Atrial Shunt Device Effects on Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction: The REDUCE LAP-HF II Randomized Clinical Trial.

Importance: Although the results of A Study to Evaluate the Corvia Medical Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF II) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status. Objective: To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status. Design, Setting, and Participants: This was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024. Interventions: Atrial shunt device or sham control. Main Outcome Measures: Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure. Results: The modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, -5.65 mL; P <.001), left atrial (LA) minimal volume (mean difference, -2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P <.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P <.001) and right atrial (RA; mean difference, 9.71 mL; P <.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P <.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs -1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading. Conclusions and Relevance: In this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03088033.

Asymptomatic Aortic Stenosis: From Risk Stratification to Treatment.

Our understanding of the natural history of aortic stenosis has significantly increased over the last decade. There have been considerable advances in the diagnosis and risk stratification of patients with aortic stenosis and in surgical and anesthetic techniques. In addition, transcatheter aortic valve replacement has established itself as a viable alternative to surgical management. Inevitably, these developments have raised questions regarding the merits of waiting for symptom onset in asymptomatic patients with severe aortic stenosis before offering treatment. Recent observational and randomized trial data suggest that early intervention in asymptomatic patients with severe aortic stenosis and normal left ventricular function may confer a prognostic advantage to a watchful waiting strategy. In this review, we highlight advances in the management and risk stratification of patients with asymptomatic severe aortic stenosis with particular consideration of recent findings supporting early valvular intervention.

International evaluation of an artificial intelligence-powered electrocardiogram model detecting acute coronary occlusion myocardial infarction.

Aims: A majority of acute coronary syndromes (ACS) present without typical ST elevation. One-third of non-ST-elevation myocardial infarction (NSTEMI) patients have an acutely occluded culprit coronary artery [occlusion myocardial infarction (OMI)], leading to poor outcomes due to delayed identification and invasive management. In this study, we sought to develop a versatile artificial intelligence (AI) model detecting acute OMI on single-standard 12-lead electrocardiograms (ECGs) and compare its performance with existing state-of-the-art diagnostic criteria. Methods and results: An AI model was developed using 18 616 ECGs from 10 543 patients with suspected ACS from an international database with clinically validated outcomes. The model was evaluated in an international cohort and compared with STEMI criteria and ECG experts in detecting OMI. The primary outcome of OMI was an acutely occluded or flow-limiting culprit artery requiring emergent revascularization. In the overall test set of 3254 ECGs from 2222 patients (age 62 ± 14 years, 67% males, 21.6% OMI), the AI model achieved an area under the curve of 0.938 [95% confidence interval (CI): 0.924-0.951] in identifying the primary OMI outcome, with superior performance [accuracy 90.9% (95% CI: 89.7-92.0), sensitivity 80.6% (95% CI: 76.8-84.0), and specificity 93.7 (95% CI: 92.6-94.8)] compared with STEMI criteria [accuracy 83.6% (95% CI: 82.1-85.1), sensitivity 32.5% (95% CI: 28.4-36.6), and specificity 97.7% (95% CI: 97.0-98.3)] and with similar performance compared with ECG experts [accuracy 90.8% (95% CI: 89.5-91.9), sensitivity 73.0% (95% CI: 68.7-77.0), and specificity 95.7% (95% CI: 94.7-96.6)]. Conclusion: The present novel ECG AI model demonstrates superior accuracy to detect acute OMI when compared with STEMI criteria. This suggests its potential to improve ACS triage, ensuring appropriate and timely referral for immediate revascularization.

Myocardial sodium-glucose cotransporter 2 expression and cardiac remodelling in patients with severe aortic stenosis: The BIO-AS study.

