MST1 mediates doxorubicin-induced cardiomyopathy by SIRT3 downregulation.

Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. However, the mechanisms underlying the development of DOX-induced heart failure need to be addressed. This study aims to test whether the serine/threonine kinase MST1, a major Hippo pathway component, contributes to the development of DOX-induced myocardial injury. C57BL/6J WT mice and mice with cardiomyocyte-specific dominant-negative MST1 (kinase-dead) overexpression received three weekly injections of DOX, reaching a final cumulative dose of 18 mg/kg. Echocardiographic, histological and biochemical analyses were performed six weeks after the first DOX administration. The effects of MST1 inhibition on DOX-induced cardiomyocyte injury were also tested in vitro. MST1 signaling was significantly activated in cardiomyocytes in response to DOX treatment in vitro and in vivo. Wild-type (WT) mice treated with DOX developed cardiac dysfunction and mitochondrial abnormalities. However, these detrimental effects were abolished in mice with cardiomyocyte-specific overexpression of dominant-negative MST1 (DN-MST1) or treated with XMU-MP-1, a specific MST1 inhibitor, indicating that MST1 inhibition attenuates DOX-induced cardiac dysfunction. DOX treatment led to a significant downregulation of cardiac levels of SIRT3, a deacetylase involved in mitochondrial protection, in WT mice, which was rescued by MST1 inhibition. Pharmacological inhibition of SIRT3 blunted the protective effects of MST1 inhibition, indicating that SIRT3 downregulation mediates the cytotoxic effects of MST1 activation in response to DOX treatment. Finally, we found a significant upregulation of MST1 and downregulation of SIRT3 levels in human myocardial tissue of cancer patients treated with DOX. In summary, MST1 contributes to DOX-induced cardiomyopathy through SIRT3 downregulation.

A new echocardiographic index to select patients for PFO suture-mediated percutaneous closure.

OBJECTIVES: To identify a simple echocardiographic predictor of procedural success to select patient for percutaneous suture-mediated patent fossa ovalis (PFO) closure. BACKGROUND: Percutaneous suture-mediated PFO closure has been shown as a safe and advantageous alternative to device-based PFO closure, yet its overall success is slightly lower in unselected patients. METHODS: Preprocedural transesophageal echocardiogram (TEE) of 302 patients (113 men, 45 ± 12 years) who underwent percutaneous suture-mediated PFO closure were reviewed. RESULTS: At echocardiographic follow-up (3-6 months), residual right-to-left shunt (RLS) ≥2 was found in 60 (19.9%) patients. At multivariable analysis, only two anatomical variables measured at preprocedural TEE were found as independent predictors of residual RLS ≥ 2 at follow-up: PFO maximum width (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.16-3.40, p = 0.02) and PFO minimal septa overlapping (OR 0.58, 95% CI 0.35-0.88, p = 0.02). An index based on the ratio of PFO maximum width to PFO minimum septal overlapping (W/SO) proved to be the most powerful predictor of RLS ≥ 2 at follow-up (OR 48.1, 95% CI 9.3-352.2, p < 0.01). The ROC curve for the W/SO ratio was found to have an AUC of 0.84 (95% CI 0.75-0.93) and a cut-off value of 0.61 yielding a sensitivity of 80% and specificity of 78% with a negative predictive value of 94%. A decision tree methodology's AUC was 0.75 (95% CI 0.67-0.83). CONCLUSIONS: The results of this study indicate that the ratio between the maximum amplitude of the PFO and the minimum overlap of the septa is the best predictive index of a favorable result by using one stitch only.

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Instantaneous wave-free ratio-guided revascularization of nonculprit lesions in STEMI patients with multivessel coronary disease: The WAVE registry.

