Tachycardias can be categorised by the location from which it originates in the heart. Two types of tachycardia are commonly encountered in clinical practice are:^1,2,3 

• Supraventricular tachycardia (SVT):  Begins in the upper portion of the heart, usually the atria. It is a broad term that includes many forms of heart rhythm problems that originate above the ventricles (supraventricular) in the atria or AV node. SVT is often associated with anxiety and fatigue, as well as excessive caffeine, alcohol, and nicotine use. Occasionally, it is associated with myocardial infarction (MI) and mitral valve disease. SVT is typically not life-threatening but can be life-altering. Patient education is vital and should focus on the diagnosis, prognosis, and treatment options. Emphasis should be placed on decreasing anxiety and alleviating the fear of the unknown and emergency plans should be in place in case of an event.^1,2,5 

• Ventricular tachycardia (VT): Occurs when the lower chamber of the heart beats too fast to pump well and the body does not receive enough oxygenated blood. VT can lead to ventricular fibrillation (VF), a potentially life-threatening condition. About 70% of cardiac arrest patients have VF and may die within minutes if unless resuscitation is started. Every minute without defibrillation decreases survival rates by about 7%–10%. The survival rates of those who suffer out of hospital cardiac arrest, have increased slightly, but many continue to have residual anoxic brain damage and neurological deficits. VF is often linked to underlying structural heart disease. Between 3% and 12% of cases of MI develop VF during the acute phase. MI patients with complete coronary occlusion on an angiogram, anterior wall infarction, AF, and pre-infarction angina are more prone to develop VF. VF is associated with electrolyte abnormalities (eg hypokalaemia, hyperkalaemia, hypomagnesaemia), acidosis, hypothermia, hypoxia, cardiomyopathies, family history of sudden cardiac death, congenital QT abnormalities, Brugada syndrome (a genetic disorder in which the electrical activity within the heart is abnormal), and alcohol use.^5,6 

Symptoms and findings indicative of VF 

Acute presentation, symptoms, and electrocardiogram (ECG) findings that are indicative of VF include:⁵ 

Presentation 

The most common presentation for VF is sudden collapse from cardiac arrest leading to sudden cardiac death (SCD), the leading cause of mortality worldwide.^5,7 

Symptoms³ 

• Dizziness or fainting 
• Shortness of breath 
• Palpitations 
• Chest pain. 

 Electrocardiogram findings⁵ 

• Fibrillation waves of varying amplitude and shape 
• No identifiable P waves, QRS complexes, or T waves 
• Heart rate anywhere between 150 to 500 per minute. 

The ECG may reveal:⁵ 

• MI 
• Brugada syndrome 
• Long or short QT interval
• Wolff-Parkinson-White syndrome
• Digitalis toxicity
• Epsilon sign (arrhythmogenic right ventricular cardiomyopathy) 

Laboratory testing⁵ 

Appropriate laboratory studies include: 

• Serum electrolytes 
• Arterial blood gas 
• Complete blood cell count 
• Cardiac enzymes 
• Levels of drugs 
• Toxicology screen 
• Brain natriuretic peptide levels. 

Surviving VF and beyond 

A thorough history – ask about unexplained cardiac death in a family member and patient’s cardiac history – and physical examination is essential in patients who survive VF.⁵  

Clinicians should also investigate and address reversible causes of VF such as electrolyte abnormalities, acidosis, and hypoxia, as well as evaluating patients for underlying ischaemic heart disease. More than 50% of patients who suffered out of hospital cardiac arrests have significant coronary artery disease.⁵ 

An echocardiogram is usually done to assess the wall motion, ejection fraction and any valvular problems. In addition, it will identify any pericardial fluid that may have resulted from cardiopulmonary resuscitation.⁵ 

Electrophysiology studies should be done after the patient is stable to differentiate patients with inducible VF from those with non-inducible VF. Patients with induced monomorphic arrhythmias may need an implantable cardioverter-defibrillator (ICD).⁵ 

Recognising a VT electric storm 

A VT electrical storm (ES) is characterised by clustering episodes of ventricular arrhythmia (VA) in a short time frame. The current definition of ES implies at least three distinct episodes of sustained VT or VF within the last 24-hours or the occurrence of incessant VT for at least 12-hours.⁷  

In patients with ICDs, ES is defined by ≥3 appropriate device interventions in the last 24-hours (separated by at least 5-min one from the other) either with anti-tachycardia pacing or direct-current shock.⁷  

Although ES mainly occurs in patients with structural heart disease and low left ventricular ejection fraction (LVEF), it may also affect patients with inherited arrhythmic syndromes and structurally normal heart (Brugada syndrome and catecholaminergic polymorphic VT).⁷ 

