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Heart India, Vol 1 / Issue 1 / Apr-Jun 2013 iHeart India, Vol 1 / Issue 1 / Apr-Jun 2013

ISSN: Print - 0000-0000, E-ISSN: 0000-0000

Associate Editors

Dr. Pablo Avanzas, Please provide Country ???

Dr. Saurabh Gupta, India Dr. Akshay Pradhan, India

Assistant Editors

Dr. Sudarshan, India Dr. Ravi Visnu, India

Dr. Naveed Ahmad, IndiaDr. Madhuri Nagori, India

Dr. A K Pandey, IndiaDr. Aman Makhija, IndiaDr. Ankit Agrawal, IndiaDr. Daljeet Kaur, India

Dr. Deepash Agrawal, IndiaDr. Dilip Kumar, India

Dr. Kartikeya Bhargava, India

Dr. M.P Tripathy, India

Dr. Manojit Lodha, India

Dr. Omar Hasan, India

Dr. P R Sinha, India

Dr. Ramanand, India

Dr. Sanjeev Gupta, India

Editorial Board Members

Editorial Board

Dr. Mimmo Tavella, Italy Dr. Sri Harsha vellury, U.S.A

Dr. Rohit Tiwari, India Dr. Rishi Sethi, India Dr. Sarad Chandra, India

Executive Editors

International Editorial Members

Dr. Alok Kumar Singh Interventional Cardiologist,

Heritage Hospital, Varanasi, India

Editor In Chief

HEART INDIA

Editorial Board

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Heart India, Vol 1 / Issue 1 / Apr-Jun 2013ii Heart India, Vol 1 / Issue 1 / Apr-Jun 2013

HEART INDIA

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Heart India (ISSN: Print - 0000-0000, E-ISSN: 0000-0000) is the official publication of Heart India Charitable Trust. It is a peer-reviewed online journal with Quarterly print on demand compilation of issues published.

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Addresses

Editorial OfficeDr. Alok Kumar SinghDepartment of Cardiology Interventional Cardiologist Heritage Hospitals Pvt Ltd Varanasi U.P India Phone: 9335078381 E-mail: [email protected]

Published byMedknow Publications and Media Pvt. Ltd.B 9, Kanara Business Centre,Off Link Road, Ghatkopar (E),Mumbai – 400075, IndiaPhone: 91-22-66491818Website: www.medknow.com

Printed atNikeda Art Printers Pvt. Ltd., Bhandup, Mumbai, India

Heart India, Vol 1 / Issue 1 / Apr-Jun 2013 iiiHeart India, Vol 1 / Issue 1 / Apr-Jun 2013

HEART INDIA

C O N T E N T S

Vol 1 | Issue 1 | Apr - Jun 2013

EDITORIAL

Preface to First Issue of Heart IndiaAlok Kumar Singh 1

REVIEW ARTICLE

Functional AngioplastyRohit Tewari 3

ORIGINAL ARTICLES

Risk Factors for Coronary Artery Diseases: A Study Among Patients With Ischemic Heart Disease in KeralaCyril James 8

Obstructive Sleep Apnea in Patients with Myocardial Infarction: Experience from a Tertiary Care Hospital in South IndiaUma Devaraj, Priya Ramachandran, George A D’souza 13

CASE REPORT

The Vanishing Right Ventricular MassesSudarshan Kumar Vijay, Bhuwan Chandra Tiwari, Mukul Misra, Lalit Mohan Joshi 18

IMAGE

A Rare Case of Double Orifice Mitral Valve with Multiple Muscular Ventricular Septal DefectShamsher Singh, Ratna Pandey, Alok Kumar Singh, Ajay Kumar Pandey 21

JOURNAL SCAN

Management of Coronary Artery Disease in 2013: Recent Insights (Journal Scan)Akshyaya Kumar Pradhan 23

Heart India, Vol 1 / Issue 1 / Apr-Jun 2013iv Heart India, Vol 1 / Issue 1 / Apr-Jun 2013

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HEART INDIA on Web

Editor Dr. Alok Kumar Singh. Printed and published by Medknow Publications and Media Pvt. Ltd on behalf of Heart India Charitable Trust and printed at Nikeda Art Printers Pvt. Ltd., Bhandup, Mumbai, India, and published at B5-12, Kanara Business Centre, Ghatkopar, Mumbai, India

1Heart India, Vol 1 / Issue 1 / Apr-Jun 2013

the pathophysiological mechanisms of CVDs. Our focus is to convert research in to knowledge, so every physician and cardiologist caring heart patients from primary to tertiary level may be benefitted. I realized that although Cardiologist in developing countries witness a range of disease spectrums, and acquire a wealth of clinical skill because of high clinical exposure, but they do not publish their experiences in journals. As a result, in spite of having good clinical and interventional experience Cardiologist from developing countries are often unable to become the authority in the absence of peer reviewed publication. Many feel strongly motivated to express their opinion in clinical meetings, but to write the same most lose the motivation.

