Safety and efficacy of drug-eluting stents for patients at high risk of bleedings: A network meta-analysis.

INTRODUCTION: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided. METHODS: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones. RESULTS: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best. CONCLUSION: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis.

Mechanical Cardiopulmonary Resuscitation Devices: Evidence Synthesis with an Umbrella Review.

AIM: Sudden cardiac arrest is a significant cause of death worldwide. Good quality cardiopulmonary resuscitation increases patients' survival. Manual cardiopulmonary resuscitation is often ineffective as rescuers may experience physical and mental fatigue. Mechanical cardiopulmonary resuscitation devices are designed to address this issue, providing an automated approach for high-quality resuscitation. In the present comprehensive umbrella review we summarize current evidence on mechanical devices. METHODS: We searched systematic reviews on mechanical devices in MEDLINE/PubMed. Effect estimates were obtained from original reports, including 95% confidence intervals and p values, when applicable and available, focusing on return of spontaneous circulation, survival to discharge or 30 days, survival with good neurological outcome, and resuscitation-related injuries. RESULTS: From 21 potentially pertinent publications, we shortlisted 10 reviews, each including between 5 and 22 studies. AutoPulse, LUCAS, and LUCAS-2 were among the investigated devices. Most reviews concluded toward mechanical devices being similar or better than manual resuscitation for return of spontaneous circulation and 30-days survival. Regarding survival with good neurological function, some reviews lacked data, while the remaining ones reported similar results or worse outcomes in patients undergoing mechanical resuscitation. Focusing on resuscitation-related injuries, data were limited or conflicting with one review reporting higher rates of injuries with mechanical devices, and two others suggesting similar outcomes. CONCLUSIONS: Manual and mechanical cardiopulmonary resuscitation appear to be similar in terms of return of spontaneous circulation and short-term survival. Mechanical devices appear to be associated with higher resuscitation-related injuries, while there are conflicting data in terms of survival with good neurological outcomes. A comprehensive and large dedicated randomized trial is urgently needed.

Kidney Injury After Minimal Radiographic Contrast Administration in Patients With Acute Coronary Syndromes.

BACKGROUND: Acute kidney injury (AKI) is common in patients with acute coronary syndromes (ACS) treated by percutaneous coronary intervention. OBJECTIVES: Contrast media (CM) volume minimization has been advocated for prevention of AKI. The DyeVert CM diversion system (Osprey Medical, Inc) is designed to reduce CM volume during coronary procedures. METHODS: In this randomized, single-blind, investigator-driven clinical trial conducted in 4 Italian centers from February 4, 2020 to September 13, 2022, 550 participants with ACS were randomly assigned in a 1:1 ratio to the following: 1) the contrast volume reduction (CVR) group (n = 276), in which CM injection was handled by the CM diversion system; and 2) the control group (n = 274), in which a conventional manual or automatic injection syringe was used. The primary endpoint was the rate of AKI, defined as a serum creatinine (sCr) increase ≥0.3 mg/dL within 48 hours after CM exposure. RESULTS: There were 412 of 550 (74.5%) participants with ST-segment elevation myocardial infarction (211 of 276 [76.4%] in the CVR group and 201 of 274 [73.3%] in the control group). The CM volume was lower in the CVR group (95 ± 30 mL vs 160 ± 23 mL; P < 0.001). Seven participants (1 in the CVR group and 6 in the control group) did not have postprocedural sCr values. AKI occurred in 44 of 275 (16%) participants in the CVR group and in 65 of 268 (24.3%) participants in the control group (relative risk: 0.66; 95% CI: 0.47-0.93; P = 0.018). CONCLUSIONS: CM volume reduction obtained using the CM diversion system is effective for prevention of AKI in patients with ACS undergoing invasive procedures. (REnal Insufficiency Following Contrast MEDIA Administration TriaL IV [REMEDIALIV]: NCT04714736).

Comparison of ultrasound- versus fluoroscopy-guidEd femorAl access In tranS-catheter aortic valve replacement In the Era of contempoRary devices: The EASIER registry.

