The effects of nicotine and cigarette smoking on cardiac electrophysiology.

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in vivo effects of nicotine and non-nicotine constituents of cigarette smoking on cardiac ion channels, (b) the direct and indirect effects of the autonomic nervous system on cardiac electrophysiology, and (c) studies of acute and chronic effects of cigarette smoking in humans. Chapter 2 consists of two studies in which we used cotinine levels to investigate the differences in baseline cardiac electrocardiogram between chronic smokers and non-smokers, and to define smoking status and its burden. We also explored the relationship between urinary catecholamines, cotinine, and electrocardiographic changes. Chapter 3 features the 2 x 2 factorial experimental study designed to compare the acute effects of cigarette smoking and nicotine, with and without a β-blocker (propranolol). We found that chronic cigarette smoking was associated with a shortened PR segment at baseline, and that dopamine possibly mediates this effect. There was also (corrected) QT interval shortening with increased cotinine levels. This experimental study revealed that the non-nicotine constituents in cigarette smoking were mainly responsible for PR segment shortening, through β-adrenoreceptors. Other evidence revealed that, although nicotine in cigarette smoke is primarily responsible for sympathetic activation and (corrected) QT interval shortening, it is the non-nicotine constituents that depress the ST segment. Collectively, acute and chronic exposure studies indicate that smoking may promote cardiac arrhythmia, primarily via β-adrenoreceptors, causing acceleration of dromotropy and ischemia (non-nicotine mediated), and ventricular repolarization (nicotine-mediated). This research elucidated a major physiological mechanism driving the effect of cigarette smoking and nicotine on cardiac electrophysiology. Consequently, these findings will inform U.S. Food and Drug Administration of tobacco and nicotine-containing products’ impact on the human cardiac electrical system, and potentially help regulate alternative forms of nicotine delivery and protect public health

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

Peer reviewe

Emergency Cardiology

This fully revised and updated second edition offers practical advice on the diagnosis and management of acute cardiac conditions. Throughout the book, the authors employ an evidence-based approach to clinical practice and provide detailed guidance for day-to-day practice in a wider variety of settings-from the emergency department to intensive care and the cardiac ward. Authored by four cardiologists with extensive experience in the emergency setting, it includes the results of the most groundbreaking clinical trials. Topics include arrhythmias, acute aortic syndromes, pericarditis, and cardiac trauma

Predicting Death in Chronic Heart Failure: Electrocardiographic, Autonomic and Neuroendocrine Risk Assessment

Chronic heart failure is a common condition with an adverse prognosis. Despite optimal treatment, ambulant patients with mild symptoms have an annual mortality of more than 15%. Clinical, exercise, echocardiographic and haemodynamic variables are known to carry prognostic information, but accurate identification of those most likely to die remains difficult. This work assessed abnormalities of ventricular activation and repolarisation respectively using the signal-averaged electrocardiogram and interlead QT interval variability of the standard 12-lead electrocardiogram. Disordered autonomic function is common in cardiac failure. This was assessed by 24 hour heart rate variability and baroreflex sensitivity. Plasma noradrenaline and plasma atrial and brain natriuretic peptide levels were used to assess neuroendocrine activation, a hallmark of chronic heart failure. These measures were determined prospectively and compared with known prognostic variables in a chronic heart failure population. Original Hypotheses 1. Sudden cardiac death in patients with heart failure is caused predominantly by malignant ventricular arrhythmias. These may be predicted by non-invasive markers of the arrhythmogenic substrate i.e. signal-averaged ECG, QT dispersion; triggers i.e. non-sustained ventricular tacycardia, and autonomic modulators i.e. heart rate variability and baroreflex sensitivity. This assessment will provide additional independent prognostic information on mortality risk in patients with chronic heart failure. 2. Markers of neuroendocrine activation and autonomic dysfunction would predict progression of chronic heart failure, and all-cause and progressive heart failure death. Discussion Chronic heart failure is a common, growing and major public health care burden. Identifying high-risk patients suitable for aggressive intervention, optimisation of treatment and prevention of death is of great importance. Despite extensive study by many investigators, identification of those patients who are most likely to deteriorate and die remains difficult. In this well-characterised cohort of patients with chronic heart failure, neuroendocrine activation assessed by plasma BNP or plasma Noradrenaline predicted cardiovascular death. This information was additive to and independent of other powerful prognostic variables including NYHA class, age, left ventricular ejection fraction, peak VO2 and presence/absence of bundle branch block. However, plasma BNP may be measured from a simple venous blood sample, and has been proven to be stable at room temperature over 72 hours. It is inexpensive, and requires no specialised equipment at the bedside. Direct assay kits are now available which both simplify and lessen the cost of its measurement. This has implication for its more widespread use. Interestingly, a positive SAECG, the presence of non-sustained ventricular tachycardia and depressed baroreflex sensitivity all identified a patient cohort at high risk of sudden death. Linking this data with the prognostic importance of depressed baroreflex sensitivity in the study cohort with recent data on "electrical storms" in patients with implantable cardioverter-defibrillators, it suggests that these markers might be used to identify patients who would benefit from these devices. (Abstract shortened by ProQuest.)

The prevalence and clinical correlates of atrial fibrillation in those aged 70 and over in the Hai district of northern Tanzania

MD ThesisBackground The elderly population in sub-Saharan Africa (SSA) is increasing rapidly, with a consequent rise in noncommunicable disease (NCD). The prevalence of stroke disease is already known to be higher in SSA than in highincome countries (HICs). There are currently no communitybased data on the prevalence of atrial fibrillation (AF) or hypertension (HTN) specifically in elderly SSAs. Design Cross-sectional community-based observational study, with case-control sub-group analysis. Methods Approximately one quarter of the population (n=2232) aged 70 and over of a demographic surveillance site in the rural Hai district of Northern Tanzania underwent screening for AF by 12-lead electrocardiography (ECG), in addition to a subgroup undergoing ambulatory cardiac monitoring looking for paroxysmal AF (n=232). Demographic data were also collected along with disability level, body mass index and blood pressure (BP). The gender-specific prevalence of AF, paroxysmal AF and hypertension in each 5-year age band was determined. ECGs were examined digitally, and P wave indices in this population were described. Results There were only 15/2232 (12 female) participants with AF, giving an age-adjusted prevalence of 0.64%. 6/233 (2.6%) had at least 1 paroxysm of AF, suggesting a total overall prevalence of AF as high as 3.2%.1553/2232 had a BP ≥140/90, giving an age-adjusted prevalence of hypertension of 69.7%. Women had a higher mean systolic (166.0 vs. 154.3mmHg) and diastolic (89.3 vs. 83.1mmHg) BP. Conclusions The prevalence of AF is much lower in this population than elsewhere in the world and points towards potential protective genetic and environmental factors and some differences in risk factor profile. However, the low prevalence of AF is particularly interesting in the setting of a prevalence of hypertension and stroke that is similar to African- Americans in HICs.Peel Medical Research Trust, Tanzania

Emergency Cardiology

This fully revised and updated second edition offers practical advice on the diagnosis and management of acute cardiac conditions. Throughout the book, the authors employ an evidence-based approach to clinical practice and provide detailed guidance for day-to-day practice in a wider variety of settings-from the emergency department to intensive care and the cardiac ward. Authored by four cardiologists with extensive experience in the emergency setting, it includes the results of the most groundbreaking clinical trials. Topics include arrhythmias, acute aortic syndromes, pericarditis, and cardiac trauma

Case Reports

Abstracts of the 29th Annual Scientific Meeting of the Indonesian Heart Association (ASMIHA) 1st ASMIHA Digital Conference, 23-25 October 202