Atrial Natriuretic Peptides as a Bridge between Atrial Fibrillation, Heart Failure, and Amyloidosis of the Atria.

ANP is mainly synthesized by the atria, and upon excretion, it serves two primary purposes: vasodilation and increasing the renal excretion of sodium and water. The understanding of ANP's role in cardiac systems has improved considerably in recent decades. This review focuses on several studies demonstrating the importance of analyzing the regulations between the endocrine and mechanical function of the heart and emphasizes the effect of ANP, as the primary hormone of the atria, on atrial fibrillation (AF) and related diseases. The review first discusses the available data on the diagnostic and therapeutic applications of ANP and then explains effect of ANP on heart failure (HF) and atrial fibrillation (AF) and vice versa, where tracking ANP levels could lead to understanding the pathophysiological mechanisms operating in these diseases. Second, it focuses on conventional treatments for AF, such as cardioversion and catheter ablation, and their effects on cardiac endocrine and mechanical function. Finally, it provides a point of view about the delayed recovery of cardiac mechanical and endocrine function after cardioversion, which can contribute to the occurrence of acute heart failure, and the potential impact of restoration of the sinus rhythm by extensive ablation or surgery in losing ANP-producing sites. Overall, ANP plays a key role in heart failure through its effects on vasodilation and natriuresis, leading to a decrease in the activity of the renin-angiotensin-aldosterone system, but it is crucial to understand the intimate role of ANP in HF and AF to improve their diagnosis and personalizing the patients' treatment.

Clinical profile and in-hospital outcome of patients supported by intra-aortic balloon pump in the clinical setting of cardiogenic shock.

Background: Despite controversial evidences, intra-aortic balloon pump (IABP) is still the most widely used temporary mechanical support device in cardiogenic shock (CS), as a bridge to recovery or to more invasive mechanical supports/heart transplantation. Methods: We analyzed retrospectively data of all patients receiving IABP for CS from 2009 to 2018 in a referral centre for advanced heart failure and heart transplantation; we included CS following acute coronary syndrome (ACS) and other CS etiologies different from ACS. We excluded patients in which IABP was implanted as a support following cardiac surgery, non-cardiac surgery in patients with severe chronic heart failure, or in elective high risk or complicated Cath Lab procedures.We focused on in-hospital outcomes (including death, recovery, heart transplantation, LVAD) and IABP complications. Results: 403 patients received IABP, 303 (75.2%) following ACS and 100 (24.8%) in non-ACS CS. Non-ACS patients were younger (59 ± 18.3 vs 73.1 ± 12.6 years, p < 0.001), had lower median left ventricular ejection fraction (LVEF) (25% [18-35] vs 38% [25-45], p < 0.001). In patients with non-ACS etiologies IABP was more frequently a bridge to heart transplantation [20% (n = 20) vs 0.3% (n = 1), P < 0.001] or LVAD [4% (n = 4) vs 0.6% (n = 2), P = 0.055], while ACS patients were more frequently discharged without transplantation/LVAD [65.7% (n = 199) vs 33% (n = 33), P < 0.001]. Non-ACS patients showed higher in-hospital mortality [46% (n = 46) vs 33.9% (n = 103), P = 0.042]. Post-transplant/LVAD outcome in non-ACS subgroup was favorable (21 out of 24 patients were discharged). Serious IABP-related adverse events occurred in 21 patients (5.2%). Ischemic/hemorrhagic complications, infections and thrombocytopenia were more frequent with longer IABP stay. Conclusions: Despite therapy including percutaneous circulatory support, mortality in CS is still high. In our experience, in the clinical setting of refractory CS an IABP support represents a relatively safe circulatory support, associated with a low rate of serious complications in complex clinical scenarios.

miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.

Despite much progress in improving graft outcome during cardiac transplantation, chronic allograft vasculopathy (CAV) remains an impediment to long-term graft survival. MicroRNAs (miRNAs) emerged as regulators of the immune response. Here, we aimed to examine the miRNA network involved in CAV. miRNA profiling of heart samples obtained from a murine model of CAV and from cardiac-transplanted patients with CAV demonstrated that miR-21 was most significantly expressed and was primarily localized to macrophages. Interestingly, macrophage depletion with clodronate did not significantly prolong allograft survival in mice, while conditional deletion of miR-21 in macrophages or the use of a specific miR-21 antagomir resulted in indefinite cardiac allograft survival and abrogated CAV. The immunophenotype, secretome, ability to phagocytose, migration, and antigen presentation of macrophages were unaffected by miR-21 targeting, while macrophage metabolism was reprogrammed, with a shift toward oxidative phosphorylation in naïve macrophages and with an inhibition of glycolysis in pro-inflammatory macrophages. The aforementioned effects resulted in an increase in M2-like macrophages, which could be reverted by the addition of L-arginine. RNA-seq analysis confirmed alterations in arginase-associated pathways associated with miR-21 antagonism. In conclusion, miR-21 is overexpressed in murine and human CAV, and its targeting delays CAV onset by reprogramming macrophages metabolism.

