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Background: Despite evidence supporting use of fractional flow reserve (FFR) and instantaneous waves-free ratio (iFR) to improve outcome of patients undergoing coronary angiography (CA) and percutaneous coronary intervention, such techniques are still underused in clinical practice due to economic and logistic issues., Objectives: We aimed to develop an artificial intelligence (AI)-based application to compute FFR and iFR from plain CA., Methods and Results: Consecutive patients performing FFR or iFR or both were enrolled. A specific multi-task deep network exploiting 2 projections of the coronary of interest from standard CA was appraised. Accuracy of prediction of FFR/iFR of the AI model was the primary endpoint, along with sensitivity and specificity. Prediction was tested both for continuous values and for dichotomous classification (positive/negative) for FFR or iFR. Subgroup analyses were performed for FFR and iFR.A total of 389 patients from 5 centers were enrolled. Mean age was 67.9 ± 9.6 and 39.2% of patients were admitted for acute coronary syndrome. Overall, the accuracy was 87.3% (81.2-93.4%), with a sensitivity of 82.4% (71.9-96.4%) and a specificity of 92.2% (90.4-93.9%). For FFR, accuracy was 84.8% (77.8-91.8%), with a sensitivity of 81.9% (69.4-94.4%) and a specificity of 87.7% (85.5-89.9%), while for iFR accuracy was 90.2% (86.0-94.6%), with a sensitivity of 87.2% (76.6-97.8%) and a specificity of 93.2% (91.7-94.7%, all confidence intervals 95%)., Conclusion: The presented machine-learning based tool showed high accuracy in prediction of wire-based FFR and iFR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Haemodynamic assessment can be determinant in phenotyping cardiogenic shock (CS) and guiding patient management. Aim of this study was to evaluate the correlation between echocardiographic and invasive assessment of haemodynamics in acute decompensated heart failure-related CS (ADHF-CS)., Methods and Results: All consecutive ADHF-CS patients (SCAI shock stage ≥B) undergoing right heart catheterization (RHC) between 2020 and 2022 were prospectively enrolled. Patients underwent echocardiography 30 min before RHC. The evaluated haemodynamic parameters and their echocardiographic estimates ('e') comprised cardiac index (CI), wedge pressure (WP), pulmonary artery pressures (PAP), cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi). Hundred and one ADHF-CS patients (56 ± 11 years, 64% SCAI shock stage C, left ventricular ejection fraction 29 ± 5%) were included. Good correlation was found for CI, systolic PAP, RAP, and CPO (Pearson r > 0.8 for all), moderate correlation for ePAPi (r = 0.67) and PVR (r = 0.51), while estimation of WP was weak. The sensitivity and specificity of eCI to identify low output state (CI ≤2.2 L/min/m2) were 0.97 and 0.73, respectively, those of eWP for elevated filling pressures (WP >15 mmHg) were 0.84 and 0.55, those of ePAPs for PAPs ≥35 mmHg were 0.87 and 0.63, those of eCPO for CPO <0.6 W were 0.76 and 0.85, those of ePAPi for PAPi <1.85 were 0.89 and 0.92. Echocardiographic phenotyping of CS showed a good agreement with invasive classification (K value 0.457, P < 0.001)., Conclusion: Echocardiographic estimation of haemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity., Methods: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters., Results: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure ( P =0.043), hepatic injury ( P =0.049), and suspected/definite infection ( P =0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P =0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P =0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; P adj =0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; P adj <0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; P adj =0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; P adj =0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; P adj =0.008)., Conclusions: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality., Competing Interests: None.

