = 0.26). TEER improved MR to ≤ moderate in 93% but was not associated with lower HFH or death rates versus conservative management on multivariable or matched analysis. However, 1‐year NYHA improved more with TEER versus conservative management in patients with baseline NYHA class III/IV (62% vs. 27%, p = 0.03). Rhythm control was associated with improved survival (HR 0.38 [0.15−0.98]). Conclusions AFMR severity was associated with symptoms and HFH but not mortality. MR severity and NYHA class improved with TEER, but the association of TEER with HF hospitalizations or death remains unproven. Randomized studies are needed to evaluate the potential role of TEER and rhythm control on outcomes in AFMR.

Over the past decade, stress echocardiography has evolved from a test for assessing epicardial artery stenosis to a comprehensive functional test, targeting multiple cardiovascular parameters. The new approach includes several structured steps: (a) evaluating regional wall motion abnormalities to detect epicardial artery stenosis or vasospasm; (b) assessing pulmonary congestion and diastolic function via B-lines with lung ultrasound; (c) gauging preload and contractile reserve with volumetric echocardiography; (d) measuring coronary microvascular reserve using Doppler-based coronary flow velocity in the middistal left anterior descending artery; and (e) determining cardiac sympathetic reserve by tracking heart rate reserve on an ECG. This evolution was supported extensively by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), which played a key role in five areas: (1) developing the initial, curiosity-driven project; (2) disseminating protocols and results at national and international conferences, supporting logistic infrastructure and publication expenses; (3) establishing a digital platform (customized Redcap) for data entry and storage; (4) facilitating patient recruitment across 19 Italian centers; and (5) offering formal endorsement through six presidencies, adding credibility and reach beyond any single institution. The protocol quickly advanced from concept to high-impact publications, earning inclusion in 2024 specialty guidelines. Initially Italian-led, the study now includes 50 centers across 20 countries (e.g. USA and China). Beyond the 50 peer-reviewed papers published in 2016–2024, this study offers a novel, sustainable approach to cardiac stress testing, providing more information at lower costs, with zero radiation and minimal environmental impact. SIECVI’s endorsement was instrumental in amplifying the study’s rigor and outreach.

Abstract Aims To develop a deep learning model that: (i) utilizes transthoracic echocardiography (TTE) clips to detect left ventricular (LV) enlargement without being provided information regarding a patient’s sex and body size; and (ii) can be accurately applied to clips acquired using either standard comprehensive TTE or handheld cardiac ultrasound (HCU). Methods and results Using retrospective TTE data (training: 8722 patients; internal validation: 468 patients), we developed a deep learning model that estimates a patient’s end-diastolic LV volume (indexed to body surface area and normalized across the sexes), and then thresholds this estimate to perform the following classifications: (1) normally sized LV vs. ≥ mild LV enlargement; (2) normal/mildly enlarged LV vs. ≥ moderate LV enlargement. For retrospective datasets, the model showed strong performance in TTE across three geographically distinct locations (Minnesota and Wisconsin: 1082 patients, AUC = 0.925 and 0.953 for classifications 1 and 2, respectively; Arizona: 1475 patients, AUC = 0.935 and 0.969; and Florida: 1481 patients, AUC = 0.934 and 0.970). Additionally, performance was strong for both TTE and HCU clips collected from a prospective cohort of 410 patients who underwent HCU immediately following TTE (TTE: AUC = 0.925 and 0.971; HCU: AUC = 0.874 and 0.902, for classifications 1 and 2, respectively). Conclusion An automated deep learning model applied to TTE or HCU images accurately categorizes LV volumes. These results lay a foundation for future work aimed at optimizing clinical outcomes for heart failure patients by enabling early detection of LV enlargement across various point-of-care settings.

Abstract Aims This study aims to describe the prevalence of discordant mild/moderate aortic stenosis (AS) in a population-based study and to identify the mechanisms that lead to reduced stroke volume (SV) and discordant moderate AS. Methods and results Discordant high-gradient (HG)-mild AS, defined as AVA &gt; 1.5 cm2 and mean pressure gradient (MG) of 20–40 mmHg, and discordant low-gradient (LG) moderate AS, defined as AVA 1.0–1.5 cm2 and MG &lt; 20 mmHg, were assessed in 883 individuals from the DANCAVAS screening study with aortic valve calcification and 257 individuals form the PROGRESSA study excluding those with left ventricular (LV) ejection fraction &lt; 50%. In the DANCAVAS cohort, 150 men had mild/moderate AS of which 34% had discordance between MG and AVA, representing 66% with moderate AS. Among 262 patients in the combined cohort, 39% had discordant LG-moderate AS and 6% discordant HG-mild AS. Compared with concordant mild and moderate AS, individuals with discordant LG-moderate AS were more likely to present with LV concentric remodelling geometry (26 vs. 33 vs. 45%, P &lt; 0.001), increased valvulo-arterial impedance (3.3 ± 0.7 vs. 3.6 ± 0.5 vs. 4.1 ± 0.7 mmHg/mL/m2, P &lt; 0.001), and reduced systemic arterial compliance (SAC) (0.74 ± 0.22 vs. 0.81 ± 0.22 vs. 0.64 ± 0.18 mL/m2/mmHg, P &lt; 0.001). Factors associated with SV index were relative wall thickness, LV end-diastolic diameter index, SAC, and LV remodelling pattern. Conclusion Discordant moderate AS is common, accounting for two-thirds of patients with moderate AS in the general male population. Patients with discordant LG-moderate AS have predominantly a concentric remodelling pattern with reduced SV. Reduced SV index was associated with signs of reduced vascular compliance, suggesting that altered vascular properties drive differences in remodelling patterns and discordant moderate AS.

This Viewpoint advocates for prompt aortic valve replacement (rather than clinical surveillance) as the default strategy for patients with asymptomatic severe aortic stenosis.

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 (&lt; 25% percentile, Group 1), median rest force group (≥ 25% percentile & ≤ 75% percentile, Group 2), and high rest force group (&gt; 75% percentile, Group 3). Results 330 (13.9%) patients presented with ischemic RWMA. The 3 groups showed a gradient with descending values (Group 3&gt;2&gt;1) for SBP, EF, GLS, AE, and VAC, with the opposite gradient (Group 1&gt; 2&gt; 3) for EDV, EDVi, ESV, ESVi, SV, SVi, and LAVI values (all P&lt;0.01). Patients in Group 3 have higher NTproBNP level and higher percentage of B-line compared to groups 1 and 2 (P&lt;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 &lt; 0.001), VAC (r = 0.194, p = 0.001), LAVI (r = 0.327, p &lt; 0.001), LVEDV (r = -0.245, p &lt; 0.001), LVEDVi (r = -0.261, p &lt; 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 &lt; 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