Heart India will provide a platform to physician from India to share their clinical experience to the global audience in a scientific way in the form of original research article, review article, case report and image format. Heart India will have 4 issues in a year, which we will be comprised of the review article, original article, case report, images and journal scan, and educational article specifically designed by an editorial board in case format with evidence based discussion by experts in the field. Heart India encourage young cardiologist to publish with Heart India.

In this issue, first article is a review article by Dr. Tewari on functional angioplasty and two original article one from Kerala by Dr. Cyril James and second original article by Dr. Devraj et al.

Next to this article an interesting case report of vanishing right ventricular mass by Dr. Sudarshan and next to it a clinical image of Double orifice mitral Valve by Dr. Pandey et al. Last article is in journal Scan section by Dr. Pradhan who has nicely summarized all landmark paper and guideline related to coronary artery disease in last 1 year.

I will like to thank all editorial board member, reviewer and authors who have contributed in the publication of this issue. Lastly, I will like to thank the editorial staff of Wolter Kluwer/Medknow who works day and night to bring out Heart India first issue in this format.

Alok Kumar Singh

Editor in Chief, Heritage Hospital Lanka, Varanasi, Uttar Pradesh, India

Preface to First Issue of Heart IndiaSir,Every year, 17.1 million lives are claimed by the cardiovascular disease (CVD) 82% of which are in the developing world. As per the prediction of World Health Organization (WHO) by 2030, nearly 23.6 million people will die from CVD. So as a scientific community it is our duty to tackle CVD by means of preventive measure as well as therapeutic advances in terms of medicines and devices that is the reason we are starting a new Journal Heart India with Wolter Kluwer/Medknow. Our aim to start this journal from India is to stimulate our cardiologist and physicians to generate our own data and publish it in our own journal from Indian subcontinent without any prejudice and bias. Rheumatic Heart Disease (RHD) is still very common in our country, but it is no more concern for Western Countries. Our problem is unique in the sense we are having the increasing incidence of diabetes, hypertension and coronary artery disease (CAD) with higher prevalence of rheumatic heart disease. In India, where the people account for one sixth of the world’s population, data suggests that CVD accounts for approximately one fourth of total deaths.[1] The World Health Day, which marks the anniversary of the establishment of WHO in 1948, is celebrated annually on April 7, with a different theme each year, features an area of priority in global public health. On the occasion of celebrating the World Health Day on April 7 this year with a theme on hypertension, the WHO called on Wednesday for greater efforts to prevent and control this disease, which is also known as high blood pressure.[2] This year theme of WHO is the shift of its focus from communicable diseases to non‑communicable diseases. The main worry of concern is the rising hypertension related cardiovascular mortality in the developing world in comparison to developed world because of less stringent implication of guideline recommendation and no proper government policy to tackle it.

Heart India covers basic scientific research to clinical practice and deals with all areas of CVD including from preventive cardiology, clinical cardiology, heart failure, electrophysiology, and interventional cardiology. We will appreciate articles on work at the molecular, and gene level with an emphasis on

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Singh: Heart India first issue

Heart India, Vol 1 / Issue 1 / Apr-Jun 2013

Address for correspondence: Dr. Alok Kumar Singh,

Heritage Hospital Lanka, Varanasi, Uttar Pradesh, India. E‑mail: [email protected]

REFERENCES1. Murray CJ, Lopez AD. The Global Burden of Disease. Cambridge,

MA: Harvard School of Public Health; 1996.2. A global brief on hypertension World Health Day, 2013. A report

from WHO 2013.

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of preceding stress test.[2] Accurate Indian data on this is not available, but certainly would be much below these figures.