Does the antibody mediated rejection grading scale have prognostic prediction? Yes, but the picture is still blurry.

PURPOSE OF REVIEW: Antibody-mediated rejection (ABMR) is a condition difficult to diagnose and treat, which may significantly impair the outcome of heart transplant recipients. In clinical practice, diagnosis is based on immunopathology grading of endomyocardial biopsies (EMB). Despite its value, the current diagnostic system has several pitfalls that have been addressed in recent literature. RECENT FINDINGS: Pathology grading of ABMR (pAMR) has a relevant prognostic factor. However, it does not capture several nuances, such as chronic vs. acute ABMR, mixed rejection or microvascular inflammation. Molecular biology-based assays are shedding new light on the mechanisms of ABMR, which could improve the precision of ABMR diagnosis. SUMMARY: These new findings have the potential to rearrange EMB grading system and to guide more precisely decision-making, but studies validating the therapeutic management based on molecular-pathology coupling are still missing.

Clinical outcomes with percutaneous coronary revascularization vs coronary artery bypass grafting surgery in patients with unprotected left main coronary artery disease: A meta-analysis of 6 randomized trials and 4,686 patients.

Some but not all randomized controlled trials (RCT) have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative to coronary artery bypass grafting (CABG) surgery for the treatment of unprotected left main coronary artery disease (ULMCAD). We therefore aimed to compare the risk of all-cause mortality between PCI and CABG in patients with ULMCAD in a pairwise meta-analysis of RCT. METHODS: Randomized controlled trials comparing PCI vs CABG for the treatment of ULMCAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. RESULTS: Six trials including 4,686 randomized patients were identified. After a median follow-up of 39 months, there were no significant differences between PCI vs CABG in the risk of all-cause mortality (hazard ratio [HR] 0.99, 95% CI 0.76-1.30) or cardiac mortality. However, a significant interaction for cardiac mortality (Pinteraction= .03) was apparent between randomization arm and SYNTAX score, such that the relative risk for mortality tended to be lower with PCI compared with CABG among patients in the lower SYNTAX score tertile, similar in the intermediate tertile, and higher in the upper SYNTAX score tertile. Percutaneous coronary intervention compared with CABG was associated with a similar long-term composite risk of death, myocardial infarction, or stroke (HR 1.06, 95% CI 0.82-1.37), with fewer events within 30 days after PCI offset by fewer events after 30 days with CABG (Pinteraction < .0001). Percutaneous coronary intervention was associated with greater rates of unplanned revascularization compared with CABG (HR 1.74, 95% CI 1.47-2.07). CONCLUSIONS: In patients undergoing revascularization for ULMCAD, PCI was associated with similar rates of mortality compared with CABG at a median follow-up of 39 months, but with an interaction effect suggesting relatively lower mortality with PCI in patients with low SYNTAX score and relatively lower mortality with CABG in patients with high SYNTAX score. Both procedures resulted in similar long-term composite rates of death, myocardial infarction, or stroke, with PCI offering an early safety advantage and CABG demonstrating greater durability.

Heart allograft preservation: an arduous journey from the donor to the recipient.

PURPOSE OF REVIEW: The discrepancy between needs and availability of organs for heart transplantation may be partially reduced by improving the utilization of organs currently deemed unsuitable. Strategies to achieve this goal need optimization of the entire process of organ procurement, transportation, and functional recovery after transplant. RECENT FINDINGS: In the latest years, several studies reported improvements in organ utilization after appropriate donor management, and management of heart transportation is approaching a new era. In particular, apart from perfecting of traditional cold static preservation techniques, novel technologies now allow continuous heart perfusion prolonging out-of-body times, and prompted to the 'resuscitation' of hearts injured by the warm ischemia of circulatory death donors. The accomplishment of the journey needs appropriate protection of the graft during and after the transplant surgery. This concept is driven by adequate donor-recipient matching and aided by the assist devices that, mimicking organ perfusion machines, may allow graft reconditioning while maintaining recipient's peripheral organ function. SUMMARY: The researches reviewed in this article support a significant improvement of the heart preservation during the multifaceted process of procurement, transport, and transplant. Future challenges will be to develop healing of currently unsuitable organs, while keeping the cost of technology within the borders of affordability for healthcare systems.