Risk Stratification for Sudden Cardiac Death in Heart Failure

Heart failure (HF) is a complex clinical syndrome in which structural / functional myocardial abnormalities result in symptoms and signs of hypoperfusion and/or pulmonary or systemic congestion at rest or during exercise. More than 80% of deaths in patients with HF recognize a cardiovascular cause, with most being either sudden cardiac death (SCD) or death caused by progressive pump failure. Risk stratification of SCD in patients with HF represents a clinical challenge. This review will give an update of current strategies for SCD risk stratification in HF.


Introduction
Heart failure is a complex clinical syndrome with structural abnormality or a myocardial which resulted in signs and symptoms of hypoperfusion and/or pulmonary or systemic congestion during rest or activity. 1,2udden cardiac death is defined as death caused by unexpected stop in blood circulation that occurs within one hour from the start of symptoms or during sleep. 3In the majority of cases, sudden cardiac death is triggered by arrythmia (e.g.ventricle tachycardia, ventricle fibrillation), although pulseless electrical activity (PEA) is recently reported as the cause of sudden cardiac death. 4isk stratification for sudden cardiac death in heart failure patients with reduced ejection fraction still becomes a clinical challenge.Recent guideline provides an algorithm according to left ventricle ejection fraction in which this parameter is considered as the only parameter to identify high risk patients. 5evertheless, current approaches cannot be used to stratify the population and risk spectrum with high accuracy.

Pathophysiology of Sudden Cardiac Death
The mechanism of sudden cardiac death in heart failure patients with reduced ejection fraction (HFrEF) is complex in nature and requires a chain of interaction between transient events with pathological basic substrate which triggers electric instability (Figure 1).In ischemic cardiomyopathy, sudden cardiac death is related to previously infarcted myocardial region near a thick scar that forms from time to time.Residual endomyocardial fiber can persist because the blood gives nutrition to this area in the ventricle (e.g. through retrograde perfusion through left atrial vein, retrograde perfusion through sinusoidal tract, or through oxygen diffusion from blood flow in ventricle through myocardium). 7In patients with systolic dysfunction that occurs after myocardial infarction, sudden cardiac death caused by non-arrythmia often occurs within the first hour to six weeks and is related to a mechanical complication of myocardial infarction itself (e.g.rupture in the left ventricle wall, rupture in the interventricular septum and acute mitral regurgitation). 8This showed that the proportion of sudden cardiac death caused by arrythmia and non-arrythmia to be the same after 1 month from myocardial infarction.This reason explains from the current guideline where implantable cardioverter defibrillator (ICD) is recommended in 40 days post myocardial infarction. 9,10In non-ischemic cardiomyopathy, the ventricular myocardium has multiple fibrosis area without significant scar. 11This finding explains why reentry only involves 40% of ventricular arrythmia mechanism in patients with non-ischemic cardiomyopathy, while the rest is caused by triggered activity process (for example early after depolarizations and delayed after depolarizations). 12,13he main mechanism of sudden cardiac arrest in heart failure patients with preserved ejection fraction (HFpEF) seems to be related to myocardial fibrosis which causes changes in regional conductive pattern and become the area of reentry. 14Furthermore, ischemia is thought to be a contributor that needs further investigation on ventricular arrythmia in HFpEF patients. 15Without considering the cause of heart failure and the value of left ventricular ejection fraction, in patients with advanced heart failure, arrythmia is triggered primarily by heart pump failure where around 60% of patients had severe bradyarrhythmia or electromechanical dissociation as the primary cause of sudden cardiac death. 16

Risk Stratification of Sudden Cardiac Failure in HFrEF
Even though several risk factors on sudden cardiac death has been known and was thought to play a role in HFrEF (Table 1), risk stratification to determine which patient is beneficial to ICD placement as an effort of primary prevention to sudden cardiac death still arises a question.

Risk Stratification of Sudden Cardiac Death in HFpEF
In a recent study involving HFpEF population, sudden cardiac death is reported to be one of the most common cause of death.In CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) study, it was shown that sudden cardiac death is found in 28% of death. 17Similar to this study, 26% of all cause of death in I-PRESERVE (Irbesartan in Patients with Hearth Failure and Preserved Ejection Fraction) study is related to sudden cardiac death. 18n daily clinical practice, risk evaluation to sudden cardiac death in patients with HFpEF specifically has still been a challenge, both from the variability of phenotype and high percentage of death due to non-cardiovascular.Table 2 described the risk factor in patients with HFpEF on sudden cardiac death.

Conclusion
Even though pharmacological and electrical therapy has advanced, sudden cardiac death is still the most common cause of mortality in patient with HFrEF.A pilot study has shown that left ventricle ejection fraction and ischemic process have been predictors to sudden cardiac death.
Nevertheless, epidemiological changes on sudden cardiac death require identification on risk stratification in the population.In regard to this, current imaging technique, ECG findings and genetic test can be used to improve the identification of individuals with high risk stratification which should be beneficial for specific approach to prevent sudden cardiac death (Figure 2).
On the other hand, patients with HFpEF also have high prevalence in sudden cardiac death.For this population, increasing the understanding of pathophysiological pattern of sudden cardiac death should improve risk stratification of sudden cardiac death.

Figure 1 .
Figure 1.Anatomical substrate and pathophysiology of sudden cardiac death in heart failure with reduced ejection fraction.PVCs: premature ventricular complex; QT: QT interval 6