▪ Infiltrative (e.g., sarcoidosis, amyloidosis, hemochromatosis, Fabry)

▪ Arrhythmogenic right ventricular cardiomyopathy

▪ Takotsubo cardiomyopathy

▪ Left ventricular non-compaction cardiomyopathy

▪ Myocarditis (e.g., acute, giant cell, chronic lymphocytic)

▪ Neuromuscular diseases (e.g., muscular dystrophy, Friedreich’s ataxia, myotonic dystrophy)

▪ Congenital cardiomyopathy (corrected or uncorrected)

▪ Commotio cordis

○Primary arrhythmias:

▪ Long QT syndromes

▪ Short QT syndrome

▪ Brugada syndrome

▪ Early repolarization syndromes

▪ Catecholaminergic polymorphic ventricular tachycardia

▪ Idiopathic ventricular fibrillation

▪ Wolff-Parkinson-White syndrome (WPW)

○Non-cardiac causes include:

▪ Sudden death during extreme physical activity

▪ Drug overdose

▪ Toxic/metabolic imbalances (e.g., hyper- or hypokalemia, thyroid storm, adrenergic storm, acidosis)

▪ Acute intracranial hemorrhage

▪ Massive pulmonary embolus

▪ Asthma (or other pulmonary condition)

▪ Aortic dissection

Epidemiology and Clinical Features

○SCD affects 200,000–300,000 per year in the United States (≈0.1% population incidence/year).

▪ It is the initial clinical presentation in up to 20% of patients with CAD.

▪ SCD accounts for up to 50% of CAD deaths.

○The highest proportion of SCD events occurs in the highest-risk subgroups.

▪ Thirty percent of all SCD events occur in the highest-risk subgroup; however, the absolute number of deaths is relatively small owing to the subgroup being very focused.

• This limits the overall population impact of intervention.

▪ Fifty percent of all SCD events occur among subgroups of patients thought to be at relatively low risk for SCD.

• Given the high absolute number of events in this population, the population impact of intervention is potentially great, if these patients could be identified.

Prognosis

○Survival falls rapidly after the initial minutes from the onset of cardiac arrest.

○The likelihood of survival to discharge is 23% for witnessed cardiac arrest, vs. 4% for unwitnessed arrest.

○Recurrence is highest in the first 6–18 months post index event.

General Risk Stratification

Table 14.1 Factors Affecting Risk of SCD

HF: heart failure; LVSD: LV systolic dysfunction (LV ejection fraction [LVEF] <30%–40%); MI: myocardial infarction; SAECG: signal-averaged electrocardiogram (ECG).

○SAECG improves the signal-to-noise ratio of a surface ECG, thus facilitating the identification of low-amplitude signals at the end of the QRS.

▪ The late potentials indicate regions of abnormal myocardium, which serve as the substrate for reentrant tachyarrhythmia.

○Abnormal findings include:

▪ Filtered QRS duration (fQRS) ≥114 ms

▪ Root mean-square voltage of terminal 40 ms (RMS40) <20 mcV

▪ Duration of low amplitude signals (<40 μV) in the terminal QRS ≥38 ms

○Interpretation

▪ Presence of abnormal SAECG increases the risk of arrhythmic events 6- to 8-fold post myocardial infarction (MI).

• May signal the need for further risk stratification (i.e., EPS).

▪ High negative predictive value (NPV; 89%–99%).

• Normal SAECG is associated with a <5% change of inducible VT at EPS.

T-Wave Alternans (TWA)

○TWA is a beat-to-beat fluctuation in the amplitude or morphology of the T wave.

○TWA is typically measured on ECG with exercise.

○Its presence identifies high-risk patients (post MI and those with ischemic or non-ischemic dilated cardiomyopathy [NIDCM]).

○Its absence offers good discriminative function (i.e., high NPV).

Heart Rate Variability (HRV)

○HRV is a beat-to-beat variation in cardiac cycle length (CL) due to the autonomic influence on the SN.

▪ It reflects a continuous assessment of the basal sympathovagal influence.

○Derived from 24-hour Holter monitoring.

○HRV independently predicts the risk of SCD and total mortality post MI (with/without LV dysfunction).

Heart Rate Turbulence (HRT)

○HRT is short-term oscillation of cardiac CLs after spontaneous PVCs.

▪ Normally, there is a brief, baroreflex-mediated HR acceleration followed by a gradual deceleration.

▪ In high-risk patients, the typical HRT response is blunted or missing, reflecting reduced baroreflex sensitivity.

