Author Correction: Impact of sacubitril/valsartan on implantable defibrillator eligibility in heart failure: a real-world experience.

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (18): 5690-5700-DOI: 10.26355/eurrev_202109_26788-PMID: 34604961, published online on 30 September 2021. After publication, the authors applied to change the first two lines of Table II as the second column results were erroneously shifted in the first column.

Impact of sacubitril/valsartan on implantable defibrillator eligibility in heart failure: a real-world experience.

Objective: Current guidelines recommend an implantable cardiac defibrillator (ICD) in patients with symptomatic heart failure and reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] ≤35%) despite ≥3 months of optimal medical therapy. Recent observations demonstrated that sacubitril/valsartan induces beneficial reverse cardiac remodeling in eligible HFrEF patients. Given the pivotal role of LVEF in the selection of ICD candidates, we sought to assess the impact of sacubitril/valsartan on ICD eligibility and its predictors in HFrEF patients.

The f subunit of human ATP synthase is essential for normal mitochondrial morphology and permeability transition.

The f subunit is localized at the base of the ATP synthase peripheral stalk. Its function in the human enzyme is poorly characterized. Because full disruption of its ATP5J2 gene with the CRISPR-Cas9 strategy in the HAP1 human model has been shown to cause alterations in the amounts of other ATP synthase subunits, here we investigated the role of the f subunit in HeLa cells by regulating its levels through RNA interference.

Echocardiographic long-term follow-up of adult survivors of pediatric cancer treated with Dexrazoxane-Anthracyclines association.

Aims: Cardiovascular disease is a well-recognized cause of increased late morbidity and mortality among survivors of childhood cancer treated with anthracyclines. Co-administration of Dexrazoxane has been shown to significantly reduce short-term and mid-term cardiotoxicity. Aim of this study was to assess cardiac function in long-term (>10 years) survivors of childhood tumors treated with dexrazoxane/anthracycline association.

Mid-term repair durability after MitraClip implantation in patients with functional mitral regurgitation.

Background: The aim of this study was to identify variables that are associated with the durability of percutaneous repair of secondary mitral regurgitation at 6-month follow-up.

Methods And Results: Thirty-five consecutive patients with functional mitral regurgitation scheduled for MitraClip implant were enrolled. Left ventricular (LV) volumes and function and mitral valve characteristics were assessed before and immediately after MitraClip implantation using three-dimensional transesophageal echocardiography.

2D/3D Echocardiographic features of patients with reverse remodeling after cardiac resynchronization therapy.

Purpose: To describe clinical and echocardiographic characteristics associated with reverse left ventricular (LV) remodeling after 6 months of cardiac resynchronization therapy (CRT) in patients with nonischemic dilated cardiomyopathy.

Methods: Twenty-four consecutive patients underwent 2D and 3D echocardiography before and after 6 months of CRT implant. Several echocardiographic parameters including global longitudinal strain (GLS) and 3D mechanical dyssynchrony (MD) index were calculated.

2D/3D echocardiographic determinants of left ventricular reverse remodelling after MitraClip implantation.

Aims: The aim of this study was to describe incidence and determinants of left ventricular reverse remodelling (r-LVR) at 6 months follow-up after MitraClip implantation in patients with secondary severe mitral regurgitation (MR) and reduced left ventricular ejection fraction (LVEF).

Methods And Results: Forty-five patients, undergoing MitralClip implantation with low ejection fraction and high surgical risk were enrolled in this study. Three of them died before the scheduled 6 months follow-up period and one patient had cardiac surgery due to MitraClip detachment.

Arginine 107 of yeast ATP synthase subunit g mediates sensitivity of the mitochondrial permeability transition to phenylglyoxal.

Modification with arginine-specific glyoxals modulates the permeability transition (PT) of rat liver mitochondria, with inhibitory or inducing effects that depend on the net charge of the adduct(s). Here, we show that phenylglyoxal (PGO) affects the PT in a species-specific manner (inhibition in mouse and yeast, induction in human and mitochondria). Following the hypotheses (i) that the effects are mediated by conserved arginine(s) and (ii) that the PT is mediated by the F-ATP synthase, we have narrowed the search to 60 arginines.

