Chaliki, Hari P.

Abstract Aims Randomized trials comparing percutaneous left atrial appendage occlusion (LAAO) with oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation have yielded conflicting results across device generations and anticoagulant eras. This Bayesian meta-analysis of randomized trials aimed to compare LAAO vs. OAC for stroke or systemic embolism (SSE) and non-procedural clinically relevant bleeding (CRB). Methods and results We conducted a systematic search across five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL) to identify randomized trials of LAAO vs. OAC. Primary outcomes of stroke or systemic embolism, non-procedural CRB and clinical benefit composite were estimated using a Bayesian hierarchical random effects model and findings confirmed across robust sensitivity and subgroup analyses. Posterior probabilities for superiority, non-inferiority and equivalence were estimated using clinically meaningful margins. Six randomized trials including 7004 participants in the intention-to-treat groups, were analysed. LAAO was not associated with lower SSE vs. OAC (pooled RR, 1.11; 95% CrI, 0.80–1.49), with a 74.6% posterior probability of favouring OAC. The posterior probability of crossing non-inferiority was P(HR < 1.4) of 89%. In contrast, LAAO reduced non-procedural CRB (pooled RR, 0.59; 95% CrI, 0.45–0.78). The net clinical benefit composite, pooling contemporary trials, demonstrated a pooled RR of 0.90 (95% CrI 0.51–1.50), with P(RR < 1) of 76%, with substantial heterogeneity for this outcome. Conclusion This Bayesian meta-analysis found no clear evidence supporting clinically meaningful non-inferiority of LAAO over OAC for stroke prevention. Despite reduced non-procedural bleeding, LAAO did not demonstrate a similar reduction in major bleeding.

Background: In patients with paradoxical low-gradient severe aortic stenosis (AS) based on aortic valve area (AVA) at rest (<1cm2) and normal left ventricular ejection fraction (LVEF >50%), the role of dobutamine stress echocardiography (DSE) is unclear. While current guidelines recommend assessing aortic valve calcium score in this context, DSE may still offer clinical value. Methods: We conducted a retrospective study on patients with paradoxical low gradient AS (LVEF >50% AVA <1cm 2 , MG < 40 mmHg) at rest who underwent DSE after Institutional Review Board approval. Data was extracted using an internal database. Patients > 18 yrs old with LVEF >50%, mean gradient (MG) < 40 mmHg, and valve area < 1 cm 2 at rest were included. Kruskal-Wallis test was used to identify which resting variables were associated with severe AS (MG >40 mm Hg and Valve area <1 cm 2 ) with DSE. Results: A total of 42 patients were included in the study and variables were reported as means (±SD). The mean age of patients was 78 years (±10) and 60% were female. The mean resting LVEF was 60% (±5%), MG at rest was 28 mmHg (±7) while it was 40 mmHg (±14) with DSE, and mean aortic valve area at rest was 0.9 cm 2 (±0.09) while it was 1.1 cm 2 (±0.23) with DSE. Of the 42 patients, 11 (26%) were found to have severe AS during DSE, defined by a MG >40 mmHg and AVA <1.0 cm 2 . Baseline AVA and MG at rest were significantly associated with severe AS on DSE (p=0.008 and p=0.024, respectively), while age, stroke volume index, and baseline LVEF were not. Univariate regression analysis showed that the area under the curve (AUC) for predicting severe AS was 0.73 for resting MG and 0.77 for resting AVA. A resting AVA cutoff of 0.78 cm 2 provided optimal sensitivity (0.63) and specificity (0.90). For resting MG, a cutoff of 29 mmHg gave a sensitivity of 0.91 and specificity of 0.68 for identifying patients with severe AS. Conclusion: Our study indicated that DSE remains useful in identifying severe AS in substantial number of patients (26%) who exhibit paradoxical low gradient severe AS. Additionally, AVA at rest and baseline mean gradient were statistically the reliable parameters to determine those who may benefit significantly from undergoing DSE. This is one of the first studies to our knowledge in the literature suggesting that DSE may still be useful in identifying severe AS patients despite “paradoxical low gradient severe AS” at rest. Further research is warranted to validate our findings.

