INFLA-score: A new diagnostic paradigm to identify pericarditis.

BACKGROUND: Diagnosis of pericarditis may be challenging because not all patients meet the conventional criteria. An overlooked diagnosis implies a longer course of symptoms and an increased risk of recurrences. C-reactive protein (CRP), widely used as an inflammation marker, has some limitations. This study aimed to assess the usefulness and prognostic value of INFLA-score, a validated index assessing low-grade inflammation, in the definite diagnosis of pericarditis. METHODS: Patients with suspected pericarditis were included. The INFLA-score was computed based on white blood cells and platelet count, neutrophil-to-lymphocyte ratio, and CRP, ranging from -16 to +16. An INFLA-score > 0 was considered positive for the presence of pericardial inflammation. The primary end point was the association of INFLA-score with diagnosis of pericarditis according to conventional criteria. The recurrence of pericarditis at 6 months was the secondary end point. RESULTS: A total of 202 patients were included, aged 47 ± 17 years, and 57% were females. Among 72 (36%) patients with a diagnosis of pericarditis, an INFLA-score > 0 was observed in 86% (vs. 36%, p < 0.001), abnormal CRP in 42% (vs. 10%, p < 0.001), pericardial effusion in 44% (vs. 19%, p < 0.001), abnormal electrocardiogram in 56% (vs. 24%, p < 0.001), and rubs in 5% (vs. 0.1%, p = 0.072). INFLA-score > 0 had the strongest predictive value for the diagnosis of pericarditis (hazard ratio 8.48, 95% confidence interval [CI] 3.39-21.21), with 86% sensitivity and 64% specificity, as opposed to CRP (hazard ratio 1.72, non-significant 95% CI 0.69-4.29). Recurrent pericarditis at 6 months was more frequent in patients with a positive INFLA-score (37% vs. 8%, p < 0.001, rate ratio 4.15, 95% CI 2.81-6.12). In patients with normal CRP, INFLA-score-confirmed ongoing inflammation in 78% of the cases. Compared with the conventional criteria, the INFLA-score had the highest accuracy (area under the curve = 0.82). Different cutoffs were valuable to rule out (INFLA-score > 0, sensitivity 86%, and negative likelihood ratio 0.22) or rule in (INFLA-score ≥ 10, specificity 97%, and positive likelihood ratio 13) the diagnosis. CONCLUSIONS: The INFLA-score is a useful diagnostic tool to assess the probability of pericarditis, with a strong prognostic value for further recurrences, outperforming CRP.

Transthyretin cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: experience of a single center.

BACKGROUND: Even if prevalent among patients with severe aortic stenosis (AS), the clinical suspicion for transthyretin cardiac amyloidosis (ATTR-CA) remains difficult in this subset. We report our single center experience on ATTR-CA detection among TAVR candidates to provide insights on the prevalence and clinical features of dual pathology as compared to lone AS. METHODS: Consecutive severe AS patients undergoing transcatheter aortic valve replacement (TAVR) evaluation at a single center were prospectively included. Those with suspected ATTR-CA based on clinical assessment underwent 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy. The RAISE score, a novel screening tool with high sensitivity for ATTR-CA in AS, was retrospectively calculated to rule-out ATTR-CA in the remaining patients. Patients were categorized as follow: "ATTR-CA+": patients with confirmed ATTR-CA at DPD bone scintigraphy; "ATTR-CA-": patients with negative DPD bone scintigraphy or a negative RAISE score; "ATTR-CA indeterminate": patients not undergoing ATTR-CA assessment with a positive RAISE score. The characteristics of ATTR-CA+ and ATTR-CA- patients were compared. RESULTS: Of 107 included patients, ATTR-CA suspicion was posed in 13 patients and confirmed in six. Patients were categorized as follow: 6 (5.6%) ATTR-CA+, 79 (73.8%) ATTR-CA-, 22 (20.6%) ATTR-CA indeterminate. Excluding ATTR-CA indeterminate patients, the prevalence of ATTR-CA was 7.1% (95% CI 2.6-14.7%). As compared to ATTR-CA - patients, ATTR-CA + patients were older, had higher procedural risk and more extensive myocardial and renal damage. They had higher left ventricle mass index and lower ECG voltages, translating into a lower voltage to mass ratio. Moreover, we describe for the first time bifascicular block as an ECG feature highly specific of patients with dual pathology (50.0% vs. 2.7%, P<0.001). Of note, pericardial effusion was rarely found in patients with lone AS (16.7% vs. 1.2%, P=0.027). No difference in procedural outcomes was observed between groups. CONCLUSIONS: Among severe AS patients, ATTR-CA is prevalent and presents with phenotypic features that may aid to differentiate it from lone AS. A clinical approach based on routine search of amyloidosis features might lead to selective DPD bone scintigraphy with a satisfactory positive predictive value.

