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.

Hemodynamic 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 hemodynamics in acute decompensated heart failure-related CS (ADHF-CS). 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 minutes before RHC. The evaluated hemodynamic 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). 101 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). Echocardiographic estimation of hemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation.

Aims: Severe functional mitral regurgitation (FMR) may benefit from mitral transcatheter edge-to-edge repair (TEER), but selection of patients remains to be optimized. Objectives: The aim of this study was to use machine-learning (ML) approaches to uncover concealed connections between clinical, echocardiographic, and haemodynamic data associated with patients’ outcomes. Methods and results: Consecutive patients undergoing TEER from 2009 to 2020 were included in the MITRA-AI registry. The primary endpoint was a composite of cardiovascular death or heart failure (HF) hospitalization at 1 year. External validation was performed on the Mitrascore cohort. 822 patients were included. The composite primary endpoint occurred in 250 (30%) patients. Four clusters with decreasing risk of the primary endpoint were identified (42, 37, 25, and 20% from Cluster 1 to Cluster 4, respectively). Clusters were combined into a high-risk (Clusters 1 and 2) and a low-risk phenotype (Clusters 3 and 4). High-risk phenotype patients had larger left ventriculars (LVs) (>107 mL/m2), lower left ventricular ejection fraction (<35%), and more prevalent ischaemic aetiology compared with low-risk phenotype patients. Within low-risk groups, permanent atrial fibrillation amplified that of HF hospitalizations. In the Mitrascore cohort, the incidence of the primary endpoint was 48, 52, 35, and 42% across clusters. Conclusion: A ML analysis identified meaningful clinical phenotypic presentations in FMR undergoing TEER, with significant differences in terms of cardiovascular death and HF hospitalizations, confirmed in an external validation cohort.

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: Heart transplantation and left ventricular assist device (LVAD) implementation are effective treatments for advanced heart failure (HF), although their use is limited by organ availability and the high incidence of adverse events. The efficacy of mitral transcatheter edge-to-edge repair (TEER) as a bridge to transplantation or as a destination therapy in advanced HF is still debated. Methods: A total of 63 patients with INTERMACS class 3 or 4 with contraindications for LVAD and severe functional mitral regurgitation (FMR) were evaluated for TEER implantation eligibility. The primary endpoint was a composite of death, urgent heart transplantation and LVAD implantation at 12 months. Results: A total of 36 patients underwent TEER, while 27 patients received optimal medical therapy (MT) alone. In the intervention group, 35 patients (97%) were discharged alive. In the MT group, two in-hospital deaths occurred, two patients underwent urgent heart transplantation, and three patients were discharged on inotropes. At the 12-month follow-up, the incidence of the primary endpoint occurring was lower in the TEER group (25% vs. 70%, HR 0.25, 95% CI 0.11–0.60, p < 0.01) and the tolerance to neurohormonal therapy was higher (53% vs. 30%, p = 0.03). Conclusions: In advanced HF patients with INTERMACS profile 3 or 4 and severe FMR, TEER on top of optimal MT was associated with a lower incidence of death, urgent heart transplantation or LVAD implantation at 12 months compared to optimal MT alone.