Relationship Between Urinary Angiotensinogen and Mortality in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Activation of the reninangi otens in-aldosterone system has an important role in the pathophysiology of heart failure with reduced ejection fraction. While the effects of systemic reninangi otens in-aldosterone system activation on heart failure with reduced ejection fraction are well known, the impact of the local reninangi otens in-aldosterone system on heart failure with reduced ejection fraction is not fully understood because of limited clinical research. This study aimed to investigate the effect of urinary angiotensinogen level, an accepted indicator of local reninangi otens in-aldosterone system activation, on all-cause mortality in patients with heart failure with reduced ejection fraction. METHODS: This retrospective, single-center study included 60 patients with baseline urinary angiotensinogen data and survival/mortality data at 4 years. Urinary angiotensinogen values were standardized to the urinary creatinine value measured from the same urine sample. The median urinary angio tensi nogen /urin ary creatinine value among all patients (114 µg/g) was used as a cutoff to divide the patients into 2 groups. Mortality data were obtained from the national registry systems or by telephone. RESULTS: Comparison of all-cause mortality in the 2 groups showed that 22 deaths (71%) occurred in the group with a urinary angio tensinogen/urinary creatinine ratio above the median and 10 deaths (35.5%) occurred in the group of patients with urinary angio tensinogen/urinary creatinine equal to or below the median value (P =.005). CONCLUSION: Our study suggests that urinary angiotensinogen can be used as a new biomarker in the prognosis and follow-up of heart failure patients.

The effect of ferric carboxymaltose treatment on the Tp-e interval and the Tp-e/QT and Tp-e/QTc ratios in heart failure patients with iron deficiency.

Aim    In heart failure (HF) patients with iron deficiency, cardiac electrical irregularity is a cause of arrhythmias. The aim of our study was to evaluate the effect of ferric carboxymaltose (FCM) treatment on T wave peak to end (Tp-e) interval and the Tp-e / QT and Tp-e / corrected QT (QTc) ratios that reflect the transmural dispersion of repolarization in HF patients with iron deficiency.Material and methods    Forty HF patients with iron deficiency that were treated with FCM were included in our single center, observational study. Repolarization parameters on electrocardiograms recorded before and 12 wks after FCM treatment were compared. Additionally, these parameters were compared with ventricular repolarization parameters of 40 healthy age and gender matched individuals and with another group of 40 HF patients without iron deficiency.Results    In the HF patients with iron deficiency, the Tp-e interval and the Tp-e / QT and Tp-e / QTc ratios before FCM treatment were 103.7±19.1 ms, 0.25± 0.04, 0.23±0.04, respectively. These values were higher compared to the healthy the group and HF group without iron deficiency (p<0.001). In the HF patients with iron deficiency, the Tp-e interval and the Tp-e / QT and Tp-e / QTc ratios after FCM treatment were lower compared to pre-treatment and similar to the HF patients without iron deficiency (89.4±18.6 ms, 0.22±0.04, 0.20±0.04, respectively; p<0.001).Conclusion    FCM treatment of HF patients with iron deficiency corrects prolonged Tp-e interval and high Tp-e / QT and Tp-e / QTc ratios, which are risk factors for ventricular arrhythmias.

A New Current to The Armamentarium: Is the CHA2DS2-Vasc-HS Score Predictive of Low Left Internal Mammary Artery (LIMA) Flow in Patients Underwent Coronary Bypass Surgery?

INTRODUCTION: Left internal mammary artery (LIMA) grafts should be used in patients undergoing CABG. No other procedure results in patency equivalent to that of the left anterior descending coronary artery (LAD)-LIMA bypass graft. The CHA2DS2-Vasc-HS scoring system can be used to successfully predict CAD severity in stable CAD patients. We aimed to investigate the relationship between LIMA flow and the CHA2DS2-Vasc-HS score. METHODS: A total of 684 patients, who underwent CABG surgery, were included in this study. Previous history of bypass surgery, emergency operations, patients with Leriche syndrome and patients with severe obstructive pulmonary and subclavian artery disease were excluded from our study. Patients with a LIMA flow that was suitable for bypass grafting, as determined during the intraoperative evaluation, were included in the low LIMA flow group, and the CHA2DS2-Vasc-HS score was calculated for all patients. RESULTS: Patients in the low LIMA flow group (Group 1) were older. The CHA2DS2-Vasc-HS score (P < 0.001), presence of mild or moderate COPD (P = 0.022), number of severely diseased vessels (P = 0.036), and BMI (P < 0.001) were independent predictors of poor LIMA flow. The cutoff value of the CHA2DS2-VASc-HS score for the prediction of poor LIMA flow was >5.5, with a sensitivity of 92.9% and specificity of 83.4% (AUC: 0.938, 95% Cl: 0.906 - 0.970, P < 0.001). CONCLUSION: A preoperative high CHA2DS2-Vasc-HS score can be used to predict low intraoperative LIMA flow. The CHA2DS2-Vasc-HS score is an easy-to-use and reliable estimation method and can be used as an additional preoperative of LIMA flow in patients undergoing CABG due to severe CAD.

