Case Presentation Asaad Khan University College Hospital Galway Rep of Ireland
Case History 32 male Married Working as a chartered accountant P/C:Admitted to a Regional hospital to be investigated for recurrent nephrolithiasis
Asymptomatic otherwise No H/O palpitations, sweating, pallor, syncope, tremor or headache No history of recreational drug abuse No family history of sudden death
Examination: P: 74/min reg BP: 112/64 mm Hg R/R:16/min Temp: Afebrile Systemic review: Unremarkable
Investigations: FBC..N U&E..N Thyroid function tests: N Iron stores: N Parathyroid hormone levels: N
Investigations: CT Abdomen: Calculus in the lower pole of right kidney. Left adrenal gland enlargement with a maximum diameter of 5 cms. MIBG scan: Abnormal uptake of tracer in left supra renal region consistent with a functioning tumor.
Pre Op investigations: ECG..ABNORMAL
Abnormalities: Coved shape ST-segment elevations in leads V1 through V3 and TWI V1, V2
Investigations: Random Cortisol: N 24 hr urinary Cortisol: N Serial Troponin levels 12 hours apart: N Urinary toxicology screen: N Plasma Metadrenaline: 197 pmol/l (0-600) Plasma Normetadrenaline: 5095 pmol/l (0-1000)
Echo Normal Valves No evidence of LVH Normal EF No evidence of Right ventricular hypertrophy or dysplasia
Cardiac MRI: No evidence of structural heart disease Normal LV function No evidence of Left ventricular hypertrophy No evidence of Right ventricular dysfunction No evidence of coronary artery disease
D/D: STEMI Hyperkalemia Early repolarization Acute pericarditis Brugada syndrome
Brugada type 1 ECG was diagnosed on the basis of absence of symptoms, presence of typical ECG changes normal electrolytes and negative cardiac biomarkers.
Medical preparation for surgery: Preoperative medical therapy was aimed at: Controlling hypertension : Initially with Doxazocin approximately 10 days prior to surgery followed by Bisoprolol initiated 3 days pre op. Volume expansion: High sodium intake in diet and intravenous hydration was started approximately 4 days prior to surgery
Per op : Continuous 12 lead ECG monitoring before induction Patient was connected to defibrillator pads and intravenous sodium nitroprusside and Isoproterenol* (β stimulator,to treat ventricular arrythmias) infusion was prepared and made available on bedside. Cardiology team and senior anaesthetic personnel were on standby. *2006 ACC/AHA/ESC guidelines
General anaesthesia was induced with IV thiamylal 4mg/kg and tracheal intubation was facilitated by Vacuronium. Atropine was given prior to Neostigmine (half dose only) post op,to reverse neuromuscular blockade.
Post op: Post op course was largely unremarkable apart from a lower respiratory tract infection in ICU after 48 hours. No ventricular arrythmias noted
Post op ECG (24 hrs):
Post op ECG (>48 hours):
Biopsy: Encapsulated Pheochromocytoma
Gene analysis Positive for SCN5A mutation
Ajmaline Test: The test is performed under continuous ECG monitoring. Sensitivity ranges from 15 to 80%. Indications for termination are 1. Development of a diagnostic type 1 Brugada ECG, 2. 2 mm increase in ST segment elevation in patients with a type 2 Brugada ECG, 3. Development of ventricular premature beats or other arrhythmias, 4. Or widening of the QRS 30 percent above baseline.
Ajmaline test: Pre procedure
Post 70 mg Ajmaline:
Brugada syndrome: Brugada syndrome (BS) is an inherited arrhythmogenic disease characterized by Typical ECG pattern of ST-segment elevation in leads V1 through V3, Incomplete right bundle-branch block (may be absent) and An increased risk of sudden cardiac death as the result of ventricular fibrillation (VF).
History: Patients with BS usually present themselves in one of two situations: 1) When a resting 12-lead ECG has shown changes compatible with BS, or 2) when the clinical picture (either in terms of symptoms or family history) suggests increased risk of SCD in the setting of a structurally normal heart.
Types of Brugada ECG:
In type 1, the ST segment gradually descends to an inverted T wave. In type 2, the T wave is positive or biphasic, and the terminal portion of the ST segment is elevated 1 mm. In type 3, the T wave is positive, and the terminal portion of the ST segment is elevated <1 mm. Wilde, AA, Antzelevitch, C, Borggrefe, M, et al. Eur Heart J 2002; 23:1648. Antzelevitch C,Brugada P et al Circulation 2005 111:659
Programmed electrical stimulation and sodium channel blockade 1: Sodium channel blocking drugs (Ajmaline,Flecainide) have been used to unmask ECG changes in concealed forms. 2: Electrophysiological studies can be used to evaluate inducibility of ventricular tachycardia/ventricular fibrillation (VT/VF).
