Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options.

Obesity is a heterogeneous disease that affects almost one-third of the global population. A clear association has been established between obesity and cardiovascular disease (CVD). However, CVD risk is known to be related more to the local distribution of fat than to total body fat. Visceral adipose tissue (VAT) in particular has a high impact on CVD risk. This manuscript reviews the role of VAT in residual CV risk and the available therapeutic strategies for decreasing residual CV risk related to VAT accumulation. Among the many pathways involved in residual CV risk, obesity and particularly VAT accumulation play a major role by generating low-grade systemic inflammation, which in turn has a high prognostic impact on all-cause mortality and myocardial infarction. In recent years, many therapeutic approaches have been developed to reduce body weight. Orlistat was shown to reduce both weight and VAT but has low tolerability and many drug-drug interactions. Naltrexone-bupropion combination lowers body weight but has frequent side effects and is contraindicated in patients with uncontrolled hypertension. Liraglutide and semaglutide, glucagon-like peptide 1 (GLP-1) agonists, are the latest drugs approved for the treatment of obesity, and both have been shown to induce significant body weight loss. Liraglutide, semaglutide and other GLP-1 agonists also showed a positive effect on CV outcomes in diabetic patients. In addition, liraglutide showed to specifically reduce VAT and inflammatory biomarkers in obese patients without diabetes. GLP-1 agonists are promising compounds to limit inflammation in human visceral adipocytes.

Understanding the role of coronary artery revascularization in patients with left ventricular dysfunction and multivessel disease.

Coronary artery disease (CAD) is the most common cause of heart failure with reduced ejection fraction (HFrEF). Advances and innovations in medical therapy have been shown to play a crucial role in improving the prognosis of patients with CAD and HFrEF; however, mortality rate in these patients remains high, and the role of surgical and/or percutaneous revascularization strategy is still debated. The Surgical Treatment for Ischemic Heart Failure (STICH) trial and the Revascularization for Ischemic Ventricular Dysfunction (REVIVED) trial have attempted to provide an answer to this issue. Nevertheless, the results of these two trials have generated further uncertainties. Their findings do not provide a definitive answer about the ideal clinical phenotype for surgical or percutaneous coronary revascularization and dispute the historical dogma on myocardial viability and the theory of myocardial hibernation, raising new questions about the proper selection of patients who are candidates for coronary revascularization. The aim of this review is to provide an overview on the actual available evidence of coronary artery revascularization in patients with CAD and left ventricular dysfunction and to suggest new insights on the proper selection and management strategies in this high-risk clinical setting.

Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Diabetes and Coronary Artery Disease: Translating the Benefits of the Molecular Mechanisms of Gliflozins into Clinical Practice.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially developed for the treatment of diabetes due to their antihyperglycemic activity. However, in the light of the most recent clinical studies, they are revolutionizing the approach to cardiovascular disease in patients with and without diabetes. We aimed to generate real-world data about the use of SGLT2i in patients with T2DM and coronary artery disease (CAD), focusing on their effectiveness in glycemic control, adherence, long-term efficacy, and safety outcomes. On the basis of the inclusion and exclusion criteria, 143 patients were enrolled. Patients were treated with canagliflozin (n = 33 patients; 23%), dapagliflozin (n = 52 patients, 36.4%), empagliflozin (n = 48 patients; 33.6%), or ertugliflozin (n = 10 patients; 7%) as monotherapy or in combination with other antidiabetic drugs. All patients performed a clinical visit, and their medical history, blood sampling, and anthropometric parameters were measured at discharge and at 1-year follow-up. The reduction in HbA1c % value at 12 months was significant (8.2 vs. 7.4; p < 0.001). Trends in body weight and body mass index also confirmed the positive effect of the treatment (p < 0.0001), as did the reduction in abdominal adiposity (expressed via waist circumference). At 1-year follow-up, 74.1% of patients were adherent to the treatment, and 81.1% were persistent to the treatment. A total of 27 patients (18.8%) had to discontinue treatment early due to drug intolerance caused by genitourinary infections (11.9%), the drub being permanently ineffective (HbA1c not at target or decreasing: 4.9%), or because of expressing. a desire not to continue (2%). No major drug-related adverse events (diabetic ketoacidosis, Fournier's gangrene, lower-limb amputations) occurred at follow-up, while MACE events occurred in 14 patients (9.8%). In real-world patients with T2DM and CAD, SGLT2i have been effective in long-term glycemic control and the improvement in anthropometric indices with good tolerance, high adherence, persistence to treatment, and no major adverse events at 1-year follow-up.