Minimally Invasive Surgery: Standard of Care for Mitral Valve Endocarditis.

Background. Minimally invasive surgery via right mini-thoracotomy has become the standard of care for the treatment of mitral valve disease worldwide, particularly at high-volume centers. In recent years, the spectrum of indications has progressively shifted and extended to fragile and higher-risk patients, also addressing more complex mitral valve disease and ultimately including patients with native or prosthetic infective endocarditis. The rationale for the adoption of the minimally invasive approach is to minimize surgical trauma, promote an earlier postoperative recovery, and reduce the incidence of surgical wound infection and other nosocomial infections. The aim of this retrospective observational study is to evaluate the effectiveness and the early and late outcome in patients undergoing minimally invasive surgery for mitral valve infective endocarditis. Methods. Prospectively collected data regarding minimally invasive surgery in patients with mitral valve infective endocarditis were entered into a dedicated database for the period between January 2007 and December 2022 and retrospectively analyzed. All comers during the study period underwent a preoperative evaluation based on their clinical history and anatomy for the allocation to the most appropriate surgical strategy. The selection of the mini-thoracotomy approach was primarily driven by a thorough transthoracic and especially transesophageal echocardiographic evaluation, coupled with total body and vascular imaging. Results. During the study period, 92 patients underwent right mini-thoracotomy to treat native (80/92, 87%) or prosthetic (12/92, 13%) mitral valve endocarditis at our institution, representing 5% of the patients undergoing minimally invasive mitral surgery. Twenty-six (28%) patients had undergone previous cardiac operations, whereas 18 (20%) presented preoperatively with complications related to endocarditis, most commonly systemic embolization. Sixty-nine and twenty-three patients, respectively, underwent early surgery (75%) or were operated on after the completion of the targeted antibiotic treatment (25%). A conservative procedure was feasible in 16/80 (20%) patients with native valve endocarditis. Conversion to standard sternotomy was necessary in a single case (1.1%). No cases of intraoperative iatrogenic aortic dissection were reported. Four patients died perioperatively, accounting for a thirty-day mortality of 4.4%. The causes of death were refractory heart or multiorgan failure and/or septic shock. A new onset stroke was observed postoperatively in one case (1.1%). Overall actuarial survival rate at 1 and 5 years after operation was 90.8% and 80.4%, whereas freedom from mitral valve reoperation at 1 and 5 years was 96.3% and 93.2%, respectively. Conclusions. This present study shows good early and long-term results in higher-risk patients undergoing minimally invasive surgery for mitral valve infective endocarditis. Total body, vascular, and echocardiographic screening represent the key points to select the optimal approach and allow for the extension of indications for minimally invasive surgery to sicker patients, including active endocarditis and sepsis.

Three-Dimensional Finger Test: A New Echocardiographic Method to Locate the Best Access Site During NeoChord Procedure.