BACKGROUND: Complete revascularization (CR) of nonculprit lesions (NCL) is strongly recommended in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), but no definitive evidence is available regarding which diagnostic strategy should be preferred. Instantaneous wave-free ratio (iFR) has never been investigated in this setting. We aimed to describe clinical outcomes of a cohort of patients undergoing iFR-guided CR. METHODS: Following primary percutaneous coronary intervention (PCI), consecutive patients with STEMI and intermediate NCL were enrolled and destinated to an iFR-guided CR. NCL with iFR ≤ 0.89 underwent PCI while NCL with iFR > 0.89 were deferred. The primary endpoint was NC target lesion failure (NC-TLF) and the secondary endpoint was major adverse cardiovascular events (MACE), at 1-year follow-up. RESULTS: Overall, 209 patients were enrolled (ischemic iFR = 83; nonischemic iFR = 126). Patients with ischemic iFR showed a higher prevalence of traditional cardiovascular risk factors and angiographically determined three-vessel disease. In the entire cohort, NC-TLF and MACE occurred in 6.7% and 10.5% of patients, respectively. Compared to the deferred group, patients with ischemic iFR experienced significantly higher rates of both NC-TLF (3.2% vs. 12.1%; p = 0.021) and MACE (7.1% vs. 16.9%; p = 0.041). These results were mostly driven by increased rates of NC-TLF PCI and further revascularizations in this latter group, while no differences were evident in terms of nonfatal myocardial infarction or death. At multivariable analysis, the strongest predictor of MACE was symptom onset to balloon time (HR = 1.17 [95% CI: 1.04-1.31], p = 0.008). CONCLUSIONS: In our study enrolling STEMI patients with MVD, iFR assessment was feasible and safe. PCI-deferring according to iFR evaluation of NCL was associated with low rates of adverse events. Further randomized studies are needed to investigate the effectiveness of iFR-guided revascularization compared to current practice in this setting.

Predictors of patent and occlusive hemostasis after transradial coronary procedures.

OBJECTIVES: To assess the independent predictors of patent and occlusive hemostasis (PH and OH, respectively) during radial hemostasis after coronary procedures. BACKGROUND: Radial artery occlusion (RAO) is a thrombotic complication of transradial catheterization that can lead to permanent occlusion of the radial artery. Sheath-vessel diameter ratio, postprocedure compression time, occlusive hemostasis, inadequate, and excessive anticoagulation are all predictors of RAO. METHODS: As a part of a previously published study investigating the relationship between residual anticoagulation and risk of RAO, 837 patients undergoing transradial diagnostic coronary angiography or percutaneous coronary interventions were enrolled. Cumulative heparin dose used during the procedure and ACT measured before sheath removal were recorded. PH with reverse Barbeau test was attempted in all patients (NCT02762344). RESULTS: PH was less frequently obtained for increasing cumulative heparin dose and ACT values (p < .0001 and p = .0034, respectively). At logistic regression analysis both cumulative heparin dose and ACT values were independent predictors of OH (OR 1.017, 95% IC 1.011-1.023 p < .0001 and OR 1.004, 95% IC 1.001-1.006, p = .0004) while adjusted probability for RAO showed exponential relationship with both parameters. CONCLUSIONS: The level of anticoagulation is strongly related to the incidence of RAO, and should be taken into account when choosing hemostasis protocol.

Trehalose, a natural disaccharide, reduces stroke occurrence in the stroke-prone spontaneously hypertensive rat.

Cerebrovascular disease, a frequent complication of hypertension, is a major public health issue for which novel therapeutic and preventive approaches are needed. Autophagy activation is emerging as a potential therapeutic and preventive strategy toward stroke. Among usual activators of autophagy, the natural disaccharide trehalose (TRE) has been reported to be beneficial in preclinical models of neurodegenerative diseases, atherosclerosis and myocardial infarction. In this study, we tested for the first time the effects of TRE in the stroke-prone spontaneously hypertensive rat (SHRSP) fed with a high-salt stroke permissive diet (JD). We found that TRE reduced stroke occurrence and renal damage in high salt-fed SHRSP. TRE was also able to decrease systolic blood pressure. Through ex-vivo studies, we assessed the beneficial effect of TRE on the vascular function of high salt-fed SHRSP. At the molecular level, TRE restored brain autophagy and reduced mitochondrial mass, along with the improvement of mitochondrial function. The beneficial effects of TRE were associated with increased nuclear translocation of TFEB, a transcriptional activator of autophagy. Our results suggest that TRE may be considered as a natural compound efficacious for the prevention of hypertension-related target organ damage, with particular regard to stroke and renal damage.

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction.

BACKGROUND AND AIMS: Low serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients. METHODS AND RESULTS: Multicenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4-41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71-12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37-0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS -0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30-9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99-14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02-18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21-10.80, p = 0.022) were associated with AEs. CONCLUSION: Low SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.

Renal arteries denervation: from the treatment of resistant hypertension to the treatment of atrial fibrillation.