The Effect of High Lactate Level on Mortality in Acute Heart Failure Patients With Reduced Ejection Fraction Without Cardiogenic Shock.

BACKGROUND: We aimed to determine the effect of blood lactate levels on cardiovascular (CV) death and hospitalization for heart failure (HF) in acute HF patients with reduced left ventricular ejection fraction (EF). METHODS: Eighty-five acute HF patients with reduced ejection fraction were divided into two groups according to admission blood lactate levels. 48 of them had low blood lactate levels (< 2 mmol/l) and 37 of them had high blood lactate levels (≥ 2 mmol/l). Patients with acute coronary syndrome, cardiogenic shock, sepsis and low blood pressure at admission were excluded from the study. Primary endpoint is the composite of cardiovascular (CV) death and hospitalization for heart failure (HHF) in 6-month follow-up. Secondary endpoint is the change in NT-proBNP levels from admission to 72 h. RESULTS: Baseline characteristics of patients were similar in two groups. On baseline echocardiographic evaluation; patients with high lactate revealed a higher mitral E/A ratio (2.34 [0.43-3.31], p = 0.008) and a lower TAPSE ratio (14 [10-27], p = 0.008) than patients with low lactate levels. Over a median follow-up period of 6 months, the primary end point occurred in 28 (75.7%) of 37 patients assigned to high lactate group and in 20 (41.7%) of 48 patients assigned to low lactate group (p = 0.006). High lactate levels significantly increased the risk of CV death and HHF at 6 months by nearly 5.35-fold in acute HF patients with reduced EF. The change in NT-proBNP levels at 72nd hour after admission were similar between two groups. CONCLUSION: Higher lactate levels at admission related with higher HHF at 6 months and may be related with higher risk of CV death in acute HF patients with reduced EF.

Myopericarditis caused by severe acute respiratory syndrome coronavirus 2.

A 25-year-old man presented to the emergency department with acute-onset chest pain and shortness of breath. A physical examination revealed coarse crackles in the both lower lungs. Consolidation and ground-glass opacities suggesting viral infection were detected in the right lower lobe on chest computed tomography. Laboratory findings revealed elevated troponin, leukocytosis, and lymphopenia. Electrocardiography revealed ST segment elevation with PR depression in leads I, aVL, V5, and V6, and ST depression and PR elevation in aVR. Echocardiography revealed diffuse cardiac hypokinesia and a decreased left ventricular ejection fraction. Suspecting coronavirus disease 2019 (COVID-19)-related myopericarditis, the patient was hospitalized. After one week of empirical antibiotics, antivirals, and supportive therapy, his condition improved. Antibody testing for COVID-19 was positive on hospitalization day 8. The presentation of myopericarditis can be vague and mislead physicians during the COVID-19 pandemic. Myopericarditis should be included as a differential diagnosis for patients with suspected COVID-19.

Association between serum adropin levels and isolated coronary artery ectasia in patients with stable angina pectoris.

OBJECTIVE: Dilation of one or more coronary artery segments to a diameter at least 1.5 times that of a normal adjacent segment is referred to as coronary artery ectasia (CAE). Adropin is a protein involved in endothelial function and is shown to have a protective effect on the regulation of cardiac functions. Atherosclerosis and endothelial dysfunction play an important role in the development of CAE. The aim of this study was to investigate the association between serum adropin levels and isolated CAE. METHODS: Patients with stable angina pectoris who underwent coronary angiography (CAG) between August 2017 and July 2018 were evaluated prospectively. A total of 92 subjects were included in the study-40 patients over 18 years old and diagnosed with isolated CAE based on CAG findings and a control group of 52 patients. RESULTS: Serum adropin level was found to be significantly lower in the isolated CAE group compared to the control group (1019.57 pg/mL and 1151.10 pg/mL, respectively, p=0.010). The isolated CAE group also exhibited a significantly higher mean platelet volume than that in the control group (10.75 fL and 10.17 fL, respectively, p=0.011). CONCLUSION: Our results show that there is an association between low serum adropin level and isolated CAE.

Rationale, design, and methodology of the EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study.