Cardiac involvement is the foremost determinant of the clinical progression of amyloidosis. The diagnostic role of cardiac magnetic resonance (CMR) imaging in cardiac amyloidosis has been established, but the prognostic role of various right and left CMR tissue characterization and functional parameters, including global longitudinal strain (GLS), late gadolinium enhancement (LGE), and parametric mapping, is yet to be delineated. We searched EMBASE, PubMed, and MEDLINE for studies analysing the prognostic use of CMR imaging in patients with light chain amyloidosis or transthyretin amyloidosis cardiac amyloidosis. The primary endpoint was all-cause mortality. A random effects model was used to calculate a pooled odds ratio using inverse-variance weighting. Nineteen studies with 2199 patients [66% males, median age 59.7 years, interquartile range (IQR) 58-67] were included. Median follow-up was 24 months (IQR 20-32), during which 40.8% of patients died. Both tissue characterization left heart parameters such as elevated extracellular volume [hazard ratio (HR) 3.95, 95% confidence interval (CI) 3.01-5.17], extension of left ventricular (LV) LGE (HR 2.69, 95% CI 2.07-3.49) elevated native T1 (HR 2.19, 95% CI 1.12-4.28), and functional parameters such as reduced LV GLS (HR 1.91, 95% CI 1.52-2.41) and reduced LV ejection fraction (EF; HR 1.20, 95% CI 1.17-1.23) were associated with increased all-cause mortality. Unlike the presence of right ventricular (RV) LGE (HR 3.40, 95% CI 0.51-22.54), parameters such as RV GLS (HR 2.08, 95% CI 1.6-2.69), RVEF (HR 1.13, 95% CI 1.05-1.22), and tricuspid annular systolic excursion (TAPSE) (HR 1.11, 95% CI 1.02-1.21) were also associated with mortality. In this large meta-analysis of patients with cardiac amyloidosis, CMR parameters assessing RV and LV function and tissue characterization were associated with an increased risk of mortality., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Comparative data after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for unprotected left main coronary artery (ULMCA) disease according to lesion site (ostial/shaft vs distal) are scant. The aim of this meta-analysis was to investigate outcomes after PCI or CABG for ULMCA disease according to lesion site., Methods: Randomized controlled trials (RCTs) and adjusted observational studies that compared PCI versus CABG in patients with ULMCA disease and reported outcomes according to lesion site were systematically identified. Major adverse cardiovascular events (MACE; a composite of all-cause death, myocardial infarction, stroke, and repeat revascularization) and all-cause death were the co-primary end points. Individual components of MACE were secondary end points. Sensitivity analysis including RCTs only were performed for each outcome., Results: Nine studies (3 RCTs, 6 adjusted observational), encompassing 6296 patients (2274 and 4022 treated for ostial/shaft or distal ULMCA, respectively) were included. At the 5-year follow-up, there were no significant differences between CABG and PCI for MACE, death, or any other secondary outcome for ostial/shaft ULMCA lesions (MACE: hazard ratio [HR], 1.0 [95% confidence interval (CI), 0.79-1.27]; death: HR, 1.10 [95% CI, 0.84-1.46]). For distal ULMCA, PCI was associated with an increased risk of MACE (HR, 1.32; 95% CI, 1.10-1.58), death (HR, 1.56; 95% CI, 1.19-2.04), and revascularization (HR, 2.07; 95% CI, 1.5-2.84). The benefit of CABG for MACE and revascularization was confirmed in the analysis limited to RCTs, whereas the benefit for mortality was not., Conclusions: Among patients with distal ULMCA disease, CABG is associated with lower incidence of MACE and revascularization compared with PCI, whereas no differences in outcomes were observed for ostial/shaft ULMCA disease., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Preprocedural right ventricular-to-pulmonary artery (RV-PA) coupling is a major predictor of outcome in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). However, clinical significance of changes in RV-PA coupling after M-TEER is unknown., Objectives: The aim of this study was to evaluate changes in RV-PA coupling after M-TEER, their prognostic value, and predictors of improvement., Methods: This was a retrospective observational study, including patients undergoing successful M-TEER (residual mitral regurgitation ≤2+ at discharge) for SMR at 13 European centers and with complete echocardiographic data at baseline and short-term follow-up (30-180 days). RV-PA coupling was assessed with the use of echocardiography as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). All-cause death was assessed at the longest available follow-up starting from the time of the echocardiographic reassessment., Results: Among 501 patients included, 331 (66%) improved their TAPSE/PASP after M-TEER (responders) at short-term follow-up (median: 89 days; IQR: 43-159 days), whereas 170 (34%) did not (nonresponders). Lack of previous cardiac surgery, low