I. Ventricular tachycardia with no Structural Heart Disease: What every physician needs to know.
Although ventricular tachycardia (VT) most commonly occurs in individuals with structurally abnormal hearts, about 10% of all VT occurs in patients with no apparent structural disease. This entity is known to be idiopathic ventricular tachycardia (IVT) and includes two types: outflow tract tachycardia (OTVT) and fascicular ventricular tachycardia (FVT).
By far the most common type of IVT, OTVTs are initiated and maintained by delayed after depolarizations (DADs), related to calcium overload states. In particular, OTVTs occur via a cyclic AMP-dependent mechanism and are uniquely terminated with adenosine. Hence, OTVT has been coined “adenosine-sensitive ventricular tachycardia.”
FVTs are reentrant tachycardias that involve the Purkinje system. Most commonly, the reentrant circuit consists of Purkinje tissue with abnormal, slow, decremental conduction due to slow inward calcium current. This region serves as the antegrade limb of the reentrant circuit. Most often, the left posterior fascicle (LPF) serves as the retrograde limb and exit site of the circuit. Less often, the retrograde limb is the left anterior fascicle (LAF) or high septal fascicle.
In 1981, Bernard Belhassen described FVT to be sensitive to verapamil, and FVT has been coined Belhassen’s VT. Based on responsiveness to calcium channel blockers, FVT has also been called “calcium-sensitive” or “verapamil-sensitive” ventricular tachycardia.
II. Diagnostic Confirmation: Are you sure your patient has Ventricular Tachycardia?
To make the diagnosis of OTVT, the following criteria should be met: 1) structurally normal heart, 2) monomorphic non-sustained or sustained VT, 3) VT focus originating from right ventricular outflow tract (RVOT) or surrounding area, and 4) VT responsive to adenosine.
To make the diagnosis of FVT, the following criteria should be met: 1) structurally normal heart, 2) monomorphic VT, 3) VT focus originating from left ventricle, and 4) VT responsive to calcium channel blockers.
A. History Part I: Pattern Recognition:
The patient with OTVT experiences palpitations and may have presyncope and chest discomfort. Based on the cyclic AMP-dependent mechanism of OTVTs, episodes are often triggered by emotional or physical stress. In females, frequency of OTVT changes with menstrual cycles. Although considered a benign arrhythmia, about 10% of the time, outflow tract tachycardias manifest with syncope. In addition, patients can present with symptomatic heart failure with reduced left ventricular ejection fraction, presumably due to tachycardia-induced cardiomyopathy.
There are three major phenotypes described. The most common, termed repetitive monomorphic nonsustained, is characterized by episodes at rest with short bursts of tachycardia. The second type, termed paroxysmal exercise-induced sustained, occurs during or shortly after exertion with sustained ventricular tachycardia that lasts from minutes to days. The third type, termed repetitive monomorphic PVCs, is characterized by frequent PVCs throughout the day.
Classically, OTVTs have been described to arise from the RVOT. However, in some case series, 10%-25% of OTVTs present from an alternative site, including the left ventricular outflow tract (LVOT), above the pulmonic valve, the aortic sinuses of Valsalva, adjacent to the His bundle, near coronary sinus, near mitral and tricuspid valve annuli, near cardiac veins, and the epicardial surface. Although the ECG characteristics vary due to different foci, clinical features, and response to pharmacologic and electrophysiologic maneuvers are uniform suggesting a common mechanism.
The typical presentation of FVT is not dissimilar to OTVT. Patients present with palpitations and less frequently presyncope. Syncope and sudden cardiac death are rare. On the basis of slow-inward calcium current which causes slow, decremental conduction in the Purkinje tissue, FVT is often precipitated by exercise.
B. History Part 2: Prevalence:
OTVT is the predominant type of IVT. Young and middle-aged (mean age 41 years) adults are affected with a slight female predominance. Changes in neurohormonal states including exercise, stress, and menstruation can all increase or decrease frequency of the tachycardia by modulating intracellular calcium levels and, as a result, triggered activity.