OBJECTIVE: The aim of this study is to assess the prevalence of polypharmacy, inappropriate drug use, and drug-drug interactions (DDIs) in elderly patients presenting at outpatient cardiology clinics in Turkey. METHODS: The EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study will be an observational, real-world, multicenter study conducted to evaluate DDIs and polypharmacy in elderly cardiac outpatients. All consecutive patients (aged ≥65 years) admitted to outpatient cardiology clinics between July 30, 2018 and July 30, 2019 who provide written, informed consent will be enrolled. A total of approximately 5000 patients are to be enrolled in this non-interventional study. All of the data will be collected at one point in time and current clinical practice will be evaluated (ClinicalTrials.gov NCT03370523). RESULTS: Patient demographics, comorbid disease characteristics, laboratory test results, and details of medication use will be collected using self-reports and medical records. The severity of comorbid disease will be recorded and scored according to Charlson Comorbidity Index (CCI) and patients will be divided into 3 groups: mild, those with a CCI score of 1-2; moderate, those with a CCI score of 3-4; and severe, those with a CCI score of ≥5. Polypharmacy will be defined as the use of 5 or more medications at one time. DDIs will be determined using the Lexicomp Online drug interaction screening tool and potentially inappropriate medications will be defined based on the 2015 update of the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Severe drug interactions will be defined as those in category D or X. CONCLUSION: EPIC will be the first large-scale study in Turkey to evaluate polypharmacy, potentially inappropriate medications, and DDIs in elderly cardiac outpatients in a real-world clinical setting.

Design and rationale for the ASSOS study: Appropriateness of aspirin use in medical outpatients a multicenter and observational study.

OBJECTIVE: The aim of this study was to describe the current status of aspirin use and the demographic characteristics of patients on aspirin for primary and secondary prevention of cardiovascular diseases. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study (ASSOS) trial was a multicenter, cross-sectional, and observational study conducted in Turkey. The study was planned to include 5000 patients from 14 cities in Turkey. The data were collected at one visit, and the current clinical practice regarding aspirin use was evaluated (ClinicalTrials.gov number NCT03387384). RESULTS: The study enrolled all consecutive patients who were admitted to the outpatient cardiology clinics from March 2018 until June 2018. Patients should be at least 18 years old, have signed written informed consent, and on aspirin (80-325 mg) therapy within the last 30 days. Cardiologists from the hospital participates in the study. Patients were divided into 2 categories according to presence or absence of atherosclerotic cardiovascular disease, namely secondary prevention group and primary prevention group, respectively. The appropriate use of aspirin in the primary and secondary prevention groups was assessed according to the European Society of Cardiology guidelines and US Preventive Services Task Force. The patients' gastrointestinal bleeding risk factors and colorectal cancer risk were evaluated. CONCLUSION: The ASSOS registry will be the most comprehensive and largest study in Turkey evaluating the appropriateness of aspirin use. The results of this study help understand the potential misuse of aspirin in a real-world setting.

Awareness of Pleiotropic and Cardioprotective Effect of Statins in Patients with Coronary Artery Disease.

BACKGROUND: Statins are commonly used in the secondary prevention of coronary artery disease. Studies have shown that the rate of statin use is low among patients with coronary artery disease. In this study, we aimed to investigate the reasons for poor patient compliance with statin treatment. METHODS: A total of 504 patients diagnosed with coronary heart disease were included in the study. Patients were asked 5 questions to assess their level of knowledge about statin therapy. RESULTS: Among the patients not using statins, 42% stated they did not take the medication because their cholesterol was not high or they did not know they should renew their prescription when they ran out and 35% because they were influenced by news reports in the media suggesting that cholesterol-lowering drugs were harmful. When patients who were aware of the pleiotropic/cardioprotective effects of statins were compared with patients who were not, the more knowledgeable patients had lower noncompliance rate and mean LDL-C level and a higher rate of LDL-C level optimization. CONCLUSION: We found that patients who are aware of the pleiotropic effects of statins were more compliant with treatment. We believe that spending more time explaining and emphasizing the mechanisms of action, reason for prescribing, and necessary treatment duration of drugs that patients must use will result in greater compliance and improve patient care. In this way, patients may be less influenced by misinformation presented by the media.

Relationship between intrarenal renin-angiotensin activity and re-hospitalization in patients with heart failure with reduced ejection fraction.

