Emre Yalcinkaya

Response to Relation Between Time of Symptom Onset of ST-Segment Elevation Myocardial Infarction and Patient Baseline Characteristics: From the National Cardiovascular Data Registry

Background The presence of a morning excess of ST-segment elevation myocardial infarction (STEMI) has been observed. The relation between patient characteristics and timing of STEMI may provide insight into the biological processes responsible for this phenomenon. Hypothesis Patient baseline characteristics will vary with timing of STEMI. Methods We performed an analysis using a large national registry of unselected patients with STEMI (N = 45 218). Patients were categorized by time of symptom onset: early (6 am–2 pm), late day (2 pm–10 pm), and overnight (10 pm–6 am) then evaluated for variations in characteristics. Results A circadian variation in the timing of symptom onset of STEMI was observed (early 41%, late day 32%, and overnight 26%, P < 0.001). Circadian variations in factors known to alter timing of events were seen, including lower rates of home β-blocker use, smoking, and diabetes, with early onset of STEMI symptoms. In addition, patients in the 6 am to 2 pm subgroup were more likely older, white race, and male, with higher rates of home aspirin use and lower rates of obesity. Higher rates of coexisting cardiovascular disease, including prior heart failure, 3-vessel coronary artery disease, and depressed left ventricular ejection fraction, were observed in the overnight group. More robust antiplatelet therapy with home clopidogrel use was not associated with a change in the timing of events. Conclusions A morning excess of STEMI continues to exist and represents a potential target for preventative strategies. Patient baseline characteristics vary with the onset of STEMI and may reflect a physiologic relationship between these factors and the timing of events.

Increased Serum Uric Acid Levels Are Correlated with Decreased Left Atrial Appendage Peak Flow Velocity in Patients with Atrial Fibrillation

Objective: We aimed to examine the relationship between serum uric acid levels and left atrial appendage (LAA) peak flow velocity, an indicator of the mechanical functions of the LAA, and atrial fibrillation (AF). Subjects and Methods: Transesophageal echocardiography was performed before cardioversion in 153 patients with AF. The patients were categorized into 2 groups based on their LAA blood flow velocity. Group 1 included 87 patients with a low LAA flow velocity (<35 cm/s), and group 2 comprised 66 patients with a normal LAA flow velocity (≥35 cm/s). The χ2 and Students t tests were used to compare categorical and quantitative data between the groups. Linear regression analyses were performed to demonstrate the independent association between serum uric acid levels and LAA peak flow velocity. Results: The LAA blood flow velocity was 24.62 ± 5.90 cm/s in group 1 and 49.28 ± 13.72 cm/s in group 2, respectively (p < 0.001). The serum uric acid levels were 6.88 ± 1.85 mg/dl in group 1 and 5.97 ± 1.51 mg/dl in group 2, and the difference was statistically significant (p = 0.001). There was a negative correlation between serum uric acid levels and LAA blood flow velocity (r = -0.216, p = 0.007). Multivariate regression analysis showed that serum uric acid levels, age and gender differences were significant predictors of the LAA peak flow velocity. Conclusions: High serum uric acid levels were associated with a low contractile function of the LAA and could provide additional prognostic information on future thromboembolic events in patients with AF.

The Effect of Age on Right Ventricular Diastolic Function in Healthy Subjects Undergoing Treadmill Exercise Test

There is an increasing interest for the value of right ventricle (RV) in predicting exercise tolerance and prognosis in cardiovascular disease. However, there is relatively few data evaluating the effect of age on RV diastolic filling velocities during rest or exercise in healthy subjects.

Response to Improvement of Arterial Stiffness in the Transition From Acute Decompensated Heart Failure to Chronic Compensated Heart Failure

Kim DB et al. Clin Cardiol. 2013;36:358–362.

Relationship between Neutrophil-To-Lymphocyte Ratio and Electrocardiographic Ischemia Grade in STEMI

