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.

Sociodemographic Factors, Comorbidities, In-Hospital Complications, and Outcomes of Ischaemic Stroke Patients in the Context of the COVID-19 Pandemic in Lithuania: A Retrospective, Record-Based, Single-Centre Study.

INTRODUCTION: The role of COVID-19 regarding in-hospital complications and poor outcomes for patients with ischaemic stroke (IS) is still important to explore. The aim of this study was to evaluate the risk of in-hospital lethality for IS patients respectively to their comorbidities and in-hospital complications in the context of the COVID-19 pandemic. METHODS: We identified 1898 acute IS patients (749 men and 1149 women) admitted to the Lithuanian University of Health Sciences Kaunas Hospital, Lithuania, from December 2020 to February 2022. The sociodemographic, clinical, and outcome features of the patients were evaluated deploying appropriate statistical tests. Hazard ratios and 95% confidence intervals were estimated by the Cox proportional hazards regression for hospital lethality. RESULTS: The risk of in-hospital lethality was 2.22 times higher in men suffering from IS and chronic ischaemic heart disease (cIHD) compared to those with IS and isolated arterial hypertension (iAH) (p < 0.05). COVID-19 elevated the risk of in-hospital lethality in men by 3.16 times (p < 0.05). In comorbid women with type two diabetes mellitus (DM) or cIHD, the risk of in-hospital lethality was two times higher compared to those with iAH (p < 0.05). The risk of in-hospital lethality increased significantly in both men and women, with the total number of in-hospital complications increasing per one unit. CONCLUSIONS: Of the comorbidities studied, DM and cIHD together with COVID-19 elevated the risk of in-hospital lethality significantly. Within the acute in-hospital complications, pneumonia with respiratory failure and acute renal failure showed the most significant prognostic value anticipating lethal outcomes for IS patients.

The Impact of Polymorphisms in ATP-Binding Cassette Transporter Genes on Anthracycline-Induced Early Cardiotoxicity in Patients with Breast Cancer.

BACKGROUND: Cardiac side effects associated with anthracycline-based treatment may seriously compromise the prognosis of patients with breast cancer (BC). Evidence shows that genes that operate in drug metabolism can influence the risk of anthracycline-induced cardiotoxicity (AIC). ATP-binding cassette (ABC) transporters could serve as one of the potential biomarkers for AIC risk stratification. We aimed to determine the link between single-nucleotide polymorphisms (SNPs) in several ABC genes (ABCB1 rs1045642, ABCC1 rs4148350, ABCC1 rs3743527) and cardiotoxicity. METHODS: The study included 71 patients with BC, who were treated with doxorubicin-based chemotherapy. Two-dimensional echocardiography and speckle-tracking echocardiography were performed. AIC was defined as a new decrease of 10 percentage points in the left ventricular ejection fraction (LVEF). SNPs in ABCB1 and ABCC1 genes were evaluated using real-time PCR. RESULTS: After a cumulative dose of 236.70 mg/m2 of doxorubicin, 28.2% patients met the criteria of AIC. Patients who developed AIC had a larger impairment in left ventricular systolic function compared to those who did not develop AIC (LVEF: 50.20 ± 2.38% vs. 55.41 ± 1.13%, p < 0.001; global longitudinal strain: -17.03 ± 0.52% vs. -18.40 ± 0.88%, p < 0.001). The ABCC1 rs4148350 TG genotype was associated with higher rates of cardiotoxicity (TG vs. GG OR = 8.000, 95% CI = 1.405-45.547, p = 0.019). CONCLUSIONS: The study showed that ABCC1 rs4148350 is associated with AIC and could be a potential biomarker to assess the risk of treatment side effects in patients with BC.

Prognostic Factors for Prolonged In-Hospital Stay in Patients with Heart Failure.

