Impact of CYP2C19 Gene Variants on Long-Term Treatment with Atorvastatin in Patients with Acute Coronary Syndromes.

The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of CYP2C19 on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the CYP2C19 gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of CYP2C19*2, CYP2C19*4, and CYP2C19*8 alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.

The Impact of Microvascular Resistance Reserve on the Outcome of Patients With STEMI.

BACKGROUND: Microvascular resistance reserve (MRR) can characterize coronary microvascular dysfunction (CMD); however, its prognostic impact in ST-segment elevation myocardial infarction (STEMI) patients remains undefined. OBJECTIVES: This study sought to investigate the prevalence of CMD in STEMI patients and to elucidate the prognostic performance of MRR. METHODS: This prospective cohort study enrolled 210 STEMI patients with multivessel disease who underwent successful revascularization and returned at 3 months for coronary physiology assessments with bolus thermodilution. The prevalence of CMD (MRR <3) and the association between MRR and major adverse cardiovascular and cerebrovascular events (MACCEs) at 12 months were investigated. RESULTS: The median age of patients was 65 years, and 59.5% were men. At the 3-month follow-up, 56 patients (27%) had CMD (MRR <3.0). The number of MACCEs at 12 months was higher in patients with vs without CMD (48.2% vs 11.0%; P < 0.001). MRR was independently associated with 12-month MACCEs (HR: 0.45 per unit increase; 95% CI: 0.31-0.67; P < 0.001) and with stroke, heart failure, and poorer recovery in left ventricular systolic function. The areas under the receiver-operating characteristic curves for predicting MACCEs at 12 months with fractional flow reserve, coronary flow reserve (CFR), the index of microvascular resistance (IMR), and MRR were 0.609, 0.762, 0.781, and 0.743, respectively. The prognostic performance of CFR, IMR, and MRR were all comparable. CONCLUSIONS: The novel parameter MRR is a prognostic marker of MACCEs in STEMI patients with a comparable performance to CFR and IMR. (Impact of TMAO Serum Levels on Hyperemic IMR in STEMI Patients [TAMIR]; NCT05406297).

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. METHODS AND RESULTS: This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CONCLUSIONS: CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

One-year initial efficacy and safety outcomes of the premounted dry-pericardium Vienna self-expandable transcatheter aortic valve system: A first-in-human VIVA feasibility study.

BACKGROUND: The dry-pericardium Vienna transcatheter aortic valve system is repositionable and retrievable, already premounted on the delivery system, eliminating the need for assembly and crimping of the device before valve implantation. METHODS: The VIVA first-in-human feasibility study, a prospective, nonrandomized, single-center trial, evaluated the Vienna aortic valve in 10 patients with severe symptomatic aortic stenosis, who were at intermediate or high surgical risk. This study, registered at ClinicalTrials.gov (NCT04861805), focused on the safety, feasibility, clinical and hemodynamic performance of the Vienna system up to 1-year follow-up. RESULTS: The mean patient age was 79 ± 5 years, 60% male. Valve sizes used: 26 mm (10%), 29 mm (30%), 31 mm (60%). Key hemodynamic improvements were significant: mean aortic valve pressure gradient (mmHg) decreased from 48.7 to 8.1, aortic valve area (cm2) increased from 0.75 to 1.91, and maximum jet velocity through the aortic valve (m/s) decreased from 4.41 to 1.95 (p < 0.0001). No moderate/severe paravalvular leakage was observed, and computed tomography scans revealed no evidence of hypo-attenuated leaflet thickening. The study recorded one life-threatening bleeding event, two cases requiring postprocedural pacemaker implantation, and three ischemic events, with only one causing lasting neurological impairment. Importantly, there were no cases of cardiovascular mortality and only one noncardiovascular death, which was confirmed as unrelated to the device. CONCLUSIONS: The study indicates the Vienna valve as a potential option for severe symptomatic aortic stenosis, designed to streamline the procedure and potentially lower healthcare costs by reducing resource and equipment needs, also procedural errors. Further research is essential to thoroughly evaluate its safety and efficacy.

Coronary artery calcium and the risk of a cardiovascular events and mortality in younger adults: a meta-analysis.