OBJECTIVE: Transventricular beating-heart mitral valve repair (TBMVR) with artificial chordae implantation is a technique to treat mitral valve prolapse. Two-dimensional (2D) echocardiography completed with simultaneous biplane view during surgeon finger pushing on the left ventricular (LV) wall (finger test [FT]) is currently used to localize the desired LV access, on the inferior-lateral wall, between the papillary muscles (PMs). We aimed to compare a new three-dimensional (3D) method with conventional FT in terms of safety and better localization of LV access. METHODS: During TBMVR, conventional FT was completed using 3D transesophageal echocardiography by placing the sample box in the bicommissural view of the LV, including the PMs and the apex. The 3D volume was subsequently edited to visualize the LV from above (surgical view) to localize the bulge of the operator's finger pushing on the LV. We asked the first operator, the second operator, and the cardiac surgery fellow, separately, to evaluate the location of their finger pushing, both with the 2D method and the 3D method, to estimate the interoperator concordance. RESULTS: From 2019 to 2021, 42 TBMVRs were performed without complications related to access using FT completed with the 3D method. Regarding the choice of the right and safe entry site, the operator's agreement was higher using 3D rendering compared with conventional FT (mean agreement 0.59 ± 0.29 for 2D vs 0.83 ± 0.20 for 3D), while full operator agreement was 10 of 42 for 2D and 23 of 42 for 3D (P = 0.004). CONCLUSIONS: Three-dimensional FT is easy to perform and facilitates surgeons choosing the best access for TBMVR in term of anatomical localization and safety.

Cardiac imaging for the prediction of sudden cardiac arrest in patients with heart failure.

The identification of heart failure (HF) patients at risk for arrhythmic sudden cardiac arrest (SCA) is a major challenge in the cardiovascular field. In addition to optimal medical treatment for HF, implantable cardioverter defibrillator (ICD) is currently recommended to prevent SCA in patients with reduced left ventricular ejection fraction (LVEF). The indication for an ICD implantation, in addition to HF etiology, New York Health Association (NYHA) class and life expectancy, mainly depends on LVEF value at echocardiography. However, the actual role of LVEF in the prediction of SCA has recently been debated, while newer multimodality imaging techniques with increased prognostic accuracy have been developed. Speckle tracking imaging allows the quantification of mechanical dispersion, a marker of electrophysiological heterogeneity predisposing to malignant arrhythmias, while advanced cardiac magnetic resonance techniques such as myocardial T1-mapping and extracellular volume fraction assessment allow the evaluation of interstitial diffuse fibrosis. Nuclear imaging is helpful for the appraisal of sympathetic nervous system dysfunction, while newer computed tomography techniques assessing myocardial delayed enhancement allow the identification of focal myocardial scar. This review will focus on the most modern advances in the field of cardiovascular imaging along with its applications for the prediction of SCA in patients with HF. Modern artificial intelligence applications in cardiovascular imaging will also be discussed.

New Echocardiographic Parameters Predicting Successful Trans-Ventricular Beating-Heart Mitral Valve Repair with Neochordae at 3 Years: Monocentric Retrospective Study.

The NeoChord procedure is an echo-guided trans-ventricular beating-heart mitral valve repair technique to treat degenerative mitral regurgitation (MR) due to prolapse and/or flail. The aim of this study is to analyze echocardiographic images to find pre-operative parameters to predict procedural success (≤moderate MR) at 3-year follow-up. Seventy-two consecutive patients with severe MR underwent the NeoChord procedure between 2015 and 2021. MV pre-operative morphological parameters were assessed using 3D transesophageal echocardiography with dedicated software (QLAB, Philips). Three patients died during their hospitalization. The remaining 69 patients were retrospectively analyzed. At follow-up, MR > moderate was found in 17 patients (24.6%). In the univariate analysis, end-systolic annulus area (12.5 ± 2.5 vs. 14.1 ± 2.6 cm2; p = 0.038), end-systolic annulus circumference (13.2 ± 1.2 vs. 14 ± 1.3 cm; p = 0.042), indexed left atrial volume (59 ± 17 vs. 76 ± 7 mL/m2; p = 0.041), and AF (25% vs. 53%; p = 0.042) were lower in the 52 patients with ≤ MR compared to those with > moderate MR. Annular dysfunction parameters were the best predictors of procedural success: 3D early-systolic annulus area (AUC 0.74; p = 0.004), 3D early-systolic annulus circumference (AUC 0.75; p = 0.003), and 3D annulus area fractional change (AUC 0.73; p = 0.035). Patient selection relying on 3D dynamic and static MA dimensions may improve the maintenance of procedural success at follow-up.

