**14. Treatment of sudden cardiac death**

*Sudden Cardiac Death*

**13. Beneficial effect of daily exercise in sudden cardiac death**

a concurrent activation of phophoinositide-3 kinase (PI3K) [73].

improved blood flow-mediated dilation [76].

Both physiological and pathological cardiac enlargement (hypertrophy) is caused by different stimuli and both are functionally distinguishable. A pathological stimulus is normally caused by a pressure overload due to either aortic stenosis or hypertension producing an increase in systolic wall stress. In turn, this results in a concentric type of hypertrophy. This process occurs when the heart develops a thick wall with relatively small cavities. [74]. ET can also induce an adaptation of the coronary artery circulation which is divided into two main processes. Firstly, angiogenesis is initiated leading to an expansion of the capillary network by the formation of new blood vessels which occur at the level of capillaries and resistance arterioles, but not in large coronary arteries [75]. The cellular and subcellular mechanisms underlying ET-induced angiogenesis are still unknown. A number of studies [76–78] have demonstrated that growth factors including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and angiopoietins (AQP) and their corresponding receptors are involved in the angiogenesis process. Studies have also shown that sprouting angiogenesis is associated with a number of proteases which are relevant for the breakdown of the capillary basement membrane. These functional proteins include matrix metalloproteinases (MMPs), urokinase, tissue plasminogen activator and plasminogen [76–79]. Cardiac muscle function is highly dependent on an adequate coronary blood flow due to high metabolic demand. Thus, coronary artery dysfunction can have a direct impact on myocardial function. It was demonstrated that an eight-week moderate-intensity exercise training regime in individuals with T2DM can significantly enhance endothelial cell function in the brachial coronary artery. This was associated with a significant

It is now known that repetitive exercise training sessions can stimulate other

adaptive changes in the myocardium contributing to both improved insulin sensitivity and metabolic health of the organ. A previous study has revealed that increased oxidative capacity and capillary density were observed in skeletal muscle in response to aerobic exercise [77]. Similarly, insulin sensitivity in adipose tissue is increased within 72-hours after completion of a 6-week exercise intervention [78]. Likewise, calcium homeostasis has a major role in the excitation contracting-coupling process of the heart and ET has been shown to improve significantly cardiac myocytes contractility during diabetes due to an improvement of Ca2+ homeostasis. It was reported that ET can also prevent the development of SCD and the dysregulation of SR protein content in an inducible animal model of T2DM [80]. It is now

The beneficial cardiac protection, following regular exercise training (ET) in diabetic patients, has been reported in both clinical and experimental animal studies. It is now known that acute endurance ET is accompanied with significant increase in maximum oxygen consumption and enhanced cardiac output, stroke volume and systolic blood pressure which are all associated with decreased peripheral vascular resistance. On the other hand, long-term cardiovascular adaptation to dynamic training results in increased maximal oxygen uptake due to increased cardiac output and arteriovenous oxygen difference. In contrast, strength exercise training induces little or no increase in oxygen uptake. Thus, endurance exercise predominantly produces volume load on the left ventricle (LV), and strength exercise causes largely a pressure load [72]. It is now well established that LV physiological hypertrophy due to daily endurance exercise training can result in a proportional increase in myocardial cell length and width without evidence of myocardial hyperplasia in the majority of cases. This beneficial process is mediated via an increase in the expression of cardiac insulin-like growth factor-1 (IGF-1) and

**146**

Therapy of SCD includes non-pharmacological and pharmacological interventions. There are a number of therapeutic options, but the main nonpharmacological therapy is the use of defibrillators [5, 6, 81–83]. However, there must be more community-based public access to defibrillation programs in order to save the lives of those patients who are more impacted. Other factors include screening of family members who are susceptible to arrhythmias and SCD and this in turn will help with early diagnosis and also and managing the arrhythmias. Generally, potential patients have to change their lifestyle habits by reducing their stress level, avoid smoking and drinking alcohol, eat a heart healthy Mediterranean diet and participate in moderate daily exercise. Moreover, potential patients should also education themselves about the signs and symptoms of SCD and how to obtain early treatment. Likewise, public health services globally should introduce health education on SCD to students, workers, patients and others. In terms of pharmacological intervention, SCD patients are treated mainly with beta blockers, ACE inhibitors, anti-arrhythmic drugs and in some cases, amiodarone. These drugs exert their beneficial effects via different cellular and subcellular mechanisms by slowing the rate and force of contraction of the myocardium [81].

It is now the general consensus that the implantable cardioverter-defibrillators (ICD) which was first implanted in patients in the 1980 is the mainstay life-saving and cost-effective clinical device in treating cardiac patients with dangerous abnormal life-threatening arrhythmias and also in the treatment of resuscitated survivors of sudden cardiac arrest substantially and with increased life expectancy compared to pharmacological therapies, including amiodarone [82]. ICD is also employed for primary prevention in high-risk patients, and in biventricular pacing of patients at high risk for arrhythmic events. More recent studies have reported that subcutaneous implantable cardioverter defibrillator (SIDC) is both safe and effective instead of the ICD as an alternative to prevent SCD [83]. The indications and use of the ICDs and SIDCs will continue to grow, resulting in increasing discussions about costs compared to other forms of therapy and the necessity of better selection of ICD/SIDC recipients depending on age, duration of the illness, risks and others [84]. Improvement of results of resuscitation from out-of-hospital cardiac arrest remains an important challenge. Both better methods to recognize asymptomatic patients at risk including genetic screening and development of new technologies to shorten the time interval between cardiac arrest and the resuscitation effort are urgently needed [84]. Further information can be found in the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and prevention of sudden cardiac death [85].