Renal denervation (RDN) is a therapeutic strategy for patients with uncontrolled arterial hypertension characterized by considerable fluctuations during its progression. After initial strong enthusiasm, the procedure came to an abrupt halt following the publication of the Symplicity HTN-3 study results. The results of recently published studies highlight the reduction in blood pressure values after RDN and justify the inclusion in the Guidelines of new recommendations for the use of RDN in clinical practice, in selected patients. Additionally, RDN findings are summarized in view of other potential indications such as atrial fibrillation. Six prospective, randomized studies are presented that evaluated RDN as an adjunct therapy to pulmonary vein isolation for the treatment of atrial fibrillation. In five studies, patients had uncontrolled hypertension despite therapy with three antihypertensive drugs. The analysis of these studies showed that RDN reduced the recurrence of atrial fibrillation (AF) by 57% compared to patients with pulmonary vein isolation (PVI) only. Modulation of the autonomic nervous system by RDN has been shown not only to reduce blood pressure but also to have an antiarrhythmic effect in symptomatic AF patients when the strategy is combined with PVI, thus opening up new therapeutic scenarios.

Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study.

AIMS: The CLIMA study, on the relationship between coronary plaque morphology of the left anterior descending artery and twelve months clinical outcome, was designed to explore the predictive value of multiple high-risk plaque features in the same coronary lesion [minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension, and presence of optical coherence tomography (OCT)-defined macrophages] as detected by OCT. Composite of cardiac death and target segment myocardial infarction was the primary clinical endpoint. METHODS AND RESULTS: From January 2013 to December 2016, 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending coronary artery in the context of clinically indicated coronary angiogram were prospectively enrolled at 11 independent centres (clinicaltrial.gov identifier NCT02883088). At 1-year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA <3.5 mm2 [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.1-4.0], FCT <75 µm (HR 4.7, 95% CI 2.4-9.0), lipid arc circumferential extension >180° (HR 2.4, 95% CI 1.2-4.8), and OCT-defined macrophages (HR 2.7, 95% CI 1.2-6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1-18.6). CONCLUSION: The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events.

Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism.

AIMS: Here, we aimed to determine the therapeutic effect of longevity-associated variant (LAV)-BPIFB4 gene therapy on atherosclerosis. METHODS AND RESULTS: ApoE knockout mice (ApoE-/-) fed a high-fat diet were randomly allocated to receive LAV-BPIFB4, wild-type (WT)-BPIFB4, or empty vector via adeno-associated viral vector injection. The primary endpoints of the study were to assess (i) vascular reactivity and (ii) atherosclerotic disease severity, by Echo-Doppler imaging, histology and ultrastructural analysis. Moreover, we assessed the capacity of the LAV-BPIFB4 protein to shift monocyte-derived macrophages of atherosclerotic mice and patients towards an anti-inflammatory phenotype. LAV-BPIFB4 gene therapy rescued endothelial function of mesenteric and femoral arteries from ApoE-/- mice; this effect was blunted by AMD3100, a CXC chemokine receptor type 4 (CXCR4) inhibitor. LAV-BPIFB4-treated mice showed a CXCR4-mediated shift in the balance between Ly6Chigh/Ly6Clow monocytes and M2/M1 macrophages, along with decreased T cell proliferation and elevated circulating levels of interleukins IL-23 and IL-27. In vitro conditioning with LAV-BPIFB4 protein of macrophages from atherosclerotic patients resulted in a CXCR4-dependent M2 polarization phenotype. Furthermore, LAV-BPIFB4 treatment of arteries explanted from atherosclerotic patients increased the release of atheroprotective IL-33, while inhibiting the release of pro-inflammatory IL-1ß, inducing endothelial nitric oxide synthase phosphorylation and restoring endothelial function. Finally, significantly lower plasma BPIFB4 was detected in patients with pathological carotid stenosis (>25%) and intima media thickness >2 mm. CONCLUSION: Transfer of the LAV of BPIFB4 reduces the atherogenic process and skews macrophages towards an M2-resolving phenotype through modulation of CXCR4, thus opening up novel therapeutic possibilities in cardiovascular disease.

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

Correction to: Atherothrombosis Prevention and Treatment with Anti-interleukin-1 Agents.

The original version of this article unfortunately contained typo in the 2nd author's family name. Instead of "Garmenda", it should be "Garmendia". The original version has been corrected.

Atherothrombosis Prevention and Treatment with Anti-interleukin-1 Agents.