Acute Modification of Hemodynamic Forces in Patients with Severe Aortic Stenosis after Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is the established first-line treatment for patient with severe aortic stenosis not suitable for surgery. Echocardiographic evaluation of hemodynamic forces (HDFs) is a growing field, holding the potential to early predict improvement in LV function. A prospective observational study was conducted. Transthoracic echocardiography was performed before and after TAVI. HDFs were analyzed along with traditional left ventricular (LV) function parameters. Twenty-five consecutive patients undergoing TAVI were enrolled: mean age 83 ± 5 years, 74.5% male, mean LV Ejection Fraction (LVEF) at baseline 57 ± 8%. Post-TAVI echocardiographic evaluation was performed 2.4 ± 1.06 days after the procedure. HDF amplitude parameters improved significantly after the procedure: LV Longitudinal Forces (LF) apex-base [mean difference (MD) 1.79%; 95% CI 1.07-2.5; p-value < 0.001]; LV systolic LF apex-base (MD 2.6%; 95% CI 1.57-3.7; p-value < 0.001); LV impulse (LVim) apex-base (MD 2.9%; 95% CI 1.48-4.3; p-value < 0.001). Similarly, HDFs orientation parameters improved: LVLF angle (MD 1.5°; 95% CI 0.07-2.9; p-value = 0.041); LVim angle (MD 2.16°; 95% CI 0.76-3.56; p-value = 0.004). Conversely, global longitudinal strain and LVEF did not show any significant difference before and after the procedure. Echocardiographic analysis of HDFs could help differentiate patients with LV function recovery after TAVI from patients with persistent hemodynamic dysfunction.

Echocardiographic Parameters to Predict Malignant Events in Arrhythmic Mitral Valve Prolapse Population.

Bileaflet Mitral Valve Prolapse (bMVP) has been linked to major arrhythmic events and sudden cardiac death (SCD). Consistent predictors in this field are still lacking. Echocardiography is the best tool for the analysis of the prolapse and its impact on the ventricular mechanics. The aim of this study was to find new echocardiographic predictors of malignant events within an arrhythmic MVP population. We evaluated 22 patients with arrhythmic bMVP with a transthoracic echocardiogram focused on mitral valve anatomy and ventricular contraction. Six of them had major arrhythmic events that required ICD implantation (ICD-MVP group), while sixteen presented with a high arrhythmic burden without major events (A-MVP group). The best predictors of malignant events were the Anterior Mitral Leaflet (AML) greater length and greater Mechanical Dispersion (MD) of basal and mid-ventricular segments, while other significant predictors were the larger mitral valve annulus (MVA) indexed area, lower MVA anteroposterior diameter/AML length ratio, higher inferolateral basal segment S3 velocity.

Imaging of Cardiac Masses: An Updated Overview.

Studying cardiac masses is one of the most challenging tasks for cardiac imagers. The aim of this review article is to focus on the modern imaging of cardiac masses proceeding through the most frequent ones. Cardiac benign masses such as myxoma, cardiac papillary fibroelastoma, rhabdomyoma, lipoma, and hemangioma are browsed considering the usefulness of most common cardiovascular imaging tools, such as ultrasound techniques, cardiac computed tomography, cardiac magnetic resonance, and in the diagnostic process. In the same way, the most frequent malignant cardiac masses, such as angiosarcoma and metastases, are highlighted. Then, the article browses through nontumoral masses such as cysts, mitral caseous degenerative formations, thrombi, and vegetations, highlighting the differential diagnosis between them. In addition, the article helps in recognizing anatomic normal variants that should not be misdiagnosed as pathological entities.

Successful Percutaneous Retrieval of an Embolized Left Atrial Appendage Occluder.

A 75-year-old man with a previous mitral valve repair experienced embolization of a left atrial appendage occlusion device in the left atrium. The device was successfully retrieved using a double snaring technique, without the need for open surgery. This is an unusual report of left atrial appendage occluder retrieval, confirming the feasibility of the technique and the high flexibility of the device. (Level of Difficulty: Advanced.).

