Novel Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles and Biochemical Valuation on F1FO-ATPase and Mitochondrial Permeability Transition Pore Formation

An efficient, eco-compatible, and very cheap method for the construction of fully substituted pyrazoles (Pzs) via eliminative nitrilimine-alkene 1,3-dipolar cycloaddition (ENAC) reaction was developed in excellent yield and high regioselectivity. Enaminones and nitrilimines generated in situ were selected as dipolarophiles and dipoles, respectively. A deep screening of the employed base, solvent, and temperature was carried out to optimize reaction conditions. Recycling tests of ionic liquid were performed, furnishing efficient performance until six cycles. Finally, a plausible mechanism of cycloaddition was proposed. Then, the effect of three different structures of Pzs was evaluated on the F1FO-ATPase activity and mitochondrial permeability transition pore (mPTP) opening. The Pz derivatives’ titration curves of 6a, 6h, and 6o on the F1FO-ATPase showed a reduced activity of 86%, 35%, and 31%, respectively. Enzyme inhibition analysis depicted an uncompetitive mechanism with the typical formation of the tertiary complex enzyme-substrate-inhibitor (ESI). The dissociation constant of the ESI complex (Ki’) in the presence of the 6a had a lower order of magnitude than other Pzs. The pyrazole core might set the specific mechanism of inhibition with the F1FO-ATPase, whereas specific functional groups of Pzs might modulate the binding affinity. The mPTP opening decreased in Pz-treated mitochondria and the Pzs’ inhibitory effect on the mPTP was concentration-dependent with 6a and 6o. Indeed, the mPTP was more efficiently blocked with 0.1 mM 6a than with 1 mM 6a. On the contrary, 1 mM 6o had stronger desensitization of mPTP formation than 0.1 mM 6o. The F1FO-ATPase is a target of Pzs blocking mPTP formation

Temporary Mechanical Circulatory Support in Acute Heart Failure

Cardiogenic shock is a challenging syndrome, associated with significant morbidity and mortality. Although pharmacological therapies are successful and can successfully control this acute cardiac illness, some patients remain refractory to drugs. Therefore, a more aggressive treatment strategy is needed. Temporary mechanical circulatory support (TCS) can be used to stabilise patients with decompensated heart failure. In the last two decades, the increased use of TCS has led to several kinds of devices becoming available. However, indications for TCS and device selection are part of a complex process. It is necessary to evaluate the severity of cardiogenic shock, any early and prompt haemodynamic resuscitation, prior TCS, specific patient risk factors, technical limitations, and adequacy of resources and training, as well as an assessment of whether care would be futile. This article examines options for commonly used TCS devices, including intra-aortic balloon pumps, a pulsatile percutaneous ventricular assist device (the iVAC), veno-arterial extra-corporeal membrane oxygenation and Impella (Abiomed), and TandemHeart (LivaNova) percutaneous ventricular assist device (pVAD)

Surgical treatment of post-infarction papillary muscle rupture: systematic review and meta-analysis

Background: Papillary muscle rupture (PMR) is a rare but potentially fatal complication following acute myocardial infarction (AMI). Surgical treatment is considered the standard of care. This systematic review and meta-analysis aims to evaluate the early outcomes after surgical correction of post-AMI PMR. Methods: Electronic databases were searched from January 1990 to December 2020. Studies reporting patients undergoing mitral valve surgery for post-AMI PMR were analysed. The primary outcome assessed was operative mortality. Differences were expressed as risk ratio (RR) with 95% confidence interval (CI) to assess the relationships between predefined surgical variables and clinical prognosis. Results: A total of 1,851 adult patients, from 12 observational studies, were identified. Operative mortality was 21%. Meta-analysis revealed reduced operative risk in patients undergoing mitral valve repair (MVr) as compared to replacement (MVR) (RR, 0.33; 95% CI: 0.14 to 0.79; P=0.01), and an increased risk of operative mortality in patients with complete PMR (RR, 2.54; 95% CI: 1.12 to 5.74; P=0.03). No significant differences in terms of operative mortality were observed between patients with or without pre/perioperative intra-aortic balloon pump (IABP) support and between subjects who underwent mitral valve surgery with or without concomitant coronary artery bypass grafting (CABG). Conclusions: Mitral valve surgery for post-AMI PMR carries a high operative mortality. Patients with complete PMR and subjects undergoing MVR have increased risks of operative mortality. The preoperative use of IABP and concomitant CABG seem not to influence the early postoperative course in this context

