Cardiophile MD

Apixaban

Johnson Francis — Mon, 06 Feb 2012 17:36:48 +0000

Apixaban is a direct factor Xa inhibitor. It has an oral bioavailability of about fifty percent. Peak plasma Levels are achieved in three hours and the half-life is about 12 hours. Apixaban is metabolized in liver via CYP3A4 and other CYP independent mechanisms. It is eliminated via multiple pathways and no laboratory monitoring required during therapeutic administration. The utility of apixaban in preventing stroke in non valvar atrial fibrillation has been evaluated in two trial. ARISTOTLE compared apixaban with warfarin and found that it reduces stroke without an increase in bleeds. AVERROES trial compared apixaban with aspirin in those in whom vitamin K antagonists were not usable as in those who were unwilling or unable to monitor INR (internationally normalized ratio of prothromibin time). In this study also, apixaban reduced stroke without increasing major bleeds.

Tecarfarin

Johnson Francis — Mon, 06 Feb 2012 17:35:45 +0000

Tecarfarin is a vitamin K analogue which acts by inhibiting vitamin K epoxide reductase. Tecarfarin is highly bound to plasma proteins and has a half life of nearly five days (119 hours). It is not metabolized by cytochrome P450 enzyme system. Instead, the metabolism is by hepatic microsomal carboxylesterases. Hence it has less potential for drug interactions, unlike warfarin. Another advantage is the availability of INR (internationally normalized ratio of prothrombin time) monitoring with a well established therapeutic range. Moreover, unlike other newer antithrombotic agents which do not have antidotes, the action of tecarfarin is reversible by the administration of vitamin K. EmbraceAC compared tecarfarin with warfarin in a randomized double blind trial of those requiring long term anticoagulation: with atrial fibrillation, prosthetic heart valve, venous thromboembolism or a history of myocardial infarction or cardiomyopathy. The primary outcome was control of INR in the form of time in therapeutic range. Six hundred odd patients were enrolled and treated for six months. The time in therapeutic INR range was 74 percent for tecarfarin and 73.2 percent for warfarin (P = 0.506). Authors attribute the surprisingly high time in therapeutic range for warfarin in this trial to be due to the skill of physicians at the dose control center.

Faster degeneration of bioprosthetic valves in diabetics

Johnson Francis — Wed, 01 Feb 2012 01:46:23 +0000

A study involving twelve centers between 1988 and 2009 by Lorusso R et al [Type 2 Diabetes Mellitus Is Associated With Faster Degeneration of Bioprosthetic Valve
Results From a Propensity Score–Matched Italian Multicenter Study. Circulation.
2012; 125: 604-614] has found that bioprosthetic valves degenerate faster in patients with type 2 diabetes mellitus. There were about six thousand and two hundred patients the database analyzed, of which over one thousand and seven hundred were having type 2 diabetes mellitus. Propensity score matching algorithm was used to match 1113 patients with type 2 diabetes mellitus with the same number of those without diabetes mellitus. The one month mortality was 7.8 percent in diabetics while it was only 2.9 percent in the non diabetics. Seven year freedom from valve deterioration was 95.4 percent in the non diabetics while its was only 73.2 percent in diabetics. Diabetes mellitus was found to be the strongest predictor for structural valve degeneration with a hazard ratio of 2.39. This association was found even after adjusting for other important risk factors.

Newer antithrombotics in atrial fibrillation

Johnson Francis — Sat, 28 Jan 2012 14:16:36 +0000

Why do we need newer antithrombotics in atrial fibrillation? It is well known that long term anticoagulation reduces the incidence of stroke in non valvar atrial fibrillation. Vitamin K antagonists like warfarin are highly effective for long term anticoagulation and stroke prevention. But they have numerous limitations including erratic control and drug interactions which are challenging for physicians and patients. Hence the search for newer antithrombotics for stroke prevention in atrial fibrillation.

Newer antithrombotics for atrial fibrillation include the direct thrombin inhibitor dabigatran, direct factor Xa inhibitors like rivaroxaban, apixaban and edoxaban as well as the vitamin K analogue tecarfarin. Otamixaban is a potential intravenous alternative for the acute care setting. In general, direct thrombin and factor Xa inhibitors are small, synthetic molecules with Predictable pharmacokinetics and pharmacodynamic effect, having few drug interactions and do not require routine therapeutic drug monitoring.