Background and Objectives: Heart failure (HF) is a threatening health condition that is associated with an increasing prevalence and high expenses because of frequent patient hospitalizations. The purpose of this study was to evaluate the factors that influence the length of in-hospital stay in HF patients. Materials and Methods: A total of 220 patients (43.2% men), admitted to the Department of Cardiology, Kaunas Hospital of Lithuanian University of Health Sciences from the 1st of January 2021 to the 31st of May 2021, were included in this study. According to the length of in-hospital stay, patients were stratified into two groups: the first group's length of stay (LOS) was from 1 to 8 days, and the second group's LOS was 9 days or more. Results: The median LOS was 8 (6-10) days. Multivariate logistic regression analysis revealed five predictors as independent factors associated with prolonged hospitalization. These predictors included treatment interruption (OR 3.694; 95% CI 1.080-12.630, p = 0.037), higher value of NT-proBNP (OR 3.352; 95% CI 1.468-7.659, p = 0.004), estimated glomerular filtration rate (eGFR) ≤ 50 mL/min/1.73 m2 (OR 2.423; 95% CI 1.090-5.383, p = 0.030), systolic blood pressure (BP) ≤ 135 mmHg (OR 3.100; 95% CI 1.421-6.761, p = 0.004) and severe tricuspid valve regurgitation (OR 2.473; 95% CI 1.086-5.632, p = 0.031). Conclusions: Several variables were identified as significant clinical predictors for prolonged length of in-hospital stay in HF patients where treatment interruption, higher NT-proBNP value and lower systolic BP at admission were the most important.

Prognostic Impact of Global Longitudinal Strain and NT-proBNP on Early Development of Cardiotoxicity in Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy.

Background. The most important anthracycline side effect is cardiotoxicity, resulting in congestive heart failure (HF). Early detection of cardiac dysfunction and appropriate treatment can improve outcomes and reduce the progression of HF. The aim of our study was to evaluate changes in clinical data, echocardiographic parameters, and NT-proBNP, as well as their associations with early anthracycline-induced cardiotoxicity (AIC) in patients treated with anthracycline-based chemotherapy. Methods and Materials. Patients with breast cancer were prospectively assessed with echocardiography, as well as NT-proBNP testing at baseline, (T0), after two cycles (T1) and four cycles (T2) of chemotherapy. AIC was defined as a new decrease in the LVEF of 10 percentage points, to a value below the lower limit of normal. Results. We evaluated 85 patients aged 54.5 ± 9.3 years. After a cumulative dose of 237.9 mg/m2 of doxorubicin, 22 patients (25.9%) met the criteria of AIC after chemotherapy. Patients who subsequently progressed to cardiotoxicity had demonstrated a significantly larger impairment in LV systolic function compared to those who did not develop cardiotoxicity (LVEF: 54.0 ± 1.6% vs. 57.1 ± 1.4% at T1, p < 0.001, and 49.9 ± 2.1% vs. 55.8 ± 1.6% at T2, p < 0.001; GLS: -17.8 ± 0.4% vs. -19.3 ± 0.9% at T1, p < 0.001, and -16.5 ± 11.1% vs. -18.5 ± 0.9% at T2, p < 0.001, respectively). The levels of NT-proBNP increased significantly from 94.8 ± 43.8 ng/L to 154.1 ± 75.6 ng/L, p < 0.001. A relative decrease in GLS ≤ -18.0% (sensitivity: 72.73%; specificity: 92.06%; AUC, 0.94; p < 0.001) and a relative increase in NT-proBNP > 125 ng/L (sensitivity: 90.0%; specificity: 56.9%; AUC, 0.78; p < 0.001) from baseline to T1 predicted subsequent LV cardiotoxicity at T2. Conclusions. Decrease in GLS and elevation in NT-proBNP were significantly associated with AIC, and these could potentially be used to predict subsequent declines in LVEF with anthracycline-based chemotherapy.

The incremental value of myocardial viability, evaluated by 18F-fluorodeoxyglucose positron emission tomography, and cardiovascular magnetic resonance for mortality prediction in patients with previous myocardial infarction and symptomatic heart failure.