Background: Patients with low gradient non-severe aortic stenosis (AS) at rest, in the context of reduced left ventricular ejection fraction (LVEF) (less than 50%), occasionally undergo dobutamine stress echocardiogram (DSE). However, limited data is available in the literature regarding the utility of DSE in this context. Methods: We conducted a retrospective study on patients with non-severe AS and LVEF less than 50% at rest who underwent DSE after Institutional Review Board approval. Retrospective data was extracted including rest and DSE parameters using an internal database. Only patients greater than 18 years old, who had an LVEF less than 50%, mean gradient (MG) less than 40 mmHg, and valve area greater than or equal to 1 cm 2 at rest were included in the study. Univariate and multivariate regression methods were used to identify which resting variables were associated with severe AS (MG greater than 40 mm Hg and valve area less than 1 cm 2 ) with DSE. Results: A total of 124 patients were included in the study. The mean age of patients was 78 years (±9) and 84% were male. The mean resting LVEF was 34% (±8%) while it was 40% (±12%) with DSE, mean stroke volume index at rest was 39 mL/m2 (±9) while it was 45 mL/m2 (±10) with DSE, MG at rest was 20 mmHg (±7) while it was 31 mmHg (±10) with DSE, and mean aortic valve area at rest was 1.27 cm 2 (±0.27) while it was 1.24 cm 2 (±0.29) with DSE. Of the 124 patients with non-severe AS at rest, 13 (10.5%) patients had severe AS with DSE. MG at rest was associated with severe AS (OR 1.3; 95% Cl: 1.1 - 1.5; p < 0.001) in a multivariate logistic regression model after adjusting for age, sex, LVEF at rest, SV index at rest. Resting aortic valve mean gradient also showed the highest AUC in relation to likelihood of having severe AS (0.87) (figure 1). Conclusion: Our study indicated that DSE remains useful in identifying severe AS in certain patients (up to 10%) who exhibit non-severe AS at rest in the setting of reduced LVEF. Additionally, MG at rest is the most reliable parameter to determine those who may benefit from undergoing DSE. This is one of the first studies to our knowledge in the literature suggesting that DSE may still be useful in identifying severe AS patients despite non-severe AS (i.e., valve area greater than or equal to 1 cm 2 ) at rest with reduced LVEF. Further research is warranted to validate our findings.

Problem Statement: The prognostic value of troponin elevation in septic ICU patients without known history of cardiac disease remains unclear, particularly after accounting for overall illness severity. Background: Minor troponin rises are frequent during sepsis, yet clinicians still lack a clear cut-point that signals danger once cardiac disease is ruled out. We asked whether a modest increase in troponin-T predicts in-hospital death beyond global illness severity. Methods: We studied 1 221 adult first ICU stays labelled “sepsis” in the eICU Collaborative Research Database and removed any case with a cardiac admission diagnosis. Implausible or missing laboratory values were imputed by multiple imputation. Hospital mortality was modelled with logistic regression that included troponin (a continuous and a binary model with threshold > 0.04 ng/mL) together with age, sex, lactate, albumin, BUN, creatinine, intubation status, vasopressor use, dialysis requirement and APACHE-IV predicted mortality. A natural-spline model explored non-linear behavior. Findings were checked in a 1:1 propensity-matched cohort. Results: Overall mortality was 11.7%. Troponin exceeded 0.04 ng/mL in 38% of patients. After adjustment for APACHE-IV probability and other covariates, a troponin level > 0.04 ng/mL was associated with almost twice the odds of death (OR ≈ 1.9), whereas the continuous model suggested only a modest trend (OR ≈ 1.1 per ng/mL). The spline curve rose steeply between 0 and 0.10 ng/mL and flattened thereafter, pinpointing an inflection near 0.05 ng/mL. Matching on all measured confounders confirmed that high-troponin patients had about three-fold greater mortality (OR ≈ 2.8, 1.55-5.05; p<0.001), highlighting that even modest troponin elevation is an independent risk marker for death in septic ICU patients. A bedside heat-map combining troponin, albumin and need for intubation illustrated a simple gradient: risk climbs from 2 % in low-troponin, well-albuminised, non-intubated patients to nearly 7 % when troponin exceeds 0.10 ng/mL in intubated, hypo-albuminemic patients. Conclusions: Even modest troponin elevations (> 0.04 ng/mL) independently predict mortality in sepsis after rigorous adjustment and matching on APACHE-IV physiology, lactate, and organ-support variables. This biologic threshold supports incorporating troponin into bedside triage and future septic cardiomyopathy trials.

