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Together with cancer cardiovascular disease remains one of the leading causes of death worldwide. A significant proportion of these deaths involve sudden cardiac death. This is defined as a sudden—non-traumatic—death occurring within one hour of the onset of any symptoms. In most cases, dangerous arrhythmias originating from the heart's ventricles are the underlying cause of sudden death. In 2022, it was estimated that every hour, a family in Belgium was confronted with the sudden loss of a loved one. Moreover, this does not affect only the elderly—up to 40% of cases occur in a younger (<60 years), working-age population. Despite the rapid advancement of healthcare, survival rates following an acute event remain very poor. Of the people who suddenly collapse outside the walls of a hospital, only 1 in 10 will leave the hospital alive. To minimize the impact of sudden death on the healthcare system, several elements are important. At the population level, it is crucial to pay sufficient attention to general cardiovascular prevention, and efforts must also be made to ensure basic knowledge of resuscitation among as large a proportion of the population as possible. Immediate action in the case of sudden cardiac arrest is key to successful resuscitation. At the individual patient level, it is important to treat heart diseases as effectively as possible and to be mindful of the risk of sudden cardiac death. In high-risk patients, additional measures are necessary to prevent a sudden cardiac death or avoid a recurrence. Since the 1980s, the option exists to implant a defibrillator capable of stopping dangerous ventricular arrhythmias through rapid pacing or a shock. That said, implantation and follow-up of such devices come with a significant cost. Even if financial resources were not a limiting factor, there remains the risk of potentially life-threatening complications. It is therefore crucial to select the right patients for an implantable defibrillator. When we take a closer look at current clinical practice regarding implantable defibrillators, it becomes apparent that only a minority of implantations are performed in women (approximately 20%), even though epidemiological data show that the difference in the prevalence of cardiovascular diseases between women and men is not that substantial. Women who did receive a defibrillator were on average younger, but with more severe symptoms of heart failure. In addition, a greater proportion of women received a defibrillator as part of secondary prevention—meaning after surviving a previous sudden cardiac arrest. The findings in Chapter 3 therefore suggest that women are under-treated and must present a more obvious risk of sudden death to be treated. Chapter 4 shows that defibrillators are rarely implanted in patients over 80, despite the fact that 11% of these patients die within a year, for example due to cancer. It is therefore essential to perform a strict cost-benefit analysis in this specific patient group, also taking into account the patient's wishes—especially since, near the end of life, some patients do not fear a sudden death. Apart from a patient's age, socioeconomic status also appears to impact survival after defibrillator implantation. Poorer patients experience worse 3-year survival after implantation. Moreover, the expertise of the implanting center also has an effect on survival: centers with a high volume of ICD implantations show better outcomes. It should be noted that in Belgium, there is a clear north-south divide, with high-volume centers predominantly located in the north and low-volume centers in the south, where average life expectancy is also lower. The findings from Chapter 5 are therefore highly relevant to healthcare policymakers. To further optimize defibrillator implantation, investment in effective risk stratification is essential. A standard electrocardiogram (ECG) is an accessible and inexpensive test that can be used for such stratification. QRS fragmentation is an ECG parameter that reflects heterogeneous electrical activation of the heart and may have prognostic value. However, visual interpretation of fragmentation is dependent on the individual observer and therefore not highly reproducible. In Chapter 6, machine learning—a form of artificial intelligence—was used to attempt to link QRS fragmentation to clinical outcomes after defibrillator implantation. Our analyses did not yield predictive value. In retrospect, it appears that our methodology requires refinement, as the current algorithm estimates the probability that a physician would label a signal as fragmented, rather than actually quantifying true fragmentation. Finally, Chapter 7 focused on further unraveling the mechanisms behind dangerous ventricular arrhythmias. Since ischemic heart disease is the most common cardiac condition leading to sudden cardiac death, a porcine model of acute myocardial infarction was used to investigate the impact of sudden blood pressure elevation—a potential trigger of arrhythmias. When comparing control pigs to infarcted pigs, inducing sudden blood pressure elevations produced a similar hemodynamic response in both groups (e.g., slowing of the heart rate). However, a sudden rise in blood pressure led to increased electrical heterogeneity only in the infarct group, which may be considered pro-arrhythmic.