Kenan Yalta

Copeptin and cardiovascular disease: a review of a novel neurohormone.

Neurohormones (NHs) in the cascade of the arginine vasopressin (AVP) system have drawn particular attention in the recent years. Copeptin, the C-terminal portion of provasopressin, is a novel NH of the AVP system, and is known to be co-released with AVP from hypothalamus (neurohypophysis). As a surrogate marker of the AVP system, copeptin has gradually replaced AVP in several clinical studies largely due to its structural and methodological advantages. Copeptin has been regarded as a marker of non-specific stress response, and has also been suggested to have clinical implications in a variety of non-cardiovascular (pneumonia, sepsis, etc.) and cardiovascular conditions (heart failure and acute coronary syndromes (ACSs, etc.)). However, current data on relation of copeptin with other cardiovascular conditions ( arrhythmias, etc.) are still insufficient. The present review primarily focuses on general features of copeptin, its general clinical implications, and specifically aims to cover its potential clinical value in a variety of cardiovascular conditions.

Statins decrease mean platelet volume irrespective of cholesterol lowering effect

BACKGROUNDnRecent clinical observations have demonstrated that the beneficial effects of statins are not limited to LDL lowering effect. They have also favourable effects on platelet activation, endothelial function, inflammation, and coagulation cascade.nnnAIMnTo investigate the effects of statins on mean platelet volume (MPV) which is a simple measure of platelet activation volume in patients who have been prescribed statins. Atorvastatin and rosuvastatin were also compared in respect to effects on MPV.nnnMETHODSnOne hundred and forty five patients were retrospectively included in the study from the outpatient cardiology clinic. Patients who had been given statin treatment were recruited based on the records. Baseline and 4-8 weeks biochemical analysis and haematological measurements and cardiovascular risk factors were recorded.nnnRESULTSnBoth statins significantly decreased the MPV. MPV of patients did not show any significant correlation with lipid parameters. Linear regression analysis revealed that there were no statistically significant associations of ∆ MPV with the ∆LDL-cholesterol (beta coefficient = 0.13; p = 0.24), ∆DL-cholesterol (beta coefficient = 0.17; p = 0.18) or ∆triglyceride (beta coefficient = -0.11; p = 0.21) after statin treatment. Both statins had comparable effects on lipid parameters at the end of the one month follow up period.nnnCONCLUSIONnStatins significantly reduce MPV irrespective of cholesterol levels, and atorvastatin and rosuvastatin have comparable effects in this regard.

Copeptin (C-terminal provasopressin): A promising marker of arrhythmogenesis in arrhythmia prone subjects?