AIM: Cardiac remodelling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Our study aimed to evaluate the expression of sodium-glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow-low gradient (LF-LG) AS and its association with cardiac functional impairments. METHODS AND RESULTS: Gene expression and protein levels of main biomarkers of cardiac fibrosis (galectin-3, sST2, serpin-4, procollagen type I amino-terminal peptide, procollagen type I carboxy-terminal propeptide, collagen, transforming growth factor [TGF]-ß), inflammation (growth differentiation factor-15, interleukin-6, nuclear factor-κB [NF-κB]), oxidative stress (superoxide dismutase 1 [SOD1] and 2 [SOD2]), and cardiac metabolism (sodium-hydrogen exchanger, peroxisome proliferator-activated receptor [PPAR]-α, PPAR-γ, glucose transporter 1 [GLUT1] and 4 [GLUT4]) were evaluated in blood samples and heart biopsies of 45 patients with AS. Our study showed SGLT2 gene and protein hyper-expression in patients with LF-LG AS, compared to controls and HG AS (p < 0.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: (i) TGF-ß (r = 0.72, p < 0.001) and collagen (r = 0.73, p < 0.001) as markers of fibrosis; (ii) NF-κB (r = 0.36, p < 0.01) and myocardial interleukin-6 (r = 0.68, p < 0.001) as markers of inflammation: (iii) SOD2 (r = -0.38, p < 0.006) as a marker of oxidative stress; (iv) GLUT4 (r = 0.33, p < 0.02) and PPAR-α (r = 0.36, p < 0.01) as markers of cardiac metabolism. CONCLUSION: In patients with LF-LG AS, SGLT2 gene and protein were hyper-expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress.

Predictors of percutaneous coronary intervention derived from CCTA in patients with chronic coronary syndrome.

BACKGROUND: To identify anatomical and morphological plaque features predictors of PCI and create a multiparametric score to increase the predictive yield. Moreover, we assessed the incremental predictive value of FFRCT (Fractional Flow Reserve derived from CCTA) trans-lesion gradient (ΔFFRCT) when integrated into the score. METHODS: Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with FFRCT available, referred to invasive coronary angiogram and assessment of fractional flow reserve. Plaque analysis was performed using validated semi-automated software. Logistic regression was performed to identify anatomical and morphological plaque features predictive of PCI. Optimal thresholds were defined by area under the receiver-operating characteristics curve (AUC) analysis. A scoring system was developed in a derivation cohort (70 â€‹% of the study population) and tested in a validation cohort (30 â€‹% of patients). RESULTS: The overall study population included 340 patients (455 vessels), among which 238 patients (320 vessels) were included in the derivation cohort. At multivariate logistic regression analysis, absence of left main disease, diameter stenosis (DS), non-calcified plaque (NCP) volume, and percent atheroma volume (PAV) were independent predictors of PCI. Optimal thresholds were: DS â€‹≥ â€‹50 â€‹%, volume of NCP>113 â€‹mm3 and PAV>17 â€‹%. A weighted score (CT-PCI Score) ranging from 0 to 11 was obtained. The AUC of the score was 0.80 (95%CI 0.74-0.86). The integration of ΔFFRCT in the CT-PCI score led to a mild albeit not significant increase in the AUC (0.82, 95%CI 0.77-0.87, p â€‹= â€‹0.328). CONCLUSIONS: Plaque anatomy and morphology derived from CCTA could aid in identifying patients amenable to PCI.

Bleeding and thrombotic risk of different antiplatelet regimens posttranscatheter edge-to-edge mitral valve repair in patients with an indication for oral anticoagulation: Results from an all-comers national registry.

