Prognostic Impact of Nutritional Status After Transcatheter Edge-to-Edge Mitral Valve Repair: The MIVNUT Registry.

Background Malnutrition is associated with poor prognosis in several cardiovascular diseases. However, its prognostic impact in patients undergoing transcatheter edge-to-edge mitral valve repair (TEER) is not well known. This study sought to assess the prevalence, clinical associations, and prognostic consequences of malnutrition in patients undergoing TEER. Methods and Results A total of 892 patients undergoing TEER from the international MIVNUT (Mitral Valve Repair and Nutritional Status) registry were studied. Malnutrition status was assessed with the Controlling Nutritional Status score. The association of nutritional status with mortality was analyzed with multivariable Cox regression models, whereas the association with heart failure admission was assessed by Fine-Gray models, with death as a competing risk. According to the Controlling Nutritional Status score, 74.4% of patients with TEER had any degree of malnutrition at the time of TEER (75.1% in patients with body mass index <25 kg/m2, 72.1% in those with body mass index ≥25 kg/m2). However, only 20% had moderate-severe malnutrition. TEER was successful in most of patients (94.2%). During a median follow-up of 1.6 years (interquartile range, 0.6-3.0), 267 (29.9%) patients died and 256 patients (28.7%) were admitted for heart failure after TEER. Compared with normal nutritional status moderate-severe malnutrition resulted a strong predictor of mortality (adjusted hazard ratio [HR], 2.1 [95% CI, 1.1-2.4]; P<0.001) and heart failure admission (adjusted subdistribution HR, 1.6 [95% CI, 1.1-2.4]; P=0.015). Conclusions Malnutrition is common among patients submitted to TEER, and moderate-severe malnutrition is strongly associated with increased mortality and heart failure readmission. Assessment of nutritional status in these patients may help to improve risk stratification.

A Score to Assess Mortality After Percutaneous Mitral Valve Repair.

BACKGROUND: Risk stratification for transcatheter edge-to-edge mitral valve repair (TEER) is paramount in the decision-making process for treating severe mitral regurgitation (MR). OBJECTIVES: This study sought to create and validate a user-friendly score (MitraScore) to predict the risk of mortality in patients undergoing TEER. METHODS: The derivation cohort was based on a multicentric international registry that included 1,119 patients referred for TEER between 2012 and 2020. Score discrimination was assessed using Harrell's c-statistic, and the calibration was evaluated with the Gronnesby and Borgan goodness-of-fit test. An external validation was carried out in 725 patients from the GIOTTO registry. RESULTS: After multivariate analysis, we identified 8 independent predictors of mortality during the follow-up (2.1 ± 1.8 years): age ≥75 years, anemia, glomerular filtrate rate <60 mL/min/1.73 m2, left ventricular ejection fraction <40%, peripheral artery disease, chronic obstructive pulmonary disease, high diuretic dose, and no therapy with renin-angiotensin system inhibitors. The MitraScore was derived by assigning 1 point to each independent predictor. The c-statistic was 0.70. Per each point of the MitraScore, the relative risk of mortality increased by 55% (HR: 1.55; 95% CI: 1.44-1.67; P < 0.001). The discrimination and calibration for mortality prediction was better than those of EuroSCORE II (c-statistic 0.61) or Society of Thoracic Surgeons score (c-statistic 0.57). The MitraScore maintained adequate performance in the validation cohort (c-statistic 0.66). The score was also predictive for heart failure rehospitalization and was correlated with the probability of clinical improvement. CONCLUSIONS: The MitraScore is a simple prediction algorithm for the prediction of follow-up mortality in patients treated with TEER.

Percutaneous Mitral Valve Repair in Patients with Severe Mitral Regurgitation and Acute Decompensated Heart Failure.