OBJECTIVE: Heart failure (HF) is a clinical syndrome resulting from structural or functional damages. Although clinical trials have shown that the plasma renin-angiotensin system (RAS) activation decreases HF functional status and increases hospitalization for HF patients, the effect of intrarenal RAS activity is still unknown. In this study, we investigated the relationship between the New York Heart Association (NYHA) class, duration, and number of hospitalizations in the previous year and urinary angiotensinogen (UAGT) in patients with HF with reduced ejection fraction (HFrEF). METHODS: This study included 85 patients who had an ejection fraction of <40% and were receiving optimal medical treatment. Among these, 22 were excluded from the study for various reasons. Demographically and biochemically, the remaining 63 patients were compared according to the NYHA functional classes and re-hospitalization status. RESULTS: When the groups were compared in terms of N-terminal pro-B-type natriuretic peptide (NT-proBNP), UAGT, and high-sensitivity C-reactive protein (Hs-CRP), it was found that these parameters were significantly higher in patients who were hospitalized more than two times in the previous year [p<0.001; p=0.007; p<0.001, respectively]. There was a significant correlation between number of hospitalizations and NT-proBNP (r=0.507, p<0.001), Hs-CRP (r=0.511, p<0.001), hemoglobin (r=-0.419, p=0.001), serum sodium (r=-0.26, p=0.04), and systolic blood pressure (r=-0.283, p=0.02). When the independence of multiple correlations was assessed using multiple linear regression analysis, NT-proBNP, Hs-CRP, and hemoglobin levels were independent predictors of re-hospitalization, but this was not the same for UAGT. CONCLUSION: Although UAGT levels are high in patients with poor NYHA functional class and repeated hospitalizations, this marker is not valuable for predicting repeated hospitalization in patients with HFrEF.

Mean platelet volume is related with ischemic stroke in patients with sinus rhythm.

Stroke is the leading cause of disability worldwide. It is known that atrial fibrillation and left atrial enlargement contribute ischemic stroke, and mean platelet volume (MPV) increases in patients with ischemic stroke and atrial fibrillation. We aimed to determine whether higher MPV is associated with ischemic stroke in patients with sinus rhythm. We evaluated 74 patients in sinus rhythm and with ischemic stroke (Group 1) and 90 age-matched and sex-matched healthy individuals as control group (Group 2). After physical and echocardiographic examination, 24-48 h Holter monitoring and complete blood counts were studied. There were no statistically significant differences in age, sex rates, and comorbidities between groups. Left atrial diameter was higher in Group 1 than Group 2 (P = 0.001), but both were in normal range. MPV was significantly higher in Group 1 (P < 0.001) and was an independent determinant [odds ratio (OR): 1.840; P < 0.001; 95% confidence interval (CI) 1.330-2.545] of ischemic stroke with left atrial (OR: 1.138; P = 0.006; 95% CI 1.037-1.248). In conclusion, higher MPV is associated with acute ischemic stroke in patients with sinus rhythm and without heart failure or left atrial enlargement. MPV and left atrial diameter are independent predictors of ischemic stroke in this patient population.

The relationship between neutrophil-to-lymphocyte ratio and coronary collateral circulation.

Neutrophil/lymphocyte ratio (NLR) has been proposed as a prognostic marker to determine systemic inflammatory response and atherosclerosis. Our aim was to determine the relationship between NLR and development of coronary collateral circulation (CCC) in patients with stable coronary artery disease (CAD). A total of 521 consecutive patients with stable CAD who underwent coronary angiography and documented total occlusion in one of those major coronary arteries were included in this study. Levels of fasting blood glucose, white blood cell, and NLR were significantly higher in patients with poor collateral than in those with good collateral. After multivariate analysis, high level of NLR was an independent predictor of CCC together with levels of fasting blood glucose. The receiver-operating characteristic analysis provided a cutoff value of 2.75 for NLR to predict poor CCC with 65% sensitivity and 68% specificity. We demonstrated an independent association between levels of NLR and development of CCC in patients with stable CAD.

Association between uric acid and coronary collateral circulation in patients with stable coronary artery disease.

Serum uric acid (SUA) levels have been proposed as a biomarker of coronary artery disease (CAD) and coronary collateral circulation (CCC). We investigated the association between SUA levels and development of CCC in patients with stable CAD. Consecutive patients (n = 480) with stable CAD who underwent coronary angiography and documented total occlusion in 1 of the major coronary arteries were included in this study. Levels of fasting blood glucose, white blood cell (WBC), creatinine, platelet count, and SUA were significantly higher in patients with poor CCC than in those with good CCC. After multivariate analysis, high levels of SUA were an independent predictor of CCC together with levels of fasting blood glucose and WBC. The receiver-operating characteristic analysis provided a cutoff value of 5.65 mg/dL for SUA to predict poor CCC with 60% sensitivity and 66% specificity. High levels of SUA may be associated with poor CCC in patients with stable CAD.

