Sercan Okutucu

Re: Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Sir, In recent years, a marked interest has emerged in the clinical evaluation of the cardiac autonomic functions and cardiorespiratory fitness. Heart rate recovery (HRR) after graded exercise is one of the commonly used techniques which reflect autonomic activity and are positively correlated with cardiovascular fitness indices such as maximum oxygen uptake and endurance capacity. HRR is defined as heart rate difference between the maximal heart rate on exercise and the heart rate during recovery phase. HRR indices are calculated by subtracting 1st, 2nd and 3rd minute heart rates during recovery phase from the maximal heart rate obtained during exercise stress testing, designated HRR1, HRR2 and HRR3, respectively. The period of recovery after exercise is accompanied by changes in autonomic tone which are clinically characterised by the gradual return of haemodynamic parameters to their previous resting levels within minutes. Upon cessation of exercise, sympathetic withdrawal and fast parasympathetic reactivation occurs, especially within the 1st minute. Therefore, HRR1 is important when evaluating the cardiorespiratory fitness and cardiac autonomic functions. We read with great interest the Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study reported by Lane-Cordova et al. published recently in BJOG. In this key paper, Lane-Cordova et al. sought to determine whether there is an association of cardiorespiratory fitness and exercise test parameters [exercise systolic blood pressure (SBP), and HRR at 2nd minute (HRR2)], measured years preceding pregnancy, with preterm birth (PTB) and small-for-gestational-age (SGA) delivery. They observed that cardiorespiratory fitness measured prior to pregnancy was lower in women who reported having PTB/SGA, whereas exercise SBP andHRR2were higher. Althoughwomen who had PTB/SGA were less fit, fitness was not associatedwith PTB or SGA once other risk factors were considered. Haemodynamic responses to exercise were not associated with PTB or SGA in the whole cohort. However, in the subset of women who performed the exercise test <5 years prior to the index birth, higher HRR2 was associated with PTB/SGA. We have two comments/questions regarding with this paper. First, the presence of higher HRR2 and lower cardiorespiratory fitness in women who reported having PTB/SGA is somehow contradictory. In previous studies, higher HRR indices and better cardiorespiratory fitness have usually been positively correlated with each other. How do the authors explain their findings about this issue? Secondly, did the authors analyse HRR1 in the study population? It might better to analyse the association between birth outcomes and HRR1, which is a better index than the other indices of HRR.&

ECG in Cardiac Chamber Enlargement

The purpose of this chapter is to review the role of the ECG in the diagnosis of cardiac chamber enlargement. Electrocardiographic criteria for the diagnosis of ventricular hypertrophy and atrial enlargement are reviewed. The electrocardiographic theory underlying the recognition of hypertrophy or dilation incorporates several physical principles that may lead to meaningful correlations with the tissue mass, chamber diameter and intracardiac blood volume. However, there are limiting factors related to the variable orientation of the heart in the chest and variable extracardiac factors. In this chapter, basic ECG criteria for cardiac chamber enlargement will be summarized. Enlargement of different cardiac chambers and different patterns of hypertrophy will be reviewed with many demonstrative ECG samples.

Fundamentals of ECG

The electrocardiogram, or ECG, is a simple diagnostic test which records the electrical activity of the heart over a set time via the process of attaching a series of electrodes on a patient’s body. Many medical students, and even some more experienced medical professionals, struggle with ECG interpretation.

ECG in Conduction Disturbances

The conducting system of the heart consists of cardiac muscle cells and conducting fibers that are specialized for initiating impulses and conducting them rapidly through the heart. They initiate the normal cardiac cycle and coordinate the contractions of cardiac chambers. Conduction disturbances can occur anywhere in the specialized conduction system beginning with the sino-atrial connections, the AV junction, the bundle branches and their fascicles, and ending in the distal ventricular Purkinje fibers. Standard 12 lead ECG can give much information regarding normal cardiac electrical conduction and its disturbances. In this chapter, normal cardiac conduction system will be reviewed, and conduction disturbances will be examined.