Treatment  

Amiodarone is one of the most commonly used antiarrhythmic drug (AAD). It was developed originally as an antianginal agent in Belgium in 1962. Subsequent studies showed that it had antiarrhythmic properties.^8,15  

The oral preparation (200mg/tablet) was approved by the American Food and Drug Administration (FDA) in 1985 for the treatment of life-threatening, recurrent VT/VF associated with haemodynamic instability.^8,15 

Intravenous (IV) amiodarone was approved by the FDA in 1995. IV amiodarone can be used to treat SVTs, most commonly atrial fibrillation, in acute settings (eg perioperative cardiovascular surgery), in intensive care units, and in emergency departments.^8,15  

Efficacy and safety of amiodarone 

Current guidelines recommend amiodarone as first-line therapy in some patient groups with SVT and VT/VF. Amiodarone has demonstrated its efficacy to control VAs in up to 40% of patients within 24-hours from IV administration, as well as to reduce recurrent VT over the long term.^{8,10,11,12,13,15} 

Santangel et al (2012) investigated the safety of amiodarone compared to placebo. According to the authors, amiodarone is both safe and effective for the acute conversion of AF and the prevention of postoperative AF, although with an increased risk of bradycardia, hypotension, nausea, or phlebitis.¹⁶  

Amiodarone administration for the maintenance of sinus rhythm has a favourable net clinical benefit (pooled number needed to treat [NNT] = 3 versus pooled number needed to harm [NNH] for either thyroid toxicity, gastrointestinal discomfort, skin toxicity or eye toxicity =11.¹⁶  

Treatment with amiodarone for the prophylaxis of SCD has less favourable net clinical benefit (NNT = 38 versus NNH for either thyroid toxicity, hepatic toxicity, pulmonary toxicity, or bradycardia = 14). Amiodarone treatment in this setting should be used in only selected cases.¹⁶ 

Vigilant surveillance 

Although its efficacy is not questioned, it has been associated with side effects involving organs such as the thyroid, liver, lungs, and eyes including many that are dose- and duration-dependent. Vigilant surveillance is required.¹⁶ 

According to Epstein et al, meticulous follow-up is central to the care of patients taking amiodarone.  Patients treated with amiodarone should be evaluated every three to six months for the first year, and every six months thereafter to assess amiodarone-related symptoms (see red flags), and to investigate possible arrhythmia recurrences, need for drug titration and laboratory testing and changes in drug therapy.⁸  

During history-taking, the clinician should enquire about fatigue (suggesting bradycardia, atrioventricular block, or hypothyroidism), dyspnoea or cough (suggesting pulmonary toxicity), palpitations (suggesting hyperthyroidism or recurrence of arrhythmias), syncope, visual changes, skin changes (including photosensitivity), weight loss (suggesting hyperthyroidism), paresthesias or weakness (suggesting peripheral neuropathy), drug interactions (especially with digoxin and warfarin) and sleep disturbances.⁸  

During the physical exam, note vital signs, regularity of pulse, skin colour, thyroid, rales, signs of left ventricular dysfunction, hepatomegaly, and neurologic abnormalities (see Red Flags).⁸   

Follow-up evaluation should include at a minimum:  

• A yearly ECG and chest x-ray study  
• Semi-annual thyroid-stimulating hormone test and liver enzymes.  

Surveillance amiodarone levels are generally of little use but can help if arrhythmias occur or recur, or if new symptoms develop, especially after dose titration or a change in drug formulation (to or from generic preparations). Amiodarone levels may help determine if the drug can be titrated downward or when another antiarrhythmic drug can be substituted. ⁸ 

In patients with ICDs, amiodarone may slow the VT rate so it falls below the rate detection. It may increase the energy required to defibrillate. Thus, the drug should not be started or dose changed without the involvement of an electrophysiologist or cardiologist.⁸  

Incidence of side-effects relooked 

Chokesuwattanaskul (2020) et al recently relooked the incidence of side effects leading to the discontinuation low-dose amiodarone (defined as 200mg/day or less), and very-low-dose amiodarone (defined as 100mg/day) or less.¹⁷   

They found: The pooled estimated incidence of overall side effects associated with low-dose amiodarone among the 10 studies included was 17%. However, the pooled estimated incidence of a side effect requiring medication discontinuation was 6%.¹⁷ 

Compared to 200mg/day of amiodarone, the pooled estimated incidence of overall side effects with a dose of 100mg/day of amiodarone was 11%, while the pooled estimated incidence of side effects requiring medication discontinuation was 2%. None of the included studies reported any instances of amiodarone-related mortality.¹⁷ 