Background/Objectives: The peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a strong predictor of all-cause mortality. The cardiac output, a key determinant of VO2, can be assessed using resting echocardiographic parameters. The heart rate recovery and ventilatory efficiency (VE/VCO2 slope) from CPET offer additional insights into cardiovascular fitness. Methods: This study aimed to identify resting echocardiographic parameters that predict the percentage of predicted peak VO2, heart rate recovery, and VE/VCO2 slope in a general cardiology population. This retrospective analysis included 1909 patients who underwent echocardiography within 3 months of CPET from 2017 to 2022. Patients with potentially confounding co-morbid conditions were removed. Spearman correlations were used to compare 19 echocardiographic parameters to peak VO2, heart rate recovery, and the VE/VCO2 slope, followed by multiple linear regression of peak VO2. Results: Eleven echocardiographic parameters correlated with peak VO2, with the strongest correlations seen with the left ventricular stroke volume index (R = 0.284, p < 0.001), mitral valve medial annular a’ wave velocity (R = 0.142, p < 0.0001), and mitral E-to-e’ ratio (R = −0.117, p < 0.0001). The left ventricular diastolic parameters and mitral E/A ratio correlated strongly with the heart rate recovery and VE/VCO2 slope. The multiple linear regression analysis identified the left ventricular mass index, stroke volume index, mitral valve E wave velocity, tricuspid valve regurgitation peak systolic velocity, tricuspid lateral annular systolic velocity S’, and left atrial volume index as independent predictors of peak VO2 (R2 = 0.191). Conclusions: The left ventricular stroke volume, diastolic function, and RV systolic function markers are significant predictors of cardiopulmonary fitness, aiding clinical decision-making in patients without CPET data.

Background: Cardiopulmonary Exercise Testing (CPET) analyzes physiologic information with gas exchange during exercise. Peak oxygen volume consumption (absolute peak VO2 and percent predicted peak VO2), minute ventilation divided by carbon dioxide volume (VE/VCO2 slope) and heart rate reduction after 1 minute of recovery (heart rate recovery, HRR) all have well-established prognostic cardiovascular implications. Aim: Given the wider use of echocardiography, we aimed to see if important CPET data could be determined from resting transthoracic echocardiography (TTE). Methods: In this retrospective study, cardiology patients above 18 years who underwent both resting TTE and a max-effort CPET within 3 months of each other (2017-2022) were included. Patients with a history of coronary artery bypass grafting, valve surgery, pacemakers, congenital heart disease, severe valve dysfunction and pulmonary hypertension were excluded before analysis. Univariate analysis with Spearman correlations was used to assess the relationship between 4 CPET measurements {absolute peak VO2 per kg, percent predicted peak VO2/kg (adjusted for age, sex and body surface area), HRR, and VE/VCO2}; and 22 quantitative TTE parameters. Bonferroni correction was applied within each set of correlations, with significance set at p-values <0.025. Multivariate linear regression models were built for all the related TTE measurements to assess relationship with the 4 CPET parameters, adjusting for age and sex. Results: Table 1 shows, out of 1909 patients analyzed, our regression model is strongest for absolute peak VO2/kg (R-squared=0.57), with 3 significantly associated TTE parameters. For percent-predicted peak VO2 per kg, 4 TTE variables were significantly associated. For heart rate recovery, only LV stroke-volume index was correlated. No TTE parameters were associated with VE/VCO2. Conclusion: Notably, echocardiographic stroke volume and tricuspid valve regurgitation peak velocity exhibited a strong correlation with absolute peak VO2/kg and percent predicted peak VO2/kg. LV stroke volume index was correlated with heart rate recovery. VE/VCO2 was not associated with any resting echocardiographic parameters, suggesting this parameter is truly exercise-dependent.