ECG in Coronary Artery Disease

The ECG remains the most commonly used and, perhaps most important of available cardiovascular diagnostic tools; especially for rapid assessment of patients with symptoms compatible with acute coronary syndromes. ST elevation is thought to represent transmural ischemia due to thrombotic occlusion of an epicardial artery. On the other hand, occasionally, patients may have acute ischemia due to complete occlusion of an epicardial artery, but their ECG may show minor degree of ST elevation. Moreover, certain distinct ECG patterns have been described in patients presenting without ST elevation that are associated with higher risk. Recognition of these specific patterns of ischemia, as well as common patterns suggesting non-ischemic ST elevation is crucial. However, resting ECG could be entirely normal in the presence of severe coronary artery disease. In this chapter, ECG changes in spectrum of coronary artery disease will be reviewed.

ECG in Miscellaneous Conditions

The ECG remains the most commonly used and, perhaps most important of available cardiovascular diagnostic tools in arrhythmia, conduction disturbances, chamber enlargement and coronary artery disease. However, ECG can be very useful in different clinical situations including acute pericarditis, electrolyte abnormalities, drug effects, hypothermia, stroke and various other conditions. In this chapter, use of ECG in miscellaneous conditions will be overviewed.

ECG Rhythm Interpretation

Electrical activation of the heart is required for the mechanical activation of the heart. The electrical activation of the heart can be picked up using skin electrodes strategically placed on the body. The ECG is simply a recording of the sum of all the electrical activity in the heart. Because of this, to be able to read an ECG we need to have a good understanding of the conduction of the electrical impulse through the heart. In this chapter; normal rhythm, classification of arrhythmias, disturbances of impulse formation, conduction disturbances and frequently encountered arrhythmia will be summarized. In addition, some of the practical key points will be addressed.

Cardiac autonomic recovery in type 2 diabetes mellitus and coexistent hypertension: Cutoff values, dipping status, and medications

We read with great interest the recent article entitled ‘Co-Existence of hypertension worsens post-exercise cardiac autonomic recovery in type 2 diabetes’ by Verma et al1 in your distinguished journal. In their well-designed article, the authors investigated the effect of coexistence of hypertension (HT) on cardiac autonomic functions assessed by heart rate recovery (HRR) and heart rate variability (HRV) in type 2 diabetes mellitus (T2DM). We have three comments regarding this study. First, HRR at 1 minute (HRR1min) and 2 minutes (HRR2min) in this study was still within the normal limits (HRR1min: 27.3 bpm and HRR2min 42.8 bpm for patients with T2DM and HT). Although several variables influence HRR, suggested thresholds for abnormality are 12 bpm at 1 min for the upright position, 18 bpm at 1 min for the supine position, and 22 bpm at 2 min for the sitting position.2 Although HRR indices were lower in patients with T2DM and HT, these values are not enough for diagnosis of cardiac autonomic dysfunction. As a second comment, circadian blood pressure patterns of patients were not reported in the present study. Nocturnal dipping of arterial blood pressure is a part of the normal circadian pattern, and non-dipping is associated with severe end-organ damage and increased risk of cardiovascular events, especially in hypertensive patients.2 Blunting of the nocturnal fall in blood pressure (BP) associates with lower HRR indices after graded maximal exercise in both normotensive and hypertensive groups, and this relationship is more prominent in the hypertensive group.3 As a final comment, use of statins was common in patients with T2DM and/or HT, and there was no use of statin in the healthy control group. It has been demonstrated that statins improve autonomic function, as reflected by an increase in HRV.4 Furthermore, statin treatment could significantly increase parasympathetic modulation of the heart rate.5

Cardiac autonomic evaluation in breast cancer patients: role of cytokines and heart rate recovery