The role of percutaneous mitral valve repair (PMVr) in management of high-risk patients with severe mitral regurgitation (MR) and acute decompensated heart failure (ADHF) is undetermined. We screened all patients who underwent PMVr between October 2015 and March 2020. We evaluated immediate, 30-day, and 1-year outcomes in patients who underwent PMVr during hospitalization due to ADHF as compared to elective patients. From a cohort of 237 patients, we identified 46 patients (19.4%) with severe MR of either functional or degenerative etiology who underwent PMVr during index hospitalization due to ADHF, including 17 (37%) critically ill patients. Patients' mean age was 75.2 ± 9.8 years, 56% were males. There were no differences in background history between ADHF and elective patients. Patients with ADHF were at higher risk for surgery, reflected in higher mean EuroSCORE II, compared with elective patients. After PMVr, we observed higher 30-day mortality rate in ADHF patients as compared to the elective group (10.9% vs. 3.1%, respectively, p = 0.042). One-year mortality rate was similar between the groups (21.7% vs. 17.9%, p = 0.493). Clinical and echocardiographic follow-up showed improvement of NYHA functional class and sPAP reduction in both groups ((54 ± 15 mmHg to 50 ±15 in the elective group (p = 0.02), 58 ± 13 mmHg to 52 ± 12 in the ADHF group (p = 0.02)). PMVr could be an alternative option for treatment of patients with severe MR and ADHF.

Acute kidney injury after MitraClip implantation in patients with severe mitral regurgitation.

INTRODUCTION: Percutaneous mitral valve repair (PMVR), such as MitraClip, is performed on high-risk patients and involves hemodynamic alternations that may cause acute kidney injury (AKI). We aimed to evaluate the incidence of AKI, predictors for developing AKI and the correlation with mortality after MitraClip. METHODS: We performed a retrospective analysis of collected data from patients who underwent PMVR in two tertiary medical centers in Israel to identify factors associated with AKI. RESULTS: The study population included 163 patients. The median age was 77 years; 60.7% of patients were male. The median eGFR significantly decreased post-procedure from 49 (35-72) to 47.8 (31-65.5) ml/min/1.73 m2 (p < .001). Forty-seven patients (29%) developed AKI. None of the patients who developed AKI required hemodialysis. Predictors of AKI included: baseline eGFR ≤30 ml/min/1.73 m2 , severity of residual MR, TMPG>5 mmHg, diuretic use, and re-do procedures. Among the patients who developed AKI there was an improvement in kidney function during follow-up, and creatinine levels significantly decreased from a peak mean creatinine of 179.5 (143-252) mmol/l to 136 (92-174) mmol/l (p < .001). However, 19% (9 out of 47) of patients experienced partial recovery and their creatinine level, when compared to their baseline, remained elevated. One-year survival showed a trend for increased mortality among patients who developed AKI (86.2% vs. 80.9%, p = .4), and patients who developed AKI that persisted had increased 1-year mortality compared with patients that had recovered their kidney function (86.8% vs. 55.6%, p = .01). CONCLUSION: The incidence of AKI after MitraClip is high. AKI is reversible in most patients; however, the persistence of kidney injury is associated with increased 1-year mortality.

Pulmonary artery pressures and outcomes after MitraClip.

AIMS: We evaluated the impact of MitraClip on systolic pulmonary artery pressure (sPAP) and the effects of baseline sPAP on outcomes. METHODS AND RESULTS: In a cohort of patients who underwent MitraClip implantation, three groups were defined according to pre-procedure sPAP levels. Clinical and echocardiographic data were compared. The study included 177 patients: 59 had severe pulmonary hypertension (PHT), 96 had mild to moderate PHT, and 22 had no PHT. In patients with pre-existing severe PHT, sPAP was reduced from 70.8 ± 9.2 to 56.8 ± 13.7 mmHg (P < 0.001), sPAP remained unchanged in patients with mild to moderate PHT but was significantly increased from 30.8 ± 4.3 to 38.6 ± 8.3 mmHg in the no-PHT group (P < 0.001). Improvement of sPAP was observed in 77% of severe PHT group, while worsening of sPAP was more common among patients with no-PHT [57% compared with 33% among the mild to moderate PHT and 7% in the severe PHT group, respectively, (P < 0.001)]. One year survival was similar among the study groups. CONCLUSIONS: MitraClip decreases PHT among patients with severe PHT. A concerning finding is that most patients with no-PHT increase their sPAP.

