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Specific Cardiovascular Diseases and Competitive Sports Participation: Channelopathies

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Textbook of Sports and Exercise Cardiology

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Abstract

Long QT Syndrome, Short QT Syndrome, Brugada Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia are inherited primary disorders with the common denominators of a genetic basis and absence of structural abnormalities. They are clinically relevant as the manifestation ranges from absence of symptoms, syncopal episodes, to sudden cardiac death. In Long QT Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia cardiac events occur either during exercise or emotional stress in otherwise healthy young individuals, being therefore quite relevant for sport physicians. By contrast, in Brugada Syndrome events mainly manifest in resting condition and when there is an increase in the vagal tone; while in Short QT Syndrome trigger is quite variable. The correct diagnosis may be challenging sometimes, but it is crucial as very effective therapies are available and can drastically reduce the risk of life-threatening arrhythmias. Restriction from competitive sport is warranted, although the recommendations are under national regulation that are quite different even within European Countries. However, at least for Long QT Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia there is a wide consensus that restriction for competitive sport should be applied. This chapter will review the principal features of these diseases, with a primary focus on diagnosis and clinical management.

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Authors and Affiliations

  1. Center for Cardiac Arrhythmias of Genetic Origin, Istituto Auxologico Italiano, IRCCS, Milan, Italy

    Silvia Castelletti & Lia Crotti

  2. Laboratory of Cardiovascular Genetics, Istituto Auxologico Italiano, IRCCS, Milan, Italy

    Lia Crotti

  3. Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy

    Lia Crotti

  4. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

    Lia Crotti

Authors
  1. Silvia Castelletti
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  2. Lia Crotti
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Correspondence to Lia Crotti .

Editor information

Editors and Affiliations

  1. Private Center for Sports and Exercise Cardiology, München, Bayern, Germany

    Axel Pressler

  2. University Institute of Sports Medicine Prevention and Rehabilitation, Paracelsus Medical University Salzburg, Salzburg, Austria

    Josef Niebauer

Review

Review

1.1 Clinical Case 1

An 18-year-old girl has a syncope whilst swimming. Her physical examination is normal. She denies taking medications and any hormonal condition. On blood tests, potassium is 4.4 mEq/lt (normal values 3.5–5 mEq/lt). Also, glycemia is normal. Her ECG is shown below (Fig. 20.6). QTc is 460 ms.

Fig. 20.6
figure 6

Clinical case 1. Basal ECG trace. It shows sinus rhythm, normal PR and QRS conduction, upper normal QTc (460 ms)

Full size image

1.1.1 Question 1

Would you perform further investigations?

  1. (a)

    The QTc is upper normal, the syncope may be of vasovagal origin. A tilt-testing is the next step.

  2. (b)

    Her ECG is normal. Electroencephalogram and head MRI should be performed to exclude an epilepsy.

  3. (c)

    The QTc is upper normal, we cannot exclude a long QT syndrome based on this ECG: detailed personal and family history collection, exercise stress testing and 12-lead 24-h ECG monitoring should be performed.

  4. (d)

    The QTc is upper normal, we cannot exclude a long QT syndrome based on this ECG: a genetic screening should be performed.

The patient reports a previous syncope when aged 16 whilst practicing sport at school. Her family history is positive for syncopal events: her mother reports loss-of-consciousness events in her teenage, all of them occurring during sport activity. Brain MRI and echocardiogram are normal. During exercise stress-testing, a QTc inability to shorten was observed. The ECG on the fourth minute of the recovery phase is shown below (Fig. 20.7). A 24-h 12-lead ECG monitoring was performed, and biphasic T-waves were observed during recording.

Fig. 20.7
figure 7

Clinical case 1. ECG trace on the fourth minute of the recovery phase of the exercise stress test. It shows marked prolonged QT interval (QTc 581 ms in lead II; QTc 589 in lead V1)

Full size image

1.1.2 Question 2

Based on the new information, what would you do next?

  1. (a)

    According to the Schwartz score (=5), this patient has a high probability to be affected with long QT syndrome: a beta-blocker therapy with metoprolol should be started.