Although the exact prevalence of fascicular VT is unknown, about 10%-15% of IVTs are FVTs. Fascicular VTs afflict younger individuals (age 15-40 years), and it would be unusual to present after age 55 years. About 60%-80% of the time, males are affected.
C. History Part 3: Competing diagnoses that can mimic Ventricular Tachycardia.
The major differential diagnosis for OTVT includes arrhythmogenic right ventricular cardiomyopathy (ARVC), idiopathic VF/polymorphic VT, reentrant VT following surgical repair of congenital heart disease, VT post myocardial infarction, and antidromic atrioventricular reentrant tachycardia (AVRT).
1) ARVC portends a much poorer prognosis in comparison to OTVT. To differentiate the two, one must search for clues suggesting presence or lack of fibrofatty infiltration that is characteristic for ARVC. During sinus rhythm, the ECG in ARVC may reveal T wave inversions in V1-V3 from abnormal repolarization and/or epsilon waves from abnormal depolarization in the right ventricle. Moreover, patients with ARVC often have an abnormal signal averaged ECG. Incomplete RBBB can be present in both entities, so this should not be used as a discriminator.
During VT, OTVT is always inferior in axis, while VT from ARVC does not have to have an inferior axis. Moreover, due to diffuse fibrofatty infiltration, a patient with ARVC may have pleomorphic VT. This is in distinct contrast to OTVT where VT is monomorphic.
The echocardiogram in OTVT is generally normal, while ARVC may show evidence of RV structural and functional abnormalities such as RV dilation, aneurysm, and systolic dysfunction that represent fibrofatty infiltration. Cardiac MRI can reveal abnormal fatty infiltration in the right ventricle. However, this finding is nonspecific, meaning that a certain percentage of OTVTs may have a small amount of fibrofatty infiltration as well. Endomyocardial biopsy has also been utilized, but sensitivity is low due to limited sampling of tissue.
A newer, exciting tool in equivocal cases is electrovoltage mapping. Low voltage during mapping is suggestive of scar. In a small study of patients with apparently normal hearts and OTVTs, low voltage seen on electrovoltage mapping predicted fibrofatty infiltration on biopsy and life-threatening ventricular tachycardia on long-term follow-up.
2) Malignant VT and polymorphic VT are rarely present in patients with structurally normal hearts. These are initiated by a PVC with a short coupling interval and demonstrate LBBB pattern. The mechanism of malignant VT and VT is unknown, but theories include chaotic ventricular conduction from a single focus and rapid firing from multiple close foci, micro-reentry, and triggered activity. Although most frequently arising from the RV apex or inferior wall, a small percentage of patients with malignant VT have a PVC that arises from the RVOT. This can lead to a surface ECG similar to that seen in OTVT. There are several clues to help differentiate OTVT and malignant VT from the RVOT. In particular, PVCs in patients with malignant VT have been shown to have a longer initiating cycle length compared to benign VT. Moreover, the VT in OTVT is monomorphic, while this does not have to hold true in malignant VT from the RVOT.
3) After surgical correction of congenital heart anomalies, a substrate for reentrant tachycardias is created. When the right ventricle is involved, VT with similar morphology to OTVT may be present. A thorough history should always be taken to make sure a patient has no history of congenital disease; patients often neglect to tell their healthcare providers because of its remote nature. ECG and echocardiography also provide important clues, such as chamber enlargement or other anatomic abnormalities that suggest congenital disease as the responsible etiology.
4) Other types of structural heart disease, including myocardial infarction, can present with VT and mimic OTVT. Careful review of the ECG for prior myocardial infarction (i.e., q waves) and echocardiogram for wall motion abnormalities can make the diagnosis of infarction leading to scar-related VT.
5) Differentiating atrioventricular reentrant tachycardia (AVRT) and OTVT can be challenging. Adenosine in both conditions may terminate the rhythm. However, electrophysiologic studies will demonstrate different His-ventricle conduction patterns.