BACKGROUND: Evidence-based recommendations for antithrombotic treatment in patients who have an indication for oral anticoagulation (OAC) after transcatheter edge-to-edge mitral valve repair (TEER) are lacking. AIMS: To compare bleeding and thrombotic risk for different antithrombotic regimens post-TEER with MitraClip in an unselected population with the need for OACs. METHODS: Bleeding and thrombotic complications (stroke and myocardial infarction) up to 3 months after TEER with mitraclip were evaluated in 322 consecutive pts with an indication for OACs. These endpoints were defined by the Mitral Valve Academic Research Consortium criteria and were compared between two antithrombotic regimens: single antithrombotic therapy with OAC (single ATT) and double/triple ATT with a combination of OAC and aspirin and/or clopidogrel (combined ATT). RESULTS: Collectively, 108 (34%) patients received single ATT, 203 (63%) received double ATT and 11 (3%) received triple ATT. Bleeding events occurred in 67 patients (20.9%), with access site related events being the most frequent cause (37%). Bleeding complications were observed more frequently in the combined ATT group than in the single ATT group: 24% versus 14% [p = 0.03, adjusted RR: 0.55 (0.3-0.98)]. Within the combined group, the bleeding risk was 23% in the double ATT and 45% in the triple ATT group. Thrombotic complications occurred in only three patients (0.9%), and all belonged to the combined ATT group. CONCLUSIONS: In patients with an indication for OACs, withholding of antiplatelet therapy post-TEER with Mitraclip was associated with a 45% reduction in bleeding and without a signal of increased thrombotic risk.

Cell Therapy Improves Quality-of-Life in Heart Failure: Outcomes From a Phase III Clinical Trial.

Patients with heart failure experience limitations in daily activity and poor quality-of-life. Prospective surveillance of health-related quality-of-life supplemented traditional death and hospitalization outcomes in the multinational, randomized, double-blinded CHART-1 clinical trial that assessed cardiopoiesis-guided cell therapy in ischemic heart failure patients with reduced left ventricular ejection fraction. The Minnesota Living with Heart Failure Questionnaire (MLHFQ), a Food and Drug Administration qualified instrument for evaluating therapeutic effectiveness, was applied through the 1-year follow-up. Cell treated (n = 109) and sham procedure (n = 140) cohorts reported improved MLHFQ scores comparable between the 2 study arms (mean treatment difference with baseline adjustment -3.2 points, P = .107). Superiority of cell treatment over sham in betterment of the MLHFQ score was demonstrated in patients with pre-existing advanced left ventricular enlargement (baseline-adjusted mean treatment difference -6.4 points, P = .009). In this highly responsive subpopulation, benefit on the MLHFQ score paralleled reduction in death and hospitalization post-cell therapy (adjusted Mann-Whitney odds 1.43, 95% CI, 1.01-2.01; P = .039). The potential of cell therapy in addressing the quality-of-life dimension of heart failure requires further evaluation for disease relief.

Characterisation of coronary microvascular dysfunction in patients with severe aortic stenosis undergoing TAVI.

BACKGROUND: Microvascular resistance reserve (MRR) is a validated measure of coronary microvascular function independent of epicardial resistances. AIMS: We sought to assess whether MRR is associated with adverse cardiac remodelling, a low-flow phenotype and extravalvular cardiac damage (EVCD) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS: Invasive thermodilution-based assessment of the coronary microvascular function of the left anterior descending artery was performed in a prospective, multicentre cohort of patients undergoing TAVI. Coronary microvascular dysfunction (CMD) was defined as the lowest MRR tertile of the study cohort. Haemodynamic measurements were performed at baseline and then repeated immediately after TAVI. EVCD and markers of a low-flow phenotype were assessed with echocardiography. RESULTS: A total of 134 patients were included in this study. Patients with low MRR were more frequently females, had a lower estimated glomerular filtration rate and a higher rate of atrial fibrillation. MRR was significantly lower in patients with advanced EVCD (median 1.80 [1.26-3.30] vs 2.50 [1.87-3.41]; p=0.038) and in low-flow, low-gradient AS (LF LG-AS) (median 1.85 [1.20-3.04] vs 2.50 [1.87-3.40]; p=0.008). Overall, coronary microvascular function tended to improve after TAVI and, in particular, MRR increased significantly after TAVI in the subgroup with low MRR at baseline. However, MRR was significantly impaired in 38 (28.4%) patients immediately after TAVI. Advanced EVCD (adjusted odds ratio 3.08 [1.22-7.76]; p=0.017) and a low-flow phenotype (adjusted odds ratio 3.36 [1.08-10.47]; p=0.036) were significant predictors of CMD. CONCLUSIONS: In this observational, hypothesis-generating study, CMD was associated with extravalvular cardiac damage and a low-flow phenotype in patients with severe AS undergoing TAVI.