Background Neutrophil-to-lymphocyte ratio (NLR) has been found to be a good predictor of future adverse cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Changes in the QRS terminal portion have also been associated with adverse outcomes following STEMI. Objective To investigate the relationship between ECG ischemia grade and NLR in patients presenting with STEMI, in order to determine additional conventional risk factors for early risk stratification. Methods Patients with STEMI were investigated. The grade of ischemia was analyzed from the ECG performed on admission. White blood cells and subtypes were measured as part of the automated complete blood count (CBC) analysis. Patients were classified into two groups according to the ischemia grade presented on the admission ECG, as grade 2 ischemia (G2I) and grade 3 ischemia (G3I). Results Patients with G3I had significantly lower mean left ventricular ejection fraction than those in G2I (44.58 ± 7.23 vs. 48.44 ± 7.61, p = 0.001). As expected, in-hospital mortality rate increased proportionally with the increase in ischemia grade (p = 0.036). There were significant differences in percentage of lymphocytes (p = 0.010) and percentage of neutrophils (p = 0.004), and therefore, NLR was significantly different between G2I and G3I patients (p < 0.001). Multivariate logistic regression analysis revealed that only NLR was the independent variable with a significant effect on ECG ischemia grade (odds ratio = 1.254, 95% confidence interval 1.120–1.403, p < 0.001). Conclusion We found an association between G3I and elevated NLR in patients with STEMI. We believe that such an association might provide an additional prognostic value for risk stratification in patients with STEMI when combined with standardized risk scores.

The Value of Frontal Planar QRS-T Angle in Patients without Angiographically Apparent Atherosclerosis

Objective: The present study was undertaken to investigate the prognostic value of the frontal planar QRS-T angle in patients without angiographically apparent coronary atherosclerosis. Subjects and Methods: Three hundred and seven patients with normal coronary arteries on coronary angiography were included. The absolute difference between the frontal QRS- and T-wave axes was defined as the frontal planar QRS-T angle, and patients were divided into 3 subgroups based on the frontal planar QRS-T angle (<45, 45-90, and >90°). Demographic, clinical, laboratory, and angiographic data were compared between groups. Based on the regression analysis results, patients were recategorized into 4 groups according to their luminal calibers of left main coronary artery (LMCA) and history of hypertension (HT) (nonhypertensive LMCA ≤4.13 mm, nonhypertensive LMCA >4.13 mm, hypertensive LMCA ≤4.13 mm, and hypertensive LMCA >4.13 mm). Results: The median value of the frontal planar QRS-T angle of all participants was 38°. Subjects with the widest frontal planar QRS-T angle were older (p = 0.027), were hypertensive (p = 0.001), and had higher corrected QT values (p = 0.001). Patients with the widest frontal planar QRS-T angle had larger LMCA and left anterior descending coronary artery diameters compared to subjects with a normal and borderline frontal QRS-T angle (p = 0.004 and p = 0.028, respectively). Corrected QT, HT, and LMCA diameter were found as independent predictors of the frontal planar QRS-T angle. Subjects with HT and a larger luminal caliber of LMCA had the widest frontal planar QRS-T angle. Conclusion: Patients with a history of HT and a larger luminal caliber of LMCA had the widest frontal planar QRS-T angle. Since HT-induced electrophysiological changes are still not well established and we observed that changes in the luminal caliber of coronary arteries are associated with an abnormal frontal QRS-T angle, the frontal QRS-T angle could serve as a marker of ventricular repolarization heterogeneity in hypertensive patients in addition to keeping track of arrhythmic events, even before overt disease.

Evaluation of inflammatory conditions associated with aspirin resistance

We read with great interest the recently published article by Tasdemir et al. (1) entitled ‘Aspirin resistance in patients with type II diabetes mellitus’. In that well-described study, the authors (1) investigated the prevalence and predictors of aspirin resistance in diabetic patients. They found that presence of diabetes mellitus had no effect on aspirin response, and hypercholesterolemia was the only predictor of aspirin resistance in multivariate analysis in diabetic patients. Although this study provides us with extensive information, and we commend the authors for the excellent data that they have provided, some comments may be of interest. The authors have mentioned that high levels of cholesterol diminish aspirin responsiveness in diabetic patients due to the reduced membrane fluidity associated with the excessive accumulation of cholesterol in platelet membranes, and infusion of reconstituted high-density lipoprotein (HDL) cholesterol is highly effective in reversing the excessive accumulation of cholesterol in platelet membranes. Nonetheless, Kotani et al. (2) have reported that decreased aspirin responsiveness was related to the increased activity of aspirin esterase in older type II diabetics, and greater aspirin hydrolysis was associated with the decreased levels of HDL cholesterol as well as increased levels of total cholesterol, thereby linking activity of aspirin esterase to cholesterol metabolism. Inflammation and oxidative stress are usually accompanied by increased platelet activation and aggregation (3–6). Increased expression of cyclooxygenase-2 associated with inflammation may induce generation of thromboxane A2, thereby resulting in a prothrombotic state (4–6). Inflammatory conditions such as hypertension, acute coronary syndrome, heart failure, stroke, connective tissue disease, Crohn’s disease, ulcerative colitis, psoriasis, and end-stage renal failure are associated with an increased platelet reactivity, and could be related with the development of inadequate response to aspirin or aspirin resistance (4–6). In conclusion: since inflammation, oxidative stress, endothelial dysfunction, and insulin resistance are essential parts of the whole, and associated with the aspirin response, it could be conceivable that inflammation and insulin resistance could increase the development of impaired platelet activation, thus playing an important role in the pathogenesis of aspirin resistance (7,8). Evaluating insulin resistance and inflammatory status more comprehensively (more than sedimentation rate), and excluding patients with inflammatory conditions in addition to end-stage renal disease, could add more consistency to the results and help in elucidating the mechanism of the observed effects. Since Pulcinelli et al. (9) have mentioned that platelets become less sensitive in patients taking aspirin for a long time, period of aspirin treatment should also be provided in detail in studies associated with aspirin resistance.