BACKGROUND: Vascular complications (VCs) still represent one of the principal concerns of trans-femoral trans-catheter aortic valve replacement (TF-TAVR). New-generation devices can minimize such complications but the arterial access management is left to the operator's choice. This study aims to describe the rate of VCs in a contemporary cohort of patients undergoing TAVR with new-generation devices and to determine whether an ultrasound-guided (USG) vs. a fluoroscopy-guided (FG) femoral access management has an impact on their prevention. METHODS: This is a prospective, observational, multicenter study. Consecutive patients undergoing TAVR with new-generation devices were analyzed from January 2022 to October 2022 in five tertiary care centers. Femoral accesses were managed according to the operator's preferences. All the patients underwent a pre-discharge peripheral ultrasound control. VCs and bleedings were the main endpoints of interest. RESULTS: A total of 458 consecutive patients were enrolled (274 in the USG group and 184 in the FG group). VCs occurred in 6.5 % of the patients (5.2 % minor and 1.3 % major). There was no difference between the USG and the FG groups in terms of any VCs (7.3 % vs. 5.4 %; p = 0.4), or any VARC-3 bleedings (6.9 % vs 6 %, p = 0.9). At logistic regression analysis, the two guidance strategies did not result as predictors of VCs (odds Ratio 0.8, 95 % Confidence Interval 0.46-1.4; P = 0.4). CONCLUSIONS: In a contemporary cohort of patients undergoing TAVR with new-generation devices, the occurrence of VCs is low and mostly represented by minor VCs. USG and FG modalities did not affect the rate of VCs.

Comparative effectiveness of Cangrelor in patients with acute coronary syndrome undergoing percutaneous coronary intervention: an observational investigation from the M.O.Ca. registry.

Cangrelor, the first intravenous P2Y12 inhibitor (P2Y12-I), has been approved on the basis of three large RCTs from the CHAMPION program which nevertheless have been criticized for the low bleeding risk of the enrolled patients, the large quote of chronic coronary syndromes, and the use of Clopidogrel as control arm even in the setting of acute coronary syndromes (ACS). We sought to investigate, in the setting of ACS, the comparative performance of Cangrelor in terms of in-hospital ischemic and haemorrhagic outcomes compared with the current gold-standard of oral P2Y12-I. The study retrospectively enrolled 686 consecutive patients admitted to the Divisions of Cardiology of Policlinico of Bari and L. Bonomo Hospital of Andria for ACS and treated with percutaneous coronary intervention. The study population was divided according to the P2Y12-I treatment strategy in two groups: patients given an oral P2Y12-I and patients receiving Cangrelor in the cath lab followed by an oral P2Y12-I. Clinical endpoints included death, ischemic and bleeding events occurring during hospital stay. Cangrelor treated patients presented higher clinical risk profile at presentation and faced higher death rate. However, after PS matching, in-hospital mortality resulted comparable between the groups and Cangrelor use was associated with reduced in-hospital definite stent thrombosis (p = 0.03). Data from our real-world registry highlight that, in the setting of ACS, Cangrelor is prevalently used in patients with very challenging clinical presentations. The adjusted analysis provides for the first time promising data on stent thrombosis reduction associated with Cangrelor use.

Revascularization strategies versus optimal medical therapy in chronic coronary syndrome: A network meta-analysis.

BACKGROUND: The impact of myocardial revascularization on outcomes and prognosis in patients with chronic coronary syndrome (CCS) without left main (LM) disease or reduced left ventricle ejection fraction (LVEF) may be influenced by the revascularization strategy adopted. METHODS: We performed a network meta-analysis including 18 randomized controlled trials comparing different revascularization strategies, including angiography-guided percutaneous coronary intervention (PCI), physiology-guided PCI and coronary artery bypass graft (CABG), in patients with CCS without LM disease or reduced LVEF. RESULTS: Compared with medical therapy, all revascularization strategies were associated with a reduction of the primary endpoint, as defined in each trial, the extent of which was modest with angiography-guided PCI (IRR 0.86, 95% CI 0.75-0.99) and greater with physiology-guided PCI (IRR 0.60, 95% CI 0.47-0.77) and CABG (IRR 0.58, 95% CI 0.48-0.70). Moreover, angiography-guided PCI was associated with an increase of the primary endpoint compared to physiology-guided PCI (IRR 1.43, 95% CI 1.14-1.79) and CABG (IRR 1.49, 95% CI 1.27-1.74). CABG was the only strategy associated with reduced myocardial infarction (IRR 0.68, 95% CI 0.52-0.90), cardiovascular death (IRR 0.76, 95% CI 0.64-0.89), and all-cause death (IRR 0.87, 95% CI 0.77-0.99), but increased stroke (IRR 1.69, 95% CI 1.04-2.76). CONCLUSIONS: In CCS patients without LM disease or reduced LVEF, physiology-guided PCI and CABG are associated with better outcomes than angiography-guided PCI. Compared with medical therapy, CABG is the only revascularization strategy associated with a reduction of myocardial infarction and death rates, at the cost of higher risk of stroke. STUDY REGISTRATION: This study is registered in PROSPERO (CRD42022313612).

Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial.

BACKGROUND: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI. METHODS: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis. DISCUSSION: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018.

Prosthesis-patient mismatch following transcatheter aortic valve replacement for degenerated transcatheter aortic valves: the TRANSIT-PPM international project.

Background: A severe prosthesis-patient mismatch (PPM) is associated with adverse outcomes following transcatheter aortic valve replacement (TAVR) for de novo aortic stenosis or a failed surgical bioprosthesis. The impact of severe PPM in patients undergoing TAV-in-TAVR is unknown. Aim: We sought to investigate the incidence and 1-year outcomes of different grades of PPM in patients undergoing TAV-in-TAVR. Materials and methods: The TRANSIT-PPM is an international registry, including cases of degenerated TAVR treated with a second TAVR. PPM severity, as well as in-hospital, 30-day, and 1-year outcomes were defined according to the Valve Academic Research Consortium-3 (VARC-3) criteria. Results: Among 28 centers, 155 patients were included. Severe PPM was found in 6.5% of patients, whereas moderate PPM was found in 14.2% of patients. The rate of severe PPM was higher in patients who underwent TAV-in-TAVR with a second supra-annular self-expanding (S-SE) TAVR (10%, p = 0.04). Specifically, the rate of severe PPM was significantly higher among cases of a SE TAVR implanted into a balloon-expandable (BE) device (19%, p = 0.003). At 1-year follow-up, the rate of all-cause mortality, and the rate of patients in the New York Heart Association (NYHA) class III/IV were significantly higher in the cohort of patients with severe PPM (p = 0.016 and p = 0.0001, respectively). Almost all the patients with a severe PPM after the first TAVR had a failed < 23 mm BE transcatheter heart valve (THV): the treatment with an S-SE resolved the severe PPM in the majority of the cases. Conclusion: After TAV-in-TAVR, in a fifth of the cases, a moderate or severe PPM occurred. A severe PPM is associated with an increased 1-year all-cause mortality. Clinical trial registration: [https://clinicaltrials.gov], identifier [NCT04500964].

Impact of pre-existing vascular disease on clinical outcomes.

AIMS: Little is known about the outcomes and processes of care of patients with non-ST-segment myocardial infarction (NSTEMI) who present with 'polyvascular' disease. METHODS AND RESULTS: We analysed 287 279 NSTEMI patients using the Myocardial Ischaemia National Audit Project registry. Clinical characteristics and outcomes were analysed according to history of affected vascular bed-coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral vascular disease (PVD)-with comparison to a historically disease-free control group, comprising 167 947 patients (59%). After adjusting for demographics and management, polyvascular disease was associated with increased likelihood of major adverse cardiovascular events (MACEs) [CAD odds ratio (OR): 1.06; 95% confidence interval (CI): 1.01-1.12; P = 0.02] (CeVD OR: 1.19; 95% CI: 1.12-1.27; P < 0.001) (PVD OR: 1.22; 95% CI: 1.13-1.33; P < 0.001) and in-hospital mortality (CeVD OR: 1.24; 95% CI: 1.16-1.32; P < 0.001) (PVD OR: 1.33; 95% CI: 1.21-1.46; P < 0.001). Patients without vascular disease were less frequently discharged on statins (PVD 88%, CeVD 86%, CAD 90%, and control 78%), and those with moderate [ejection fraction (EF) 30-49%] or severe left ventricular systolic dysfunction (EF < 30%) were less frequently discharged on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) (CAD 82%, CeVD 77%, PVD 77%, and control 74%). Patients with polyvascular disease were less likely to be discharged on dual antiplatelet therapy (DAPT) (PVD 78%, CeVD 77%, CAD 80%, and control 87%). CONCLUSION: Polyvascular disease patients had a higher incidence of in-hospital mortality and MACEs. Patients with no history of vascular disease were less likely to receive statins or ACE inhibitors/ARBs, but more likely to receive DAPT.