Combined Cardiac Damage Staging by Echocardiography and Cardiac Catheterization in Patients With Clinically Significant Aortic Stenosis.

BACKGROUND: Cardiac damage (CD) staging enhances risk stratification in patients with clinically significant aortic stenosis (AS). We aimed to assess the prognostic value and reclassification rate of right heart catheterization (RHC) compared with transthoracic echocardiography (TTE) in characterising CD staging at 3-year follow-up in patients with clinically significant AS, to identify patients that would benefit from RHC for prognostic stratification, and to test the prognostic value of combined CD staging. METHODS: An observational cohort study of 432 AS patients undergoing TTE and RHC were divided into moderate or asymptomatic severe (m/asAS) and symptomatic severe (ssAS) AS. Kaplan-Meier curves were used to compare survival. The accuracy in prognostic stratification was tested by area under the receiver operating characteristic curve analysis and Delong test. RESULTS: In both cohorts, TTE- and RHC-derived staging systems had prognostic value, although the agreement between them appeared moderate. A higher proportion of patients were assigned to stage 2 by TTE than by RHC. Patients in TTE-derived stage 2 had a high reclassification rate, with 40%-50% presenting with right chamber involvement (stages 3-4) according to RHC. Discordant cases were significantly older, with higher prevalence of atrial fibrillation, markedly elevated N-terminal pro-B-type natriuretic peptide, and higher indexed left atrial volume, E/e', and systolic pulmonary artery pressure vs concordant cases (P < 0.05). The combined CD staging, integrating TTE and RHC, was more accurate in predicting mortality than the TTE-derived system (P < 0.05). CONCLUSIONS: In patients with m/asAS and ssAS, the combined CD staging, derived from TTE and RHC, was more accurate in predicting mortality than TTE alone. In a subset of AS patients, the integration of RHC may significantly improve prognostic stratification.

Coronary Microvascular Dysfunction in Patients With Heart Failure: Characterization of Patterns in HFrEF Versus HFpEF.

BACKGROUND: Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF). METHODS: Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery-related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery-related mass. RESULTS: Patients with HFrEF showed a higher left ventricular and left anterior descending artery-related myocardial mass compared with HF with preserved ejection fraction (P<0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P=0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P≤0.030). CONCLUSIONS: Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up.

Continuous vs Bolus Thermodilution to Assess Microvascular Resistance Reserve.

BACKGROUND: Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) can, in principle, be derived by any method assessing coronary flow. OBJECTIVES: The aim of this study was to compare CFR and MRR as derived by continuous (CFRcont and MRRcont) and bolus thermodilution (CFRbolus and MRRbolus). METHODS: A total of 175 patients with chest pain and nonobstructive coronary artery disease were studied. Bolus and continuous thermodilution measurements were performed in the left anterior descending coronary artery. MRR was calculated as the ratio of CFR to fractional flow reserve and corrected for changes in systemic pressure. In 102 patients, bolus and continuous thermodilution measurements were performed in duplicate to assess test-retest reliability. RESULTS: Mean CFRbolus was higher than CFRcont (3.47 ± 1.42 and 2.67 ± 0.81 [P < 0.001], mean difference 0.80, upper limit of agreement 3.92, lower limit of agreement -2.32). Mean MRRbolus was also higher than MRRcont (4.40 ± 1.99 and 3.22 ± 1.02 [P < 0.001], mean difference 1.2, upper limit of agreement 5.08, lower limit of agreement -2.71). The correlation between CFR and MRR values obtained using both methods was significant but weak (CFR, r = 0.28 [95% CI: 0.14-0.41]; MRR, r = 0.26 [95% CI: 0.16-0.39]; P < 0.001 for both). The precision of both CFR and MRR was higher when assessed using continuous thermodilution compared with bolus thermodilution (repeatability coefficients of 0.89 and 2.79 for CFRcont and CFRbolus, respectively, and 1.01 and 3.05 for MRRcont and MRRbolus, respectively). CONCLUSIONS: Compared with bolus thermodilution, continuous thermodilution yields lower values of CFR and MRR accompanied by an almost 3-fold reduction of the variability in the measured results.