Temporal trends in management and outcome of patients with acute coronary syndrome according to admission low-density lipoprotein cholesterol levels.

BACKGROUND: The importance of differences in baseline low-density lipoprotein cholesterol (LDL-C) levels and pretreatment with statins on the temporal improvement in outcome of acute coronary syndrome (ACS) patients has not been studied yet. METHODS: Patients were divided into two groups according to baseline LDL-C levels: LDL-C <130 mg/dl and LDL-C ≥130 mg/dl. Baseline characteristics, clinical data and outcomes were compared for each LDL-C group between patients enrolled in early (2000-2006), mid (2008-2010) and recent (2013-2016) surveys. RESULTS: The study population was comprised of 8343 patients. Patients with LDL-C <130 mg/dl were older and were more commonly pretreated with aspirin and statins compared to patients with LDL-C ≥130 mg/dl. Patients included in recent surveys were more frequently selected for an invasive strategy with coronary angiography and subsequent revascularization, and were more commonly treated with guideline-based medical therapy. For patients with a LDL-C ≥130 mg/dl, the temporal improvements in therapy were associated with lower 1-year mortality rates (7.2, 4.4 and 3.5% for patients in early, mid and late surveys, respectively, P = 0.006). That temporal improvement in outcomes existed only in statin-naïve patients. For patients with LDL-C <130 mg/dl, temporal improvement in treatment was not accompanied by a reduction in 30 day or 1-year mortality rates. CONCLUSION: Treatment of ACS patients has improved over the past decades regardless of LDL-C levels. This improvement was accompanied by lower mortality rates in ACS patients with LDL-C ≥130 mg/dl, but not in patients with LDL-C <130 mg/dl.

Mitochondrial STAT3 plays a major role in IgE-antigen-mediated mast cell exocytosis.

BACKGROUND: The involvement of mitochondrial oxidative phosphorylation (OXPHOS) in mast cell exocytosis was recently suggested by the finding that mitochondria translocate to exocytosis sites upon mast cell activation. In parallel, mitochondrial signal transducer and activator of transcription 3 (STAT3) was found to be involved in ATP production. However, the regulation of mitochondrial STAT3 function and its connection to mast cell exocytosis is unknown. OBJECTIVE: We sought to explore the role played by mitochondrial STAT3 in mast cell exocytosis. METHODS: Experiments were performed in vitro with human and mouse mast cells and rat basophilic leukemia (RBL) cells and in vivo in mice. OXPHOS activity was measured after immunologic activation. The expression of STAT3, extracellular signal-regulated kinase 1/2, and protein inhibitor of activated STAT3 in the mitochondria during mast cell activation was determined, as was the effect of STAT3 inhibition on OXPHOS activity and mast cell function. RESULTS: Here we show that mitochondrial STAT3 is essential for immunologically mediated degranulation of human and mouse mast cells and RBL cells. Additionally, in IgE-antigen-activated RBL cells, mitochondrial STAT3 was phosphorylated on serine 727 in an extracellular signal-regulated kinase 1/2-dependent manner, which was followed by induction of OXPHOS activity. Furthermore, the endogenous inhibitor of STAT3, protein inhibitor of activated STAT3, was found to inhibit OXPHOS activity in the mitochondria, resulting in inhibition of mast cell degranulation. Moreover, mice injected with Stattic, a STAT3 inhibitor, had a significant decrease in histamine secretion. CONCLUSION: These results provide the first evidence of a regulatory role for mitochondrial STAT3 in mast cell functions, and therefore mitochondrial STAT3 could serve as a new target for the manipulation of allergic diseases.