Further, traditional understanding makes us endorse bypassing all lesions more than 50% stenosis. We as care providers proudly feel, we have given the benefit of “complete revascularization” to our patient and ensured better outcomes. By passing functionally insignificant proximal stenosis has now been rendered debatable with poorer graft patency rates.[5]

Use of objective ischemia based percutaneous coronary intervention (PCI) improves the functional status and the clinical outcomes.[6 8] Non invasive functional evaluation suffers from poor spatial resolution and low sensitivity[9 10] so revascularization should be guided by objective ischemia.

Revascularization in coronary artery diseases (CAD) is thought to be life saving[11] while in contrast, COURAGE, and BARI- 2D trials failed to demonstrate any benefit of stenting over optimal medical therapy in preventing death, non fatal MI, unplanned revascularization. [12,13] However, stable CAD patients having poor exercise capacity or large ischemia burden do benefit from revascularization. A large SPECT study showed benefits of revascularization were confined to those patients who have >10% ischemic burden.[1]

A recent study in JACC by Kim et al[14] showed the benefits

Functional AngioplastyRohit TewariDwarka Heart Institue, Delhi India

A B S T R A C TCoronary angiography underestimates or overestimates lesion severity, but still remains the cornerstone in the decision making for revascularization for an overwhelming majority of interventional cardiologists. Guidelines recommend and endorse non invasive functional evaluation ought to precede revascularization. In real world practice, this is adopted in less than 50% of patients who go on to have some form of revascularization. Fractional flow reserve (FFR) is the ratio of maximal blood flow in a stenotic coronary relative to maximal flow in the same vessel, were it normal. Being independent of changes in heart rate, BP or prior infarction; and take into account the contribution of collateral blood flow. It is a majorly specific index with a reasonably high sensitivity (88%), specificity (100%), positive predictive value (100%), and overall accuracy (93%). Whilst FFR provides objective determination of ischemia and helps select appropriate candidates for revascularization (for both CABG and PCI) in to cath lab itself before intervention, whereas intravascular ultrasound/optical coherence tomography guidance in PCI can secure the procedure by optimizing stent expansion. Functional angioplasty simply is incorporating both intravascular ultrasound and FFR into our daily Intervention practices.

Key words: FFractional flow reserve, intravascular ultrasound, optical coherence tomography, percutaneous coronary interventionn

Address for correspondence: Dr. Rohit Tewari, A 16, Sector 51, Noida, Uttar Pradesh, India. E‑mail: [email protected]

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R eview A r t ic le

INTRODUCTION

Coronary angiography underestimates or overestimates lesion severity, but still remains the cornerstone in the decision making for revascularization for an overwhelming majority of interventional cardiologists. Inducible ischemia during the functional testing has prognostic significance in determining when and whether to intervene.[1] In real world practice, this is adopted in less than 50% of patients who go on to have some form of revascularization.[2] Guidelines recommend and endorse non invasive functional evaluation ought to precede revascularization.[3] Twenty years ago, Topol et al.[4] reported that only 29% patients had undergone exercise testing prior to stenting. Even now, less than 45% patients have any form

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of ischemia guided PCI in multivessel CAD. Major adverse cardiac events (MACE) was significantly lower in ischemia guided PCI over non ischemia guided, largely driven by lower repeat revascularization (9.9% vs. 22.8%, hazard ratio 0.66, 95% CI 0.49 0.90, P= 0.009).

FRACTIONAL FLOW RESERVE ‑ NOT A NEW CONCEPT,

WE ALL KNOW, BUT ARE RELUCTANT TO USE AS GUIDE

Coronary pressure measurement has been around for more than 20 years now. FFR is the ratio of maximal blood flow in a stenotic

coronary relative to maximal flow in the same vessel, were it normal. Being independent of changes in heart rate, BP or prior infarction; and take into account the contribution of collateral blood flow. It is a majorly specific index with a reasonably high sensitivity (88%), specificity (100%), positive predictive value (100%), and overall accuracy (93%).

Values> 0.80 are associated with negative ischemic results with predictive accuracy of 95%. The validation of these lesion specific values has been made in numerous clinical situations[15]

Figure 3: (a) A 60‑year‑old man with stable angina. Angiographic DS was 80% (black arrow) and intravascular ultra sound‑minimal lumen area (IVUS‑MLA) was 2.3 mm2, whereas fractional flow reserve (FFR) was 0.84 (mismatch). The lack of inducible ischemia of the stenosis was supported by normal perfusion on thallium scan and negative treadmill test. (b) A 55‑year‑old man with unstable angina. Angiographic DS was 40% (black arrow) and IVUS‑WLA was 4 1 mm2. Plaque rupture was shown (red arrow). FFR was reduced to 0.74 (reverse mismatch). (c) A 50‑year‑old man with unstable angina. Angiographic DS at the proximal LMCA was only 35%. IVUS showed MLA 5.2 mm2 and ruptured plaque (red arrow). FFR of LMCA was 0.71 (reverse mismatch).