○HRT is derived from 24-hour Holter monitoring.

▪ RR intervals surrounding spontaneous PVCs (that fulfill criteria with respect to prematurity and compensatory pause) are averaged to create a “local tachogram.”

○HRT independently predicts the risk of SCD and total mortality post MI (with/without LV dysfunction).

○Baroreflex sensitivity offers a quantitative assessment of the ability of the autonomic system to respond to acute stimulation.

▪ Most commonly it is performed by analyzing bradycardic response to intravenous phenylephrine bolus.

▪ HR slowing in response to increased blood pressure (BP) indicates the baroreflex tone; a reduced response indicates increased risk.

○Baroreflex sensitivity independently predicts risk of SCD and is additive to HRV and TWA.

Cardiac Meta-Iodobenzylguanidine (MIBG) Scintigraphy or Positron Emission Tomography (PET)

○MIBG indicates sympathetic innervation; PET shows myocardial metabolism.

○Both are possibly better than SAECG, HRV, and QT dispersion at predicting SCD in patients with chronic HF.

Cardiac Magnetic Resonance Imaging (MRI)

○MRI allows for scar quantification and characterization (dense vs. heterogeneous).

○MRI is also useful to identify patients at high risk for ventricular arrhythmias (dilated cardiomyopathy [DCM], HCM, ARVC, post-MI).

Electrophysiology Testing (EPS)

○In general, the positive predictive value (PPV) is about 10% with a NPV of about 95%; however, the overall utility depends on the underlying pathology.

▪ EPS is most useful for ischemic heart disease as well as VT induction in the context of ablation.

▪ EPS for dilated cardiomyopathy or inherited arrhythmia syndromes suffer from the following issues:

• Low inducibility

• Low reproducibility of EPS

• Limited PPV of induced VT

▪ EPS for syncope due to suspected bradyarrhythmia suffers from the following issues:

• Limited sensitivity with episodic bradycardia and syncope

• Common false positive (~25%) and false negative tests

CAD

○Epidemiology

▪ CAD is present in 60%–75% of SCD deaths.

• A high proportion of those experiencing SCD have multivessel disease.

• Only 30%–40% of these will have acute infarction.

• It is estimated that 20% of first MI present as SCD.

○Risk factors for SCD:

▪ Risk factor with good sensitivity but poor specificity:

• Reduced LVEF (<40%; particularly if the LVEF is <30%)

▪ Risk factors with good specificity but poor sensitivity include:

• Previous cardiac arrest or a history of aborted SCD

▫ Transmural MI (STEMI): VT/VF <48 h post event does not imply a worse prognosis.

▫ Non-transmural MI (NSTEMI): VT/VF <48 h post event confers increased long-term risk.

• Syncope

• Non-sustained VT (spontaneous)

• Inducible VT at EPS

▫ If LVEF <40%, there is a 35%–45% yearly risk of SCD with an inducible VT at EPS.

▫ If no inducible VT is present at EPS the annual risk of SCD is <5%.

• Other

▫ Late potentials on SAECG

▫ Decreased HRV, microvolt TWA, HRT

▫ Increased QRS duration, QT dispersion, or TWA

Non-Ischemic Dilated Cardiomyopathy (NIDCM)

○Epidemiology

▪ 5-year mortality of ~20%

▪ 30% of all deaths are sudden: VT/VF > bradyarrhythmia

○Risk factors for SCD:

▪ Previous cardiac arrest or a history of aborted SCD

▪ History of syncope

▪ EF <35%

▪ Non-sustained VT

▪ Induction of monomorphic VT at EPS (absence of VT does not confer lower risk)

Incidence

○Annually, 1–3 SCD per 100,000 (RR of 2 to 3 vs. non-athletic peers)

Causes

○HCM (30%–40%)

○Congenital coronary artery anomalies (15%–20%)

○ARVC (5%)

○Ion channel disorders (<5%)

○Autopsy negative (<5%)

○Other causes include:

▪ Myocarditis

▪ Trauma: Commotio cordis or trauma involving structural cardiac injury

▪ Aortic: Ruptured aortic aneurysm, aortic valve stenosis

▪ Atherosclerotic CAD

▪ Asthma (or other pulmonary condition), heat stroke, drug abuse (i.e., cocaine)

Screening

○Annual clinical history (personal and family) and physical examination

○ECG

▪ Common abnormalities in athletes (95%)

