Cardiac Rhythm (Clinical Problems) (LeGrice) Flashcards
28 year old woman, her identical twin died suddenly. This patient was asymptomatic. ECG seemed normal.
Discovered inducable arrhythmia.
Transient prolongation of QT interval.
She had a defribrillator implanted
Two years later, the patient had an episode of presyncope, interrupted by a
spontaneous defibrillator shock, about 90 minutes after taking a single 10 mg tablet of loratadine (a non-prescription anti-histamine preparation) for minor symptoms of
nasal congestion; this was the patient’s first exposure to this drug.
What are the possible causes of this arrhythmia?
Long QT syndrome
- family history
- presyncope
- ECG – QT interval & VT morphology
Polymorphic Ventricular Tachycardia
Describe the long QT syndrome
Long QT syndrome (LQTS) is a heart rhythm condition that can potentially cause fast, chaotic heartbeats. These rapid heartbeats might trigger a sudden fainting spell or seizure. In some cases, the heart can beat erratically for so long that it causes sudden death.
You can have a genetic mutation that puts you at risk of being born with congenital long QT syndrome. In addition, certain medications, imbalances of the body’s salts and minerals (electrolyte abnormalities), and medical conditions might cause acquired long QT syndrome.
Long QT syndrome is treatable. You might need to take medications to prevent an erratic heart rhythm. In some cases, treatment for long QT syndrome involves surgery or an implantable device.
You’ll also need to avoid certain medications that could trigger your long QT syndrome. After treatment, you likely can live and thrive, even with this condition. You may be able to continue being active in recreational — and even competitive — sports.
How would you diagnose Long QT syndrome?
Scoring system
One of the criteria is QT duration (corrected for heart rate = QTc)
QTc = QT interval/square root of RR interval
QTc > = 480 msc - 3points
QTc > = 460-470 msec - 2 points
QTc > = 450 msc and male gender - 1 point
Is this due to a mutation? Is it acquired? Or is it on top of a pre-existing preposition? (Did taking the antihsitamine preparation ‘cause’ the VT?)
In this patient, did taking the antihistamine preparation ‘cause’ the VT?
Probably.
Modern non-sedating antihistamines are known to inhibit potassion channels and have been implicated in inducing VT in people with lQT snydrome
Loratadine is thought to reduce iKr though this effect is small
Any extra prolongation of QT in a person with already long QT has potential VT risk
Describe Long QT syndrome and EADs
LQTS can cause ventricular arrhythmias, leading to fainting and sudden death. It is thought to be cause of much unexplained sudden death in young persons.
In LQTS, there is after-depolarizations late in plateau phase or early in repolarization. This is called early after-depolarizations (EADs), which are caused by prolonged AP.
Early after depolarizations are caused by prolonged action potnetials which enable ICalcium(L) to re-activate
- Prolonged AP provides sufficient time for L-type calcium channels ICa(L) to recover and reactivate.
- There is increased sensitivity of these channels to adrenergic stimulation. This means risk of sudden death with LQTS is increased during exercise or emotional stimulation.
- Activation during vulnerable window carries significant risk of reentrant arrhythmia, even in the normal heart. Increased non-uniformity of repolarization in LQTS may amplify this risk.
What can increase the AP duration in LQTS?
Causes
In LQTS, prolonged AP duration may be caused by:
- Drugs and diet, e.g. hypokalaemia and the anti-arrhythmic drug amiodarone increase QT interval
- Reduced extracellular potassium concentration (hypokalaemia) (decreased [K+]o ® decreases IKr)
- Potassium ion channel mutations which lead to reduced effectiveness of delayed rectifier IK (LQT1 [IKs] and LQT2 [IKr]), thus increased probability of EAD formation.
- Sodium ion channel mutations that affect inactivation of INa (LQT3), thus increased probability of EAD formation.
Describe the Action Potential prolongation in hypokalaemia
What is this?
Polymorphic Ventricular Tachycardia
NOT VF
Explain the changing axis of the ventricular electrogram in Polymorphic Ventricular Tachycardia
- The variable amplitude of the ECG complexes with time indicates polymorphic VT.
- It is n_ot VF_, because the rate is relatively constant and the QRS complexes remain identifiable and relatively ordered.
- Unlike monomorphic VT, in which electrical activation circulates around a fixed anatomic substrate (for instance caused by deposition of collagen throughout a healed MI) reentry is occurring here within a region of functional block.
- In this case, the reentrant path varies on a cycle-to-cycle basis.
- The potentials measured at specific sites on the body surface vary temporally as a result, reflecting the unstable trajectory of reentrant electrical activity within the myocardium.