PURPOSE OF REVIEW: Despite major advances in terms of prevention, diagnosis, risk-stratification, management and rehabilitation, atherosclerosis and atherothrombosis continue to have major morbidity and mortality implications worldwide. Since the unraveling of the pivotal role of inflammation in atherothrombosis pathophysiology, several focused treatments have been proposed with the ultimate goal of preventing or treating myocardial infarction, stroke, and peripheral artery disease. In particular, given the centrality of interleukin-1 (IL-1), targeted anti-IL-1 agents have attracted substantial attention and efforts. Yet, uncertainty persists on the real risk-benefit and cost-benefit balance of anti-IL-1 agents in patients with or at risk of atherothrombosis. RECENT FINDINGS: Several trials have been recently completed on atherothrombosis prevention and treatment with anti-IL-1 agents, ranging, for instance, from the large Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial to the series of translational studies conducted within the Virginia Commonwealth University-Anakinra Remodeling Trial (VCU-ART) platform. In light of the present scoping umbrella review, it appears evident that anti-IL-1 agents can reduce systemic inflammation and improve surrogate markers of cardiac and vascular function, with potential benefits on the risk of new/worsening heart failure. One trial suggested an increased risk of major adverse events with anti-interleukin-1 agents, possibly due to a rebound phenomenon, but this was based on a post-hoc analysis of a small number of events, and it was not supported by all other pertinent trials. The CANTOS study showed a potential hazard due to an increased risk of fatal infections, but the effect size was rather small. In addition, cost issues limit the foreseeable scope of these treatment strategies in unselected patients, calling instead for more refined prescribing. The evidence base on the risk-benefit and cost-benefit profile of anti-IL-1 agents for atherothrombosis prevention and treatment has expanded substantially in the last decade. While largely dominated by the landmark CANTOS trial, effect estimates also including the VCU-ART trials suggest complex short- and long-term effects which may prove favorable in carefully selected patients with acute or chronically sustained inflammation. Conversely, more liberal use appears less promising, and further studies with currently available agents or novel ones are eagerly needed to better define their role in the era of precision molecular medicine.

Profiling the Acute Effects of Modified Risk Products: Evidence from the SUR-VAPES (Sapienza University of Rome-Vascular Assessment of Proatherosclerotic Effects of Smoking) Cluster Study.

PURPOSE OF REVIEW: Modified risk products (MRP) are promoted as a safer alternative to traditional combustion cigarettes (TCC) in chronic smokers. Evidence for their lower hazardous profile is building, despite several controversies. Yet, it is unclear whether individual responses to MRP differ among consumers. We hypothesized that different clusters of subjects exist in terms of acute effects of MRP. RECENT FINDINGS: Pooling data from a total of 60 individuals, cluster analysis identified at least three clusters (labelled 1 to 3) of subjects with different electronic vaping cigarettes (EVC) effects and at least two clusters (labelled 4 to 5) of subjects with different heat-not-burn cigarettes (HNBC) effects. Specifically, oxidative stress, platelet aggregation, and endothelial dysfunction after EVC were significantly different cluster-wise (all p < 0.05), and oxidative stress and platelet aggregation after HNBC were significantly different (all p < 0.05). In particular, subjects belonging to Cluster 1 appeared to have less detrimental responses to EVC usage than subjects in Cluster 2 and 3, as shown by non-significant changes in flow-mediated dilation (FMD) and less marked increase in Nox2-derived peptide (NOX). Conversely, those assigned to Cluster 3 had the worst reaction in terms of changes in FMD, NOX, and P-selectin. Furthermore, individuals belonging to Cluster 4 responded unfavorably to both HNBC and EVC, whereas those in Cluster 5 interestingly showed less adverse results after using HNBC than EVC. Results for main analyses were consistent employing different clusters, tests, and bootstrap. Individual responses to MRP differ and smokers aiming at using EVC or HNBC as a risk reduction strategy should consider trying different MRP aiming at finding the one which is less detrimental, with subjects resembling those in Cluster 1 preferably using EVC and those resembling Cluster 5 preferably using HNBC.

A Stepwise Approach to Systematic Reviews and Meta-analyses of Endovascular Interventions.