AIMS: ACC/AHA 2019 prevention guidelines recommend utilizing coronary artery calcium (CAC) to stratify cardiovascular risk in selected cases. However, data regarding CAC and risk in younger adults is less robust due to the lower prevalence of CAC and lower incidence of events. The objective of this meta-analysis is to determine the ability of CAC to predict the risk of cardiovascular events and mortality in adults less than 50. METHODS: PubMed and Cochrane CENTRAL databases were electronically searched through May 2022 for studies with a primary prevention cohort under age 55 who underwent CAC scoring. RESULTS: Six observational studies with a total of 45,919 individuals with an average age of 43.1 and mean follow-up of 12.1 years were included. The presence of CAC was associated with an increased risk of adverse events (pooled hazard ratio (HR) = 1.80, 95% confidence interval (CI) 1.26-2.56, P = 0.012, I2 = 65.5). Compared to a CAC of 0, a CAC of 1-100 did carry an increased risk of cardiovascular events (pooled HR = 1.85, 95% CI 1.08-3.16, p = 0.0248, I2 = 50.3), but not mortality (pooled HR = 1.20, 95% CI 0.85-1.69, p = 0.2917), while a CAC > 100 did carry an increased risk of cardiovascular events (pooled HR = 6.57, 95% CI 3.23-13.36, p < 0.0001, I2 = 72.6) and mortality (pooled HR = 2.91, 95% CI 2.23-3.80, p < 0.0001) . CONCLUSIONS: In a meta-analysis of younger adults undergoing CAC scoring, a CAC of 1-100 was associated with a higher likelihood of cardiovascular events, while a CAC>100 was associated with a higher likelihood of cardiovascular events and mortality.

This paper compiles prior studies into a meta-analysis to clarify the ability of coronary artery calcium (CAC) to predict cardiovascular risk and mortality risk in adults < 55 years. A mildly elevated CAC (1-100) in adults < 55 likely has an increased cardiovascular risk but does not appear to have an increased mortality risk.A moderately or highly elevated CAC (>100) in adults < 55 has a substantial increase in cardiovascular risk and mortality risk.

The impact of primary percutaneous coronary intervention strategies during ST-elevation myocardial infarction on the prevalence of coronary microvascular dysfunction.

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. This is a non-randomized, observational, prospective study of STEMI patients with multivessel disease who underwent primary PCI, grouped based on whether they underwent balloon pre-dilatation stenting or direct stenting of the culprit lesion. Coronary physiology measurements were performed 3 months post-PCI including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements at the culprit vessel. The primary endpoint was the prevalence of CMD at 3 months, defined as IMR ≥ 25 or CFR < 2.0 with a normal fractional flow reserve. Secondary endpoints included major adverse cardiovascular events (MACE) at 12 months. Two hundred ten patients were enrolled; most were men, 125 (59.5%), with a median age of 65 years. One hundred twelve (53.2%) underwent balloon pre-dilatation before stenting, and 98 (46.7%) underwent direct stenting. The prevalence of CMD at 3 months was lower in the direct stenting group than in the balloon pre-dilatation stenting group (12.24% vs. 40.18%; p < 0.001). Aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with lower odds of CMD (OR = 0.175, p = 0.001 and OR = 0.113, p = 0.001, respectively). Notably, MACE in patients who underwent direct stenting was lower than in those who underwent balloon pre-dilatation before stenting (14.29% vs. 26.79%; p = 0.040). In STEMI patients with multivessel disease, direct stenting of the culprit lesion, aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with a lower prevalence of CMD at 3 months and lower incidence of MACE at 12 months compared with balloon pre-dilatation stenting.This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT05406297 .

Early Safety and Performance of the Premounted Dry-Pericardium Vienna Self-Expandable Transcatheter Aortic Valve System: 30-Day Outcomes of the First-in-Human VIVA Feasibility Study.

