Ivabradine is a selective inhibitor of the Funny Current (If) or the pacemaker current in the sinoatrial (SA) node. This results in pure heart rate reduction. This can have cardiovascular benefit when added to optimal medical management. It specifically binds the Funny channel and reduces the slope for diastolic depolarization and hence prolongs diastolic duration, thereby reducing the sinus rate. The greatest effect occurs when heart rates are highest. Ivabradine does not alter the ventricular repolarization, myocardial contractility or the blood pressure.
BEAUTIFUL Study [Ferrari R et al. The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population. Cardiology. 2008;110(4):271-82.] was a randomized, double-blind, placebo controlled study involving eleven thousand coronary artery disease patients on optimal medical management. They had a heart rate above sixty per minute and an ejection fraction less than forty percent. Eighty seven percent of them were on beta blockers, eighty nine percent on angiotensin converting enzyme blockers or angiotensin receptor blockers and twenty seven percent were on aldosterone antagonists. They were followed up for three year. The initial dosage was five milligrams twice daily and if the heart rate was more than sixty per minute at two weeks, it was increased to seven and a half milligrams.The primary endpoint was a composite of cardiovascular death and hospitalizations for myocardial infarctions and congestive heart failure. A subgroup analysis was also done in those with a basal heart rate above seventy per minute, which constituted about five thousand and four hundred patients. Though there was no difference in total cardiovascular mortality, ivabradine was found to reduce readmissions due to coronary artery disease in those with initial resting heart rate above seventy per minute. The rates of percutaneous coronary interventions were also reduced by thirty percent.
SHIFT study was a randomized, double-blinded, placebo controlled trial involving about
six thousand and five hundred subjects in Class II – IV heart failure with left ventricular ejection fraction less than thirty five percent and a heart rate above seventy beats per minute. They have had an admission for heart failure in the previous two months and was on optimal medical management. Ninety percent of them were on beta blocker, eighty four percent on angiotensin converting enzyme inhibitors or angiotensin receptor blockers. They follow up period was three years. The primary end point was a composite of cardiovascular death or hospitalization for heart failure. Though there was no difference in the total cardiovascular mortality, ivabradine was found to reduce mortality due to heart failure and admissions for heart failure.
Indication for ivabradine
Currently ivabradine in indicated for the treatment of chronic stable angina in those with normal sinus rhythm, specially in those who cannot take or tolerate beta-blockers and in them whose angina is not controlled with beta-blockers and having a heart rate above sixty beats per minute.
Tolvaptan is vasopressin antagonist which acts on the V2 receptors in the renal tubules. Activation of V2 receptors increases water permeability in the renal collecting duct resulting in passive reabsorption of water. This causes aquaresis or free water clearance. Syndrome of inappropriate anti-diuretic hormone secretion (SIADH), heart failure and cirrhosis can be associated with increased secretion of arginine vasopressin (AVP). This leads to water retention or inadequate water excretion and hyponatremia (dilutional hyponatremia). Tolvaptan binds to V2 receptors and induces excretion of electrolyte-free water without altering the electrolyte excretion.
Tolvaptan is indicated for the treatment of hypervolemic and euvolemic hyponatremia, with serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction. Such situations occur with heart failure, cirrhosis, and SIADH.
Tolvaptan – Adverse Effects
As expected from its therapeutic action, important adverse effects of tolvaptan are increased thirst, dryness of mouth, increased urination and sometime dehydration leading to hypotension and syncope. Gastrointestinal hemorrhage may occur in those with cirrhosis liver. Hypernatremia and hyperkalemia are potential problems and very rarely osmotic demyelination is possible due to rapid correction of hyponatremia.
Tolvaptan – Contraindications
Tolvaptan is not the treatment when there is an urgent need to raise serum sodium acutely. It should also be proscribed in those with inability to sense or appropriately respond to thirst. Hypovolemic hyponatremia is not an indication for tolvaptan therapy. Concomitant use of strong CYP 3A inhibitors can increase the effect of tolvaptan. There is no point in giving tolvaptan to anuric patients as no fluid is delivered to renal collecting ducts, the site of action of tolvaptan.