OBJECTIVES: To find the imaging mortality predictors in patients with previous myocardial infarction (MI), symptomatic heart failure (HF), and reduced left ventricle (LV) ejection fraction (EF). METHODS: for the study 39 patients were selected prospectively with prior MI, symptomatic HF, and LVEF ≤40%. All patients underwent transthoracic echocardiography (TTE), single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI), 18F-FDG positron emission tomography (FDG PET). 31 patients underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Patients were divided into two groups: 1 group - cardiac death; 2 group - no cardiac death. Myocardial scars were assessed on a 5-point-scale. Follow-up data was obtained. RESULTS: Imaging features disclosed significant difference (p < 0.05) of defect score (CMR and SPECT-PET), LV end-diastolic diameter (EDD) (TTE), LVEDD index (CMR), LV global longitudinal strain (CMR) and LV global circumferential strain (CMR) between the groups. Predictors of cardiac death were: LVEDD index (TTE) and LV global longitudinal strain. The cut-off values to predict cardiac death were: defect score (CMR) 25 (AUC, 79.5%; OR 1.8, 95% CI 1.2-2.7), SPECT-PET defect score 22 (AUC, 73.9%; OR 0.5, 95% CI 0.3-0.7), LVEDD (TTE) 58 mm (AUC, 88.4%; OR 23.6, 95% CI 2.6-217.7), LVEDDi 30 mm/m2 (TTE) (AUC, 73.6%; OR 22.0, 95% CI 1.9-251.5), LVEDDi 33.6 mm/m2 (CMR) (AUC, 73.6%; OR 22.0, 95% CI 1.9-251.5), LV global longitudinal strain -13.4 (AUC, 87.8%; OR 2.1, 95% CI 1.2-3.7) and LV global circumferential strain -16.3 (AUC, 76.1%; OR 1.9, 95% CI 1.2-3.0). CONCLUSIONS: Imaging features, such as defect score (CMR) >25, SPECT-PET defect score >22, LVEDD (TTE) >58 mm, LVEDDi (TTE) >30 mm/m2, LVEDDi (CMR) >33.6 mm/m2, LV global longitudinal strain -13.4 and LV global circumferential strain -16.3, may increase sensitivity and specificity of FDG PET and LGE CMR predicting of late mortality.

Soluble CD146 in the detection and grading of intravascular and tissue congestion in patients with acute dyspnoea: analysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort.

OBJECTIVES: To evaluate the potential of soluble cluster of differentiation 146 (sCD146) in the detection and grading of congestion in patients with acute dyspnoea. DESIGN: Subanalysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort. SETTING: Two Lithuanian university centres. PARTICIPANTS: Adult patients with acute dyspnoea admitted to the emergency department. METHODS: Congestion was assessed using clinical and sonographic parameters. All patients underwent sCD146 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing. RESULTS: The median value of sCD146 concentration in the study cohort (n=437) was 405 (IQR 315-509) ng/mL. sCD146 was higher in patients with peripheral oedema than in those without (median (IQR) 472 (373-535) vs 400 (304-501) ng/mL, p=0.009) and with pulmonary rales than in those without (439 (335-528) vs 394 (296-484) ng/mL, p=0.001). We found a parallel increase of estimated right atrial pressure (eRAP) and sCD146 concentration: sCD146 was 337 (300-425), 404 (290-489) and 477 (363-572) ng/mL in patients with normal, moderately elevated and high eRAP, respectively (p=0.001). In patients with low NT-proBNP, high sCD146 distinguished a subgroup with a higher prevalence of oedema as compared with patients with low levels of both biomarkers (76.0% vs 41.0%, p=0.010). Moreover, high sCD146 indicated a higher prevalence of elevated eRAP, irrespective of NT-proBNP concentration (p<0.05). CONCLUSION: sCD146 concentration reflects the degree of intravascular and tissue congestion assessed by clinical and echocardiographic indices, with this association maintained in patients with low NT-proBNP. Our data support the notion that NT-proBNP might represent heart stretch while sCD146 rather represents peripheral venous congestion.

Familial Hypercholesterolemia and Its Current Diagnostics and Treatment Possibilities: A Literature Analysis.

Familial hypercholesterolemia (FH) is a common, inherited disorder of cholesterol metabolism. This pathology is usually an autosomal dominant disorder and is caused by inherited mutations in the APOB, LDLR, and PCSK9 genes. Patients can have a homozygous or a heterozygous genotype, which determines the severity of the disease and the onset age of cardiovascular disease (CVD) manifestations. The incidence of heterozygous FH is 1: 200-250, whereas that of homozygous FH is 1: 100.000-160.000. Unfortunately, FH is often diagnosed too late and after the occurrence of a major coronary event. FH may be suspected in patients with elevated blood low-density lipoprotein cholesterol (LDL-C) levels. Moreover, there are other criteria that help to diagnose FH. For instance, the Dutch Lipid Clinical Criteria are a helpful diagnostic tool that is used to diagnose FH. FH often leads to the development of early cardiovascular disease and increases the risk of sudden cardiac death. Therefore, early diagnosis and treatment of this disease is very important. Statins, ezetimibe, bile acid sequestrants, niacin, PCSK9 inhibitors (evolocumab and alirocumab), small-interfering-RNA-based therapeutics (inclisiran), lomitapide, mipomersen, and LDL apheresis are several of the available treatment possibilities that lower LDL-C levels. It is important to say that the timeous lowering of LDL-C levels can reduce the risk of cardiovascular events and mortality in patients with FH. Therefore, it is essential to increase awareness of FH in order to reduce the burden of acute coronary syndrome (ACS).