The major differential diagnosis for FVT includes interfascicular VT, SVT with aberrancy, and other left-sided VT in setting of structural heart disease. Interfascicular VT has three differentiating characteristics: 1) bifascicular block during both VT and normal sinus rhythm, 2) reversal of activation sequence of His bundle and LBB during VT, and 3) changes in VT cycle length. SVT with bifascicular block due to aberrancy will demonstrate differences in His-ventricle conduction patterns during electrophysiologic study. Similar to OTVT, echocardiography and baseline ECG are crucial to uncover structural heart disease that could be responsible for VT. Of note, the VT QRS duration in FVT is almost always < 140 msec.
D. Physical Examination Findings.
The physical examination findings for both OTVTs and FVTs are unremarkable. This is because both occur in structurally normal hearts. Thus, when a patient is in normal sinus rhythm, one should expect a normally placed point of maximal impulse and normal heart sounds (i.e., S1, S2 without murmurs, rubs or gallops). An active precordium or physiologic flow murmur may be present due to the young age of the affected individuals. In patients with frequent PVCs, extrasystoles may be auscultated.
In some cases of incessant OTVT and perhaps FVT, manifestations of heart failure may be present. Thus, a thorough examination for volume overload should be performed, including assessment of jugular vein distention, hepatojugular reflux, pedal edema, and S3.
During an episode of VT, careful assessment of perfusion is critical to assess stability of the patient. This includes blood pressure and appraisal of mental status, warmth of extremities, skin pallor, chest discomfort, diaphoresis, and nonspecific gastrointestinal symptoms. The patient may also be tachypneic from pulmonary edema and anxiety. Also, findings nonspecific for AV disassociation may be found including cannon A-waves and varying intensity of S1 due to loss of AV synchrony.
E. What diagnostic tests should be performed?
Various diagnostic tests can be performed to make the diagnosis for both OTVTs and FVTs. These tests can be considered to have two purposes: 1) establish a diagnosis and 2) localize the lesion for therapy.
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Laboratory testing is a useful adjunct to help eliminate other etiologies that lead to similar clinical syndromes. For instance, if a patient presents with palpitations, a TSH and electrolytes may be useful. If chest pain is the presenting complaint, a troponin level, CK, CK-MB, and/or a D-dimer may be considered. There are no laboratory tests that are diagnostic for OTVTs or FVTs.
2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Electrocardiogram (ECG) as a diagnostic tool
The ECG is a critical diagnostic tool in the assessment of OTVT. In normal sinus rhythm, one should attempt to rule out evidence of structural heart disease that could cause other types of VT. This is particularly important when trying to differentiate OTVT from ARVC. Patients with OTVT will generally have a normal ECG, although 10% of the time incomplete RBBB is present. In ARVC, T wave inversions and epsilon waves in the right precordial leads and incomplete RBBB are often present. Some centers also utilize signal-averaged ECG, as patients with ARVC will have abnormalities while those with OTVT should not.
Depending on the phenotype, the ECG during VT will demonstrate short bursts of nonsustained VT, sustained VT, or multiple PVCs. These are characteristically all monomorphic. The QRS duration is usually < 140 msec. AV dissociation on ECG to make the diagnosis of VT is a specific but not sensitive finding. Following this, one should localize the lesion that suggests an OTVT-type origin. As noted above, an inferior axis with LBBB-type morphology would suggest such a focus.
Electrocardiogram (ECG) as a localizing tool
Aside from establishing VT and differentiating from ARVC, the ECG is a key tool for precise localization of the lesion when pursuing ablative therapy. Although 75%-90% of OTVTs arise from the RVOT, in the remaining, other VT foci include left ventricular outflow tract, above the pulmonic valve, aortic sinus of Valsalva, near the His bundle, and epicardial locations. Moreover, even in RVOT VT, the ECG can help narrow the focus further (i.e., septal versus free wall and anterior versus posterior).