Polymer free amphilimus stent better than paclitaxel eluting stent?

Johnson Francis — Sat, 28 Jan 2012 01:35:55 +0000

Carrid D and colleagues [A Multicenter Randomized Trial Comparing Amphilimus- With Paclitaxel-Eluting Stents in De Novo Native Coronary Artery Lesions. J Am Coll Cardiol, doi:10.1016/j.jacc.2011.12.009 (Published online 25 January 2012)] from Europe have compared polymer free amphilimus eluting stents with permanent polymer coated paclitaxel eluting stents in percutaneous coronary interventions of de novo lesions. The primary end point was angiographic late lumen loss at six months. One fifth of the patients had also undergone intravascular ultrasound (IVUS) evaluation. The duration of clinical follow up was five years. Among the three hundred and twenty odd patients studied, the clinical end points of cardiac death, myocardial infarction, target vessel revascularization (TLR) and stent thrombosis was similar between the two groups at one year. In stent late lumen loss was lower with amphilimus stent (0.14 ± 0.36 mm vs. 0.34 ± 0.40 mm, with p for both noninferiority and superiority <0.0001). The authors claim that the polymer free amphilimus stent has a significantly lower in stent late lumen loss and a trend towards better one year clinical safety and efficacy in the treatment of de novo coronary lesions. The stent technology is based on polymer free abluminal reservoir elution which avoids the exposure of the vessel wall to polymers present in the luminal side of conventional drug eluting stents which are potentially proinflammatory and may impair the healing of the vessel. The authors also claim that this feature may potentially reduce the need for prolonged dual anti platelet therapy with its attendant complications. We need more large scale randomized head to head comparisons of the various new generation coronary stents to get the final answer on which is the better of the lot.

Role of PCI in CAD associated with severe aortic stenosis

Johnson Francis — Fri, 27 Jan 2012 07:21:26 +0000

Conventionally CAD (coronary artery disease) associated with severe aortic stenosis is an indication for coronary artery bypass grafting along with surgical aortic valve replacement. But in this era of transcatheter aortic valve replacement (TAVR; also known as transcatheter aortic valve implantation or TAVI), is there a role of PCI (percutaneous coronary intervention) in those awaiting TAVR? Goel SS and colleagues evaluated this aspect in a retrospective analysis of their PCI database. They could identify over two hundred and fifty patients with severe aortic stenosis who had undergone PCI for their associated CAD. They also identified over five hundred patients without aortic stenosis who had undergone PCI using propensity matching. The investigators concluded that percutaneous coronary intervention could be performed in those with severe symptomatic aortic stenosis and CAD with no significant increased risk of short term mortality compared to propensity matched patients without significant aortic stenosis. They also observed that patients with severe left ventricular dysfunction (ejection fraction thirty percent or less) and those with STS (Society of Thoracic Surgeons) score of 10 percent or more are at a highest risk of 30 day mortality after PCI. Online STS risk calculator is available at: http://riskcalc.sts.org/STSWebRiskCalc273/

AV interval optimization in CRT

Johnson Francis — Fri, 27 Jan 2012 05:51:34 +0000

The aim of AV (atrioventricular) interval optimization in CRT (cardiac resynchronization therapy or biventricular pacing) is to prevent too early or too late atrial contraction. Too late an atrial contraction will cause it to overlap with ventricular systole so that atrial contraction will occur against a closed AV valve. This will lead to a sudden elevation of atrial and pulmonary as well as systemic venous pressure. Echocardiographic methods to optimize AV delay are Ritter’s method and Ishikawa’s method. In Ritter’s method, long AV delay is calculated when there is partial fusion of E and A waves on mitral Doppler and short AV delay is calculated when A wave truncation occurs due to ventricular contraction before completion of A wave. From these two values, the optimal AV delay is calculated using the Ritter’s formula.

Ishikawa’s method is used when there is significant diastolic mitral regurgitation. Long AV delay is chosen so that it results in diastolic mitral regurgitation or diastasis until isovolumetric contraction, which is the time at which systolic mitral regurgitation starts. It may be noted that there is no true isovolumetric phase when there is systolic mitral regurgitation as mitral valve starts leaking in the potential isovolumetric phase and reduces the ventricular volume. The duration of diastolic mitral regurgitation is subtracted from the long AV delay to get the optimal AV delay.