postprocedural mitral mean gradient, low baseline TAPSE, high baseline PASP, and baseline tricuspid regurgitation were independently associated with TAPSE/PASP improvement after M-TEER. Compared with nonresponders, responders had lower New York Heart Association functional class and less heart failure hospitalizations at short-term follow-up. Improvement in TAPSE/PASP was independently associated with reduced risk of mortality at long-term follow-up (584 days; IQR: 191-1,243 days) (HR: 0.65 [95% CI: 0.42-0.92]; P = 0.017)., Conclusions: In patients with SMR, improvement in TAPSE/PASP after successful M-TEER is predicted by baseline clinical and echocardiographic variables and postprocedural mitral gradient, and is associated with a better outcome., Competing Interests: Funding Support and Author Disclosures Dr Adamo has received speaker fees from Abbott Vascular and Medtronic. Dr Estévez-Loureiro is a consultant for Abbott Vascular, Boston Scientific, and Edwards Lifesciences. Dr Pascual is a proctor for Abbott Vascular. Dr Jimenez-Quevedo has received speaker fees from Abbot Vascular. Dr Nombela-Franco is a proctor for Abbott; and has received consulting fees for Abbott and Edwards Lifesciences. Dr Petronio is a consultant for Abbott Vascular, Boston Scientific, and Medtronic. Dr Bedogni is a consultant for Medtronic; and has received speaker fees from Abbott Vascular. Dr Sinagra has received personal fees Novartis, Bayer, AstraZeneca, Boston Scientific, Vifor Pharma, Menarini, and Akcea Therapeutics. Dr Metra has received consulting honoraria for participation in steering committees or advisory boards or for speeches from Abbott Vascular, Amgen, AstraZeneca, Bayer, Edwards, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Aim: To evaluate short-term changes in tricuspid regurgitation (TR) after transcatheter edge-to-edge mitral valve repair (M-TEER) in secondary mitral regurgitation (SMR), their predictors and impact on mortality., Methods and Results: This is a retrospective analysis of SMR patients undergoing successful M-TEER (post-procedural mitral regurgitation ≤2+) at 13 European centres. Among 503 patients evaluated 79 (interquartile range [IQR] 40-152) days after M-TEER, 173 (35%) showed ≥1 degree of TR improvement, 97 (19%) had worsening of TR, and 233 (46%) remained unchanged. Smaller baseline left atrial diameter and residual mitral regurgitation 0/1+ were independent predictors of TR ≤2+ after M-TEER. There was a significant association between TR changes and New York Heart Association class and pulmonary artery systolic pressure decrease at echocardiographic re-assessment. At a median follow-up of 590 (IQR 209-1103) days from short-term echocardiographic re-assessment, all-cause mortality was lower in patients with improved compared to those with unchanged/worsened TR (29.6% vs. 42.3% at 3 years; log-rank p = 0.034). Baseline TR severity was not associated with mortality, whereas TR 0/1+ and 2+ at short-term follow-up was associated with lower all-cause mortality compared to TR 3/4+ (30.6% and 35.6% vs. 55.6% at 3 years; p < 0.001). A TR ≤2+ after M-TEER was independently associated with a 42% decreased risk of mortality (p = 0.011)., Conclusion: More than one third of patients with SMR undergoing successful M-TEER experienced an improvement in TR. Pre-procedural TR was not associated with outcome, but a TR ≤2+ at short-term follow-up was independently associated with long-term mortality. Optimal M-TEER result and a small left atrium were associated with a higher likelihood of TR ≤2+ after M-TEER., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Current guidelines support the use of transcatheter edge-to-edge repair (TEER) for patients with both primary and secondary mitral regurgitation. We aimed to compare the prognoses of TEER in degenerative mitral regurgitation (DMR) vs. functional mitral regurgitation (FMR). A total of 208 consecutive patients who underwent TEER over a ten-year period were analyzed. Primary endpoints included rates of all-cause death and major adverse cardiac events (MACE: composite of all-cause death, hospitalizations for heart failure, mitral valve surgery, or TEER re-intervention). A total of 148 (71%) patients were identified with FMR, while 60 (29%) were identified with DMR. Patients in the FMR group were younger (77.2 ± 8.4 vs. 80.2 ± 7.2, p = 0.02), suffered more frequently from coronary artery disease (54.1% vs. 10.0%, p = 0.02), and atrial fibrillation/flutter (70.9% vs. 38.3%, p = 0.02). Rates of 1-year death (21.6% vs. 10.0%, p = 0.03) and MACE (41.2% vs. 21.7%, p = 0.02) were higher for the FMR group, as compared to the DMR group. After correcting for variables, FMR independently predicted rates of MACE (HR-1.78, 95% CI 1.23-2.48, p = 0.04) and had a non-significant effect on one-year mortality (HR-1.67, 95%CI 0.98-3.74, p = 0.07). In our experience, worse overall 1-year composite MACE outcomes were observed after TEER in patients with FMR as compared to patients with DMR.