Figure 4: (a) The stenotic lesion (70% of DS) without plaque rupture showed fractional flow reserve (FFR) = 0.68. (b) In the same degree of stenosis (70% of DS), the lesion with large opening plaque rupture showed FFR = 0.66. (c) In the same degree of stenosis (70% of DS), the lesion with a small opening plaque rupture showed FFR = 0.58. The small opening of plaque rupture makes a higher velocity turbulence of fluid (blue arrows), which may Induce more energy loss of fluid compared to the larger opening plaque rupture and result in a lower FFR. (3D: 3‑dimensional.

Aq1

Figure 2: Visual functional mismatch

Figure 1: Correlation of FFR and IVUS

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and holds true in estimating different lesions in the same vessel by pullback technique.

FFR >0.80, STENTS NOT NEEDED, <0.80 STENTS JUSTIFIED

A total of 5 year results of the DEFER study[16] showed similar event free survival in deferred versus PCI group(80% vs. 73%, P = 0.5) while death and MI were 3.3% in the deferral group versus 7.9% in PCI group, (P = 0.21). This implies an annual risk of cardiac death or MI in FFR negative patients is < 1% per year and was not decreased by stenting. One could safely defer revascularization in such patients for up to 5 years.

The two year clinical outcomes of the FAME study showed the deferred group to have a 0.2% incidence of MI and 3.2% need for a repeat revascularization.[17]

Five years follow up of functionally insignificant lesions left on optimal medical therapy(even those with a proximal LAD) showed 5year survival of 92.9% in the medical group versus 89.6% in the re vascularized group (P = 0.74).

Stent implantation in patients with functionally insignificant disease implies greater possibility of stent thrombosis and restenotic disease– A risk that does not seem worth taking when we know that left alone on medical therapy the overall risk was very low!! Even DES usage does not alter this scenario of detrimental risk in multiple lesions as in single lesions.[18]

The FAME II trial was designed to compare the clinical outcomes, safety, and cost effectiveness of PCI guided by FFR plus optimal medical therapy versus optimal medical therapy alone in stable CAD.[19] Preliminary results showed 7.6 times greater risk of hospital readmission with revascularization for the optimal medical therapy alone group and 11.2 times greater need for urgent revascularization. Thus, stenting lesions with FFR < 0.8 seems fully justified.

VISUAL‑FUNCTIONAL MISMATCH

The IRIS FFR DEFER study published a few months back in JACC interventions attempted to resolve this issue.[20] Sub analysis of the FAME trial showed that 2/3rd of the lesions with a diameter stenosis of > 50% were not ischemia producing! However, the scenario was totally different in for the left main where at least 20% of such lesions were ischemia producing. Angio FFR mismatch was defined as angiographic diameter stenosis >50% and FFR> 0.80, whereas “reverse mismatch” was defined as angiographic diameter stenosis <50% and FFR< 0.80 [Figure 1]. QCA, intravascular ultrasound, and FFR were performed and it was shown that visual functional mismatch was as high as 40%. The Figure 2 highlights the visual functional mismatch.

Patient’s age affected the physiologic effect of a stenosis. Older patients have higher FFR than younger counterparts. Aging related loss of functional myocytes or the attenuation of vasodilatory response to adenosine could account for this.[21,22]

Lesion location influences functional severity. Isolated left main lesions frequently show reverse mismatch. The area of supply of left main being much greater renders even a modest stenosis to assume notable functional significance.

In simpler words, this means one should consider doing FFR for even the visually innocuous lesions in left main disease.

Plaque rupture may influence the functional significance of a stenosis.[23] The impact of innocent plaque rupture on the functional significance is improperly understood. Theoretically, a complex lesion with irregular lumen would provide greater flow resistance and energy losses; thus, resulting in more pressure drop and reduction in FFR.

So, we now know that not just lumen size but also plaque shape, length, surface roughness or plaque rupture may be associated with changes in FFR [Figure 3-4]. Thrombotic material superimposed on a ruptured plaque site may increase roughness of vessel surface and subsequently increase flow resistance; thus, adding to its functional significance.