Myocardial longitudinal strain as the first herald of cardiac impairment in very early iron overload state: an echocardiography and biosusceptometry study on beta-thalassemia patients.

BACKGROUND: Heart diseases due to iron overload are still the main cause of mortality in patients affected by beta-thalassemia. Detection of cardiac iron overload in pre-clinical stage allows tailoring of chelation therapy and follow-up strategies. Echocardiographic longitudinal strain analysis may be a useful tool for early detection of cardiac functional impairment iron-related. METHODS: We examined 58 patients with beta-thalassemia on regular blood transfusion and iron chelation, without overt cardiac disease who had recent Biosusceptometry SQUID to quantify liver iron concentration and cardiac assessment by CMR T2*. RESULTS: Average global longitudinal strain (GLS) was able to identify abnormal (<20 ms) cardiac T2* values with 96% specificity and negative predictive value of 92% (AUC 0.84, P=0.01). Apical 4-ch GLS may help identify early longitudinal impairment associated with severe liver iron overload with 96% specificity and negative predictive value of 92% (AUC 0.84, P=0.02). Patients with severe liver iron overload had lower average Global Longitudinal Strain values compared to other patients (P-value =0.005). CONCLUSION: GLS was a sensitive marker to detect both myocardial and liver iron overload in a population that is still free from cardiac symptoms. Thus, strain echocardiography may be a useful tool for early detection of iron overload in Beta-thalassemia.

Clinical Outcomes Following Isolated Transcatheter Tricuspid Valve Repair: A Meta-Analysis and Meta-Regression Study.

OBJECTIVES: The aim of this study was to assess the pooled clinical and echocardiographic outcomes of different isolated transcatheter tricuspid valve repair (ITTVR) strategies for significant (moderate or greater) tricuspid regurgitation (TR). BACKGROUND: Significant TR is a common valvular heart disease worldwide. METHODS: Published research was systematically searched for studies evaluating the efficacy and safety of ITTVR for significant TR in adults. The primary outcomes were improvement in New York Heart Association (NYHA) functional class and 6-minute walking distance and the presence of severe or greater TR at the last available follow-up of each individual study. Random-effect meta-analysis was performed comparing outcomes before and after ITTVR. RESULTS: Fourteen studies with 771 patients were included. The mean age was 77 ± 8 years, and the mean European System for Cardiac Operative Risk Evaluation II score was 6.8% ± 5.4%. At a weighted mean follow-up of 212 days, 209 patients (35%) were in NYHA functional class III or IV compared with 586 patients (84%) at baseline (risk ratio: 0.23; 95% CI: 0.13-0.40; P < 0.001). Six-minute walking distance significantly improved from 237 ± 113 m to 294 ± 105 m (mean difference +50 m; 95% CI: +34 to +66 m; P < 0.001). One hundred forty-seven patients (24%) showed severe or greater TR after ITTVR compared with 616 (96%) at baseline (risk ratio: 0.29; 95% CI: 0.20-0.42; P < 0.001). CONCLUSIONS: Patients undergoing ITTVR for significant TR experienced significant improvements in NYHA functional status and 6-minute walking distance and a significant reduction in TR severity at mid-term follow-up.

Valve-in-Valve-in-Ring: A Bailout Strategy to Tackle Paravalvular Leaks due to Device Malapposition.

A 55-year-old male with a history of severe organic mitral regurgitation treated with surgical mitral valve (MV) repair was referred for a transcatheter MV replacement due to recurrent regurgitation. After the release of the first transcatheter MV, a severe paravalvular leak coming from the lateral side was observed. To promptly tackle this issue, a second valve with further postdilation was successfully implanted and the paravalvular leak disappeared. This case highlights the feasibility of implanting a second valve in case of severe paravalvular leaks after MV-in-ring procedures due to device malapposition.

In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis.

BACKGROUND: One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients. CLINICAL CASE: We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively. CONCLUSION: In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

Impact of extracorporeal shockwave myocardial revascularization on the ischemic burden of refractory angina patients: a single photon emission computed tomography study.