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.

Cardiovascular Disorder after Cardiotoxic Non-Hodking's Lymphoma Treatment: A Case Report.

The non-Hodgkin's lymphomas are a diverse group of lymphoid neoplasms that collectively rank fifth in cancer incidence and mortality. Patients treated with mediastinal radiotherapy and/or anthracycline-containing chemotherapy are known to have increased risks of coronary heart disease, valvular heart disease, and heart failure. This may be the result of cancer treatment cardiotoxicity or may be due to accelerated development of cardiovascular disease. We presented 41-year-old male who was admitted to the hospital because of congestive heart failure. He has a medical history of non-Hodgkin's lymphoma treated with anthracycline-based chemotherapy and mediastinal radiotherapy almost 20 years ago. Echocardiography showed significant aortic valve stenosis, thickened and fibrotic pericardium. Coronary angiography showed diffuse three-vessel coronary artery disease. The patient was referred for surgical treatment. Aortic valve replacement, coronary artery bypass grafting and pericardiectomy were successfully performed, symptoms of heart failure reduced.

Comparative Analysis of Myocardial Viability Multimodality Imaging in Patients with Previous Myocardial Infarction and Symptomatic Heart Failure.

Background and Objectives: To compare the accuracy of multimodality imaging (myocardial perfusion imaging with single-photon emission computed tomography (SPECT MPI), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), and cardiovascular magnetic resonance (CMR) in the evaluation of left ventricle (LV) myocardial viability for the patients with the myocardial infarction (MI) and symptomatic heart failure (HF). Materials and Methods: 31 consecutive patients were included in the study prospectively, with a history of previous myocardial infarction, symptomatic HF (NYHA) functional class II or above, reduced ejection fraction (EF) ≤ 40%. All patients had confirmed atherosclerotic coronary artery disease (CAD), but conflicting opinions regarding the need for percutaneous intervention due to the suspected myocardial scar tissue. All patients underwent transthoracic echocardiography (TTE), SPECT MPI, 18F-FDG PET, and CMR with late gadolinium enhancement (LGE) examinations. Quantification of myocardial viability was assessed in a 17-segment model. All segments that were described as non-viable (score 4) by CMR LGE and PET were compared. The difference of score between CMR and PET we named reversibility score. According to this reversibility score, patients were divided into two groups: Group 1, reversibility score > 10 (viable myocardium with a chance of functional recovery after revascularization); Group 2, reversibility score ≤ 10 (less viable myocardium when revascularisation remains questionable). Results: 527 segments were compared in total. A significant difference in scores 1, 2, 3 group, and score 4 group was revealed between different modalities. CMR identified "non-viable" myocardium in 28.1% of segments across all groups, significantly different than SPECT in 11.8% PET in 6.5% Group 1 (viable myocardium group) patients had significantly higher physical tolerance (6 MWT (m) 3892 ± 94.5 vs. 301.4 ± 48.2), less dilated LV (LVEDD (mm) (TTE) 53.2 ± 7.9 vs. 63.4 ± 8.9; MM (g) (TTE) 239.5 ± 85.9 vs. 276.3 ± 62.7; LVEDD (mm) (CMR) 61.7 ± 8.1 vs. 69.0 ± 6.1; LVEDDi (mm/m2) (CMR) 29.8 ± 3.7 vs. 35.2 ± 3.1), significantly better parameters of the right heart (RV diameter (mm) (TTE) 33.4 ± 6.9 vs. 38.5 ± 5.0; TAPSE (mm) (TTE) 18.7 ± 2.0 vs. 15.2 ± 2.0), better LV SENC function (LV GLS (CMR) −14.3 ± 2.1 vs. 11.4 ± 2.9; LV GCS (CMR) −17.2 ± 4.6 vs. 12.7 ± 2.6), smaller size of involved myocardium (infarct size (%) (CMR) 24.5 ± 9.6 vs. 34.8 ± 11.1). Good correlations were found with several variables (LVEDD (CMR), LV EF (CMR), LV GCS (CMR)) with a coefficient of determination (R2) of 0.72. According to the cut-off values (LVEDV (CMR) > 330 mL, infarct size (CMR) > 26%, and LV GCS (CMR) < −15.8), we performed prediction of non-viable myocardium (reversibility score < 10) with the overall percentage of 80.6 (Nagelkerke R2 0.57). Conclusions: LGE CMR reveals a significantly higher number of scars, and the FDG PET appears to be more optimistic in the functional recovery prediction. Moreover, using exact imaging parameters (LVEDV (CMR) > 330 mL, infarct size (CMR) > 26% and LV GCS (CMR) < −15.8) may increase sensitivity and specificity of LGE CMR for evaluation of non-viable myocardium and lead to a better clinical solution (revascularization vs. medical treatment) even when viability is low in LGE CMR, and FDG PET is not performed.