Interplay between COVID-19, pollution, and weather features on changes in the incidence of acute coronary syndromes in early 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area. METHODS AND RESULTS: Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI cases. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all p<0.05), concomitantly with COVID-19 spread and institution of national countermeasures. Changes in STEMI and NSTEMI were inversely associated with daily COVID-19 tests, cases, and/or death (p<0.05). In addition, STEMI and NSTEMI incidences were associated with daily NO2, PM10, and O3 concentrations, as well as temperature (p<0.05). Multi-stage and multiply adjusted models highlighted that reductions in STEMI were significantly associated with COVID-19 data (p<0.001), whereas changes in NSTEMI were significantly associated with both NO2 and COVID-19 data (both p<0.001). CONCLUSIONS: Reductions in STEMI and NSTEMI in the COVID-19 pandemic may depend on different concomitant epidemiologic and pathophysiologic mechanisms. In particular, recent changes in STEMI may depend on COVID-19 scare, leading to excess all-cause mortality, or effective reduced incidence, whereas reductions in NSTEMI may also be due to beneficial reductions in NO2 emissions in the lockdown phase.

Impact of temporary traffic bans on the risk of acute coronary syndromes in a large metropolitan area.

BACKGROUND: Strong epidemiologic evidence has highlighted the role of pollution, on top of adverse climate features, as a novel cardiovascular risk factor. However, mechanistic proof that reducing pollution may be beneficial to prevent atherothrombotic events is limited. We aimed at appraising the impact of temporary traffic bans in a large metropolitan area on the risk of acute coronary syndromes. METHODS: Aggregate and anonymized data from 15 tertiary cardiac care centers were obtained detailing precoronavirus disease 2019 (COVID-19) daily cases of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including those treated with percutaneous coronary intervention (PCI). Data on pollutants and climate were sought for the same days. Mixed level regression was used to compare the week before vs after the traffic ban (Fortnight analysis), the 3 days before vs. after (Weekly analysis) and the Sunday before vs. after (Sunday analysis). RESULTS: A total of 8 days of temporary traffic bans were included, occurring between 2017 and 2020, totaling 802 STEMI and 1196 NSTEMI in the Fortnight analysis, 382 STEMI and 585 in the Weekly analysis, and 148 STEMI and 210 NSTEMI in the Sunday analysis.Fortnight and Sunday analyses did not disclose a significant impact of traffic ban on STEMI or NSTEMI (all P>0.05). Conversely, Weekly analysis showed non-significant changes for STEMI, but a significant decrease in daily NSTEMI when comparing the 3 days before the traffic ban with the ban day (P=0.043), as well as the 3 days before vs. the 3 days after the ban (P=0.025). No statistically significant effect of traffic ban was found at Fortnight, Weekly or Sunday analyses for daily mean concentrations of benzene, carbon monoxide, nitric oxide, nitrogen dioxide, ozone, sulfur dioxide, particulate matter (PM) <2.5 µm or PM <10 µm (all P>0.05). However, minimum daily concentrations showed a significant reduction of ozone during the ban in comparison to the week preceding it (P=0.034), nitric oxide during the ban in comparison to the 3 days preceding it (P=0.046), and an increase in benzene during the ban in comparison to the Sunday before (P=0.039). CONCLUSIONS: Temporary traffic ban may favorably reduce coronary atherothrombotic events, and in particular NSTEMI, even if not globally and immediately impacting on environmental pollution. Further controlled studies are required to confirm and expand this hypothesis-generating results.

339 Interplay between COVID-19, pollution, and weather features on changes in the incidence of acute coronary syndromes in early 2020.

Aims: Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area. Methods and results: Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all P < 0.05), concomitantly with COVID-19 spread and institution of national countermeasures. Changes in STEMI and NSTEMI were inversely associated with daily COVID-19 tests, cases, and/or death (P < 0.05). In addition, STEMI and NSTEMI incidences were associated with daily NO2, PM10, and O3 concentrations, as well as temperature (P < 0.05). Multi-stage and multiply adjusted models highlighted that reductions in STEMI were significantly associated with COVID-19 data (P < 0.001), whereas changes in NSTEMI were significantly associated with both NO2 and COVID-19 data (both P < 0.001). Conclusion: Reductions in STEMI and NSTEMI in the COVID-19 pandemic may depend on different concomitant epidemiologic and pathophysiologic mechanisms. In particular, recent changes in STEMI may depend on COVID-19 scare, leading to excess all-cause mortality, or effective reduced incidence, whereas reductions in NSTEMI may also be due to beneficial reductions in NO2 emissions in the lockdown phase.