Neurohormones have drawn particular attention in the recent years possiblyduetotheirpotentialdiagnosticandprognosticvalues inavarietyof clinical conditions includingcongestiveheart failure(CHF), acutemyocardial infarction (AMI), etc. Among neurohormones, arginine vasopressin (AVP) has been known to be secreted by hypothalamus in response to hypovolemia and increased plasma osmolality [1], and was also demonstrated to be a marker of the presence and severity of CHF [2]. However as described below, the potential association between AVP system and arrhythmogenesis may also confer some important therapeutic and prognostic implications in arrhthmia-prone patients. In the recent years, due to the instability and rapid clerance [1], the clinical utility of AVP has beengraduallyabandonedtosomedegree, andcopeptin(CP), anothernovel neurohormone of the AVP system, has come into use in the clinical practice. CP, the C-terminal portion of provasopressin [1], is co-released with AVP from hypothalamus. CP is structurally more stable, and hence may mirror the stable levels of AVP associated with the severity of the related disease [1]. CP was recently demonstrated to be a strong predictor of mortality and morbidity in patients suffering heart failure after an AMI [1]. In another study [3], CP was found to be associated with left ventricular dysfunction (inverse correlation between copeptin levels and left ventricular ejection fraction (LVEF)) in the early (at discharge) and late stages (on follow-up) of AMI indicating that hyperactivation of the AVPsystemseems tobea contributor (via inducing remodelling) and/or a consequence in the process of heart failure development. However, as an absolute clinical implication inCHF, substantial levels of CPmay indirectly denotepoor systemicperfusionassociatedwithdepressed left ventricular systolic function (a notion consistent with a previous study that demonstrated a negative correlation between AVP and cardiac index [2]). CHF is a well known trigger for malign ventricular arrhythmias through various mechanisms including structural alterations of myocardium, increased myocardial wall tension, adrenergic activation, enhanced effects of the AVP system on the heart, etc. AVP (co-secreted with CP) was suggested to induce protein synthesis, cardiac hypertrophy [4] and collagen synthesis in cardiac fibroblasts [5] in rats that may not only induce myocardial remodelling but may also create an arrhythmogenic substrate for malign ventricular arrhythmias indicating direct arrhythmogenic effects of AVP on myocardium in patients with CHF. It may be suggested that the association between CP levels and arrhythmogenesis may be dependent on left ventricular function, to some extent. However, this association may still persist even after adjustment for parameters of left ventricular function (LVEF, etc.) suggesting CP as an arrhythmogenic marker in arrhythmia-prone patients without heart failure as well. In the absence of heart failure, CP may still remain associated with arrhythmogenesis through various potentialmechanisms: CPwas found to be associatedwith the individual stress level [6]. In a very recently published study, CP was reported to have an additional diagnostic value in AMI (for rapid rule out) as an endogenous stress marker [7]. Hyperactivation of the adrenergic system is generally suggested to trigger malign ventricular arrhythmias and sudden cardiac death (SCD) in arrhythmia-prone subjects [8], and iswell known to be associated with the endogenous stress level. Therefore, CP may be regarded as a promising biochemical marker of arrhythmogenesis in arrhytmia-prone patients with and without heart failure. It may be suggested that besides conventional indices of arrhythmogenesis (QT dispersion, T wave alternance (TWA), heart rate variability (HRV), etc.), clinicians are in need of novel biochemicalmarkers thatmay rapidly and reliably predict the risk for arrhythmogenesis and arrhythmic mortality in arrhythmia-prone patients. CP, the novel and promising marker with strong predictive values, may help predict arrhythmia risk, and may help determine the therapeutic strategy in these patients. However, future large scale studies particularly focusing on the link between arrhythmogenesis and CP in arrhythmia-prone subjects are still warranted to confirm the clinical utility of CP in these patients. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [9].

Neuropeptide Y-induced coronary microvascular dysfunction: A significant contributor to the adverse outcomes in stress cardiomyopathy?

⁎ Corresponding author. E-mail address: kyalta@gmail.com (K. Yalta). In their recently published article, Szardien et al. reported a 78year-old female patient who had suffered stress cardiomyopathy (SCM) accompanied by increased serum levels of neuropeptide Y (NPY) [1]. We agree with the authors that increased serum NPY levels may contribute to myocardial contractile dysfunction and hence may also be regarded as a prognostic marker in patients with SCM [1]. However, in the setting of SCM with substantial NPY levels, NPYinduced coronary microvascular dysfunction, as described below, may also contribute significantly to the adverse clinical outcomes including ischemic malign arrhythmias, etc. Transient wall motion abnormalities including left ventricular apical ballooning have been regarded as one of the main characteristics of SCM [2]. Catecholamine-induced myocardial dysfunction, coronary microvascular dysfunction and coronary spasm etc have been suggested as potential etiologies of this entity. Recently, NPY has also been suggested to contribute to myocardial dysfunction in SCM indicating its potential prognostic value [1]. Notwithstanding the generally accepted benign nature of SCM, relatively high rates of malign ventricular arrhythmias and mortality were reported in some patient series [3]. Even though the exact mechanisms leading to adverse events (malign ventricular arrhythmia, etc.) in SCM is still largely unknown, severe coronary microvascular dysfunction may be considered as a potential trigger in some patients. Endothelial dysfunction [4] and increased serum NPY (a vasoconstrictor hormone) [5] levels are well known to play the central role in the pathogenesis of coronary microvascular syndromes. Among these syndromes, coronary syndrome Y (characterized by coronary slow flow (CSF)) is associated with enhanced coronary resistance, and may present with the clinical picture of acute coronary syndrome (ACS) along with an increased proclivity to cardiac arrhythmias [4]. Similarly, in the setting of SCM, severe and transient coronary microvascular dysfunction induced by excessive levels of NPY may be associated with adverse clinical outcomes including ischemic malign arrhythmic events and sudden cardiac death (SCD), etc. (regardless of the presence of severe left ventricular systolic dysfunction). Therefore, besides clinical presentation, SCM with excessive NPY levels may resemble ACSs in terms of prognostic features. Even though, the case reported by Szardien et al. [1] did not suffer any SCM-related adverse event, substantial levels of NPY might indicate the possibility of severe coronary microvascular dysfunction (with or without CSF) in this case. It may be suggested that NPY-induced severe coronary microvascular dysfunction may account for life-threatening ischemic adverse events including malign ventricular arrhythmias in SCM patients with substantial levels of NPY during the disease course. Therefore, these patients may be regarded as a subgroup with potentially worse prognosis due to severe coronary microvascular dysfunction indicating the need for close monitoring and aggressive management as in the event of ACSs. Besides conventional therapeutic strategies including management of heart failure, arrhythmias and anticoagulation, etc., targeting enhancement of coronary blood flow along with the use of intensive anti-ischemic regimens may be of clinical value during the disease course and may help improve prognosis in SCM patients with substantial serum levels of NPY. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6].