INTRAVASCULAR ULTRASOUND: THE INTERVENTIONISTS’ FRIEND!!

Do an intravascular ultrasound if you want to intervene: An FFR if you don’t!! The 360 degree tomographic saggital scan of the vessel has enriched our understanding of not only atherosclerosis, but also of angioplasty. However again we know it provides anatomical information and not physiological. Attempts to integrate target lesion anatomy physiology have also been made.

Figure 5: Scatter plot of intravascular ultra sound fractional flow reserve correlation

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The conventional teaching of stenting all lesions that reveal an intravascular ultrasound minimal lumen area (MLA) < 4 mm2 needs to be requisitioned. Can intravascular ultrasound MLA adequately predict functional significance and does it truly correspond to ischemic threshold? A 50% diameter stenosis roughly equals a 75% area stenosis and has been held significant. An MLA of 4 mm2 is equal approximately 24% diameter stenosis for a 3mm vessel and roughly equals 43% stenosis for a 4mm vessel. Other than the diameter of the stenotic vessel, we know that flow is influenced by lesion length, plaque burden, vessel size, lesion morphology, plaque characteristics, blood viscosity, collateral circulatory flow, and subtended perfusion bed.[24] Not all of these are as easily measurable as MLA and the summation of all these aspects would determine hemodynamic severity. It would thus be simplistic to think of MLA as being enough as a standalone criterion.

An interesting work appeared in the circulation interventions last year where intravascular ultrasound criteria were validated with FFR. Multivariate analysis showed that MLA (beta= 0.02, P= 0.032), plaque burden (beta = −0.002, P = 0.001), lesion length with a lumen area <3 mm (beta = −0.035, P = 0.001) and LAD location (beta = −0.035, =0.001) were independent predictors of FFR< 0.80. Using the ROC analysis, Kang et al[25] proposed new intravascular ultrasound MLA criteria for predicting FFR< 0.80 was 2.4 mm2 (which was much lower than the currently held standard).

The Figure 5 shows that FFR values if lesions with MLA< 4 mm2 were widely scattered and 66% had MLA< 4mm, but FFR flow reserve>0.8. Using the 2.4mm MLA criterion, only 30% lesions had a MLA< 2.4, but FFR> 0.80.

So, it shows that whatever anatomical cutoff we use, MLA alone does not seem to be a sufficient standalone criterion.

THEN WHAT’S THE ROLE OF INTRAVASCULAR ULTRASOUND IN

INTERVENTION?

Intravascular ultrasound has a key role in stent optimization and influences long term outcomes. In a study intravascular ultrasound MLA and stent length appeared to be the only predictors of restenosis.[26] Moreover, intravascular ultrasound guided DES implantation was found to significantly reduce rates of subacute stent thrombosis and cumulative stent thrombosis at 12 months.[27] Possible mechanisms were unclear, but as intravascular ultrasound post stenting would identify factors such as stent under expansion, malposition, inflow/outflow disease, edge dissections and thrombosis, it can be assumed that this is the manner in which intravascular ultrasound helps.

Intravascular ultrasound guidance has shown to improve long

term mortality, again possibly by lowering the risk of stent thrombosis in high risk PCI including left main and bifurcation disease,[28,29] which again means that intravascular ultrasound is a very important tool and has a definite place in the armamentarium of the Interventionist.

WHAT ABOUT OPTICAL COHERENCE TOMOGRAPHY THEN?

The CLI OPCI study[30] published in Euro Interventions showed that optical coherence tomography group had a lower risk of cardiac death, MI or repeat revascularization. Where optical coherence tomography scores clearly over intravascular ultrasound is the spatial y structures. Resolution and enabling are much better appreciation of lumen contour, struts, and nearby structures and hence superior stent optimization.

INCORPORATE THEM BOTH INTO YOUR PRACTICE: THAT’S

FUNCTIONAL ANGIOPLASTY

Functional angioplasty simply is incorporating both intravascular ultrasound and FFR into our daily Intervention practices. These are complementary and not competitive modalities. Whilst FFR provides objective determination of ischemia and helps select appropriate candidates for revascularization (for both CABG and PCI). Intravascular ultrasound/optical coherence tomography guidance in PCI can secure the procedure– pre intervention and it helps assess anatomical and post intervention helps optimize stent. This is the future of an angioplasty!!!