The accrual of clinical studies poses important challenges to researchers and practitioners, especially in the field of endovascular therapy, where patient, lesion, technique, and device subtleties abound. Systematic reviews and meta-analyses may prove particularly fruitful in such settings by increasing statistical precision and bolstering external validity if the evidence base on a specific topic is consistent or by highlighting important discrepancies in the opposite scenario. However, mastering the correct approach to systematic review and meta-analysis is challenging for careful readers or for those interested in conducting such an evidence synthesis exercise. The present article highlights a stepwise approach to systematic reviews and meta-analyses, focusing on endovascular interventions, which will prove useful to anyone reading or wishing to synthesize the evidence base on endovascular topics to optimize decision making or shape future research efforts.

Umbrella review and multivariate meta-analysis of diagnostic test accuracy studies on hybrid non-invasive imaging for coronary artery disease.

BACKGROUND: The diagnosis of coronary artery disease (CAD) remains challenging. It is uncertain whether hybrid imaging can improve diagnostic accuracy for CAD. METHODS: This is a systematic review and multivariate meta-analysis. We searched PubMed and The Cochrane Library for recent (≥ 2010) systematic reviews of diagnostic test accuracy studies on non-invasive imaging for CAD. Study-level data were extracted from them, and pooled with pairwise and multivariate meta-analytic methods, using invasive coronary angiography (ICA) or invasive fractional flow reserve (FFR) as reference standards, focusing on sensitivity and specificity. RESULTS: Details from 661 original studies (71,823 patients) were pooled. Pairwise meta-analysis using ICA as reference showed that anatomic imaging was associated with the best diagnostic accuracy (sensitivity = 0.95 [95% confidence interval 0.94-0.96], specificity = 0.83 [0.81-0.85]), whereas using FFR as reference identified hybrid imaging as the best test (sensitivity = 0.87 [0.83-0.90], specificity = 0.82 [0.76-0.87]). Multivariate meta-analysis confirmed the superiority of anatomic imaging using ICA as reference (sensitivity = 0.96, specificity = 0.83), and hybrid imaging using FFR as reference (sensitivity = 0.88 [0.86-0.91], specificity = 0.82 [0.77-0.87]). CONCLUSIONS: Non-invasive hybrid imaging tests appear superior to anatomic or functional only tests to diagnose ischemia-provoking coronary lesions, whereas anatomic imaging is best to diagnose and/or rule out angiographically significant CAD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registry Number CRD42018088528.

Renal arteries denervation with second generation systems: a remedy for resistant hypertension?

Initial studies on renal denervation (RDN) for the treatment of non-controlled arterial hypertension (HTN) through radiofrequency ablation of renal arteries demonstrated that RDN is an effective therapeutic strategy to reduce arterial blood pressure (BP). Nonetheless, the first randomized study, SYMPLICITY-HTN-3, failed to demonstrate a clear benefit for RND over the control group. Technologic evolution, with the introduction of new second generation multi-electrode devices, allowed deep energy delivery along the full circumference of the vessel. Two recent randomized studies involving patients assuming (SPYRAL HTN-ON MED) or not (SPYRAL HTN-OFF MED) antihypertensive pharmacologic treatment, demonstrated the efficacy and safety of RDN using second generation systems for radiofrequency ablation. Another recent randomized study demonstrated that RDN with ultrasounds (RADIANCE-HTN SOLO) of the main renal arteries led to a significant BP reduction compared to the control group. These studies have once again raised the interest of the scientific community towards attempting to define the appropriate role of RDN in the treatment of hypertension. Nonetheless, larger and longer clinical trials will be necessary to draw further conclusions.

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

Aims: 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 and results: Aggregate and anonymized data from 15 tertiary cardiac care centers were obtained detailing pre-coronarivus 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). 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 analysis 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). Conclusion: Temporary traffic bans 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.

Neoangiogenesis connecting a left internal mammary artery proximal stump to an ischemic area of the heart after bypass occlusion.

Internal mammary arteries (IMAs), via angiogenesis/arteriogenesis, have great potential for developing collaterals. This generally occurs when ischemia involves the inferior limbs or heart. Although this phenomenon may be spontaneous, it seems to be promoted by iatrogenic or voluntary occlusion of the IMAs. We present a patient who underwent triple coronary artery bypass grafting with two saphenous vein grafts and a free-graft left IMA and suffered an acute myocardial infarction 6 weeks after surgery. Emergency coronary angiography revealed occlusion of the grafts and an amazing branch arising from the proximal stump of the surgically-cut and clipped IMA, leading to the anterior wall of the heart, functionally creating an effective natural bypass, probably stimulated both by anterior wall ischemia and interrupted flow within the proximal left IMA.