A large randomized clinical trial involving over four thousand seven hundred patients from seventy nine centres across nineteen countries has been published in NEJM [Lamy A et al. Effects of Off-Pump and On-Pump Coronary-Artery Bypass Grafting at 1 Year. N Engl J Med 2013; 368:1179-1188]. One year after coronary artery bypass grafting, there was no significant difference between on pump and off pump bypass surgery in the rate of repeat revascularisation, quality of life or neurocognitive function. The same group had reported earlier that there was no significant difference in the composite outcome of myocardial infarction, death, stroke and new onset renal failure requiring dialysis support.
Detection of vegetations on prosthetic material within the heart is often difficult as these structures may cause acoustic shadowing and reverberation artifacts. Even though trans esophageal echocardiography (TEE) is better than trans thoracic echocardiography (TTE) in detecting intracardiac vegetations, intracardiac echo may have an additional advantage due to the higher resolutions possible. Intracardiac echo (ICE) uses transducer frequencies in the range of 5.5 – 10 MHz and the probe is usually a 10F device, which can be introduced into the right sided cardiac chamber through the femoral vein and inferior vena cava. A recent study by Maria Lucia Narducci et al [Usefulness of Intracardiac Echocardiography for the Diagnosis of Cardiovascular Implantable Electronic Device–Related Endocarditis. J Am Coll Cardiol. 2013;61(13):1398-1405.] evaluated over one hundred and sixty two patients who underwent lead extraction, of which one hundred and fifty two had device related infection and ten had lead malfunction. The detection of intracardiac masses suggesting vegetations were higher with ICE than with TEE.
ARMYA-9 CAROTID study [Patti G et al. Strategies of Clopidogrel Load and Atorvastatin Reload to Prevent Ischemic Cerebral Events in Patients Undergoing Protected Carotid Stenting: Results of the Randomized ARMYDA-9 CAROTID (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting) Study. J Am Coll Cardiol. 2013;61(13):1379-1387.] has concluded that a loading dose of 600 mg of clopidogrel and high dose atorvastatin in those undergoing carotid stenting protects against early ischemic cerebral events. The study involved over one hundred and fifty patients who underwent protected carotid stenting. Clopidogrel loading was either 600 or 300 mg given six hours prior to the procedure. Eighty milligrams of atorvastatin was given 12 hours prior to the procedure and forty milligrams about two hours before the procedure. The control arm received no statin reload. All were on long term statin therapy. The primary end points were the incidence of transient ischemic attack / stroke at thirty days or new ischemic lesions noted on diffusion weighted magnetic resonance imaging of the brain in one two days. Primary end points were lower in the 600 mg clopidogrel arm (18% vs 35.9%) as well as in the atorvastatin reload arm (18.4% vs 35%).
Implantable loop recorder is an implantable cardiac electronic device which is usually implanted subcutaneously in the pectoral region like a pacemaker. It monitors the electrocardiogram continuously, but transfers to permanent memory either on demand or when an event is sensed. It can transfer up to forty minutes of data prior to the event and one or two minutes after the event into the permanent memory which can be retrieved from the device using a wireless programmer. Modern implantable loop recorders have additional facility of transmitting data to the health care provider as well. The devices once implanted, can function up to three years depending on the battery capacity of various versions. Implantable loop recorders are very useful in evaluating symptoms that are intermittent so that it cannot be picked up by a twenty four hour Holter monitoring or a short term external loop recorder which typically records for about a week. Aniket Puri and associates give a good review of the utility of implantable loop recorders [Use of Implantable Loop Recorders to Unravel the Cause of Unexplained Syncope. Indian Pacing Electrophysiol. J. 2013;13(2):66-75].