The purpose of this first-in-human (FIH) study was to determine the safety and feasibility of the transfemoral premounted dry-pericardium Vienna Self-Expandable Supra-Annular Aortic Valve System. This novel system is repositionable and retrievable and comes already premounted on the delivery system, eliminating the need for assembly and crimping of the device before valve implantation. This is a prospective, nonrandomized, single-arm, single-center, first-stage FIH feasibility study, which will be followed by a second-stage pivotal, multicenter, multinational study in symptomatic patients with severe aortic stenosis. The first-stage FIH study evaluated the safety and feasibility of the device in 10 patients with severe aortic stenosis based on recommendations by the Valve Academic Research Consortium-2 for transcatheter aortic valve implantations. The mean patient age was 79 ± 5 years, 60% were male, and all patients were in New York Heart Association functional class II to III. The primary safety end point was successful when all patients were alive at 30-day follow-up. Device and technical success were observed in all patients. Two patients had a stroke, 1 of which occurred 5 days after the procedure. New permanent pacemakers were implanted in 2 patients (22.2%), of which only 1 was because of complete heart block. Only 1 patient (10%) had moderate paravalvular leak at 30 days. After the procedure, the mean aortic valve gradient decreased from 48.7 ± 10.8 mm Hg to 8.8 ± 4.3 mm Hg. In conclusion, this FIH feasibility study demonstrates successful procedural feasibility, with no 30-day mortality and favorable valve hemodynamic performance, leading to an improvement in quality of life. ClinicalTrials.gov identifier NCT04861805.

Safety and performance of the Vienna self-expandable transcatheter aortic valve system: 6-month results of the VIVA first-in-human feasibility study.

Background: The novel Vienna TAVI system is repositionable and retrievable, already pre-mounted on the delivery system, eliminating the need for assembly and crimping of the device prior to valve implantation. Aims: The purpose of this first-in-human feasibility study was to determine the safety, feasibility, clinical and hemodynamic performance of the Vienna TAVI system at 6-month follow-up. (ClinicalTrials.gov identifier NCT04861805). Methods: This is a prospective, non-randomized, single-arm, single-center, first-stage FIH feasibility study, which is followed by a second-stage pivotal, multicenter, multinational study in symptomatic patients with severe aortic stenosis (SAS). The first-stage FIH study evaluated the safety and feasibility, clinical and hemodynamic performance of the device in 10 patients with SAS based on recommendations by the VARC-2. Results: All patients were alive at 3-month follow-up. 1 non-cardiovascular mortality was reported 5 months after implantation. There were no new cerebrovascular events, life-threatening bleeding or conduction disturbances observed at 6-month follow-up. The mean AV gradient significantly decreased from 48.7 ± 10.8 to 7.32 ± 2.0 mmHg and mean AVA increased from 0.75 ± 0.18 to 2.16 ± 0.42 cm2 (p < 0.00001). There was no incidence of moderate or severe total AR observed. In the QoL questionnaires, the patients reported a significant improvement from the baseline 12-KCCQ mean score 58 ± 15 to 76 ± 20. NYHA functional class improved in two patients, remained unchanged in one patient. There was an increase in mean 6-min-walk distance from baseline 285 ± 97 to 347 ± 57 m. Conclusions: This study demonstrates that using Vienna TAVI system has favourable and sustained 6-month safety and performance outcomes in patients with symptomatic severe aortic stenosis.

The Impact of Trimethylamine N-Oxide and Coronary Microcirculatory Dysfunction on Outcomes following ST-Elevation Myocardial Infarction.

INTRODUCTION: Persistent coronary microcirculatory dysfunction (CMD) and elevated trimethylamine N-oxide (TMAO) levels after ST-elevation myocardial infarction (STEMI) may drive negative structural and electrical cardiac remodeling, resulting in new-onset atrial fibrillation (AF) and a decrease in left ventricular ejection fraction (LVEF). AIMS: TMAO and CMD are investigated as potential predictors of new-onset AF and left ventricular remodeling following STEMI. METHODS: This prospective study included STEMI patients who had primary percutaneous coronary intervention (PCI) followed by staged PCI three months later. Cardiac ultrasound images were obtained at baseline and after 12 months to assess LVEF. Coronary flow reserve (CFR), and index of microvascular resistance (IMR) were assessed using the coronary pressure wire during the staged PCI. Microcirculatory dysfunction was defined as having an IMR value ≥25 U and CFR value <2.5 U. RESULTS: A total of 200 patients were included in the study. Patients were categorized according to whether or not they had CMD. Neither group differed from the other with regards to known risk factors. Despite making up only 40.5% of the study population, females represented 67.4% of the CMD group p < 0.001. Similarly, CMD patients had a much higher prevalence of diabetes than those without CMD (45.7% vs. 18.2%; p < 0.001). At the one-year follow-up, the LVEF in the CMD group had decreased to significantly lower levels than those in the non-CMD group (40% vs. 50%; p < 0.001), whereas it had been higher in the CMD group at baseline (45% vs. 40%; p = 0.019). Similarly, during the follow-up, the CMD group had a greater incidence of AF (32.6% vs. 4.5%; p < 0.001). In the adjusted multivariable analysis, the IMR and TMAO were associated with increased odds of AF development (OR: 1.066, 95% CI: 1.018-1.117, p = 0.007), and (OR: 1.290, 95% CI: 1.002-1.660, p = 0.048), respectively. Similarly, elevated levels of IMR and TMAO were linked with decreased odds of LVEF improvement, while higher CFR values are related to a greater likelihood of LVEF improvement. CONCLUSIONS: CMD and elevated TMAO levels were highly prevalent three months after STEMI. Patients with CMD had an increased incidence of AF and a lower LVEF 12 months after STEMI.