According to the authors, most of the reported side effects are incidentally revealed through routine laboratory screenings. Some life-threatening side effects have been reported in patients only on short-term amiodarone, although these extreme adverse events are very rare.¹⁷  

Furthermore, many well-designed studies show that amiodarone is safe under vigilant surveillance. Systematic screening and regular follow-up are the essential elements.¹⁷  

The available data to clarify the side effects and propose preventive strategies remain under discussion. Moreover, most side effects are diagnosed only after the exclusion of other causes, which could lead to an altered estimation of their incidence rates, they concluded.¹⁷ 

Red flags 

Neurologic and visual changes: For example ‘halos’ around lights, are usually dose-related, and often occur in the first phases of loading. Thus, the lowest effective dose should be used. Early assessment and intervention are necessary to prevent serious organ toxicity. Continued assessment of drug efficacy, titration of drug dose after achieving a steady-state, evaluation and management of adverse effects, and attention to drug-drug and drug-device interactions are crucial. Referral to a neurologist or ophthalmologist might be required.⁸ 

Pulmonary toxicity: Clinical presentation is most commonly diffuse interstitial lung disease or a hypersensitivity syndrome that may mimic infection. Patients may also manifest acute respiratory distress syndrome, pulmonary nodules, or solitary masses, or (rarely) pleural effusions. Pathologic findings include interstitial pneumonitis, organising pneumonia, diffuse alveolar haemorrhage, or diffuse alveolar damage.⁸  

Thyroid function:  Amiodarone use can lead to hypo- or hyperthyroidism. Acutely, there is an increase in thyroid-stimulating hormone, an increase in free T4, and a decrease in free T3. After three months, a new equilibrium is reached, and TSH normalises, again becoming the most reliable marker of thyroid status.⁸ 

Gastrointestinal/liver toxicity: Nausea, anorexia, and constipation are among the most common gastrointestinal effects of amiodarone, are dose-related, and rarely require specific treatment or intervention.⁸ 

Neurological toxicity: For example cognitive impairment and at high doses, quadriplegia has been seen. More commonly, weakness and tremor occur. Peripheral neuropathy is possible. Myopathy, polyneuropathy, and ataxia may not necessarily be reversible with amiodarone discontinuation. There is no specific treatment for neurological toxicity except to discontinue or decrease the amiodarone dose and wait for its elimination or decreased effects.⁸ 

REFERENCES: 

1. Pacific Rim Electrophysiology. Supraventricular & Ventricular Tachycardia. https://www.pacificrimep.com/conditions-treated/supraventricular-ventricular-tachycardia/ 
2. Mayo Clinic. Supraventricular tachycardia. https://www.mayoclinic.org/diseases-conditions/supraventricular-tachycardia/symptoms-causes/syc-20355243 
3. Mayo Clinic. Ventricular fibrillation. https://www.mayoclinic.org/diseases-conditions/ventricular-fibrillation/symptoms-causes/syc-20364523 
4. Salerno JC and Seslar SP. Supraventricular Tachycardia. Arch Pediatr Adolesc Med, 2009. 
5. Ludhwani D, Goyal A and Jagtap M. Ventricular Fibrillation. StratPearls (Internet), 2020. https://www.ncbi.nlm.nih.gov/books/NBK537120/ 
6. Szabo Z, Ujvarosy D and Otov T. Handling of ventricular fibrillation in the emergency setting. Front. Pharmacol, 2020. 
7. Muser D, Santangeli P and Liang JJ. Management of ventricular tachycardia storm in patients with structural heart disease. World J Cardiol, 2017. 
8. Epstein A et al. Practical Management Guide for Clinicians Who Treat Patients with Amiodarone. The American Journal of Medicine, 2016. 
9. Florek JB and Girzadas D. Amiodarone. StatPearls [Internet], 2021. 
10. Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med, 1997. 
11. Kuck KH, Cappato R, Siebels J and Rüppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH) Circulation, 2000. 
12. Kowey PR, Crijns HJ, Aliot EM et al on behalf of the ALPHEE Study Investigators. Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: the ALPHEE study. Circulation, 2011. 
13. Connolly SJ, Dorian P, Roberts RS et al. Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) Investigators. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA, 2006. 
14. Van Herendael H and Dorain P. Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia. Vasc Health Risk Manag, 2016. 
15. Connolly SJ. Evidence-Based Analysis of Amiodarone Efficacy and Safety. Circulation, 1999. 
16. Santangeli P, et al. Examining the safety of amiodarone. Expert Opin. Drug Saf, 2012. 
17. Chokesuwattanaskul R, Shah N et al. Low-dose Amiodarone Is Safe: A Systematic Review and Meta-analysis. J Innov Card Rhythm Manag, 2020.