Tolvaptan – Precautions
Serum sodium has to be closely monitored while initiating tolvaptan therapy. Too rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination (the erstwhile central pontine myelinolysis). Slower rates of correction may be considered in those susceptible patients who include those with severe malnutrition, alcoholism and advanced liver disease.
What is the rhythm?
a) Sinus rhythm
b) Low atrial rhythm
c) Idioventricular rhythm
d) None of the above
Answer: b) Low atrial rhythm
ECG showing negative P waves in inferior leads – II, III and aVF. A superior P wave axis means that the atrial activation is proceeding from below upwards. This occurs when the focus is in the low atrium (low atrial rhythm or coronary sinus rhythm). In addition the ECG also shows an intraventricular conduction defect (IVCD) in the form of notched R wave in lead II and aVF and an rSR’ pattern in lead III. Sometimes this pattern occurs in atrial septal defect and it is known as chrochetage sign. The QRS width seems to be a little more than that in usual chrochetage sign. (Low atrial rhythm can occur in sinus venosus ASD as the region of the sinus node is defective and an ectopic atrial focus takes over.
Contrast enhanced cardiac magnetic resonance (CMR) imaging is considered to be the gold standard for assessment of coronary microvascular obstruction. Magnetic resonance imaging of the heart is obtained ten to fifteen minutes after injecting a gadolinium-based contrast at a dose of 0.1 mmol/kg. Infarcted tissue is seen as a region of hyper enhancement. A dark core of hypoenhancement within the infarct tissue is taken as a region of coronary microvascular obstruction [McGeoch R et al.The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2010 Jul;3:715-22].
What is the rhythm?
a) Sinus bradycardia
b) Idioventricular rhythm
c) Junctional rhythm
d) None of the above
Answer: c) Junctional rhythm
Regular narrow QRS rhythm at 60 per minute is seen with normal QRS and T waves. P waves are not seen. The first possibility is a junctional rhythm. In a mid junctional rhythm the P waves will be within the QRS and not visible. In a high junctional rhythm the P waves will be inverted in leads II, III and aVf, occuring with a shor PR interval. In low junctional rhythm the P waves are inverted in these same leads, but will occur after the QRS with a short RP interval. In mid junctional and low junctional rhythm there will be regular cannon waves in the jugular venous pulse as the atrial contraction is during ventricular systole when the AV valves are closed, resulting in back flow of blood from right atrium to the superior vena cava.
A slow and regular narrow QRS rhythm with absent P waves can also occur in atrial paralysis due to severe hyperakalemia or due to any other reason. But in this case hyperkalemia is unlikely as the T waves are normal in amplitude. Moreover, the QRS can also become wide in severe hyperkalemia. Atrial standstill can rarely occur as an idiopathic disorder, in some muscular dystrophies and following radiofrequency ablation procedures in the right atrium.
A third possibility for a slow, regular narrow QRS rhythm with absent P waves is fine atrial fibrillation with complete heart block. In that situation, the QRS is regular because it is initiated by a junctional focus and not by the irregularly conducted fibrillary waves. It is unlikely that all the 12 leads will not pick up the fibrillary waves in fine atrial fibrillation.
In this particular case this rhythm was transiently seen after conversion of supraventricular tachycardia with intravenous verapamil. Normal sinus rhythm was recorded after some time.
This X-ray shows a semilunar shadow of intimal calcification in aortic knuckle (yellow arrow). The position of this calcification can be helpful in the diagnosis of:
b) Aortic aneurysm
c) Aortic dissection
d) None of the above
Answer: c) Aortic dissection
Calcification of the intima of aortic knuckle (arrow) is a common finding in the elderly. Usually it is of no significance. But a separation of the intimal calcification from the edge of the aortic knuckle shadow indicates a separation of the intima from the media as in aortic dissection. This has been called the “calcium sign” in aortic dissection. A separation of more than 1 cm is considered significant.