- This process is more u_nstable than monomorphic VT._
Explain why after depolarisations associated with long QT interval carry a high risk
of sudden death even in fit young people.
- EADs occur at a time when _most sodium channels are inactivate_d – late in the APD.
- (vulnerable period – relative refractory period, supernormal period)
- Most of the inward current causing depolarization is therefore due to reactivation of the ICa,L channel.
- This gives rise to v_ery slow electrical propagation._ (see determinants of conduction velocity from past lectures – yrs II & III)
- Slow conduction markedly increases the risk that VT and VF will be initiated.
What advice would you give to a patient with Polymorphic Ventricular Tachycardia (e.g. like Long QT syndrome)?
- Treatment of LQTS is guided by the individual’s risk of sudden cardiac death.
- Patients who have already had an aborted sudden cardiac arrest are considered to have the highest risk of a recurrent event.
- In these patients, medical treatment with beta-blockers and placement of an implantable cardioverter-defibrillator (ICD) is strongly recommended.
- For patients without prior cardiac events, therapy is initiated with a beta-blocker medication and lifestyle modifications.
- This treatment is especially important for those patients with prolonged QTc intervals, as increasing QTc interval is directly related to increased risk of sudden cardiac death.
- Lifestyle modification includes _avoiding triggers of cardiac events a_nd medications that prolong the QT interval.
- Avoid “anti” drugs e.g. antibiotics, antiepileptics etc.
- Triggers for LQT1 include stress and exercise, especially swimming.
- Triggers for LQT2 include auditory stimuli and stress.
- Triggers for LQT3 are primarily rest and sleep - hence, there there are no specific triggers to avoid.
- Triggers for all other subtypes have not yet been defined.
- If patients continue to suffer from syncope and/or ventricular arrhythmia despite lifestyle modification and beta-blocker therapy, ICD placement is recommended.
- Another controversial option for these patients is left cervicothoracic sympathetic ganglionectomy - this surgical procedure involves removal of nerve plexi that are believed to modulate sympathetic activity on the heart.
How would you describe this arrhythmia?
Monomorphic Ventricular Tachycardia
- Tachycardia
- Regular
- Not using His-Purkinje system
- Ventricles invovled
A 64 year old man is brought to the hospital by his wife, having fainted ten minutes
after feeling the onset of a sensation of a very rapid heartbeat. He is monitored and found to have a heart rate of 180 beats per minute and a blood pressure of
90/70 mmHg. The patient is conscious and responsive, but anxious. He complains
of tightness in his chest and feels short of breath.
He notes that he was admitted to hospital with a myocardial infarction 14 months previously and that his medications include aspirin and an ACE inhibitor. The man states that he seemed to have recovered well from his heart attack and that he leads a busy life. Although he has experienced dizziness and palpitations on one or two occasions, these episodes have been short-lived.
Explain the patient’s syncope, low blood pressure and chest discomfort.
- VT leads to impaired cardiac pump function.
- High rate results in reduced filling time.
- Poorly coordinated ventricular activation leads to poor mechanical coordination and hence poor pump function.
- This results in r_educed cardiac outpu_t and therefore mean arterial pressure(remember: flow = pressure gradient / vascular resistance)
- Low arterial pressure leads to poor brain perfusion (when standing)
- Chest discomfort
- ? palpitations
- ? imparied myocardial perfusion (global ishaemia)
- ?? pulmonary congestion - poor (LV) pump function.
A 64 year old man is brought to the hospital by his wife, having fainted ten minutes
after feeling the onset of a sensation of a very rapid heartbeat. He is monitored and found to have a heart rate of 180 beats per minute and a blood pressure of
90/70 mmHg. The patient is conscious and responsive, but anxious. He complains
of tightness in his chest and feels short of breath.
He notes that he was admitted to hospital with a myocardial infarction 14 months previously and that his medications include aspirin and an ACE inhibitor. The man states that he seemed to have recovered well from his heart attack and that he leads a busy life. Although he has experienced dizziness and palpitations on one or two occasions, these episodes have been short-lived.
What is meant by monomorphic ventricular tachycardia and what are the most
likely causes of this patient’s arrhythmia?
Scar tissue = Re-entrant activation
- Re-entrant activation requires:
• A trigger
• Unidirectional block
• Slow conduction / shortened APD (ERP)
• A circuit - Re-entrant circuits can be anatomic or
functional - Slow conduction and unidirectional block
can occur when repolarisation is not
spatially homogeneous - NOTE: Atria continue to activate and
contract independently
A 64 year old man is brought to the hospital by his wife, having fainted ten minutes
after feeling the onset of a sensation of a very rapid heartbeat. He is monitored and found to have a heart rate of 180 beats per minute and a blood pressure of
90/70 mmHg. The patient is conscious and responsive, but anxious. He complains
of tightness in his chest and feels short of breath.