The idebenone metabolite QS10 restores electron transfer in complex I and coenzyme Q defects.

Idebenone is a hydrophilic short-chain coenzyme (Co) Q analogue, which has been used as a potential bypass of defective complex I in both Leber Hereditary Optic Neuropathy and OPA1-dependent Dominant Optic Atrophy. Based on its potential antioxidant effects, it has also been tested in degenerative disorders such as Friedreich's ataxia, Huntington's and Alzheimer's diseases. Idebenone is rapidly modified but the biological effects of its metabolites have been characterized only partially.

The unique histidine in OSCP subunit of F-ATP synthase mediates inhibition of the permeability transition pore by acidic pH.

The permeability transition pore (PTP) is a Ca-dependent mitochondrial channel whose opening causes a permeability increase in the inner membrane to ions and solutes. The most potent inhibitors are matrix protons, with channel block at pH 6.5.

Alisporivir rescues defective mitochondrial respiration in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtained from muscle biopsies of DMD patients display a decrease of the respiratory reserve, a consequence of inappropriate opening of the permeability transition pore (PTP).

Hidden in the heart: A peculiar type of left ventricular remodeling after acute myocardial infarction.

We reported an unusual case of left ventricular pouch, in a 72-year-old man who had an acute coronary syndrome treated with percutaneous revascularization. The echocardiogram showed a sort of pouch, delimited by epicardium and endocardium, confirmed by 3D echo. This finding appeared as an echo free area, with a really slight color flow inside.

Calcium and regulation of the mitochondrial permeability transition.

Recent years have seen renewed interest in the permeability transition pore, a high conductance channel responsible for permeabilization of the inner mitochondrial membrane, a process that leads to depolarization and Ca release. Transient openings may be involved in physiological Ca homeostasis while long-lasting openings may trigger and/or execute cell death. In this review we specifically focus (i) on the hypothesis that the PTP forms from the F-ATP synthase and (ii) on the mechanisms through which Ca can reversibly switch this energy-conserving nanomachine into an energy-dissipating device.

Ca binding to F-ATP synthase β subunit triggers the mitochondrial permeability transition.

F-ATP synthases convert the electrochemical energy of the H gradient into the chemical energy of ATP with remarkable efficiency. Mitochondrial F-ATP synthases can also undergo a Ca-dependent transformation to form channels with properties matching those of the permeability transition pore (PTP), a key player in cell death. The Ca binding site and the mechanism(s) through which Ca can transform the energy-conserving enzyme into a dissipative structure promoting cell death remain unknown.

Significant increase of flow kinetic energy in "nonresponders" patients to cardiac resynchronization therapy.

Backgrounds: It's still unclear if different patterns of intraventricular flow dynamics may be detected in patients nonresponders to cardiac resynchronization therapy (CRT) as compared to responders ones. Aim of this study was to evaluate the characteristics of left ventricular (LV) flow dynamics 6-months after CRT to identify Echo-particle imaging velocity (PIV) patterns were more frequently detected in nonresponders patients.

Methods: Thirty-two patients with dilated cardiomyopathy, undergoing CRT, were enrolled in this study.

Melanocytes from Patients Affected by Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy have Dysfunctional Mitochondria That Can be Rescued with Cyclophilin Inhibitors.

Ullrich congenital muscular dystrophy and Bethlem myopathy are caused by mutations in collagen VI (ColVI) genes, which encode an extracellular matrix protein; yet, mitochondria play a major role in disease pathogenesis through a short circuit caused by inappropriate opening of the permeability transition pore, a high-conductance channel, which causes a shortage in ATP production. We find that melanocytes do not produce ColVI yet they bind it at the cell surface, suggesting that this protein may play a trophic role and that its absence may cause lesions similar to those seen in skeletal muscle. We show that mitochondria in melanocytes of Ullrich congenital muscular dystrophy and Bethlem myopathy patients display increased size, reduced matrix density, and disrupted cristae, findings that suggest a functional impairment.

Quantitative analysis of intraventricular blood flow dynamics by echocardiographic particle image velocimetry in patients with acute myocardial infarction at different stages of left ventricular dysfunction.