Introduction- Two dimensional speckle tracking echocardiography is a novel non-invasive method to assess subtle changes in left ventricular (LV) function such as strain and rotational dynamics. Limited data exists for assessing the impact of severity of aortic stenosis (AS) on LV apical rotation Objective- To determine the impact of severity of AS on LV longitudinal strain as well as LV apical rotation in patients with preserved LV ejection fraction and various degrees of AS. Methods- We prospectively measured longitudinal LV strain and apical rotation in 74patients with preserved LV ejection fraction but no (n= 22), mild (MG 10-25 mmHg; n= 20), moderate (MG 25-40 mmHg; n= 18), or severe (MG >40 mmHg; n= 14) AS who were undergoing echocardiographic examination at our institution. Two dimensional speckle tracking method was used to obtain average peak longitudinal strain using apical 4, 2-chamber and long-axis views while apical short axis view was used to obtain the LV apical rotation. Results- Mean age between no vs. mild vs. mod vs. severe AS groups (73±11yrs; 70±13yrs; 77±6yrs; 76±14 yrs) was not different (p=0.26). Presence of hypertension (64%, 65%, 78%, 71%) and coronary artery disease (14%, 6%, 25%, 29%) were also not different between the groups (p = 0.76 and p = 0.23 respectively). Average LV peak global longitudinal strain was not different between groups (-17.5±3%; -17.5±5%;-16.6±4%; -16.6±3% (p=0.82). However LV peak apical rotation was higher with worsening severity of aortic stenosis (14.8±8°; 14.7±9°; 21.3±11°; 23.7±12°) (overall p=0.02) (Figure). Conclusions- 1) LV peak longitudinal strain was not different between patients with no stenosis when compared to patients with various levels of aortic stenosis. 2) However, LV apical rotation increases with worsening levels of AS probably to maintain the LV stroke volume. Further studies are needed to evaluate the role of LV apical rotation in deciding the timing of surgery in patients with severe AS.

Introduction- Recent studies based on echocardiographic data have described an entity termed paradoxical low-flow, low-gradient severe aortic stenosis (AS) with preserved ejection fraction (EF). It is not clear whether this condition is also seen in patients who undergo hemodynamic catheterization. Objective- To determine the prevalence of low-flow in patients with low mean gradient (MG) severe AS despite preserved EF as determined by echocardiography who subsequently undergo hemodynamic catheterization. Methods- We retrospectively reviewed medical records of 259 patients who underwent hemodynamic catheterization at Mayo Clinic from 2000-2009 to assess the severity of AS within 6 months of their echocardiographic study. Results- A total of 35 patients (mean age 75±9yrs; 49% males) had MG (≤ 40 mm Hg) and aortic valve area (AVA ≤ 1 cm2) despite preserved EF (≥50%) as determined by echocardiography. A total of 7/35 patients (20%) had low flow by echocardiography, defined as stroke volume index (SVI) ≤ 35 ml/m2 (median SVI of 32 ml/m2, inter-quartile range 30-33 ml/m2). Among the same 35 patients, there were 23 patients who had both low MG (≤ 40 mm Hg) and severe AS (AVA ≤ 1 cm2), while a total of 14/35 patients (40%) had low MG, severe AS as well as low flow (median SVI of 32 ml/m2, inter-quartile range 29-33 ml/m2) as determined by hemodynamic catheterization. A statistically significant correlation with modest association was observed between invasive and noninvasive measurements of MG, SVI, and AVA (r=0.48 ; p = 0.003; r=0.48; p = 0.004 ; r=0.36; p=0.03 respectively) in our study group of 35 patients. In most patients (94%) MG by catheterization was also ≤ 40 mm Hg. However, agreement between echocardiography and catheterization to identify patients with paradoxical low-flow, low MG, severe AS was poor (kappa = 0.03). Conclusions- 1) Paradoxical low flow, low-gradient severe aortic stenosis is also observed in patients who undergo hemodynamic catheterization. 2) Further studies are needed to better understand the pathophysiology, best method for diagnosis and true prevalence of this entity.