We read with great interest the recent article entitled “Cardiac autonomic modulation impairments in advanced breast cancer patients” by Arab et al. [1] in your distinguished journal. In their well-designed paper, the authors compared cardiac autonomic modulation in early versus advancedstage breast cancer patients before any type of cancer treatment and investigated associated factors. They evaluated cardiac modulation by heart rate variability (HRV) and assessed factors of anxiety, depression, physical activity, and other detailed clinical parameters. The advanced-stage cancer group had lower vagal modulation than early stage and benign pathologies; also, the advanced-stage group had lower overall HRV compared to benign conditions. Authors concluded that vagal cardiac autonomic modulation is inversely associated with breast cancer staging. In addition, they suggested implementation of HRV analysis in baseline assessment and clinical follow-up of cardiac monitoring in cancer patients. We have two comments and contributions regarding this issue. First, we suggest the authors to include serum cytokines in their future studies about cardiac autonomic evaluation in breast cancer. Cytokines are highly inducible secretory proteins that mediate intercellular communication in the immune system [2, 3]. They are grouped into several protein families which are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. The cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) are critical mediators of the inflammatory response. Inflammation correlates with increased invasiveness and poor prognosis in many types of cancer, including breast cancer. Numerous studies have also linked these cytokines to breast cancer progression [2–4]. The cross-talk between the immune system and the brain relies, therefore, not only on classical humoral pathways, but also substantially on recently discovered neural pathways [5, 6]. Vagal afferent sensory fibers play a vital role in the communication between body and brain when inflammation is occurring. Cytokines stimulate vagal afferents and IL-1, IL-6, and tumor necrosis factor-α (TNFα), correlate negatively with different HRV parameters of parasympathetic activity [5, 6]. The immune system is a still underestimated physiological and pathophysiological determinant of HRV dynamics. Thus, it would be better to include the levels of cytokines in a study evaluating the cancer stages and cardiac autonomic indices. As a second comment, it would be interesting to assess heart rate recovery (HRR) in this study. HRR after graded exercise is one of the commonly used techniques which reflect autonomic activity [7]. HRR indices show the rate of decline in the heart rate (HR) after the cessation of exercise test and are defined as HR difference between the maximal HR on exercise and the HR during recovery phase. An attenuated HRR, which is defined as the inadequate decline in HR immediately after exercise, reflects reduced parasympathetic activity [8]. The decline in HR during recovery is principally due to a reactivation of parasympathetic activity, mostly in the early recovery period [7]. HRR indices have been identified as a powerful and independent predictor of cardiovascular and all-cause mortality in healthy adults, in those with cardiovascular diseases and systemic disorders. Currently, the most common method used to detect anthracycline-induced cardiotoxicity is the evaluation of functional parameters by echocardiography. Detection of anthracycline-induced cardiotoxicity at an early stage is still disputed. We have ongoing research assessing HRR indices * Sercan Okutucu sercanokutucu@yahoo.com

Inflammatory Biomarkers for Predicting High SYNTAX and SYNTAX II Scores

We read the recent article entitled “Assessment of relationship between C-reactive protein to albumin ratio and coronary artery disease severity in patients with acute coronary syndrome” by Cagdas et al with great interest. They demonstrated that the inflammatory status, reflected by the decreased albumin level, increased C-reactive protein (CRP) level, and higher CRP to albumin ratio (CAR), was closely associated with severe coronary artery disease (CAD) determined using the synergy between percutaneous coronary intervention with TAXUS and cardiac surgery (SYNTAX) and SYNTAX II scores. Moreover, they indicated that decreased albumin and increased CAR were independent predictors of high SYNTAX and SYNTAX II scores. SYNTAX score, which was established during the SYNTAX trial, is a helpful tool for treatment decisions regarding the complexity of the (CAD). SYNTAX II provides greater prognostic accuracy in clinical settings for patients with CAD and acute myocardial infarction. Endothelial dysfunction, oxidative stress, and many inflammatory biomarkers play a crucial role in the formation and progression of atherosclerosis. Many easily available inflammatory and oxidative biomarkers including red cell distribution width, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, monocyte to high-density lipoprotein cholesterol ratio, serum total bilirubin, serum uric acid, and serum vitamin D have been demonstrated to be independent risk factors and novel prognostic markers for the extent, severity, and complexity of CAD and cardiovascular events. In their study, Cagdas et al did not report data regarding these easily available hematological and biochemical parameters related to inflammation and oxidative stress. In addition, there was no information regarding medication usage. Finally, the multivariate logistic regression analysis lacks these parameters. So, the study findings regarding independent predictors of a high SYNTAX and SYNTAX II scores may be misleading. In conclusion, we believe that the combined information of multiple inflammatory biomarkers could be useful and more accurate for predicting the severity of CAD.