Aims: Left ventricular (LV) diastolic filling is characterized by the formation of a vortex that supports an efficient transit into systolic ejection. Aim of this study was to assess the intraventricular (IV) blood flow dynamics among patients with ST elevated myocardial infarction (STEMI) at different degrees of LV dysfunction, in the attempt to find novel indicators of LV pump efficiency.

Methods And Results: Sixty-four subjects, 34 consecutive STEMI patients and 30 healthy controls, underwent before hospital discharge 2D speckle tracking echocardiography to assess global longitudinal strain (GLS), and echo-particle image velocimetry analysis to assess flow energetic parameters.

Value of two-dimensional longitudinal strains analysis to assess the impact of thrombus aspiration during primary percutaneous coronary intervention on left ventricular function: a speckle tracking imaging substudy of the EXPIRA trial.

Background: Thrombectomy during primary percutaneous coronary intervention (Th-PCI) improves myocardial reperfusion in the absence of significant changes, in the acute phase, in traditional two-dimensional (2D) echo indexes of left ventricular (LV) function. The aim of this study was to evaluate the potential of 2D speckle tracking echocardiography (2DSTE) analysis in assessing the efficacy of thrombectomy as compared to standard 2D echo and cardiac magnetic resonance (CMR) data.

Methods: Two-dimensional speckle tracking echocardiography analysis was performed in 60 anterior ST-segment elevation myocardial infarction (STEMI) patients to assess global (GLS), segmental (SLS) and regional longitudinal strain (RLS).

Peptide-based carbon nanotubes for mitochondrial targeting.

In the present study, we report the design and synthesis of peptide-based-multi-walled carbon nanotubes (MWCNTs) to target mitochondria. Targeting these intracellular organelles might open the way to develop alternative systems to address diseases related to genetic mutations in mitochondrial (mt)-DNA, by delivering therapeutic oligonucleotides. The first step towards mitochondrial delivery of this type of nucleic acid was to target MWCNTs to mitochondria by covalent functionalization with a well-known endogenous mitochondrial targeting sequence (MTS).

Dimers of mitochondrial ATP synthase form the permeability transition pore.

Here we define the molecular nature of the mitochondrial permeability transition pore (PTP), a key effector of cell death. The PTP is regulated by matrix cyclophilin D (CyPD), which also binds the lateral stalk of the FOF1 ATP synthase. We show that CyPD binds the oligomycin sensitivity-conferring protein subunit of the enzyme at the same site as the ATP synthase inhibitor benzodiazepine 423 (Bz-423), that Bz-423 sensitizes the PTP to Ca(2+) like CyPD itself, and that decreasing oligomycin sensitivity-conferring protein expression by RNAi increases the sensitivity of the PTP to Ca(2+).

Global and regional longitudinal strain assessed by two-dimensional speckle tracking echocardiography identifies early myocardial dysfunction and transmural extent of myocardial scar in patients with acute ST elevation myocardial infarction and relatively preserved LV function.

Aims: Global and regional longitudinal strain (GLS-RLS) assessed by two-dimensional speckle tracking echocardiography (2D-STE) are considered reliable indexes of left-ventricular (LV) function and myocardial viability in chronic ischaemic patients when compared with delayed-enhanced cardiac magnetic resonance (DE-CMR). In the present study, we tested whether GLS and RLS could also identify early myocardial dysfunction and transmural extent of myocardial scar in patients with acute ST elevation myocardial infarction (STEMI) and relatively preserved LV function.

Methods And Results: Twenty STEMI patients with LVEF ≥40%, treated with PPCI within 6 h from symptoms onset, underwent DE-CMR and 2D-echocardiography for 2D-STE analysis 6 ± 2 days after STEMI.

The effects of idebenone on mitochondrial bioenergetics.

We have studied the effects of idebenone on mitochondrial function in cybrids derived from one normal donor (HQB17) and one patient harboring the G3460A/MT-ND1 mutation of Leber's Hereditary Optic Neuropathy (RJ206); and in XTC.UC1 cells bearing a premature stop codon at amino acid 101 of MT-ND1 that hampers complex I assembly. Addition of idebenone to HQB17 cells caused mitochondrial depolarization and NADH depletion, which were inhibited by cyclosporin (Cs) A and decylubiquinone, suggesting an involvement of the permeability transition pore (PTP).