Golden Ratio and the heart: A review of divine aesthetics

In human history, certain mathematical figures or concepts had gained a significant reputation largely due to their occult and esoteric meanings. Among these, Golden Ratio and associated concepts, namely golden proportions, had elicited a tremendous breakthrough in our human awareness and perception regarding mundane and spiritual aspects of physical existence. Golden Ratio or Number (with a numerical value of 1.618) that is also referred to as the Greek letter Phi (φ), has been universally expressed on a line partitioned into two unequal lengths (L, the longer and S, the shorter) in such a manner that L/S=(L+S)/L. Besides, appearing in certain number sequences (Fibonacci Series, etc.), golden proportions, to the consternation of observers, appear to be strikingly prevalent across all levels of physical existence from the innermost structures to the colossal galaxies of the universe potentially labeling these concepts as the measures of divine aesthetics. Accordingly, the human body also serves as an epitome of these mysterious concepts as exemplified by its outward appearance including general stature and extremities along with a variety of inner organ systems. Based on preliminary studies, the human cardiovascular system might also be suggested to serve as a major predilection site of divine aesthetics as measured with Golden Ratio and its allies. This appears to be completely in line with the ancient knowledge associating the human heart with the esoteric and spiritual components of human nature including human soul. Within this context, the present paper primarily aims to discuss human manifestations of divine aesthetics as measured with Golden Ratio and associated indices with a particular and detailed emphasis on their potential link with the human cardiovascular system.

Sahaja yoga: A unique adjunctive approach for the management of cardiac arrhythmias?

Sahaja yoga (SY) is a unique meditative technique that has both spiritual and mundane aspects. Although SY has generally been regarded as a practice of spiritual and mental well-being, it is also closely associated with a variety of subtle influences on some organ systems. SY has been suggested to have some beneficial effects in a variety of psycho-somatic diseases [1]. Besides subtle effects throughout the whole body, sympatho-vagal regulation associated with SY technique has been proposed as the direct evidence of its beneficial effects on some organ systems including cardiovascular system etc. As describedbelow,SYpracticemaybe regarded as anadjunctiveoption for the management of a variety of cardiac arrhythmias primarily on the basis of its potential effects on the autonomic nervous system largely through unknown mechanisms. Autonomic imbalance including hyperactivation of sympathetic system has been known to be associated with the occurrence of life threatening conditions including acute coronary syndromes (ACS) and may directly trigger malign arrhythmic events in arrhythmia-prone subjects [2]. Hyperactivation of sympathetic system is also well known to prolong QT interval, and impair some indices of autonomic nervous system including heart rate variability (HRV) and heart rate turbulence (HRT) etc. thatmay serve asmarkers of arrhythmogenesis in susceptible subjects. Therefore, therapeutic strategies aiming at management of autonomic imbalance on topof conventional anti-arrhythmic therapy in arrhythmia-prone subjects have gained particular importance in the recent years. However, therapeutic options including beta blockers, sympathetic ganglion blockage etc. have limited value for the management of autonomic imbalance as these approaches generally

