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.

Coronary artery disease, its associations with ocular, genetic and blood lipid parameters.

BACKGROUND/OBJECTIVES: To investigate the associations between ophthalmic parameters, CYP4F2 (rs2108622) and ABCA1 (rs1883025) polymorphisms and coronary artery disease, considering the accessibility, non-invasive origin of retinal examination and its possible resemblance to coronary arteries. SUBJECTS/METHODS: Overall 165 participants divided into groups based on the coronary angiography results and clinical status: control group (N = 73), MI group (N = 63), 3VD (three vessel disease) (N = 24). All the participants underwent total ophthalmic examination - optical coherence tomography (OCT) and OCT angiography of the macula region were performed and evaluated. Total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride cholesterol (Tg-C) were tested. A standard manufacturer's protocol for CYP4F2 (rs2108622) and ABCA1 (rs1883025) was used for genotyping with TaqMan probes. RESULTS: GCL+ layer was thicker in control group vs. 3VD group (74.00; 62.67-94.67 (median; min.-max.) vs. 71.06; 51.33-78.44, p = 0.037). T allele carriers under ABCA1 rs1883025 dominant model were shown to have ticker retina and smaller foveal avascular zone in superficial capillary plexus and smaller Tg-C concentration. ABCA1 rs1883025 was associated with retinal thickness (OR = 0.575, 95% CI 0.348-0.948, p = 0.030). Univariate logistic regression showed that ABCA1 rs1883025 CT genotype is associated with decreased risk for coronary artery disease development under overdominant genetic model (OR = 0.498, 95% CI 0.254-0.976; p = 0.042) and codominant genetic model (OR = 0.468, 95% CI 0.232-0.945, p = 0.034). CONCLUSIONS: Results of this study confirmed that non-invasive methods such as OCT of eye might be used for identification of patients at risk of CAD.

Imaging Predictors of Left Ventricular Functional Recovery after Reperfusion Therapy of ST-Elevation Myocardial Infarction Assessed by Cardiac Magnetic Resonance.

BACKGROUND: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. RESULTS: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up (p < 0.001). AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF (r = -0.479, p < 0.001), LV GLS (r = 0.441, p < 0.001) and LV GCS (r = 0.396, p = 0.001) as well as between AAR and LVEF (r = -0.430, p = 0.003), LV GLS (r = 0.501, p < 0.001) and weak with LV GCS (r = 0.342, p = 0.020). At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation (r = -0.347, p = 0.021). Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. CONCLUSION: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI.

Is this dyspnea because of coronary artery disease? A rare case report of primary neuroendocrine tumor in anterior mediastinum.

INTRODUCTION: Mediastinal neuroendocrine tumors are rare malignancies with aggressive behavior and a grim prognosis. These malignancies often go undetected until they are diagnosed at advanced stages. CASE REPORT: We present the case of 74 -years old man who was hospitalized because of non-ST elevation myocardial infarction and in case of three vessels coronary artery disease, coronary bypass surgery was planned. During preoperative investigation, computer tomography revealed a huge tumor (20 cm × 11 cm × 21 cm in size) in the anterior mediastinum. Successful simultaneous operation coronary bypass surgery and removal of the mediastinal tumor was performed. DISCUSSION: Surgery is the treatment of choice for neuroendocrine tumors but the relapse rate ranges between 5% and 30% and is higher (65%) in atypical neuroendocrine tumors and patients with mediastinal node involvement. Despite the poor prognosis of neuroendocrine tumors, the spread to the lymph nodes, the patient continues chemotherapy treatment 49 months after the operation.

Anterior basal left ventricular pseudoaneurysm in a single vessel disease.

INTRODUCTION: Left ventricular pseudoaneurysm is a rare but serious clinicopathologic entity. MATERIALS AND RESULTS: This article describes a case report of 51-year-old man who experienced recurrence of chest pain and dyspnea 4 months later after anterior ST elevation myocardial infarction of first diagonal branch. Anterior basal left ventricular pseudoaneurysm was diagnosed and successful surgical treatment was performed. One year after operation, patient has no cardiovascular events and remains in NYHA class II. CONCLUSION: Cardiac magnetic resonance should be performed, if there is a suspicion of left ventricular pseudoaneurysm from transthoracic echocardiography. Surgery is the treatment of choice in case of left ventricular pseudoaneuryms because untreated lesions carry a significantly high risk of rupture.