Relationship between platelet indices and international normalized ratio in patients with non-valvular atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia and associated with adverse outcomes and increased risk for thromboembolic events. Warfarin is still the most extensively prescribed oral anticoagulant in AF to prevent ischemic complications. We aimed to determine the differences at platelet indices with warfarin usage layered by International Normalized Ratio (INR). A total of 250 patients with permanent non-valvular AF (mean age 70.2 ± 9.1; 153 female) were divided into two groups. Group 1 included 125 patients whose INR is between 2.0 and 3.0 (called as "effective") and Group 2 included 125 patients whose INR is <2.0 (called as "ineffective"). Also 123 age- and sex-matched individuals in sinus rhythm enrolled as control group (Group 3). After physical and echocardiographic examination, complete blood counts and INR were studied. There was no statistically significant difference in age, sex, co-morbidities and medications, also hemoglobin, white blood cell and platelet counts among the groups. The CHA2DS2-VASc scores were similar between Groups 1 and 2. The mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) were significantly higher in Group 2 than Groups 1 and 3 and similar between Groups 1 and 3. MPV was positively correlated with PDW and PCT and also inversely correlated with INR value and platelet count. On multivariate logistic regression analysis, MPV, PDW and PCT were independent predictors of ineffectiveness of INR. The results of this study showed that MPV, PDW and PCT are increased in patients with non-valvular AF without effective warfarin treatment. Warfarin usage adjusted by INR is associated with lower values of these platelet indices, even lower as the values of subjects in sinus rhythm. MPV, PDW and PCT are independent predictors of INR ineffectiveness and seem to be useful parameters for monitoring the effectiveness of warfarin treatment.

Influence of the Timing of Percutaneous Coronary Intervention on Clinical Outcomes in Non-ST-Elevation Myocardial Infarction.

BACKGROUND AND OBJECTIVES: We have intended to investigate the influence of the timing of invasive procedures on all-cause mortality, recurrent myocardial infarction (MI), re-hospitalization due to cardiac causes and left ventricular function over a 3-month period among patients with Non-ST-elevation myocardial infarction (NSTEMI). SUBJECTS AND METHODS: A total of 131 NSTEMI patients with moderate-high Thrombolysis in Myocardial Infarction risk scores, who had been admitted to our department between July 2011-December 2011 were included in our study. They had been randomized into 2 groups according to the timing of the percutaneous coronary intervention (PCI). Patient undergoing PCI in the first 24 hours of hospitalization were named the "Early Invasive Group" and those undergoing PCI between 24-72 hours of hospitalization were named the "Delayed Invasive Group". All patients were followed up for 3 months. RESULTS: Third month left ventricular ejection fraction (LVEF) values were higher in the early invasive group (59.9±6.0% vs. 54.1±8.7%; p<0.001). Recurrent MI rates were lower in the early invasive group (2.9% vs. 14.5%; p=0.016). Similarly, hospitalization rates due to cardiac events were lower in the early invasive group (8.7% vs. 30.6%; p=0.001). All cause mortality appeared to be lower in the early invasive group, although not to a statistically significant degree (0% vs. 4.8%; p=0.065). CONCLUSION: The early invasive strategy appears to be more effective for the reduction of recurrent MI, re-hospitalization due to cardiac events, and the preservation of 3rd month LVEF in patients with moderate-high risk NSTEMI when compared to a delayed invasive strategy.

Mean platelet volume and extent and complexity of coronary artery disease in diabetic and nondiabetic patients with ST elevation myocardial infarction.

We investigated whether the mean platelet volume (MPV) is associated with the extent and complexity of coronary artery disease in patients with ST elevation myocardial infarction (STEMI). We prospectively included 912 STEMI patients (663 male and 249 female; mean age 58.7 ± 12.4 years) who underwent primary percutaneous coronary intervention. The patients were divided into 3 groups according to MPV tertiles. Highest SYNTAX score (SS) was observed in MPVhigh group compared with MPVmid and MPVlow groups (P < .001 for all). The SS of MPVmid group was higher than MPVlow group (P = .036). The MPV in diabetic STEMI patients was higher than in nondiabetic STEMI patients (P < .001). Multivariate linear regression analysis showed that the MPV was associated with diabetes (ß = .115, P = .001), troponin level (ß = .131, P = .001), platelet count (ß = -.241, P < .001), and SS (ß = .216, P < .001). The relation between MPV and SS in diabetic STEMI patients was stronger than for nondiabetic STEMI patients (r = .473, P < .001 vs r = .129, P = .001).