Systemic Inflammation and Arrhythmogenesis: A Review of Mechanistic and Clinical Perspectives

In the recent decades, systemic inflammation, as a clinical phenomenon, has been the focus of extensive research particularly with regard to its potential association with a variety of cardiovascular diseases including atherogenesis and acute coronary syndromes. Within this context, there also exists a potential link between systemic inflammation and cardiac arrhythmogenesis in various aspects. Accordingly, systemic inflammation response as measured with inflammation markers (cytokines, etc) has been investigated in the setting of well-known cardiac arrhythmias including atrial fibrillation and ventricular tachycardia. Based on current literature, clinical utility of these markers might potentially yield important prognostic implications in the setting of certain arrhythmogenic conditions. On the other hand, there exists limited data regarding therapeutic implications including clinical benefit of primary anti-inflammatory agents (corticosteroids, colchicine, etc) in the setting of arrhythmia management. The present review primarily aims to discuss potential triggers and fundamental mechanisms of inflammation-related arrhythmias along with a particular emphasis on clinical implications of systemic inflammation in the setting of cardiac arrhythmogenesis.

Golden ratio: A subtle regulator in our body and cardiovascular system?

Golden ratio, which is an irrational number and also named as the Greek letter Phi (φ), is defined as the ratio between two lines of unequal length, where the ratio of the lengths of the shorter to the longer is the same as the ratio between the lengths of the longer and the sum of the lengths. The so-called formula is a mathematical ratio and there exist a variety of examples in natural and man-made structures of great beauty. Moreover, golden ratio is expressed throughout the human body in some ways, including digits, uterus, teeth, and cardiovascular system. Although the association of Fibonacci series or golden ratio with systems and organs of human being has not been assessed in depth yet, the mainstream regulation of cardiovascular system seems to be associated with golden ratio. This raises the idea that there might have been a fine and subtle regulator in our body. In this article, we aimed to elaborate the relationship between the existence of golden ratio and the human body and to discuss the golden ratio and its association with cardiovascular system.

Anticoagulation in Patients With Left Ventricular Systolic Dysfunction and Sinus Rhythm When

Left ventricular (LV) systolic dysfunction and chronic systolic heart failure (HF) predispose to intraventricular thrombus formation and embolization resulting in stroke. Current guideline recommends the use of oral anticoagulants in patients with atrial fibrillation and history of previous thromboembolism. However, anticoagulant treatment in patients with LV systolic dysfunction with sinus rhythm and without history of previous thromboembolism is still on debate. Recent epidemiologic date has reported increased stroke rate in patients with systolic HF shortly after diagnosis. This review focuses on the possible causes of increased stroke rate shortly after the diagnosis of HF and subsequently suggests a rationale for the use of oral anticoagulant in these patient groups.

Headache response to nitrate in patients with coronary artery disease and systolic heart failure

countershock: effect of paddle electrode size and time interval between discharges. Circulation 1974;50:956–61. [11] Joglar JA, Kessler DJ, Welch PJ, et al. Effects of repeated electrical defibrillations on cardiac troponin I levels. Am J Cardiol 1999;83:270–2. [12] Ditchey RV, LeWinter MM. Effects of direct-current electrical shocks on systolic and diastolic left ventricular function in dogs. Am Heart J 1983;105:727–31. [13] Schluter T, Baum H, Plewan A, et al. Effects of implantable cardioverter defibrillator implantation and shock application on biochemical markers of myocardial damage. Clin Chem 2001;47:459–63. [14] Daubert JP, Zareba W, Cannom DS, et al. MADIT II Investigators. Inappropriate implantable cardioverter–defibrillators shocks in the MADIT II study: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008;51: 1357–65.