In most patients, an RVOT focus is present and PVCs or VT have a characteristic LBBB pattern with an inferior axis and QRS transition (negative to positive) in V3 or V4 (Figure 1). The RVOT focus can be further localized. In contrast to septal RVOT VT, free wall RVOT VTs manifest with notched R waves in the inferior leads with a QRS duration > 140 msec. When a QS is present in lead I and/or QS amplitude in aVL > aVR, a focus on the left side (anterior) of the RVOT is likely present rather than a right-sided (posterior) focus.
It must be recognized, however, that 10%-25% of OTVT, arise from alternative sites, including above the pulmonic valve, LVOT, and aortic root. Classically, LVOT VT presents with RBBB pattern with inferior axis but can also have a LBBB with inferior axis similar to RVOT VT. In such patients, an LVOT origin is suggested by a terminal S wave in V6 and early precordial transition (R>S in V1 or V2) (Figure 2). These parameters are all “rough guides” due to the close proximity of these various locations.
The primary purpose for echocardiography is to assess LV and RV function and structure. Particular emphasis should be placed on the right ventricle. RV dilation, aneurysm, and systolic dysfunction may represent fibrofatty infiltration that is characteristic for ARVC and may mimic OTVT. In addition, the presence of LV dysfunction should not exclude OTVT from your differential diagnosis. This is because in a sizeable percentage of patients with OTVT, a reversible tachymyopathy can develop. Thus, with treatment of the VT, LV function should improve.
Long-term monitoring tools can be helpful in patients with non-specific symptoms such as palpitations and lightheadedness who are otherwise healthy. Frequency of PVCs, nonsustained VT, and sustained VT may be seen. Moreover, correlation between dysrhythmia and symptoms can be established.
Exercise stress testing
In 25%-50% of patients with OTVT, exercise induces VT during exercise or in the recovery phase. This can be diagnostically useful in individuals who have normal ECG at rest, and require documentation of arrhythmia.
In some patients, a clear differentiation between OTVT and ARVC remains challenging. Cardiac MRI may be a useful adjunct in these settings. Fatty deposition seen as high-intensity intramyocardial lesions on T1-weighted images and thinning of the RV (<2 mm) suggests ARVC. Cine studies provide information similar to echocardiography, revealing areas of hypokinesis, dyskinesis, or aneurysm. This technique, however, is not without major pitfalls. It is known that a number of normal patients may also have some fatty infiltration of the right ventricle. Thus, one has to be cautious when interpreting MRI findings and using them alone to make the diagnosis.
Endomyocardial biopsy can be considered to discriminate RVOT VT versus ARVC. Given the robust techniques mentioned above, poor sensitivity of endomyocardial sampling, and risk of biopsy, this diagnostic modality is rarely used.
Electrovoltage mapping (EVM)
This is a relatively novel technique in the diagnostic algorithm for OTVT. It has been recognized that low amplitude voltage during electrophysiologic studies suggests scar. Thus, the presence of low amplitude voltage signals in the RV could distinguish ARVC from OTVT. This was tested in a recent study examining twenty-seven patients who had electrocardiographic features of RVOT VT but were deemed high risk for ARVC based on family history, including sudden death. They all underwent EVM and endomyocardial biopsy. Seven of the twenty-seven patients had EVM suggestive of scar. Of those seven patients, six had a biopsy demonstrating fibrofatty infiltration. More importantly, three of the twenty-seven patients during follow-up had life-threatening VT, and all three were from the group with low amplitude on EVM. Thus, this technique may facilitate appropriate placement of ICD therapy for primary prevention in patients with some high risk features.