What is this imaging modality?
a) Magnetic resonance angiography
b) Conventional coronary angiography
c) Cardiac 3D mapping
d) Coronary CT angiogram with 3D reconstruction
Answer: d) Coronary CT angiogram with 3D reconstruction
Cardiac CT angiograms are increasing in popularity as a non-invasive screening tool for detecting significant coronary artery disease. The angiograms are reconstructions from 64 or more slice CT scans following intravenous injection of radiocontrast dye. As of now it cannot replace conventional coronary angiograms for assessing the detailed coronary anatomy. More pictures at: http://cardiophile.org/2012/06/normal-cardiac-ct-images-coronaries-on-reconstructed-views/
ECG is suggestive of:
a) Acute anterior wall myocardial infarction
b) Old inferior wall infarction
c) Hyperacute inferior wall infarction
d) Posterior wall infarction
Answer: c) Hyperacute inferior wall infarction
The ECG show ST segment elevation in leads II, III and aVf of about 3mm. ST segment depression is seen in leads I, aVl and V1 to V5. Overall features are suggestive of hyperacute phase of inferior wall myocardial infarction with “reciprocal” ST segment depression in anterior leads. The hyperacute phase is diagnosed when the ST segment is elevated and the T waves are upright in those leads. The segment is upsloping in hyperacute phase as the T waves are upright and sometime a bit tall. ST segment becomes “coved” as the T waves get inverted in the later phase. The “reciprocal” ST depression in anterior leads could be just an electrical phenomenon due to the ST segment elevation in the inferior leads or due to ischemia in the corresponding territory. We will see what exactly was there in this case in the still pictures of left and right coronary angiograms below.
Angiographic pictures can be viewed at: http://cardiophile.org/2008/11/ecg-quiz-22/
The cut off value for septal thickness above which the risk of sudden cardiac death is considered high in hypertrophic cardiomyopathy is:
a) 15 mm
b) 20 mm
c) 30 mm
d) 40 mm
Answer: c) 30 mm. Generally the risk of sudden cardiac death in hypertrophic cardiomyopathy is considered to be high in those with a septal thickness of 30 mm or more. Implantation of an ICD (Implantable Cardioverter Defibrillator) may be considered in such situations. Those with a family history of premature sudden death also have a high risk and so do those with a history of resuscitated cardiac arrest. Recurrent episodes of non sustained ventricular tachycardia and syncope are also considered as risk factors.
The rhythm in this ECG is suggestive of
a) Sinus tachycardia
b) Atrial fibrillation
c) Supraventricular tachycardia
d) None of the above
Correct answer: c) Supraventricular tachycardia
Supraventricular tachycardia is seen here at a rate of around 150 / min (RR interval 10 mm or 400 msec). The QRS is narrow in supraventricular tachycardia without any aberrant conduction as in this case. If there is aberrant conduction, it can be wide and usually showss a right bundle branch block pattern as aberrancy is more common in right bundle. The P waves are not very evident in this case and may be buried within the QRS complex. This can occur in AV nodal re-entrant tachycardia (AVNRT) and junctional tachycardia due to simultaneous activation of the atria and ventricles. When there is simultaneous contraction of the atria and ventricles, clinical examination will reveal cannon waves.
When a supraventricular tachycardia at a rate of 150 per minute is seen, atrial flutter with 2:1 conduction should also be borne in mind as the flutter waves may not be evident in all leads. Carotid sinus massage may alter the AV conduction ratio to make the flutter waves evident, if they are within the QRS or T waves.
The two common forms of supraventricular tachycardia are AVNRT and atrioventricular re-entrant tachycardia (AVRT) of WPW syndrome. The latter often manifest the typical pattern of WPW syndrome (short PR interval and delta wave) after termination of the tachycardia.