Efficacy of new medical therapies in patients with heart failure, reduced ejection fraction, and chronic kidney disease already receiving neurohormonal inhibitors: a network meta-analysis.

AIMS: We assessed the efficacy of the drugs developed after neurohormonal inhibition (NEUi) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD). METHODS AND RESULTS: The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction <45%, of whom <30% were acutely decompensated, and with published information about the subgroup of estimated glomerular filtration rate <60 mL/min/1.73 m2. Six RCTs were included in a study-level network meta-analysis evaluating the effect of NEUi, ivabradine, angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil (OM) on a composite outcome of cardiovascular death or hospitalization for HF. In a fixed-effects model, SGLT2i [hazard ratio (HR) 0.78, 95% credible interval (CrI) 0.69-0.89], ARNI (HR 0.79, 95% CrI 0.69-0.90), and ivabradine (HR 0.82, 95% CrI 0.69-0.98) decreased the risk of the composite outcome vs. NEUi, whereas OM did not (HR 0.98, 95% CrI 0.89-1.10). A trend for improved outcome was also found for vericiguat (HR 0.90, 95% CrI 0.80-1.00). In indirect comparisons, both SLGT2i (HR 0.80, 95% CrI 0.68-0.94) and ARNI (HR 0.80, 95% CrI 0.68-0.95) reduced the risk vs. OM; furthermore, there was a trend for a greater benefit of SGLT2i vs. vericiguat (HR 0.88, 95% CrI 0.73-1.00) and ivabradine vs. OM (HR 0.84, 95% CrI 0.68-1.00). Results were comparable in a random-effects model and in sensitivity analyses. Surface under the cumulative ranking area scores were 81.8%, 80.8%, 68.9%, 44.2%, 16.6%, and 7.8% for SGLT2i, ARNI, ivabradine, vericiguat, OM, and NEUi, respectively. CONCLUSION: Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD.

Predictors, Treatments, and Outcomes of Do-Not-Resuscitate Status in Acute Myocardial Infarction Patients (from a Nationwide Inpatient Cohort Study).

Little is known about how frequently do-not-resuscitate (DNR) orders are placed in patients with acute myocardial infarction (AMI), the types of patients in which they are placed, treatment strategies or clinical outcomes of such patients. Using the United States (US) National Inpatient Sample (NIS) database from 2015 to 2018, we identified 2,767,549 admissions that were admitted to US hospitals and during the hospitalization received a principle diagnosis of AMI, of which 339,270 (12.3%) patients had a DNR order (instigated both preadmission and during in-hospital stay). Patients with a DNR status were older (median age 83 vs 65, p < 0.001), more likely to be female (53.4% vs 39.3%, p < 0.001) and White (81.0% vs 73.3%, p < 0.001). Predictors of DNR status included comorbidities such as heart failure (OR: 1.47, 95% CI: 1.45 to 1.48), dementia (OR: 2.53, 95% CI: 2.50 to 2.55), and cancer. Patients with a DNR order were less likely to undergo invasive management or be discharged home (13.5% vs 52.8%), with only 1/3 receiving palliative consultation. In hospital mortality (32.7% vs 4.6%, p < 0.001) and MACCE (37.1% vs 8.8%, p < 0.001) were higher in the DNR group. Factors independently associated with in-hospital mortality among patients with a DNR order included a STEMI presentation (OR: 2.90, 95% CI: 2.84 to 2.96) and being of Black (OR: 1.29, 95% CI: 1.26 to 1.33), Hispanic (OR: 1.36, 95% CI: 1.32 to 1.41) or Asian/Pacific Islander (OR: 1.56, 95% CI:1.49-race. In conclusion, AMI patients with a DNR status were older, multimorbid, less likely to receive invasive management, with only one third of patients with DNR status referred for palliative care.

Transcatheter Aortic Valve Replacement for Degenerated Transcatheter Aortic Valves: The TRANSIT International Project