  2. (b)

    According to the Schwartz score (=5), this patient has a high probability to be affected with long QT syndrome: a genetic testing should be performed. If positive, she will be started on betablocker therapy.

  3. (c)

    According to the Schwartz score (=5), this patient has a high probability to be affected with long QT syndrome: a genetic testing should be performed, and the patient should be started on bisoprolol.

  4. (d)

    According to the Schwartz score (=5), this patient has a high probability to be affected with long QT syndrome: a genetic testing should be performed and beta-booker therapy (propranolol or nadolol) should be prescribed. She should also be advised to avoid QT-prolonging drugs and to keep within a normal range potassium levels. Participation in competitive sports should be forbidden.

The patient was started on Propranolol 2 mg/kg/die. Genetic screening was performed and a KCNQ1 mutation was identified. Cascade genetic screening was carried out and the mother was found to carry the same mutation. Since started on therapy, the patient has been asymptomatic.

1.1.3 Question 3

Which one of the following may be included among the ECG features of SQTS?

  1. (a)

    Biphasic T-waves

  2. (b)

    Long QT segment

  3. (c)

    tall, sharp, narrow, symmetrical T waves

  4. (d)

    a long PQ interval

1.1.4 Question 4

Which one of the following may be responsible of a shorter QTc?

  1. (a)

    Hypokalaemia

  2. (b)

    Androgens use

  3. (c)

    Alkalosis

  4. (d)

    Hydroquinidine toxicity

1.1.5 Question 5

Which one of the following is false? A diagnosis of BrS can be performed

  1. (a)

    in the presence of a type 1 ECG recorded at fourth intercostal space

  2. (b)

    in the presence of a type 1 ECG recorded at third or second intercostal space

  3. (c)

    when a type 2 to type 1 pattern conversion is observed after sodium channel blocker administration at fourth intercostal space

  4. (d)

    when drug-induced conversion of type 3 to type 2 ST-segment elevation after sodium channel blocker administration is observed in fourth intercostal space

1.1.6 Question 6

Which one of the following is not responsible of BrS pattern?

  1. (a)

    Hyperkalaemia

  2. (b)

    Fever

  3. (c)

    Hypothermia

  4. (d)

    Anti-allergic drugs

1.2 Clinical Case 2

A 30-year-old swimmer with no family history for sudden death, syncope, or seizures started to report palpitations mainly during exercise and emotional stress. Basal ECG is shown below (Fig. 20.8).

Fig. 20.8
figure 8

Basal ECG of clinical case 2

Full size image

1.2.1 Question 7

Based on the ECG, what is the most likely diagnosis?

  1. (a)

    Long QT Syndrome

  2. (b)

    Short QT Syndrome

  3. (c)

    Brugada Syndrome

  4. (d)

    None of them

Echocardiogram was normal. A 12-leads 24-h Holter monitoring showed a run of non-sustained polymorphic ventricular tachycardia whilst exercising.

1.2.2 Question 8

What would be the most useful test to perform?

  1. (a)

    Exercise stress testing

  2. (b)

    Cardiac Magnetic Resonance

  3. (c)

    Flecainide drug challenging test

  4. (d)

    Electrophysiological study

Exercise stress testing was performed (Bruce protocol). Isolated ventricular ectopic beats were noted when his heart rate was 113 bpm (Fig. 20.9a). A triplet and a couple appeared at 115 bpm (Fig. 20.9b) and a NSVT appeared at 123 bpm (Fig. 20.9c). The test was therefore interrupted, and arrhythmias disappeared as soon as he stopped cycling. The patient was started on Nadolol 2 mg/kg/die. Genetic analysis was performed on the major CPVT-related genes and a disease-causing mutation was identified on RyR2. The same mutation was then detected in the father.

Fig. 20.9
figure 9

Electrocardiographic strips of the exercise stress test of clinical case 2. They show increasing frequency and complexity of ventricular arrhythmias with the increase in the workload

Full size image

1.2.3 Answers

  1. 1.

    Correct answer: (c).