Corrigendum to: Sutured and sutureless repair of postinfarction left ventricular free-wall rupture: A systematic review (Eur J Cardiothorac Surg DOI: 10.1093/ejcts/ezz101)

In the version of this article initially published on 1 April 2019, author Mariusz Kowalewski?s surname was misspelled. The error has been corrected here and in the full article online

Surgical treatment of post-infarction papillary muscle rupture: systematic review and meta-analysis

Background: Papillary muscle rupture (PMR) is a rare but potentially fatal complication following acute myocardial infarction (AMI). Surgical treatment is considered the standard of care. This systematic review and meta-analysis aims to evaluate the early outcomes after surgical correction of post-AMI PMR. Methods: Electronic databases were searched from January 1990 to December 2020. Studies reporting patients undergoing mitral valve surgery for post-AMI PMR were analysed. The primary outcome assessed was operative mortality. Differences were expressed as risk ratio (RR) with 95% confidence interval (CI) to assess the relationships between predefined surgical variables and clinical prognosis. Results: A total of 1,851 adult patients, from 12 observational studies, were identified. Operative mortality was 21%. Meta-analysis revealed reduced operative risk in patients undergoing mitral valve repair (MVr) as compared to replacement (MVR) (RR, 0.33; 95% CI: 0.14 to 0.79; P=0.01), and an increased risk of operative mortality in patients with complete PMR (RR, 2.54; 95% CI: 1.12 to 5.74; P=0.03). No significant differences in terms of operative mortality were observed between patients with or without pre/peri-operative intra-aortic balloon pump (IABP) support and between subjects who underwent mitral valve surgery with or without concomitant coronary artery bypass grafting (CABG). Conclusions: Mitral valve surgery for post-AMI PMR carries a high operative mortality. Patients with complete PMR and subjects undergoing MVR have increased risks of operative mortality. The preoperative use of IABP and concomitant CABG seem not to influence the early postoperative course in this contex

Surgical Repair of Postinfarction Ventricular Septal Rupture: Systematic Review and Meta-Analysis

Background: Ventricular septal rupture (VSR) is a rare but life-threatening complication after acute myocardial infarction. Although surgical correction is challenging and associated with high mortality, it remains the treatment of choice. This systematic review and meta-analysis aimed to evaluate the early outcome of surgical VSR repair. Methods: We searched electronic databases from January 1998 to February 2020. Studies reporting patients undergoing surgical treatment for VSR were analyzed. The primary outcome assessed was operative mortality. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships of predefined surgical variables and clinical prognosis. Results: A total of 6361 adult patients from 41 studies were identified. Operative mortality was 38.2%. Pooled ORs showed increased odds of operative mortality in patients with preoperative or perioperative intraaortic balloon pump insertion (OR = 3.48; 95% CI, 3.01-4.02; P <.001), right ventricular dysfunction (OR = 2.85; 95% CI, 1.47-5.52; P =.002), posterior VSR (OR = 1.73; 95% CI, 1.30-2.31; P <.001), and emergency surgery (OR = 3.79; 95% CI, 2.52-5.72; P <.001). Temporal trend evaluation revealed no difference over time in the operative mortality rate; it was 34% in both time-related groups (1971-2000 versus 2001-2018). Conclusions: Ventricular septal rupture repair has a high operative mortality. Patients with preoperative or perioperative intraaortic balloon pump support, right ventricular dysfunction at presentation, or posterior defects, and those undergoing emergent VSR correction have increased odds of operative mortality