Introduction: Tricuspid regurgitation is a common echocardiographic finding leading to excess morbidity and mortality in adult population. Hypothesis: Racial and ethnic disparities have been observed in various cardiovascular disorders’ prevalence and natural course, including valvular lesions. However, little is known about the epidemiology and clinical correlations of TR among non-Hispanic Black adults. Methods: To examine risk factors and clinical outcomes in non-Hispanic Black adults with moderate or more severe TR, 685 patients (7%) self-identified as non-Hispanic Black and 9127 (93%) self-identified as non-Hispanic White with a first echocardiographic report of moderate or more severe TR between 2005-2016 were studied. Results: Non-Hispanic Black patients had more severe TR when compared to white patients (25% vs. 20%, p<0.001). After adjusting for age and sex, non-Hispanic Black patients had significantly higher 10-year all-cause mortality (HR=1.34 (1.18, 1.52), p<0.001). Black race remained a risk factor for all-cause mortality even after adjustment for comorbidities like CHF, COPD, DM, CKD, hypertension, and ischemic heart disease (HR=1.23 (1.08, 1.40), p=0.002). Conclusions: Significant racial disparities exist in demographic, clinical and echocardiographic characteristics between non-Hispanic Black and White patients with moderate or more severe TR. Black race is a potential disease modifier leading to excess mortality.

Introduction: The consequences of external cardiovascular compression and cardiac displacement from pectus excavatum (PEx) are debated. The complex geometry of the right (RV) and left ventricle (LV) along with distortion from the extrinsic chest deformity pose significant limitations to reliable assessment of LV and RV volumes and function using transthoracic 2D-echocardiography in this population. Hypothesis: A 3D-echocardiography approach can reliably assess the effects of external cardiac compression and the benefits of surgical correction on RV and LV function in PEx patients. Methods: Adult patients undergoing minimally invasive repair of PEx between Oct-2021 and Feb-2023 were included in this prospective study. Intraoperative transesophageal (TEE) 6 beat full volume video loops incorporating LV and RV were captured and compared before and after surgical correction of the PEx. TomTec Software® was used for offline 3D/4D reconstruction ( Figure 1 shows changes in 3D RV and LV shape pre- and post-surgery). Result: The study included 102 patients (mean age of 32.1 ±11.8 years; Haller index 4.9 ±2.5; 60.8% males). Post PEx repair, there was a significant (p<0.001) increase in the 3D RV volumes, RV ejection fraction (EF), RV stroke volume and RV strain ( Figure 1 ). Additionally, there was a significant improvement in 3D LVEF, 3D LV strain (longitudinal and circumferential), LV twist, and torsion ( Figure 1 ). Conclusion: In this PEx cohort, 3D/4D TEE imaging demonstrated significant increases in RV volumes and in RV and LV systolic function after surgical repair. These findings support the negative cardiovascular consequences of PEx compression and benefits of surgical repair.