Instantaneous wave free ratio value impact on left internal mammary artery graft patency.

OBJECTIVES: To assess whether instantaneous wave - free ratio (iFR) value is associated with left internal mammary artery (LIMA) graft failure at 12 months follow-up post coronary artery bypass graft (CABG). BACKGROUND: Data suggests bypass to a non-significant left anterior descending artery (LAD) lesion due to visual over-estimation may lead to LIMA graft failure. Implementing iFR may result in better arterial graft patency. METHODS: In iCABG (iFR guided CABG) study patients planned to undergo an isolated CABG procedure was prospectively enrolled and iFR was performed for LAD. Coronary computed tomography angiography was performed at 2 and 12 months follow-up. The primary endpoint of this study was to determine the rate of LIMA graft occlusion or hypoperfusion at 2 and 12-months follow-up. We considered a composite secondary endpoint of Major adverse cardiovascular and cerebrovascular event (MACCE) as a secondary outcome. RESULTS: In total 69 patients were included with no differences regarding age, sex and risk factors. At 2 months, 50 of LIMAs with pre-CABG iFR median 0.855 (0.785 - 0.892) were patent. Hypoperfusion was found in 8 LIMAs (median iFR 0.88 (0.842 - 0.90)). While, 7 LIMAs (median iFR 0.91 (0.88 - 0.96)) were occluded (p = 0.04). At 12 months, when iFR of LAD was >0.85: just 12 (31.6% out of all patent LIMAS) grafts were patent and 24 (100.0% out of all hypoperfused/occluded) grafts were hypoperfused or occluded (p < 0.001). In terms of MACCE, no difference (p = 1.0) was found between all 3 groups divided according to iFR value. CONCLUSIONS: Instantaneous wave - free ratio value above 0.85 in LAD is a powerful tool predicting LIMA graft failure at 1-year follow up period.

A prospective observational study on impact of epinephrine administration route on acute myocardial infarction patients with cardiac arrest in the catheterization laboratory (iCPR study).

BACKGROUND: Epinephrine is routinely utilized in cardiac arrest; however, it is unclear if the route of administration affects outcomes in acute myocardial infarction patients with cardiac arrest. OBJECTIVES: To compare the efficacy of epinephrine administered via the peripheral intravenous (IV), central IV, and intracoronary (IC) routes. METHODS: Prospective two-center pilot cohort study of acute myocardial infarction patients who suffered cardiac arrest in the cardiac catheterization laboratory during percutaneous coronary intervention. We compared the outcomes of patients who received epinephrine via peripheral IV, central IV, or IC. RESULTS: 158 participants were enrolled, 48 (30.4%), 50 (31.6%), and 60 (38.0%) in the central IV, IC, and peripheral IV arms, respectively. Peripheral IV epinephrine administration route was associated with lower odds of achieving return of spontaneous circulation (ROSC, odds ratio = 0.14, 95% confidence interval = 0.05-0.36, p < 0.0001) compared with central IV and IC administration. (There was no difference between central IV and IC routes; p = 0.9343.) The odds of stent thrombosis were significantly higher with the IC route (IC vs. peripheral IV OR = 4.6, 95% CI = 1.5-14.3, p = 0.0094; IC vs. central IV OR = 6.0, 95% CI = 1.9-19.2, p = 0.0025). Post-ROSC neurologic outcomes were better for central IV and IC routes when compared with peripheral IV. CONCLUSION: Epinephrine administration via central IV and IC routes was associated with a higher rate of ROSC and better neurologic outcomes compared with peripheral IV administration. IC administration was associated with a higher risk of stent thrombosis. Trial registration This trial is registered at NCT05253937 .