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.

Long Noncoding RNAs CARMN, LUCAT1, SMILR, and MALAT1 in Thoracic Aortic Aneurysm: Validation of Biomarkers in Clinical Samples.

MATERIALS AND METHODS: Relative expression of lncRNAs CARMN, LUCAT1, SMILR, and MALAT1 was tested in clinical aortic tissue and blood plasma samples from TAA and non-TAA patients using the qRT-PCR method. The Mann-Whitney U test was used to compare ΔCt values between the study groups. ROC curve analysis was performed to evaluate the diagnostic value of plasma lncRNAs. RESULTS: We found significantly reduced CARMN (p = 0.033) and LUCAT1 (p = 0.009) expression in aortic tissue samples from TAA patients. Relative expression of MALAT1 (p = 0.117) and SMILR (p = 0.610) did not differ in aortic tissue between the TAA and non-TAA groups. Expression of both LUCAT1 and SMILR was significantly decreased in TAA patients' blood plasma compared to controls (p = 0.018 and p = 0.032, respectively). However, only LUCAT1 showed the ability to discriminate aneurysmal disease in patients' blood plasma (AUC = 0.654, 95%CI = 0.534-0.775, p = 0.018). CONCLUSIONS: We have shown that the expression of lncRNAs CARMN and LUCAT1 is reduced in dilated aortic tissue and that the LUCAT1 and SMILR expression is lower in the blood plasma of TAA patients. Decreased LUCAT1 expression in TAA patients' blood plasma may have diagnostic potential in discriminating patients with TAA.

Tissue-Specific miRNAs Regulate the Development of Thoracic Aortic Aneurysm: The Emerging Role of KLF4 Network.

MicroRNAs (miRNAs) are critical regulators of the functional pathways involved in the pathogenesis of cardiovascular diseases. Understanding of the disease-associated alterations in tissue and plasma will elucidate the roles of miRNA in modulation of gene expression throughout development of sporadic non-syndromic ascending thoracic aortic aneurysm (TAA). This will allow one to propose relevant biomarkers for diagnosis or new therapeutic targets for the treatment. The high-throughput sequencing revealed 20 and 17 TAA-specific miRNAs in tissue and plasma samples, respectively. qRT-PCR analysis in extended cohort revealed sex-related differences in miR-10a-5p, miR-126-3p, miR-155-5p and miR-148a-3p expression, which were the most significantly dysregulated in TAA tissues of male patients. Unexpectedly, the set of aneurysm-related miRNAs in TAA plasma did not resemble the tissue signature suggesting more complex organism response to the disease. Three of TAA-specific plasma miRNAs were found to be restored to normal level after aortic surgery, further signifying their relationship to the pathology. The panel of two plasma miRNAs, miR-122-3p, and miR-483-3p, could serve as a potential biomarker set (AUC = 0.84) for the ascending TAA. The miRNA-target enrichment analysis exposed TGF-ß signaling pathway as sturdily affected by abnormally expressed miRNAs in the TAA tissue. Nearly half of TAA-specific miRNAs potentially regulate a key component in TGF-ß signaling: TGF-ß receptors, SMADs and KLF4. Indeed, using immunohistochemistry analysis we detected increased KLF4 expression in 27% of TAA cells compared to 10% of non-TAA cells. In addition, qRT-PCR demonstrated a significant upregulation of ALK1 mRNA expression in TAA tissues. Overall, these observations indicate that the alterations in miRNA expression are sex-dependent and play an essential role in TAA via TGF-ß signaling.