Lia Crotti and colleagues along with Peter Schwartz [Calmodulin Mutations Associated With Recurrent Cardiac Arrest in Infants. Circulation. 2013; 127: 1009-1017.] , the pioneer in studies on congenital long QT syndrome, have described three denovo mutations in CALM1 and CALM2 mutations associated with QT prolongation and recurrent cardiac arrests in infants. The infants had life threatening ventricular arrhythmias, epilepsy and variable delay in neurodevelopment. There was a several fold decrease in the calcium binding efficacy of the mutant calmodulins. This will affect the calcium signaling in the membrane ion channels of the heart and lead on to deadly arrhythmias. We know that 13 gene mutations have been described in congenital long QT syndromes (LQTS1 to LQTS13). Will this new discovery be soon designated as LQT14 (LQTS14)?
Brugada syndrome is an inherited arrhythmogenic syndrome with life threatening ventricular arrhythmias, right bundle branch like pattern and ST segment elevation in right precordial leads. The first gene abnormality to be described was in SCN5A, the sodium channel gene. This has been designated as Brugada syndrome 1. Brugada syndrome 2 was described as defect in the GPD1L gene. The genetic defect in Brugada syndrome 3 is localized to the calcium channel gene CACNA1C. Brugada syndrome 4 has an abnormality in another calcium channel gene CACNB2. Brugada syndrome 5 has sodium channel gene defect n SCN1B. Potassium channel KCNE3 is defective in Brugada syndrome 6. Sodium channel SCN3B is defective in Brugada syndrome 7. HCN4 defect characterises Brugada syndrome 8 [Brugada R et al. Brugada Syndrome. http://www.ncbi.nlm.nih.gov/books/NBK1517/]
Progression of atrial fibrillation (AF) can be defined as a change from paroxysmal atrial fibrillation to persistent/permanent atrial fibrillation. Progression of AF is less likely if a rhythm control strategy is pursued [De Vos CB et al. Progression of atrial fibrillation in the REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation cohort: clinical correlates and the effect of rhythm-control therapy. Am Heart J. 2012;163:887-93]. This information is from RecordAF, a worldwide prospective registry of atrial fibrillation. More than two thousand and one hundred patients were followed up for one year. The chance for progression of atrial fibrillation was only eleven percent in the rhythm control group while it was twenty six percent in the rate control group (P<0.001). The associations with progression were higher age and diastolic blood pressure, coronary artery disease, stroke, transient ischemic attack (TIA) and heart failure.
Vernakalant is a rapidly acting drug useful in the treatment of recent onset atrial fibrillation. Unlike amiodarone which is a slow acting drug, vernakalant is a rapidly acting medication. Both intravenous and oral preparations have been tried. It is an atrial selective agent with actions on Kv1.5 channel conducting IKur current and Kir3.1/3.4 channel which conducts IKAch current. It has actions on Ito (transient outward current), late sodium current and mild effect on the rapid component of the delayed rectifying current IKr. Side effects listed include bad taste, paraesthesias, sneezing, nausea and rarely hypotension and very rarely ventricular arrhythmias [Tian D et al. Vernakalant: a new drug to treat patients with acute onset atrial fibrillation. Cardiol Rev. 2011;19:41-4.]. Long term studies documenting efficacy and safety may be needed further.
Following features may help in thinking of a cardioembolic etiology for stroke:
Sudden onset to maximal neurological deficit
Decreased level of consciousness at onset
Wernicke’s aphasia or global aphasia without hemiparesis
A Valsalva manoeuvre at the time of onset of stroke (can facilitate right to left shunt across a patent foramen ovale and consequently paradoxical emboli originating in the right side of the circulation and terminating the left side of the circulation)
Co-occurrence of cerebral and systemic emboli
[Arboix A et al. Acute cardioembolic cerebral infarction: answers to clinical questions. Curr Cardiol Rev. 2012;8:54-67]
Common causes for cardioembolic stroke would be atrial fibrillation, more so in the presence of mitral stenosis, previous large myocardial infarction with an akinetic segment or aneurysm, dilated cardiomyopathy, mechanical prosthetic heart valves and fragile atheromas in the proximal aorta.
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.