A comparison of risk scores' long-term predictive abilities for patients diagnosed with ST elevation myocardial infarction who underwent early percutaneous coronary intervention.

Objective. To compare the long-term (5 year) prognostic values of commonly used risk scores on major adverse cardiovascular events (MACE) in a cohort of patients who underwent primary PCI for STEMI. Design. We created a composite endpoint of MACE, defined as the occurrence of any of the following events within 5 years: ischemic or hemorrhagic stroke, target vessel revascularization, nonfatal myocardial infarction, cardiovascular death. We dichotomized risk scores into high risk and not high risk according to the literature's pre-existing cutoffs as follows: GRACE score >127 = high risk, SYNTAX I score ≥33 = high risk, SYNTAX II ≥32 high risk, TIMI >8 = high risk. We utilized the area under the receiver operating characteristic curve (AUC) as the metric for predictive ability. Results. There were 768 patients in this study and 416 (54.2%), 209 (27.2%), 511 (66.5%), and 74 (9.6%) were at high risk according to the GRACE, SYNTAX I, SYNTAX II, and TIMI scores, respectively. The AUCs for 5-year MACE were 0.54 (95% confidence interval (CI): 0.49-0.59, p = .0947), 0.79 (95% CI: 0.75-0.83, p < .0001), 0.58 (95% CI: 0.54-0.62, p = .0004), and 0.5 (95% CI: 0.48-0.53, p = .7259), respectively. Conclusion. SYNTAX I score was superior in predicting MACE in patients with STEMI and a high burden of CAD. Utilizing the basal SYNTAX I score in STEMI patients with significant non-culprit CAD may improve risk stratification, decision-making, and outcomes.

Blood direct PCR: impact of CYP2C19 and CYP4F2 variants for bleeding prediction in ST-elevation myocardial infarction patients with ticagrelor.

Aims: The goals of this study were to develop a new technique that could pave the way for a quicker determination of CYP4F2 rs3093135 and CYP2C19 rs4244285 variants directly from a patient's blood and to attempt to apply this technique in clinical practice. Patients & methods: The study included 144 consecutive patients admitted with ST elevation myocardial infarction. A blood-direct PCR and real-time PCR were used to detect variants of interest. Results & conclusion: Patients with bleeding events had the CYP2C19 GG (*1*1) variant more frequently than patients without bleeding events. The CYP4F2 TT variant was more frequently detected in patients with bleeding events 3 months after hospitalization.

Ticagrelor is one of the main antiplatelet drugs used for prevention of coronary blood clots after interventional procedures in patients with acute coronary syndromes. It has previously been shown that gene variants of CYP2C19 and CYP4F2 may affect antiplatelet therapy. This paper reports a novel instrument and the results of genetic tests obtained using this instrument. Our instrument can detect variants of the genes associated with ticagrelor antiplatelet therapy in only 40 min. These findings might facilitate individualized treatment with ticagrelor of patients with ST-elevation myocardial infarction.

Impact of Mineralocorticoid Receptor Gene NR3C2 on the Prediction of Functional Classification of Left Ventricular Remodeling and Arrhythmia after Acute Myocardial Infarction.

Background: The NR3C2 gene encodes the mineralocorticoid receptor, which is present on cardiomyocytes. Prior studies reported an association between the presence of NR3C2 single-nucleotide polymorphisms (SNPs) and an increased cortisol production during a stress response such as acute myocardial infarction (AMI), which may lead to adverse cardiac remodeling. Objective: To study the impact of the NR3C2 rs2070950, rs4635799 and rs5522 gene polymorphisms on left ventricular (LV) remodeling, rhythm and conduction disorders in AMI patients. Methods: A cohort of 301 AMI patients who underwent revascularization was included. SNPs of the NR3C2 gene (rs2070950, rs4635799 and rs5522) were evaluated. A total of 127 AMI patients underwent transthoracic echocardiography follow-up after 72 h and 6 months. Results: The rs2070950 GG genotype and rs4635799 TT genotype were most common in patients who had LV end-diastolic volume increase < 20% and the same or increased LV ejection fraction, indicating a possible protective effect of these SNPs. The rs5522 TT genotype was associated with a higher frequency of arrhythmias, while the presence of at least one rs5522 C allele was associated with a lower risk of arrhythmias. Conclusion: SNPs of the NR3C2 gene appear to correlate with better ventricular remodeling and a reduced rate of arrhythmias post-AMI, possibly by limiting the deleterious effects of cortisol on cardiomyocytes.