Comprehensive invasive evaluation of coronary microcirculation in patients with Takotsubo syndrome.

BACKGROUND AND AIMS: The etiology and pathophysiology of Takotsubo syndrome (TTS) remain a matter of debate. In murine models of coronary microvascular dysfunction (CMD), abnormalities in myocardial perfusion led to the development of TTS. Importantly, TTS was reversible when normal perfusion was restored. However, in clinical practice, the assessment of coronary microcirculation in patients with TTS has primarily relied on non-invasive or indirect, angiography-derived methods. METHODS AND RESULTS: For the first time, we performed invasive microcirculatory assessment, by both validated techniques currently available in the catheterization laboratory, namely intracoronary bolus and continuous thermodilution, in patients with TTS, upon hospital admission and at short term follow-up. Our findings demonstrate that CMD was consistently present in all patients upon hospital admission, as assessed by both techniques. At a median follow-up of 3 months, after the recovery of left ventricular ejection fraction, two third of patients no longer exhibited CMD. CONCLUSIONS: These findings support the hypothesis that an acute and transient worsening in coronary microvascular function plays a pivotal role in the pathophysiology of TTS.

Association of Mild-to-Moderate Aortic Regurgitation With Outcomes in Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF). METHODS: Consecutive patients hospitalized with de novo or worsened HFpEF between 2014 and 2020 were enrolled. Patients with more than moderate aortic and/or mitral valve disease were excluded. Based on the presence and degree of AR, patients were divided into those without AR, those with mild, and those with moderate AR. Data on cardiovascular death, heart failure (HF) rehospitalization, and their composite (major adverse cardiovascular events) were collected. RESULTS: The final study population consisted of 458 HFpEF patients: 156 (34.1%) with mild-AR, 153 (33.4%) with moderate-AR, and the remaining 149 (32.5%) with no AR. Mild-to-moderate AR patients were older, with larger left atrium-left ventricle (LV) volumes, greater LV mass index, higher filling pressure, and prevalence of diastolic dysfunction compared with the no-AR group (all P<.05). During 5-year follow-up, 113 patients died of cardiovascular causes, 124 patients were rehospitalized for HF, whereas 196 experienced the composite endpoint. Mild-to-moderate AR was identified as an independent predictor of all-cause death (HR, 1.62; 95% CI, 1.14 to 1.58; P=.04) and major adverse cardiovascular event occurrence (HR, 1.48; 95% CI, 1.05 to 2.09; P=.02). A total of 126 (35.5%) of 355 patients showed progression of AR at follow-up echocardiography. CONCLUSION: Mild-to-moderate AR is common among patients hospitalized for HFpEF. It is associated with adverse LV remodeling and worse long-term outcomes. These findings warrant further prospective studies addressing the importance of AR in prognostic stratification and exploring therapeutic strategies to mitigate its hemodynamic effect on HF.

Dual left anterior descending coronary artery and anomalous origin of left circumflex artery: a novel coronary anomaly revealed by CCTA.