Impact of Insulin-Treated and Noninsulin-Treated Diabetes Mellitus in All-Comer Patients Undergoing Percutaneous Coronary Interventions With Polymer-Free Biolimus-Eluting Stent (from the RUDI-FREE Registry).

Patients with diabetes mellitus (DM) have worse outcomes after percutaneous coronary intervention (PCI). Recent evidences suggest a differential impact of insulin-treated and noninsulin-treated DM on prognosis. We evaluated the clinical outcome of diabetic patients after PCI with polymer-free biolimus-eluting stent from the RUDI-FREE Registry, investigating a possible different prognostic impact of insulin-treated and noninsulin-treated DM. A total of 1,104 consecutive patients who underwent PCI with polymer-free biolimus-eluting stent, enrolled in the RUDI-FREE observational, multicenter, single-arm registry, were stratified by diabetic status; diabetic population was further divided on the basis of insulin treatment. Primary end points of the study were target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, target lesion revascularization) and major adverse cardiac and cerebrovascular events (composite of cardiac death, stroke, and myocardial infarction). Multiple ischemic adverse events were also single-handedly considered as secondary end points. At 1 year, TLF was significantly higher in the diabetic cohort, as compared with nondiabetic patients (6.0% vs 3.1%, p 0.022). None of the end points resulted significantly different between nondiabetics and noninsulin-treated diabetic patients. Divergently, compared with nondiabetic, insulin-treated diabetic patients faced significant higher rates of TLF (10.8% vs 3.1%, p 0.003), major adverse cardiac and cerebrovascular events (10.8% vs 3.4%, p 0.004), and of most of the analyzed adverse events. In conclusion, patients with DM had a higher risk of TLF compared with nondiabetics; nonetheless, the worse outcome of the diabetic population seems to be driven by the insulin-treated diabetic subpopulation. This finding suggests a different risk profile of insulin-treated and noninsulin-treated diabetic patients in the modern era of PCI.

Safety and efficacy of polymer-free biolimus-eluting stents in all-comer patients: the RUDI-FREE study.

AIMS: Polymer-free biolimus-eluting stents (PF-BES) have been shown to be superior to bare metal stents in high bleeding risk (HBR) patients treated with one-month dual antiplatelet therapy (DAPT). However, limited evidence is available on PF-BES in non-HBR patients. We aimed to evaluate the safety and efficacy of PF-BES in all-comer patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients with stable coronary artery disease or acute coronary syndromes (ACS) undergoing PCI with PF-BES in routine clinical practice were included in a multicentre, prospective registry. DAPT duration was left to the discretion of the operator. The primary endpoint was the composite of cardiovascular death, myocardial infarction (MI), and definite/probable stent thrombosis (ST) at one year. Overall, 1,104 consecutive patients treated with PF-BES were included at 16 Italian centres. Mean age was 68.7±11.2 years, 77.2% of patients were male, 30% had diabetes, 15.1% had chronic kidney disease, and 40.5% had ACS at baseline. Mean CRUSADE score was 24.1±13.1, and 83.7% of patients did not have high bleeding risk features. At one year, the primary endpoint occurred in 4.1% of patients, cardiovascular death in 2.4%, MI in 1.8%, and definite/probable ST in 1.1%. With respect to efficacy, target lesion revascularisation occurred in 1.2% of patients. CONCLUSIONS: This is the first study providing clinical evidence on the use of PF-BES in all-comer patients irrespective of HBR status. Our findings suggest that PF-BES has a favourable safety and efficacy profile in a real-world clinical setting. Further investigation in randomised clinical trials against new-generation DES is warranted.

Genetic analysis of CHCHD10 in French familial amyotrophic lateral sclerosis patients.

Mutations in CHCHD10 have been reported as the cause of a large panel of neurologic disorders. To confirm the contribution of this gene to amyotrophic lateral sclerosis (ALS) disease, we analyzed the 4 coding exons of CHCHD10 by Sanger sequencing in a cohort of 118 French familial ALS already excluded for all known ALS-related genes. We did not find any pathogenic mutation suggesting that CHCHD10 is not a major genetic cause of familial ALS, in France.