Prognostic Value of Cortisol Index of Endobiogeny in Acute Myocardial Infarction Patients.

Background and Objectives: Serum cortisol has been extensively studied for its role during acute myocardial infarction (AMI). Reports have been inconsistent, with high and low serum cortisol associated with various clinical outcomes. Several publications claim to have developed methods to evaluate cortisol activity by using elements of complete blood count with its differential. This study aims to compare the prognostic value of the cortisol index of Endobiogeny with serum cortisol in AMI patients, and to identify if the risk of mortality in AMI patients can be more precisely assessed by using both troponin I and cortisol index than troponin I alone. Materials and methods: This prospective study included 123 consecutive patients diagnosed with AMI. Diagnostic coronary angiography and revascularization was performed for all patients. Cortisol index was measured on admission, on discharge, and after 6 months. Two year follow-up for all patients was obtained. Results: Our study shows cortisol index peaks at 7-12 h after the onset of AMI, while serum cortisol peaked within 3 h from the onset of AMI. The cortisol index is elevated at admission, then significantly decreases at discharge; furthermore, the decline to its bottom most at 6 months is observed with mean values being constantly elevated. The cortisol index on admission correlated with 24-month mortality. We established combined cut-off values of cortisol index on admission > 100 and troponin I > 1.56 µg/las a prognosticator of poor outcomes for the 24-month period. Conclusions: The cortisol index derived from the global living systems theory of Endobiogeny is more predictive of mortality than serum cortisol. Moreover, a combined assessment of cortisol index and Troponin I during AMI offers more accurate risk stratification of mortality risk than troponin alone.

Six-Month Outcomes for COVID-19 Negative Patients with Acute Myocardial Infarction Before Versus During the COVID-19 Pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic has changed the way patients seek medical attention and how medical services are provided. We sought to compare characteristics, clinical course, and outcomes of patients presenting with acute myocardial infarction (AMI) during the pandemic compared with before it. This is a multicenter, retrospective cohort study of consecutive COVID-19 negative patients with AMI in Lithuania from March 11, 2020 to April 20, 2020 compared with patients admitted with the same diagnosis during the same period in 2019. All patients underwent angiography. Six-month follow-up was obtained for all patients. A total of 269 patients were included in this study, 107 (40.8%) of whom presented during the pandemic. Median pain-to-door times were significantly longer (858 [quartile 1=360, quartile 3 = 2,600] vs 385.5 [200, 745] minutes, p <0.0001) and post-revascularization ejection fractions were significantly lower (35 [30, 45] vs 45 [40, 50], p <0.0001) for patients presenting during vs. prior to the pandemic. While the in-hospital mortality rate did not differ, we observed a higher rate of six-month major adverse cardiovascular events for patients who presented during versus prior to the pandemic (30.8% vs 13.6%, p = 0.0006). In conclusion, 34% fewer patients with AMI presented to the hospital during the COVID-19 pandemic, and those who did waited longer to present and experienced more 6-month major adverse cardiovascular events compared with patients admitted before the pandemic.