In the rare coronary anomaly of Dual LAD, two segments of the vessel reside within the anterior interventricular sulcus. In our case, the short LAD originated from the Left Coronary Sinus (LCS), while the long LAD emerged from the Right Coronary Sinus (RCS). The LCx arose from the RCS, and the RCA displayed typical features. This anomaly was deemed incidental, prompting routine follow-up. It underscores the significance of integrating CCTA for a thorough assessment, offering crucial insights for patient management.

Detection of transthyretin amyloid cardiomyopathy by automated data extraction from electronic health records.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive and fatal cardiomyopathy, is frequently misdiagnosed or entails diagnostic delays, hindering patients from timely treatment. This study aimed to generate a systematic framework based on data from electronic health records (EHRs) to assess patients with ATTR-CM in a real-world population of heart failure (HF) patients. Predictive factors or combinations of predictive factors related to ATTR-CM in a European population were also assessed. METHODS AND RESULTS: Retrospective unstructured and semi-structured data from EHRs of patients from OLV Hospital Aalst, Belgium (2012-20), were processed using natural language processing (NLP) to generate an Observational Medical Outcomes Partnership Common Data Model database. NLP model performance was assessed on a random subset of EHRs by comparing algorithm outputs to a physician-generated standard (using precision, recall, and their harmonic mean, or F1-score). Of the 3127 HF patients, 103 potentially had ATTR-CM (age 78 ± 9 years; male 55%; ejection fraction of 48% ± 16). The mean diagnostic delay between HF and ATTR-CM diagnosis was 1.8 years. Besides HF and cardiomyopathy-related phenotypes, the strongest cardiac predictor was atrial fibrillation (AF; 72% in ATTR-CM vs. 60% in non-ATTR-CM, P = 0.02), whereas the strongest non-cardiac predictor was carpal tunnel syndrome (21% in ATTR-CM vs. 3% in non-ATTR-CM, P < 0.001). The strongest combination predictor was AF, joint disorders, and HF with preserved ejection fraction (29% in ATTR-CM vs. 18% in non-ATTR-CM: odds ratio = 2.03, 95% confidence interval = 1.28-3.22). CONCLUSIONS: Not only well-known variables associated with ATTR-CM but also unique combinations of cardiac and non-cardiac phenotypes are able to predict ATTR-CM in a real-world HF population, aiding in early identification of ATTR-CM patients.

Innovative Device-Based Strategies for Managing Acute Decompensated Heart Failure.

Acute decompensated heart failure (ADHF) is a major cause of hospitalizations in older adults, leading to high mortality, morbidity, and healthcare costs. To address the persistent poor outcomes in ADHF, novel device-based approaches targeting specific pathophysiological mechanisms are urgently needed. The recently introduced DRI2P2S classification categorizes these innovative therapies based on their mechanisms. Devices include dilators (increasing venous capacitance), removers (directly removing sodium and water), inotropes (enhancing left ventricular contractility), interstitials (accelerating lymph removal), pushers (increasing renal arterial pressure), pullers (decreasing renal venous pressure), and selective drippers (selective intrarenal drug infusion). Some are tailored for chronic HF, while others focus on the acute setting. Most devices are in early development, necessitating further research to understand mechanisms, assess clinical effectiveness, and ensure safety before routine use in ADHF management. Exploring these innovative device-based strategies may lead to improved outcomes and revolutionize HF treatment in the future.

Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).

State-of-the-Art: Noninvasive Assessment of Left Ventricular Function Through Myocardial Work.

The assessment of myocardial work (MW) using noninvasive pressure-strain loop analysis is a novel echocardiographic method that provides a more precise assessment of cardiac performance by considering the left ventricular loading condition. By integrating various MW components such as index, efficiency, and constructive and wasted work, an extensive analysis of left ventricular mechanics and energetics can be achieved. This approach offers a more comprehensive assessment of global cardiac function and performance, surpassing conventional surrogate indices. In this review, we aim to summarize the existing knowledge on MW and its distinctive characteristics in various cardiac pathologies.