Other precipitants of the Brugada type ECG include: 1. Alcohol/cocaine toxicity 2. Fever 3. Hypercalcemia 4. Hyperkalemia (by causing inactivation of the cardiac sodium channel) 5. Hypokalemia 6. Increased alpha-adrenergic tone 7. Pacing
Cause in our case? We feel that the ECG changes in our patient appeared because of the increased alpha adrenergic tone secondary to high levels of circulating catecholamines.
Type 1 In a consensus report, it was proposed that type 1 BS should be strongly considered in patients who meet the following criteria : Appearance of type 1 ST segment elevation (coved type) in more than one right precordial lead (V1 - V3) in the presence or absence of a sodium channel blocker, plus at least one of the following: a) Documented ventricular fibrillation b) Self-terminating polymorphic ventricular tachycardia (VT) c) Family history of sudden cardiac death at <45 years d) Type 1 ST segment elevation in family members e) Electrophysiologic inducibility of VT f) Unexplained syncope suggestive of a tachyarrhythmia g) Nocturnal agonal respiration Proposed diagnostic criteria for the Brugada syndrome.wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P,et al, Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology Eur Heart J. 2002;23(21):1648.
Type 2 and type 3 Should meet both of the following criteria : Appearance of type 2 or type 3 ST segment elevation in more than one right precordial lead under baseline conditions, with conversion to type 1 following challenge with a sodium channel blocker One of the features (a-g) described above Proposed diagnostic criteria for the Brugada syndrome.wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P,et al, Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology Eur Heart J. 2002;23(21):1648
Genetic mutations: Approximately 15%-20% of patients have a mutation in the sodium channel gene, SCN5A. In addition to mutations of the sodium channel itself, mutations in genes that modulate sodium channel function and in genes encoding the cardiac L-type calcium channel also are associated with BS. MOG gene has been discovered recently.
Mechanism: The ST segment elevation and T wave inversions seen in the right precordial leads in BS are thought to be due to an alteration in the action potential in the epicardial and possibly the M cells, but not the endocardial cells
Mechanism:
Arrhythmogenesis Ventricular arrhythmias may result from 1. The heterogeneity of myocardial refractory periods in the right ventricle and 2. From the differential impact of the sodium current in the three layers of the myocardium
Treatment: Pharmacologic therapy: There are no proven pharmacologic treatments for preventing SCD in BS, although there are data suggesting benefit from Quinidine* and Isoproterenol. No proven benefit of Bisoprolol or Amiodarone. *Efficacy of quinidine in high-risk patients with Brugada syndrome. Belhassen B, Glick A, Viskin S.Circulation. 2004;110(13):1731. +Right bundle-branch block and ST-segment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. Brugada J, Brugada R, Brugada.Circulation. 1998;97(5):457.
ICD implantation can prevent SCD in patients with BS. However, selecting which patients should receive an ICD is challenging. Patients with the BS who have had aborted SD or syncope should be treated with an implantable defibrillator (ICD)*. *Report of the Second Consensus Conference Circulation. 2005;111:659-670
Risk stratification summary The 2006 ACC/AHA/ESC guidelines for the management of ventricular arrhythmias and the prevention of SCD include: 1: A history of syncope together with spontaneous ST segment elevation is included as a predictor of SCA. 2: There is agreement that patients with spontaneous ST-segment elevation have a worse prognosis than individuals with ST-segment elevation only after pharmacologic drug challenge.
3: Clinical monitoring is reasonable for the management of patients with ST-segment elevation induced only with provocative pharmacological challenge. 4: Family history is not endorsed as a risk factor. The evidence is less well established for the use of EP study to risk-stratify patients with a spontaneous ST elevation with or without mutation in the SCN5A gene.
The second consensus conference on BS recommended EP testing in most asymptomatic patients. While in symptomatic patients, it should only be done for assessment of supraventricular arrhythmias. Consesus statement,circulation. 2005;111:659-670.
FINGER study: The overall event rate for asymptomatic patients was quite low (0.5 percent per year). Neither spontaneous type 1 ECG nor positive EP studies were predictive of arrhythmic outcomes (0.8 versus 0.4 percent for spontaneous ECG and 1.1 versus 0.4 percent for positive EPS).
Summary: Young asymptomatic patient diagnosed with Type 1 Brugada ECG while being assessed for a Pheochromocytoma. No evidence of structural heart disease. ECG changes resolved following tumor resection. Deemed not suitable for ICD implantation. Active out patient follow up. Asymptomatic for 4 years.
Acknowledgement: Dr Ehsan Ullah UCHG, Dr Emer Joyce UCHG, Dr Patrick Nash UCHG (Clincial lead in cardiac Imaging)
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