BACKGROUND: Extracorporeal shockwave myocardial revascularization (ESMR) is a non-invasive treatment designed to improve symptoms in refractory angina (RA) patients. Enhanced perfusion through local vasodilation and neo-capillarization is postulated to be the mechanism of the observed clinical benefit. However, the impact of ESMR on the ischemic burden of RA patients has not been adequately assessed. METHODS: One-hundred twenty-one consecutive RA patients suitable for ESMR were treated. Twenty-nine RA patients not suitable for treatment were clinically followed-up as a control group for clinical endpoints. ESMR-treated patients underwent baseline and 6-month single photon emission computed tomography (SPECT) to evaluate the changes in ischemic burden. The operator was blinded to the pre/post-treatment status of the SPECT exam. The primary endpoint was the difference in summed stress score (SSS) and summed difference score (SDS) between follow-up and baseline SPECTs. Secondary endpoints included the changes in Canadian Cardiovascular Society (CCS) angina class and nitroglycerin use between 6-month follow-up and baseline. Clinical endpoints were further compared between ESMR-treated patients and the control group. RESULTS: Following ESMR, a significant reduction in the ischemic burden was observed (follow-up SSS: 14.2±10 vs. baseline SSS: 21.2±9.42, P<0.0001; follow-up SDS: 4.6±5.9 vs. baseline SDS 10.2±7.9, P<0.0001) including less patients with moderate to severe ischemia (19% vs. 46% P<0.0001). CCS class and nitroglycerin use were significantly reduced (CCS: 1.5±0.6 vs. 2.7±0.6, P<0.0001; patients needing nitroglycerin: 24% vs. 64%, P<0.0001). When compared to the control group, CCS class reduction, nitroglycerin use and hospitalizations were significantly lower for ESMR treated vs. non-treated RA patients at 6-month follow-up. CONCLUSIONS: In this single-center cohort of RA patients undergoing ESMR treatment and serial myocardial perfusion imaging, ESMR was associated with a significant reduction in the ischemic burden. These findings provide a physiological rationale and mechanism for the observed clinical benefit.

Prognostic impact of MitraClip in patients with left ventricular dysfunction and functional mitral valve regurgitation: A comprehensive meta-analysis of RCTs and adjusted observational studies.

The real prognostic impact of MitraClip in patients with significant functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction remains to be elucidated. Two randomized controlled trials (RCTs) with conflicting results have been recently published. We conducted a comprehensive meta-analysis of all RCTs and adjusted observational studies to evaluate the clinical impact of percutaneous mitral valve repair when compared with optimal medical therapy (OMT) alone, in patients with symptomatic FMR and LV dysfunction. Death from any cause and heart failure rehospitalizations at the longest available follow-up were the primary endpoints. Cardiac death, one year and short-term death were the secondary ones. 2255 patients (1207 for MitraClip and 1048 for OMT-only) from 8 studies (2 RCTs and 6 observational studies) were included. At a median (mid-term) follow-up of 438 days (IQR 360-625) MitraClip was associated with a significant reduction of all-cause death (odds Ratio [OR] 0.55, 95%CI 0.41-0.73, p < 0.001; [ORadj] 0.66, 95%CI 0.49-0.90, p = 0.009) and rehospitalization (OR 0.49, 95%CI 0.24-1.00, p = 0.05 and ORadj 0.63, 95%CI 0.43-0.94, p = 0.02). At one year, adjusted analysis demonstrated a trend favoring the experimental cohort (ORadj 0.73, 95%CI 0.53-1.02, p = 0.07). Meta-regression suggested that benefit of MitraClip on mid-term survival persists even after accounting for the prevalence of implanted CRT, burden of comorbidities, NYHA class, cardiomyopathy etiology and LV function and dimensions. In conclusion, MitraClip for FMR in patients with LV dysfunction is associated with a considerable reduction of death and HF hospitalization at mid-term follow-up. Further ongoing RCTs are needed to strengthen present results.