Delays in Presentation in Patients With Acute Myocardial Infarction During the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has had a major impact on the behavior of patients, as well as on the delivery of healthcare services. With older and more medically vulnerable people tending to stay at home to avoid contracting the virus, it is unclear how the behavior of people with acute myocardial infarction (AMI) has changed. The aim of this study was to determine if delays in presentation and healthcare service delivery for AMI exist during the COVID-19 pandemic compared to the same period a year prior. METHODS: In this single-center, retrospective study, we evaluated patients admitted with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) during early months of the COVID-19 pandemic (March 11, 2020 to April 20, 2020) compared to patients admitted with same diagnosis during the same period a year prior. RESULTS: There were 30 and 62 patients who presented with NSTEMI in the pandemic and pre-pandemic eras, respectively. The median pain-to-door time was significantly larger during the pandemic compared to pre-pandemic era (1,885 (880, 5,732) vs. 606 (388, 944) min, P < 0.0001). There was a significant delay in door-to-reperfusion time during the pandemic with a median time of 332 (182, 581) vs. 194 (92, 329) min (P = 0.0371). There were 24 (80%) and 25 (42%) patients who presented after 12 h of pain onset in pandemic and pre-pandemic eras, respectively (P = 0.0006). There were 47 and 60 patients who presented with STEMI during the pandemic timeframe of study and pre-pandemic timeframe, respectively. The median pain-to-door time during the pandemic was significantly larger than that of the pre-pandemic (620 (255, 1,500) vs. 349 (146, 659) min, P = 0.0141). There were 22 (47%) and 14 (24%) patients who presented after 12 h of pain onset in the pandemic and pre-pandemic eras, respectively (P = 0.0127). There was not a significant delay in door-to-reperfusion time (P = 0.9833). There were no differences in in-hospital death, stroke, or length of hospitalization between early and late presenters, as well as between pandemic and pre-pandemic eras. CONCLUSIONS: In conclusion, this study found that patients waited significantly longer during the pandemic to seek medical treatment for AMI compared to before the pandemic, and that pandemic-specific protocols may delay revascularization for NSTEMI patients. These findings resulted in more than a threefold increase from the onset of symptoms to revascularization increasing the risks for future complications such as left ventricular dysfunction and cardiovascular death. Efforts should be made to increase patients' awareness regarding consequences of delayed presentation, and to find a balance between hospital evaluation strategies and goals of minimizing total ischemic time.

Characteristics and Outcomes in Patients Presenting With COVID-19 and ST-Segment Elevation Myocardial Infarction.

There is limited information regarding clinical characteristics and outcomes of patients with SARS-CoV-2 (COVID-19) disease presenting with ST-segment elevation myocardial infarction (STEMI). In this multicenter retrospective study, we reviewed charts of patients admitted with symptomatic COVID-19 infection and STEMI to a total of 4 hospitals spanning Italy, Lithuania, Spain and Iraq from February 1, 2020 to April 15, 2020. A total of 78 patients were included in this study, 49 (63%) of whom were men, with a median age of 65 [58, 71] years, and high comorbidity burden. During hospitalization, 8 (10%) developed acute respiratory distress syndrome, and 14 (18%) required mechanical ventilation. 19 (24%) patients were treated with primary Percutaneous Coronary Intervention (PCI) and 59 (76%) were treated with fibrinolytic therapy. 13 (17%) patients required cardiac resuscitation, and 9 (11%) died. For the 19 patients treated with primary PCI, 8 (42%) required intubation and 8 (42%) required cardiac resuscitation; stent thrombosis occurred in 4 patients (21%). A total of 5 patients (26%) died during hospitalization. 50 (85%) of the 59 patients initially treated with fibrinolytic therapy had successful fibrinolysis. The median time to reperfusion was 27 minutes [20, 34]. Hemorrhagic stroke occurred in 5 patients (9%). Six patients (10%) required invasive mechanical ventilation; 5 (9%) required cardiac resuscitation, and 4 (7%) died. In conclusion, this is the largest case series to-date of COVID-19 positive patients presenting with STEMI and spans 4 countries. We found a high rate of stent thrombosis, indicating a possible need to adapt STEMI management for COVID-19 patients.

Considerations for Management of Acute Coronary Syndromes During the SARS-CoV-2 (COVID-19) Pandemic.

Accumulating evidence suggests that influenza and influenza-like illnesses can act as a trigger for acute myocardial infarction. Despite these unprecedented times providers should not overlook acute coronary syndrome (ACS) guidelines, but may choose to modify the recommended approach in situations with confirmed or suspected COVID-19 disease. In this document, we suggest recommendations as to how to triage patients diagnosed with ACSs and provide with algorithms of how to manage the patients and decide the appropriate treatment options in the era of COVID-19 pandemic. We also address the inpatient logistics and discharge to follow-up considerations for the function of already established ACS network during the pandemic.