He notes that he was admitted to hospital with a myocardial infarction 14 months previously and that his medications include aspirin and an ACE inhibitor. The man states that he seemed to have recovered well from his heart attack and that he leads a busy life. Although he has experienced dizziness and palpitations on one or two occasions, these episodes have been short-lived.
Why is this patients VT “monomorphic”?
- Automatic trigger within - Or reentry around -
- scar tissue (from old healed MI)
- The circuit does not move – is stabilized around or within the region of scar.
How can a slow conduction be set up in Myocardial Ischaemia?
• Low ATP
• Sodium/potassium ATPase reduced
• Transmembrane Na+, K+ gradients reduced
• Partial membrane depolarization
• Inactivation of sodium channels
• Reduced gap junction coupling (low pH due
to regional metabolic acidosis)
How can action potnetials change in MI?
- Sodium/potassium ATPase reduced
- Transmembrane potassium gradient reduced
- INa reduced
- Hyperkalemia shortens AP duration (increased [K+]o increases IKr)
- Activation of IK,ATP channels (reduced [ATP]i) shortens action potential duration
- In the ischaemic regions – hence inhomogeneous electrical properties
How can DADs be set up in Myocardial ischaemia?
• Impaired calcium homeostasis in
myocardial ischaemia leads to
elevated intracellular Ca2+
concentration in diastole
• This may lead to episodic calciuminduced
Ca2+ release from SR
• Increased efflux of Ca2+ via sodium
calcium exchanger
• Due to the stoichiometry of the
sodium calcium exchanger membrane
is depolarized and this may trigger
activation
• (Delayed After-Depolarizations)
The following ECG rhythm strip was recorded on a V1 chest lead for a 56 year-old
man admitted to hospital with a suspected acute myocardial infarction.
Which features of the ECG at A are consistent with an acute infarct?
The ST segment elevation and T wave inversion are suggestive of an acute myocardial
infarction (MI).
The following ECG rhythm strip was recorded on a V1 chest lead for a 56 year-old
man admitted to hospital with a suspected acute myocardial infarction.
Where might the MI be located?
These abnormalities are seen on V1 and therefore could be consistent with an anterior
infarct – LAD territory.
The following ECG rhythm strip was recorded on a V1 chest lead for a 56 year-old
man admitted to hospital with a suspected acute myocardial infarction.
What is a possible cause of the premature complex seen at B?
• Delayed afterdepolarisations (DADs) are thought to be the most common ectopic
trigger for reentrant arrhythmia immediately after MI.
• They are related to i_mpaired calcium homeostasis_ in ischaemic myocytes.
What is the likely cause of the short run of ventricular tachycardia during C?
• The short run of VT during C is almost certainly due to reentrant electrical
activation associated with the ischaemia.
- During acute ischaemia cellular homeostasis is perturbed in the affected region of the heart producing conditions that markedly increase the probability of reentrant arrhythmia.
- Internal ATP concentration decreases and the Na+/K+ ATPase is inhibited.
- As a result, both [K+]o and [Na+]i rise (along with the rise in [Ca2+]i).
- Ischaemia also leads to regional metabolic acidosis.
• These changes give rise to: (i) slow conduction (ii) reduced APD (iii) nonuniform
repolarisation, and (iv) after-depolarisations which generate ectopic activation.
• An ectopic trigger can set up a reentrant electrical circuit if slow unidirectional
propagation occurs around a region of electrical block.
- The path length required to set up reentry in these circumstances is the product of the conduction velocity (CV) and the effective refractory period (ERP).
- That is, the wavelength for reentry is given by l = CV*ERP.
• In an ischaemic region, conduction velocity is slowed for a variety of reasons:
• The increased [K+]o reduces the resting membrane potential which inactivates
Na+ channels and gives rise to slowed conduction.
• Acidosis leads to decoupling of gap junction hemi-channels increasing electrical
resistance between adjacent cells, which further reduces conduction velocity in
ischaemic myocardium.
Explain the broad QRS complexes during C.
• The broad QRS complexes during C indicate that electrical activation is propagating
slowly.
• The “sharp” QRS complex in normal sinus rhythm reflects the rapid programmed
spread of electrical activation throughout right and left ventricles via the specialised
conduction system.
• This is not happening here because activation is driven by a reentrant circuit in the
LV.
• As explained above, slow conduction is a characteristic feature of myocardial
ischaemia.
• Finally, the fact that activation throughout the ventricle is occurring in the relative
refractory period or shortly afterward will also contribute to conduction slowing and
thus widening of the QRS.