REFERENCES

1. Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107:2900 7.

2. Lin GA, Dudley RA, Lucas FL, Malenka DJ, Vittinghoff E, Redberg RF. Frequency of stress testing to document ischemia prior to elective percutaneous coronary intervention. JAMA 2008;300:1765 73.

3. Winjs W, Kolh P, Garg S, Huber K, Falk V, Folliguet T, et al. Guidelines for myocardial revascularization: The task force for ESC and ECATS. Eur H J 2010;31:2501 55.

4. Topol EJ, Ellis SG, Cosgrove DM, Bates ER, Muller DW, Schork NJ, et al. Analysis of coronary angioplasty practice in the United States with an insurance claims data base. Circulation 1993;87:1489 97.

5. Botman CJ, Schonberger J, Koolen S, Penn O, Botman H, Dib N, et al. Does stenosis severity of native vessels influence bypass graft patency? A prospective fractional flow reserve guided study. Ann Thorac Surg 2007;83:2093 7.

6. Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: Results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008;117:1283 91.

7. Davies RF, Goldberg AD, Forman S, Pepine CJ, Knatterud GL, Geller N, et al. Asymptomatic Cardiac Ischemia Pilot (ACIP) study two year

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follow up: Outcomes of patients randomized to initial strategies of medical therapy versus revascularization. Circulation 1997;95:2037 43.

8. Erne P, Schoenenberger AW, Burckhardt D, Zuber M, Kiowski W, Buser PT, et al. Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: The SWISSI II randomized controlled trial. JAMA 2007;297:1985 91.

9. Lima RS, Watson DD, Goode AR, Siadaty MS, Ragosta M, Beller GA, et al. Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three vessel coronary artery disease. JAm Coll Cardiol 2003;42:64 70.

10. Melikian N, De Bondt P, Tonino P, De Winter O, Wyffels E, Bartunek J, et al. Fractional flow reserve and myocardial perfusion imaging in patients with angiographic multivessel coronary artery disease. JACC Cardiovasc Interv 2010;3:307 14.

11. Anderson, Adams, Antman, Bridges CR, Califf RM, Donald E, et al. ACC/AHA guidelines for unstable angina/NSTEMI. Circulation 2007;116:e148 304.

12. Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503 16.

13. BARI 2D Study Group, Frye RL, August P, Brooks MM, Hardison RM, Kelsey SF, et al. A randomized trial of therapies for type2 diabetes and coronary artery disease. N Engl J Med 2009;360:2503 15.

14. Kim YH, Ahn JM, Park DW, Song HG, Lee JY, Kim WJ, et al. Impact of ischemia guided revascularization with myocardial perfusion imaging for patients with multivessel coronary disease. J Am Coll Cardiol 2012;60:181 90.

15. Kern MJ, Lerman A, Bech JW, De Bruyne B, Eeckhout E, Fearon WF, et al. Physiological assessment of coronary artery disease in the cardiac catheterization laboratory: A scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Circulation 2006;114:1321 41.

16. Pijls NH, van Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van’t Veer M, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5 year follow up of the DEFER Study. J Am Coll Cardiol 2007;49:2105 11.

17. Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2 year follow up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol 2010;56:177 84.

18. Beohar N, Davidson CJ, Kip KE, Goodreau L, Vlachos HA, Meyers SN, et al. Outcomes and complications associated with off label and untested use of drug eluting stents. JAMA 2007;297:1992 2000.

19. AQ14De Bryune B, for the FAME II Study Group. Fractional flow

reserve guided PCI plus optimal medical therapy vs. optimal medical therapy alone in patients with stable CAD. Presented at Euro PCR; 2012.

20. Park SJ, Kang SJ, Ahn JM, Shim EB, Kim YT, Yun SC, et al. Visual functional mismatch between coronary angiography and fractional flow reserve. JACC Cardiovasc Interv 2012;5:1029 36.

21. Burgess ML, McCrea JC, Hedrick HL. Age associated changes in cardiac matrix and integrins. Mech Ageing Dev 2001;122:1739 56.

22. Pandya K, Kim HS, Smithies O. Fibrosis, not cell size, delineates beta myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo. Proc Natl Acad Sci U S A 2006;103:16864 9.

23. Kang SJ, Lee JY, Ahn JM, Song HG, Kim WJ, Park DW, et al. Intravascular ultrasound derived predictors for fractional flow reserve in intermediate left main disease. JACC Cardiovasc Interv 2011;4:1168 74.