Background: Right ventricular dysfunction (RVD) is a major issue in patients with advanced heart failure because it precludes the implantation of left ventricular assist device, usually leaving heart transplantation (HTx) as the only available treatment option. The pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating information of right ventricular function and of pulmonary circulation. Our aim is to evaluate the association of preoperative RVD, hemodynamically defined as a low PAPi, with post-HTx survival., Methods and Results: Consecutive adult HTx recipient at 2 Italian transplant centers between 2000 and 2018 with available data on pre-HTx right heart catheterization were included retrospectively. RVD was defined as a value of PAPi lower than the 25th percentile of the study population. The association of RVD with the 1-year post-HTx mortality and other secondary end points were evaluated. Multivariate logistic regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by pulmonary vascular resistance (PVR) status (≥3 Woods units vs <3 Woods units) were also performed. Among 657 HTx recipients (female 31.1%, age 53 ± 11 years), patients with pre-HTx RVD (PAPi of <1.68) had significantly lower 1-year survival rates (77.8% vs 87.1%, P = .005), also after adjusting for estimated glomerular filtration rate, total bilirubin, PVR, serum sodium, inotropes, and mechanical circulatory support at HTx (hazard ratio 2.0, 95% confidence interval, 1.3-3.1). RVD was also associated with post-HTx renal replacement therapy (hazard ratio 2.0, 95% confidence interval 1.05-3.30) and primary graft dysfunction (hazard ratio 1.7, , 95% confidence interval 1.02-3.30). When stratifying patients by estimated PVR status, RVD was associated with worse 1-year survival among patients with normal PVR (76.9% vs 88.3%, P = .003), but not in those with increased PVR (78.6% vs 83.2%, P = .49)., Conclusions: Preoperative RVD, evaluated through PAPi, is associated with mortality and morbidity after HTx, providing incremental prognostic value over traditional clinical and hemodynamic parameters., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Aims: Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF-specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients., Methods and Results: We performed a global miRNome analysis using next-generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real-time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty-two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR-210-3p, miR-22-5p, miR-22-3p, miR-21-3p, miR-339-3p, and miR-125a-5p) significantly correlated with HF biomarkers, among which N-terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR-125a-5p, miR-10b-5p, and miR-9-5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio-HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82)., Conclusions: This discovery study has characterized, for the first time, the advanced chronic HF-specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Diuretic resistance portends a poor prognosis in acute heart failure, especially in advanced stages. Early identification of a poor response to diuretics may help to improve treatment and outcomes. Spot natriuresis (UNa + ) at 2 h from the start of intravenous furosemide has been proposed as an early indicator of diuretic response. Our paper aimed to determine the role of early natriuresis in patients hospitalized with advanced chronic heart failure (ACHF) and high risk of diuretic resistance., Methods and Results: We performed a sub-analysis of the DRAIN trial, a randomized clinical trial on 80 patients with acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with low systolic blood pressure (≤ 110 mmHg) and dilutional hyponatremia (sodium ≤ 135 mMol/L) at admission. Patients were divided into two groups according to spot urinary sodium excretion (high: UNa +   > 50 or low: ≤ 50 mEq/L) at 2 h from furosemide administration. Twenty-eight patients (35%) showed a low natriuretic response. As compared to the other patients, this group showed lower daily urinary output (2275 ± 790 vs 3849 ± 2034 mL, p < 0.001), lower body weight reduction after 48 h (1.55 ± - 1.66 vs - 3.55 ± - 2.93 kg, p < 0.001), higher incidence of worsening renal function (32% vs 10%, p 0.02) and increasing rather than reducing NT-proBNP at 72 h (p 0.02)., Conclusions: In patients with ACHF and dilutional hyponatremia, low natriuresis after furosemide is an early marker of poor diuretic response and correlates with higher NT-proBNP and higher incidence of worsening renal function at 72 h.