Relative Leukocyte Telomere Length and Genetic Variants in Telomere-Related Genes and Serum Levels Role in Age-Related Macular Degeneration.

Telomere shortening is well known to be associated with ageing. Age is the most decisive risk factor for age-related macular degeneration (AMD) development. The older the individual, the higher the AMD risk. For this reason, we aimed to find any associations between telomere length, distribution of genetic variants in telomere-related genes (TERT, TERT-CLPTM1, TRF1, TRF2, and TNKS2), and serum TERF-1 and TERF2 levels on AMD development. METHODS: Our study enrolled 342 patients with AMD and 177 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by DNA salting-out method. The genotyping of TERT rs2736098, rs401681 in TERT-CLPTM1 locus, TRF1 rs1545827, rs10107605, TNKS2 rs10509637, rs10509639, and TRF2 rs251796 and relative leukocyte telomere length (T/S) measurement were carried out using the real-time polymerase chain reaction method. Serum TERF-1 and TERF2 levels were measured by enzymatic immunoassay (ELISA). RESULTS: We found longer telomeres in early AMD patients compared to the control group. Additionally, we revealed that minor allele C at TRF1 rs10107605 was associated with decreases the odds of both early and exudative AMD. Each minor allele G at TRF2 rs251796 and TRF1 rs1545827 C/T genotype and C/T+T/T genotypes, compared to the C/C genotype, increases the odds of having shorter telomeres. Furthermore, we found elevated TERF1 serum levels in the early AMD group compared to the control group. CONCLUSIONS: In conclusion, these results suggest that relative leukocyte telomere length and genetic variants of TRF1 and TRF2 play a role in AMD development. Additionally, TERF1 is likely to be associated with early AMD.

Multisystem Inflammatory Syndrome in a Young Adult (MIC-A) Following SARS-CoV-2 Infection.

Multisystem Inflammatory Syndrome (MIS) is a rare but increasingly recognized complication of SARS-CoV-2 infection, usually presenting 2 to 6 weeks after the onset of COVID-19 infection symptoms and affecting mainly children. However, there have been reported several cases of a similar multisystem inflammatory syndrome in adults (MIS-A). We describe the case of a previously healthy 28-year-old male who presented with a clinical profile with multiorgan involvement within four weeks after confirmed SARS-CoV-2 infection, suggestive for multisystem inflammatory syndrome (MIS-A). The clinical presentation included persistent high grade of fever, gastrointestinal and mucocutaneous lesions, lymphadenopathy, elevated cardiac and inflammatory biomarkers, cytopenia and shock. This case report illustrates the wide range of presentations, diagnosis, and treatment modalities of multisystem inflammatory syndrome. The pathophysiology and the mechanisms by which SARS-CoV-2 triggers an abnormal immune response leading to MIS remain poorly understood. Better characterization of MIS-A and early recognition of MIS is important because it is associated with high mortality if left untreated.

Retinal and Choroidal Thinning-A Predictor of Coronary Artery Occlusion?

Introduction. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) allowed visualization of retina and choroid to nearly the capillary level; however, the relationship between systemic macrovascular status and retinal microvascular changes is not yet known well. Aim. Our purpose was to assess the impact of retinal optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters on prediction of coronary heart disease (CHD) in acute myocardial infarction (MI) and chronic three vessel disease (3VD) groups. Methods. This observational study included 184 patients-26 in 3VD, 76 in MI and 82 in healthy participants groups. Radial scans of the macula and OCTA scans of the central macula (superficial (SCP) and deep (DCP) capillary plexuses) were performed on all participants. All participants underwent coronary angiography. Results. Patients in MI groups showed decreased parafoveal total retinal thickness as well as GCL+ retinal thickness. Outer circle total retinal thickness and GCL+ retinal thickness were lowest in the 3VD group. The MI group had thinner, while 3VD the thinnest, choroid. A decrease in choroidal thickness and vascular density could predict 3VD. Conclusions. A decrease in retinal and choroidal thickness as well as decreased vascular density in the central retinal region may predict coronary artery disease. OCT and OCTA could be a significant, safe, and noninvasive tool for the prediction of coronary artery disease.