Identifying a therapeutic window in acute and subacute inflammatory sensory neuronopathies.

BACKGROUND: Patients with inflammatory sensory neuronopathy (SNN) may benefit from immunomodulatory or immunosuppressant treatments if administered timely. Knowing the temporal profile of neuronal loss in dorsal root ganglia will help to ascertain whether a final diagnosis may be reached before the occurrence of irreversible neuronal injuries. Thus, we addressed the evolution of neuronal loss in SNN by using sensory nerve action potentials (SNAPs) as a surrogate marker of neuron degeneration. METHODS: Eighty-six patients with acute/subacute inflammatory SNN (paraneoplastic, associated with dysimmune diseases, or idiopathic) were retrospectively studied. The monthly SNAP reduction was determined and normalized with the lower limit of normal. Disability progression was expressed by the modified Rankin score and correlated with SNAP reduction. RESULTS: The monthly SNAP reduction was similar in the four limbs although the median nerve was less severely affected. The monthly SNAP reduction was very severe within the first two months of evolution, began to slow down after seven months, and stabilized after ten months. It was tightly correlated with disability progression. Kaplan-Meier analysis showed that the median time until matching the diagnostic criteria of SNN was 8.5 months. Within this period, 42% of nerves remained excitable. CONCLUSIONS: Developing treatment aiming at the stabilization of SNN is possible within the first 8 months of evolution. An improvement of the disease is possible if patients are treated within two months, which needs an early referral to an expert center and ENMG testing of the radial and ulnar nerves, which are most sensitive to changes.

Potential additive effects of ticagrelor, ivabradine, and carvedilol on sinus node.

A 51-year-old male patient presented to the emergency room with an anterior ST-elevation myocardial infarction. After a loading dose of both ticagrelor and aspirin, the patient underwent primary-PCI on the left anterior descending coronary artery with stent implantation. After successful revascularization, medical therapy included beta-blockers, statins, and angiotensin II receptor antagonists. Two days later, ivabradine was also administered in order to reduce heart rate at target, but the patient developed a severe symptomatic bradycardia and sinus arrest, even requiring administration of both atropine and adrenaline. Ivabradine and ticagrelor have been then suspended and this latter changed with prasugrel. Any other similar event was not reported during the following days. This clinical case raised concerns about the safety of the combination of beta-blockers and ivabradine in patients treated with ticagrelor, particularly during the acute phase of an acute coronary syndrome. These two latter drugs, in particular, might interact with the same receptor. In fact, ivabradine directly modulates the If-channel which is also modulated by the cyclic adenosine monophosphate levels. These latter have been shown to increase after ticagrelor assumption via inhibition of adenosine uptake by erythrocytes. Further studies are warrant to better clarify the safety of this association.

Testing the validity of a set of diagnostic criteria for sensory neuronopathies: a francophone collaborative study.

There are no validated criteria for the diagnosis of sensory neuronopathy (SNN) yet. In a preliminary monocenter study a set of criteria relying on clinical and electrophysiological data showed good sensitivity and specificity for a diagnosis of probable SNN. The aim of this study was to test these criteria on a French multicenter study. 210 patients with sensory neuropathies from 15 francophone reference centers for neuromuscular diseases were included in the study with an expert diagnosis of non-SNN, SNN or suspected SNN according to the investigations performed in these centers. Diagnosis was obtained independently from the set of criteria to be tested. The expert diagnosis was taken as the reference against which the proposed SNN criteria were tested. The set relied on clinical and electrophysiological data easily obtainable with routine investigations. 9/61 (16.4 %) of non-SNN patients, 23/36 (63.9 %) of suspected SNN, and 102/113 (90.3 %) of SNN patients according to the expert diagnosis were classified as SNN by the criteria. The SNN criteria tested against the expert diagnosis in the SNN and non-SNN groups had 90.3 % (102/113) sensitivity, 85.2 % (52/61) specificity, 91.9 % (102/111) positive predictive value, and 82.5 % (52/63) negative predictive value. Discordance between the expert diagnosis and the SNN criteria occurred in 20 cases. After analysis of these cases, 11 could be reallocated to a correct diagnosis in accordance with the SNN criteria. The proposed criteria may be useful for the diagnosis of probable SNN in patients with sensory neuropathy. They can be reached with simple clinical and paraclinical investigations.