Evaluating the Balance Regulating Matrix Remodeling

though we thank the authors for their valuable study, some further comments about the evaluation of MMP-12 may be beneficial. MMPs play a major role in tissue development and vascular wall remodeling [2– 5] . Tissue inhibitors of metalloproteinases (TIMPs) regulate local MMP activity and are usually secreted together with variable amounts of MMPs [3–5] . Extracellular matrix remodeling and MMP activation and functionality in the tissue are largely regulated by the balance between MMPs and We read with great interest the article by Del Porto et al. [1] entitled ‘The multitasking role of macrophages in Stanford type A acute aortic dissection’, which has recently been published in Cardiology . The authors aimed to determine whether the release of matrix metalloproteinase (MMP)-12 and vascular endothelial growth factor by macrophages, leading to inflammation, matrix degradation and neoangiogenesis, represents an effective pathway that underlies aortic wall remodeling in Stanford type A acute aortic dissection. AlReceived: January 27, 2014 Accepted: January 27, 2014 Published online: June 5, 2014

Cardiac magnetic resonance imaging in cardiomyopathies that look alike.

We read with great interest the article by Mesquita et al. entitled ‘‘Cardiac amyloidosis: Diagnosis using delayed enhancement cardiac magnetic resonance imaging sequences’’, recently published in the Portuguese Journal of Cardiology. The authors presented 10 patients with the suspicion of a cardiomyopathy on echocardiography. Patients were diagnosed and managed with late gadolinium enhancement patterns on cardiac magnetic resonance (MR) imaging. Although we commend the authors for their valuable article and the management of the patients, some comments may be of interest. Cardiac amyloidosis is characterized by diffuse global subendothelial late gadolinium enhancement. Increased gadolinium washout from blood results in higher blood T1 over time, resulting in a dark blood pool, which does not occur in other cardiomyopathies. If cardiac wall thickness is increased, a decrease in QRS amplitude associated with dyssynchronous activation of atrophic myocytes is an important finding. Fabry disease is characterized by symmetrical hypertrophy, and men are commonly affected due to X-linked inheritance. Progressive diastolic dysfunction is generally observed without a restrictive filling pattern on echocardiography. Hypertrophic cardiomyopathy is characterized by asymmetrical hypertrophy which can result in ventricular outflow obstruction. Although cardiac myocytes are hypertrophic, they do not contribute significantly to effective contraction. Tagged MR images can show the disordered and ineffective contraction patterns in cardiomyopathies accompanied by septal hypertrophy, thereby distinguishing hypertensive cardiomyopathy. In conclusion, cardiomyopathies accompanied by increased wall thickness are characterized by impeded ventricular filling and progressive diastolic dysfunction. They are relatively rare and usually tend to be overlooked or misdiagnosed. Comprehensive assessment of patients, including clinical manifestations, electrocardiography, and echocardiography in addition to MR imaging, play an important role in instituting appropriate management and therapy.

Electrocardiographic criteria of proximal left anterior descending artery occlusion: sign of de Winter or Wellens?

the ECG in Fig. 2B showing theWellens syndrome.Wellens syndrome, or left anterior descending artery (LAD) coronary T-wave syndrome, is an acute coronary syndrome characterized by ECG changes of symmetric, deeply inverted T waves or biphasic T waves in the anterior leads with preserved R-wave progression and without pathologic Q waves and ST-segment elevation. Interestingly, pain is usually resolved at the time of these ECG changes and presented with this case presentation. These ECG findings are suggestive of significant LAD stenosis, and patients are at high risk for anterior wall myocardial infarction [2]. The sensitivity, specificity, and positive predictor value of T-wave inversion for significant LAD stenosis are 69%, 89%, and 86%, respectively [3].