• Sinus bradycardia, first-degree AV block

• Notched QRS in V1 (incomplete RBBB), early repolarization, Isolated voltage criteria for left ventricular hypertrophy (LVH)

▪ Uncommon abnormalities in athletes (<5%)

• Chamber enlargement or hypertrophy: Left atrium, right ventricle

• Bundle branch or fascicular block

• Pathologic Q waves, ST segment depression, T-wave inversion

• Brugada-like early repolarization

• Long or short QT interval

• Ventricular arrhythmias

○If the history or ECG is positive, then proceed to further investigations:

▪ ECG, stress test, 24-hour Holter monitor, cardiac MRI, angiogram, EPS

○HCM

▪ Restrict the patient to low-intensity/recreational sports (particularly with obstructive variant).

○Gene carriers without a phenotype (HCM, ARVC, DCM, channelopathies)

▪ Restrict to low-intensity/recreational sports (European Society of Cardiology); no restriction (Bethesda 36).

○Ion channelopathies (QTc >440 ms in men and >460 ms in women):

▪ Restrict to low-intensity/recreational sports.

▪ A recent trend is to favor less restriction, especially if adequately β-blocked.

○Brugada syndrome, catecholamine-induced polymorphic VT

▪ Restrict to low-dynamic/low-static sport.

▪ Recent trend to less restriction

○Marfan syndrome

▪ Restrict to low-intensity/recreational sports unless the aortic root <40 mm.

▪ If < moderate-severe MR and no family history of aortic dissection or SCD, restrict to moderate-intensity competitive sports.

○WPW syndrome

▪ No restriction if asymptomatic (use care in dangerous environments)

▪ Post-ablation may resume competitive sports after 1–3 months

○PVCs or NSVT (<10 beats; <150 bpm; suppresses with exercise)

▪ No restriction if asymptomatic or structurally normal heart

▪ If CV disease, only allowed to participate in low-intensity/non-competitive sports

○ICDs

▪ Restrict to low-intensity/recreational sports without risk of device trauma.

CHANNELOPATHIES

Channelopathies are rare, heritable syndromes.

Long QT Syndrome (LQTS)

General Information

○The incidence of LQTS is 1 in 2500.

○LQTS accounts for 3000–4000 annual sudden deaths in childhood in the United States.

○Mutations are more frequent than the clinical phenotype:

▪ The average QTc penetrance is 25%–60%.

▪ Only 35%-40% of gene carriers are identified by clinical diagnostic criteria.

▪ Exercise testing improves detection and genetic prediction.

Table 14.3 Classification of LQTS Types

○LQT7 – Andersen-Tawil syndrome

▪ KCNJ2 mutation leads to loss of function alters inward rectifier K current through the Kir2.1 channel.

▪ Clinical

• Potassium-sensitive periodic paralysis

• Dysmorphic features: Short stature, hypertelorism, palate defect, broad nasal root

▪ ECG: Pseudo long QT with prominent U wave

▪ Ventricular arrhythmias: Very large PVC burden (up to 50% ectopy), bidirectional VT

▪ Prognosis: Benign

Epidemiology and Clinical Features

○LQTS is mostly asymptomatic.

○Common symptoms include syncope, seizures, and cardiac arrest.

▪ Sensorineural deafness (Jervell & Lange-Nielsen: Autosomal recessive)

▪ Periodic paralysis (Andersen-Tawil: Autosomal dominant heterozygote)

○Family history

▪ Positive for LQT or SCD

12-Lead ECG

○Measuring the QT interval

▪ Average QT and RR interval over ≥3 QRS complexes in ≥3 ECG leads.

▪ Measure from the onset of the QRS complex to the end of the T wave (the point where the tangential line from the steepest terminal portion of the T wave crosses the isoelectric line).

▪ Corrected QT (QTc)

• Bazett’s formula: QTc _{= QT/√(RR in seconds)}

• Normal: 390–450 ms (men) or 390–460 ms (women)

• Most borderline prolonged intervals are normal when repeated.

Diagnosis: Schwartz Score

○The Schwartz score combines ECG and clinical parameters to estimate the probability of inherited LQTS with high specificity (80%–100%) but low sensitivity (70% for score ≥4; >30% for <4).

▪ ECG parameters include:

• QTc: ≥480 ms: 3 points; 460–470 ms: 2 points; >450–460 ms (males): 1 point

• Torsade de pointes: 2 points

• T-wave alternans: 1 point

• Notched T wave in three leads: 1 point

• Resting HR below second percentile for age (children): 0.5 point