AF ablation during therapeutic warfarin levels

Johnson Francis — Wed, 25 Jan 2012 02:03:31 +0000

Conventionally, invasive procedures are undertaken by switching over from warfarin to unfractionated heparin to have a better control over bleeding. Santangeli P and associates [Ablation of Atrial Fibrillation under Therapeutic Warfarin Reduces Periprocedural Complications: Evidence from a Meta-Analysis. CIRCEP.111.964916 Published online before print January 23, 2012, doi: 10.1161/?CIRCEP.111.964916] have conducted a meta analysis of published data on the utility of proceeding with atrial fibrillation (AF) ablation while on therapeutic anticoagulation with warfarin. This was prompted by data from observational studies which had suggested that procedures under continuous warfarin usage may reduce the risk of periprocedural complications like thromboembolic events compared to the discontinuation of warfarin and bridging with heparin. They could identify nine studies with a total of over twenty seven thousand patients in which six thousand and four hundred had undergone AF ablation with continuous warfarin regimen. Continuous warfarin usage was associated with a significant decrease in thromboembolic complications (odds ratio = 0.10, P < 0.001) and minor bleeding complications (odds ratio = 0.38, P = 0.002) as compared to discontinuation of warfarin and bridging with heparin. This would call for a large randomized controlled trial to evaluate this concept further.

Optical coherence tomography (OCT)

Johnson Francis — Sat, 21 Jan 2012 02:12:05 +0000

Optical coherence tomography (OCT) has much higher resolution compared to intravascular ultrasound. It has the resolution of the range of 10 20 microns, which is an order of magnitude better than that of intravascular ultrasound. But the limitation is the lower depth of tissue penetration which is only 2 to 3 millimeters, compared to the 10 millimeter tissue penetration of current intravascular ultrasound probes. Hence it has limitations while imaging large vessels like left main coronary artery and proximal left anterior descending coronary artery. The excellent resolution of optical coherence tomography is very useful in examining the coronary lesion characteristics like plaque rupture and also for monitoring the results of percutaneous interventions with stent deployment. OCT uses light waves instead of ultrasound for imaging. A light emitting source and system to collect the reflected light which checks the intensity of back scatter from internal microstructures with varying optical properties and the time delay of receiving the return signal are part of the OCT device. Since the speed of light is very much faster than that of sound, it is practically impossible to detect time delay of reflected waves electronically. A special device known as time domain OCT interferometer is used for this purpose. OCT is useful in plaque characterisatiion including the measurement of thickness of the fibrous cap which is an important determinant of plaque stability. The macrophage content of the plaque can also be estimated as the macrophages are of relatively large size (20 to 50 microns) and have a high degree of optical contrast. Hence plaques rich in macrophages have a high OCT signal variance. An excellent review on OCT is available at: Cardiac optical coherence tomography. Heart 2008;94:1200-1210, written by Raffel OC and colleagues, in the technology and guidelines section.

Ultrasonography for detecting radial access site complications

Johnson Francis — Wed, 18 Jan 2012 17:25:57 +0000

Uhlemann M et al have reported radial access site complications in their prospective vascular ultrasound registry [The Leipzig Prospective Vascular Ultrasound Registry in Radial Artery Catheterization. Impact of Sheath Size on Vascular Complications. J Am Coll Cardiol Intv, 2012; 5:36-43]. The primary objective of the study was to find the impact of sheath size on the chance of radial artery occlusion. They evaluated over four hundred and fifty patients between 2009 and 2010. Duplex ultrasound studies were done in all patients before discharge. Symptomatic radial artery occlusions were treated with low molecular weight heparin. Total access site vascular complication rate was 14.4 percent with a 5 F sheath and 33.1 percent with a 6 F sheath. Occlusion of the radial artery occurred in 13.7 percent with 5F sheaths and 30.5 percent with 6 F sheath. Other access site complications assessed in the study were hemorrhage, pseudoaneurysm, arteriovenous fistula. 42.5 percent of the radial artery occlusions were immediately symptomatic while seven percent became symptomatic within a mean of four days. Recanalization rates were higher in those who received low molecular weight heparin (55.6% vs. 13.5%, p < 0.001) after a mean period of 14 days. The incidence of radial artery occlusions noted by ultra sound evaluation in this study was surprisingly high, more so in those whom a larger sheath had been deployed.