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has determined a paradigm shift in the treatment of patients with severe aortic stenosis. However, the durability of bio prostheses is still a matter of concern, and little is known about the management of degenerated TAV. We sought to evaluate the outcomes of patients with a degenerated TAV treated by means of a second TAVR. METHODS: The TRANSIT is an international registry that included cases of degenerated TAVR from 28 centers. Among around 40 000 patients treated with TAVR in the participating centers, 172 underwent a second TAVR: 57 (33%) for a mainly stenotic degenerated TAV, 97 (56%) for a mainly regurgitant TAV, and 18 (11%) for a combined degeneration. Overall, the rate of New York Heart Association class III/IV at presentation was 73.5%. RESULTS: Valve Academic Research Consortium 2 device success rate was 79%, as a consequence of residual gradient (14%) or regurgitation (7%). At 1 month, the overall mortality rate was 2.9%, while rates of new hospitalization and New York Heart Association class III/IV were 3.6% and 7%, respectively, without significant difference across the groups. At 1 year, the overall mortality rate was 10%, while rates of new hospitalization and New York Heart Association class III/IV were 7.6% and 5.8%, respectively, without significant difference across the groups. No cases of valve thrombosis were recorded. CONCLUSIONS: Selected patients with a degenerated TAV may be safely and successfully treated by means of a second TAVR. This finding is of crucial importance for the adoption of the TAVR technology in a lower risk and younger population.

Efficacy and safety of novel oral anticoagulants versus low molecular weight heparin in cancer patients with venous thromboembolism: A systematic review and meta-analysis.

Novel Oral Anticoagulants (NOACs) have been considered for treating cancer-related venous thromboembolism (VTE), but safety issues have been raised. We performed a systematic review and pairwise meta-analysis of the efficacy and safety of NOACs versus low molecular weight heparin (LMWH) in this setting. Four randomized controlled trials were included, providing data on 2894 patients. Compared to LMWH, NOACs were associated with a significantly lower risk of VTE recurrence and were not associated with an increased risk of major bleedings (MB). NOACs were non inferior to LMWH for a composite outcome of VTE recurrence and MB, pulmonary embolism recurrence and all-cause mortality; however, NOACs were associated with an increased risk of clinically relevant nonmajor bleedings (CRNMB) and gastrointestinal MB. In conclusion, in patients with cancer-related VTE, NOACs are effective and safe in reducing VTE recurrence compared to LMWH. An increased risk of CNRMB and GI MB should nonetheless be considered.

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.

On the Road to Regeneration: "Tools" and "Routes" Towards Efficient Cardiac Cell Therapy for Ischemic Cardiomyopathy.

PURPOSE OF REVIEW: Cardiac regenerative medicine is a field bridging together biotechnology and surgical science. In this review, we present the explored surgical roads to cell delivery and the known effects of each delivery method on cell therapy efficiency. We also list the more recent clinical trials, exploring the safety and efficacy of delivery routes used for cardiac cell therapy approaches. RECENT FINDINGS: There is no consensus in defining which way is the most suitable for the delivery of the different therapeutic cell types to the damaged heart tissue. In addition, it emerged that the "delivery issue" has not been systematically addressed in each clinical trial and for each and every cell type capable of cardiac repair. Cardiac damage occurring after an ischemic insult triggers a cascade of cellular events, eventually leading to heart failure through fibrosis and maladaptive remodelling. None of the pharmacological or medical interventions approved so far can rescue or reverse this phenomenon, and cardiovascular diseases are still the leading cause of death in the western world. Therefore, for nearly 20 years, regenerative medicine approaches have focused on cell therapy as a promising road to pursue, with numerous preclinical and clinical testing of cell-based therapies being studied and developed. Nonetheless, consistent clinical results are still missing to reach consensus on the most effective strategy for ischemic cardiomyopathy, based on patient selection, diagnosis and stage of the disease, therapeutic cell type, and delivery route.

Cardiovascular Pleiotropic Effects of Natriuretic Peptides.

Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects that contribute to maintain water-salt balance and regulate blood pressure. Besides these systemic properties, ANP displays important pleiotropic effects in the heart and in the vascular system that are independent of blood pressure regulation. These functions occur through autocrine and paracrine mechanisms. Previous works examining the cardiac phenotype of loss-of-function mouse models of ANP signaling showed that both mice with gene deletion of ANP or its receptor natriuretic peptide receptor A (NPR-A) developed cardiac hypertrophy and dysfunction in response to pressure overload and chronic ischemic remodeling. Conversely, ANP administration has been shown to improve cardiac function in response to remodeling and reduces ischemia-reperfusion (I/R) injury. ANP also acts as a pro-angiogenetic, anti-inflammatory, and anti-atherosclerotic factor in the vascular system. Pleiotropic effects regarding brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were also reported. In this review, we discuss the current evidence underlying the pleiotropic effects of NPs, underlying their importance in cardiovascular homeostasis.