24. Hamilos M, Peace A, Kochiadakis G, Skalidis E, Ntalianis A, De Bruyne B, et al. Fractional flow reserve: An indispensable diagnostic tool in the cardiac catheterisation laboratory. Hellenic J Cardiol 2010;51:133 41.

25. Kang SJ, Lee JY, Ahn JM, Mintz GS, Kim WJ, Park DW, et al. Validation of intravascular ultrasound derived parameters with fractional flow reserve for assessment of coronary stenosis severity. Circ Cardiovasc Interv 2011;4:65 71.

26. Hong MK, Mintz GS, Lee CW, Park DW, Choi BR, Park KH, et al. Intravascular ultrasound predictors of angiographic restenosis after sirolimus eluting stent implantation. Eur Heart J 2006;27:1305 10.

27. Roy P, Steinberg DH, Sushinsky SJ, Okabe T, Pinto Slottow TL, Kaneshige K, et al. The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug eluting stents. Eur Heart J 2008;29:1851 7.

28. Park SJ, Kim YH, Park DW, Lee SW, Kim WJ, Suh J, et al. Impact of intravascular ultrasound guidance on long term mortality in stenting for unprotected left main coronary artery stenosis. Circ Cardiovasc Interv 2009;2:167 77.

29. Kim SH, Kim YH, Kang SJ, Park DW, Lee SW, Lee CW, et al. Long term outcomes of intravascular ultrasound guided stenting in coronary bifurcation lesions. Am J Cardiol 2010;106:612 8.

30. Prati F, Di Vito L, Biondi Zoccai G, Occhipinti M, La Manna A, Tamburino C, et al. Angiography alone versus angiography plus optical coherence tomography to guide decision making during percutaneous coronary intervention: The Centro per la Lotta contro l’Infarto Optimisation of Percutaneous Coronary Intervention (CLI OPCI) study. Euro Intervention 2012;8:823 9.


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8 Heart India, Vol 1 / Issue 1 / Apr-Jun 2013

Risk Factors for Coronary Artery Diseases: A Study Among Patients With Ischemic Heart Disease in KeralaCyril JamesDepartment of Cardiology, Lourdes Heart Institute and Neuro Center, Cochin, Kerala, India

heartindia_1_13R7

of death attributable to the disease has declined in developed countries in the past several decades, it is still the leading cause of death and extorts a heavy social and economic toll globally. In low and middle income countries, the prevalence of cardiovascular disease has increased dramatically. By 2020, the disease is forecasted to be the major cause of morbidity and mortality in most developing nations.[2,3] CAD includes a spectrum of disease manifestation ranging from asymptomatic atherosclerotic disease to acute coronary syndrome, which includes ST elevation myocardial infarction (STEMI), Non‑ST elevation myocardial infarction (NSTEMI) and unstable angina.

The risk factors for CAD are broadly classified as modifiable and non‑modifiable risk factors. Modifiable risk factors include hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking. Non‑modifiable risk factors include age, sex, race, and family history for CAD.[4] The Systematic Coronary Risk Evaluation system is recommended to assess an individual’s total cardiovascular risk. CAD is closely related to life‑style and modifiable physiological factors, and risk factor modification has been shown to reduce cardiovascular morbidity and mortality.

A B S T R A C TObjective: The objective of this study was to analyses the major risk factors for coronary artery disease (CAD) for patients with ischemic heart disease in Kerala. Design: A cross‑sectional study among patients with established CAD admitted in the Department of Cardiology during the month of June‑Dec 2012. Setting: Study was carried out in a tertiary cardiac center in Kerala. Participants: A total of 496 patients who were admitted in the Cardiology department between June 2012 and December 2012 with acute coronary syndrome or coronary angiographic or Electrocardiography evidence of ischemic heart disease. Risk factors studied were the conventional risk factors for coronary artery disease – hypertension, diabetes mellitus, dyslipidemia, body mass index (BMI), smoking, and family history of coronary artery disease. Data are collected from the patients, old medical records, Clinical Examination and Laboratory results of the patients were analyzed for the study. Results: From the study, it was seen that in Keralites‑irrespective of gender, diabetes or impaired glucose tolerance (79%) and dyslipidemia (71%) are the major risk factor for Coronary artery disease. Hypertension (39%) and cigarette smoking (24%) were not seen to be a major risk factors for coronary artery disease as only a minority of the study population had hypertension or gives a history of cigarette smoking. 57% of the study population had a family history of coronary artery disease. Among the studied population, 55% of females are with increased BMI, whereas only 16% of males with CAD were with BMI above 30. Conclusion: Among South Indian population irrespective of gender, diabetes mellitus and dyslipidemia are the major Risk factor for Coronary artery disease. So early detection of diabetes mellitus and dyslipidemia and proper treatment of both, before developing the end organ damage, play a vital role for the prevention of coronary artery disease.