    Swimming is a well-known arrhythmic trigger in LQTS and the diagnosis cannot be excluded by a ECG [6]. Family history would elucidate her probability of being affected with a congenital Long QT Syndrome. The workup for clinical diagnosis includes exercise stress test and 12-lead 24-h ECG monitoring [2]. Genetic screening is recommended when there is an established strong clinical suspicious of LQTS [8].

  2. 2.

    Correct answer: (d).

    The Schwartz score of the patient is 5, this equals high probability of being affected with Long QT Syndrome (Table 20.1) [44, 53]. Therefore, betablocker therapy should be started [2]. Propranolol and nadolol are the two betablockers more effective in preventing arrhythmic events in patients with LQTS [57]. The trigger of the event and the morphology of the ECG are suggestive for LQT1 [6]. In this form, events typically occur upon exercise or stress, as the impairment of the IKs current prevents the shortening of the QT during increases in heart rate [6]. Therefore patients are not allowed to participate in competitive sport activities [53]. Genetic screening is mandatory to confirm diagnosis: it would allow the genetic screening of family members and a genetic-specific therapy [8].

  3. 3.

    Correct answer: (c).

    Besides the short QTc, basal ECG of affected patients present with the T wave initiating immediately from the S wave, therefore with a short or absent ST segment [78]. T waves are tall, sharp, narrow, fine and symmetrical, especially in leads V2–V4, suggesting increased transmural dispersion of repolarization [78]. The heterogeneous abbreviation of atrial repolarization is responsible for the presence of a PQ depression ≥0.05 mV [82].

  4. 4.

    Correct answer: (b).

    Acquired causes of short QTc include electrolyte imbalance, such as hyperkalemia and hypercalcemia, acidosis, digitalis toxicity, increased vagal tone, and androgen use. A study in orchiectomized male rabbits showed that dihydrotestosterone (DHT) increased IK1 and IKr current densities and produced a left-shift in the V(1/2) for IKr that could account, at least in part, for the observed differences in QTc between males and females [84].

  5. 5.

    Correct answer: (d).

    BrS is definitively diagnosed when a type I ST-segment elevation is observed

    1. (a)

      either spontaneously or after intra-venous administration of a sodium channel blocking agent (ajmaline, flecainide, pilsicainde or procainamide)

    2. (b)

      in at least one right precordial lead (V1 and V2), which are placed in a standard or a superior position (up to the second intercostal space) [2, 65].

    Drug-induced conversion of type 3 to type 2 ST-segment elevation is considered inconclusive for a diagnosis of Brugada syndrome.

  6. 6.

    Correct answer: (d).

    Several conditions may mimic a BrS, including medical illness [152,153,154,155,156,157], mechanical compression of RVOT [158, 159], cardiomyopathies [160, 161], electrolyte imbalances, hyperkalaemia, hypercalcemia [162,163,164,165], hyperthermia and hypothermia [166, 167], thiamin deficiency, elevated insulin level [168]. Anti-allergic drugs are not included. A list of drugs able to induce a type 1 ECG and VF is available on the website www.brugadadrugs.org.

  7. 7.

    Correct answer: (d).

    ECG shows sinus rhythm at 52 bpm, normal PR (160 ms) and QRS duration (90 ms), with a normal QTc. Therefore, LQTS and SQTS should be excluded. The repolarization is normal, therefore there are no criteria for a Brugada Syndrome diagnosis, even though this cannot be excluded, as the diagnostic ECG pattern is not always present.

  8. 8.

    Correct answer: (a).

    As echocardiogram is normal, an exercise stress testing should be performed to better evaluate the correlation with heart rate. Indeed, the ECG is normal. The absence of arrhythmias during the night-time on the 12-lead 24-h Holter monitoring and the correlation of the symptoms with exercise and emotional stress should arise the suspicious of CPVT diagnosis [65, 188, 189, 195].

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Castelletti, S., Crotti, L. (2020). Specific Cardiovascular Diseases and Competitive Sports Participation: Channelopathies. In: Pressler, A., Niebauer, J. (eds) Textbook of Sports and Exercise Cardiology. Springer, Cham. https://doi.org/10.1007/978-3-030-35374-2_20

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