Electrocardiogram (ECG) in FVT
In normal sinus rhythm, one should attempt to rule out evidence of structural disease that could cause other types of VT. Patients with FVT generally have a normal ECG. The tachycardia is monomorphic and relatively narrow. Because the circuit most often involves the left posterior fascicle, a RBBB with superior axis is present (Figure 3). However, in the case of a left anterior fascicle FVT, a RBBB with right axis deviation will be present, while in a high septal FVT, a narrow QRS with normal axis will be present (Table 1)
The treatment algorithm of IVT must be divided into acute and long-term. The two major acute goals are to exclude malignant forms of VT and terminate the VT. Long-term goals include confirmation of OTVT or FVT as the mechanism, risk stratification, and prevention of further VT.
A. Immediate management.
Due to varied presentations, a patient with OTVT may present to the emergency department or clinic with palpitations, chest discomfort, syncope, and/or heart failure symptoms. Urgent vital signs, electrocardiography, and intravenous access should be attained. If regular, monomorphic ventricular tachycardia with inferior axis +/- LBBB pattern is noted, one should suspect an OTVT. An electrogram in sinus rhythm is helpful to diagnose alternative causes of VT, including myocardial infarction and ARVC. Of course, if the patient demonstrates instability, one should proceed down the ACLS algorithm for wide complex tachycardias which may include urgent cardioversion and anti-arrhythmic therapy.
If the patient is stable and OTVT is likely, vagal maneuvers should be attempted. If unsuccessful, adenosine 6mg intravenous push should be administered. The dose can be increased up to 24mg for termination. If adenosine is contraindicated (i.e., bronchospasm), one can administer verapamil 5-10mg over 1 min. If medications remain unsuccessful, anesthesia should be consulted to administer deep sedation, and synchronized cardioversion should be performed. Alternatively, if repetitive, non-sustained monomorphic VT or frequent PVCs are encountered, calcium channel blockers or beta-blockers can be utilized to suppress the triggered activity.
If the patient is stable and FVT is likely, verapamil intravenously is usually successful.
B. Long-term management.
As emphasized in other sections, a careful assessment of alternative causes of VT must be performed because mislabeling a patient with OTVT could be fatal. Once a patient has been diagnosed confidently with OTVT, a long-term plan can be developed that targets prevention of recurrent VT and treatment of VT-related consequences.
Because OTVT occurs in the setting of cyclic AMP-related calcium overload, therapies that decrease calcium in the myocardial cells are often successful in preventing both frequency and burden of VT and non-sustained VT. Beta-blockers and non-dihydropyridine calcium channel blockers (i.e., diltiazem or verapamil) are effective in 25%-50% of patients. Class IA, IC, and III anti-arrhythmics may also be effective. In patients who have a tachymyopathy related to OTVT, diuretics and positive remodeling agents (i.e., ace-inhibitors and beta-blockers) may be useful until ventricular function recovers. Despite this, a significant proportion of patients are refractory to medications or prefer not to be on lifelong medications. In these patients, radiofrequency ablation is an excellent therapeutic option.
ICD therapy is rarely required due to success of medical and ablative techniques along with generally preserved LV systolic function. In the setting of medically-refractory IVT with a focus not amenable to ablation, there may be a role for ICD therapy.
OTVTs can be difficult to induce in the electrophysiology laboratory. Prior to induction of VT in the electrophysiology laboratory, anti-arrhythmic drugs should be withheld for at least five half-lives and sedation should be minimized. If spontaneous tachycardia is not observed, programmed electrical stimulation with rapid burst pacing or ventricular stimuli is performed with or without isoproterenol infusion. Aminophylline, calcium infusion, and atropine may also be added. The VT, when induced, should have a QRS morphology that is the same as documented on a surface ECG prior to EP testing. The His potential will follow the onset of QRS, and ventriculoatrial (VA) conduction may or may not be present.
Localization and mapping
ECG features provide clues for localization, but due to close anatomical relationship of various structures, the ECG cannot provide an exact location. Thus, three mapping techniques are employed to localize the VT focus accurately, enabling success following ablation: pace mapping, activation mapping, and electroanatomic mapping.
