Alternatives to Transplantation in the Treatment of Heart Failure: New Diagnostic and Therapeutic Insights

none4siThe aim of our current special issue was to present a series of original researches and reviews on recent advances in the diagnosis, medical therapy, and surgical approaches of heart failure. As reported in the introductive review of Agnetti et al., cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndromes are leading to an increasing number of “survivors” who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be o ered only to a small percentage of patients who could bene t from a new heart due to the limited availability of donor organs. e authors reported in this comprehensive review the evaluation of the safety and e cacy of innovative approaches in the diagnosis and treatment of patients refrac- tory to standard medical therapy and excluded from cardiac transplantation lists.mixedNicolini, Francesco; Piepoli, Massimo F.; Agnetti, Giulio; Siniscalchi, GiuseppeNicolini, Francesco; Piepoli, Massimo F.; Agnetti, Giulio; Siniscalchi, Giusepp

New Insights in the Diagnosis and Treatment of Heart Failure

Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of "survivors" who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists

Induced pluripotent stem cell-based models: Are we ready for that heart in a dish?

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IDENTIFICATION OF E. COLI O157 IN A BOVINE MILK FARM BY MULTIPLEX REAL-TIME PCR

Law provisions about direct sell of raw bovine milk require VTEC O157 monitoring in bovine milk farms (milk and faeces). It has been showed that culture-based methods used for this scope, besides being cumbersome and time-consuming, may be also less sensitive, compared to molecular approaches. In this study, a multiplex Real-Time PCR, able to identify VTEC O157, Salmonella spp and Listeria monocytogenes, has been used to analyse milk, filter, sewage and stool samples from a milk farm, in comparison with standard OIE methods. The performances of the molecular protocol have been preliminary assessed with lyophilized samples from proficiency testing VLA, showing 100% accordance. Results from field samples indicated the absence of the pathogen in milk, and the higher sensitivity of Real-Time PCR with other matrices, suggesting its potential use for fast VTEC O157 identification

The RainBO Platform for Enhancing Urban Resilience to Floods: An Ecient Tool for Planning and Emergency Phases

Many urban areas face an increasing flood risk, which includes the risk of flash floods. Increasing extreme precipitation events will likely lead to greater human and economic losses unless reliable and efficient early warning systems (EWS) along with other adaptation actions are put in place in urban areas. The challenge is in the integration and analysis in time and space of the environmental, meteorological, and territorial data from multiple sources needed to build up EWS able to provide efficient contribution to increase the resilience of vulnerable and exposed urban communities to flooding. Efficient EWS contribute to the preparedness phase of the disaster cycle but could also be relevant in the planning of the emergency phase. The RainBO Life project addressed this matter, focusing on the improvement of knowledge, methods, and tools for the monitoring and forecast of extreme precipitation events and the assessment of the associated flood risk for small and medium watercourses in urban areas. To put this into practice, RainBO developed a webGIS platform, which contributes to the “planning” of the management of river flood events through the use of detailed data and flood risk/vulnerability maps, and the “event management” with real-time monitoring/forecast of the events through the collection of observed data from real sensors, estimated/forecasted data from hydrologic models as well as qualitative data collected through a crowdsourcing app

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Protein post-translational modifications and misfolding: new concepts in heart failure.

A new concept in the field of heart-failure (HF) research points to a role of misfolded proteins, forming preamyloid oligomers (PAOs), in cardiac toxicity. This is largely based on few studies reporting the presence of PAOs, similar to those observed in neurodegenerative diseases, in experimental and human HF. As the majority of proteinopathies are sporadic in nature, protein post-translational modifications (PTMs) likely play a major role in this growing class of diseases. In fact, PTMs are known regulators of protein folding and of the formation of amyloid species in well-established proteinopathies. Proteomics has been instrumental in identifying both chemical and enzymatic PTMs, with a potential impact on protein mis-/folding. Here we provide the basics on how proteins fold along with a few examples of PTMs known to modulate protein misfolding and aggregation, with particular focus on the heart. Due to its innovative content and the growing awareness of the toxicity of misfolded proteins, an \u201cAlzheimer\u2019s theory of HF\u201d is timely. Moreover, the continuous innovations in proteomic technologies will help pinpoint PTMs that could contribute to the process. This nuptial between biology and technology could greatly assist in identifying biomarkers with increased specificity as well as more effective therapies