Mapping is started in the RVOT, because this is the most frequent area of VT focus. If it fails to identify the origin, mapping is performed above the pulmonic valve and in the coronary sinus to identify an LV epicardial focus. These are rare but easily accessible locations when the RVOT mapping is taking place. If focus is still not identified, the LVOT and aortic cusps can be mapped via a transseptal or retrograde aortic approach.
Once the VT focus is determined via mapping, radiofrequency energy is delivered for 60-90 seconds at a temperature of 60°-70° C with a power limit of 50 W. In rare cases of aortic cusp VT, special care must be taken to avoid injury of the coronary vessels and ablation should be performed with a power limit of 15-25 W. Often, several radiofrequency deliveries are required. Cryoablation has also been used successfully and may have its place in certain clinical scenarios. With these techniques, the long-term success rate of ablation approaches 90%. Complications are rare and include development of RBBB (2%) and cardiac tamponade.
C. Common Pitfalls and Side-Effects of Management
Adenosine: Administer 6mg IV push to terminate OTVT; can administer up to 24mg if needed.
Verapamil: For acute termination of OTVT when adenosine is contraindicated or in FVT, administer 5mg over 1 minute; can increase to 10mg after 15 minutes if no response. For prevention, typical dosing is 120-360mg of total short-acting or sustained oral preparation.
Diltiazem: For acute termination of OTVT when adenosine contraindicated or in FVT, administer ~0.25mg/kg over 2 minutes; can increase to 0.35mg/kg over 2 minutes, after 15 minutes if no response. For prevention, typical dosing is 180-240mg of total short-acting or sustained oral preparation.
Metoprolol: For acute termination of OTVT when adenosine contraindicated, administer 2.5-5mg over 2-5 minutes; can give up to 15mg in a 15-minute period. For prevention, typical dosing is 25-200mg of total short-acting or sustained oral preparation.
Amiodarone: For acute termination of IVT when the aforementioned therapies are ineffective or diagnosis is in question, administer 150mg bolus over 10 minutes followed by 1mg/min for 6 hours followed by 0.5mg/min for remaining 18 hours (and longer if required). For prevention of IVT, load patient with oral amiodarone (i.e., 1200mg/day for ~2 weeks, 800mg/day for ~2 weeks, followed by 200mg to 400mg daily indefinitely). Close monitoring for adverse effects (i.e., pulmonary, thyroid or hepatic toxicity) is required.
Class IA, IC, and III anti-arrhythmics have been used if those above are contraindicated or not efficacious.
What is the Evidence for specific management and treatment recommendations?
Crosson, JE, Callans, DJ, Bradley, DJ, Dubin, A, Epstein, M, Etheridge, S, Papez, A, Phillips, JR, Rhodes, LA, Saul, P, Stephenson, E, Stevenson, W, Zimmerman, F. “PACES/HRS expert consensus statement on the evaluation and management of ventricular arrhythmias in the child with a structurally normal heart”. Heart Rhythm. vol. 11. 2014 Sep. pp. e55-78.
Aliot, EM, Stevenson, WG, Almendral-Garrote, JM. “EHRA/HRS expert consensus on catheter ablation of ventricular arrhythmias: Developed in a partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA)”. Heart Rhythm. vol. 6. 2009. pp. 886-933.
Zipes, DP. “ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American heart association task force and the European Society of Cardiology committee for practice guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death)”. J Am Coll Cardiol. vol. 48. 2006. pp. e247-346.
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- I. Ventricular tachycardia with no Structural Heart Disease: What every physician needs to know.
- II. Diagnostic Confirmation: Are you sure your patient has Ventricular Tachycardia?
- A. History Part I: Pattern Recognition:
- B. History Part 2: Prevalence:
- C. History Part 3: Competing diagnoses that can mimic Ventricular Tachycardia.
- D. Physical Examination Findings.
- E. What diagnostic tests should be performed?
- 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- III. Management.
- A. Immediate management.
- B. Long-term management.
- C. Common Pitfalls and Side-Effects of Management