Key words: Body mass index, coronary artery disease, diabetes mellitus, dyslipidemia, hypertension, risk factors

Address for correspondence: Dr. Cyril James, Puthenveettil, Ayarkunnam P.O, Kottayam, Kerala, India. E‑mail: [email protected]

INTRODUCTION

Coronary artery disease (CAD) is a condition that develops due to the accumulation of atherosclerotic plaque in the pericardial coronary arteries leading to myocardial ischemia. It is a common multifarious public health crisis today and a leading cause of morbidity and mortality in both developing and developed countries.[1] Cardiovascular disease is affecting millions of people in both developed and developing countries. Although, the rate


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James: Risk factors for coronary artery disease

CAD is the most common cause of mortality in India,[5] homing an approximately one‑sixth of the world population. Hence, understanding the predominant risk factors among the Indian Population is important.[6,7] Furthermore, the South Asian population, especially that of the Indian subcontinent, is believed to have a higher risk and prevalence of CAD as compared with European and African population.[8,9]

The prevalence and incidence of CAD along with the risk factor profile vary greatly across the regions of the world. Regional differences in the prevalence and incidence of Atherosclerotic coronary disease may depend upon the genetic variability, life‑style differences and regional differences in the medical care system among others.

A key factor that hampers the development of preventive strategies in developing countries such as India is the meager amount (8%) of published literature on CAD research available from these countries.[10] Much of the knowledge of risk factors for CAD has been acquired from studies conducted in the Western population. It is widely believed that the association of these risk factors with CAD in other populations needs to be ascertained, and there is speculation that differences might range from the frequency of presence of classical risk factors to their total absence or irrelevance in these populations. Therefore, it is imperative to undertake large population‑based, prospective studies in developing countries such as India to identify CAD risk factors, both conventional and novel. However, careful scrutiny of available scientific evidence for modifiable CAD risk factors (elevated serum total and low‑density lipoprotein cholesterol [LDL‑C], low high‑density lipoprotein cholesterol [HDL‑C], smoking, diabetes, hypertension, low level of physical activity, and obesity) in this population may be helpful in formulating a more immediate CAD prevention strategy. A cost‑effective preventive strategy will need to focus on reducing risk factors both in the individual and in the population at large.

AimThe aim of the study was to analyses the major risk factors for CAD among the patients with Ischemic heart disease in Kerala.

MATERIALS AND METHODS

The study was conducted at a tertiary hospital in Cochin in the state of Kerala located in the southernmost part of India. Ethical approval for the study was obtained from the Institutional Ethical Review Committee.

The study was carried out on 496 patients, admitted to the Department of Cardiology in the hospital during the study period from June 2012 to December 2012 and met the inclusion criteria. The inclusion criteria were:• Acute coronary syndrome – STEMI, NSTEMI or unstable

angina;

• Post‑myocardial infarction state – with history of coronary bypass graft or percutaneous coronary intervention with or without stenting or with history of medical management either with fibrinolytics or with heparins;

• Chronic ischemic heart disease‑evidence from coronary angiogram or from a positive stress test.

The data used for the study was the history taken from the patients and their previous medical records. Smoking was defined as use of bidis (bidis are small, thin hand‑rolled cigarettes found primarily in India, consisting of tobacco wrapped in a tendu or temburni leaf [plants native to Asia]) or cigarettes. Physical examination of the patient included height, weight, abdominal circumference, and two blood pressure measurement: At the time of admission and on the following day. Hypertension was classified based on the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) classification for hypertension (reviewed).[11] Laboratory investigations included random blood sugar, fasting blood sugar, 2‑h post‑prandial blood sugar, glycosylated hemoglobin – (HbA1c), fasting lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride level), and Troponin T and electrocardiography (ECG). Patients were defined as Diabetic or with impaired glucose tolerance based on their blood sugar levels and HbA1c value. Dyslipidemia was defined based on the Fasting Lipid Profile. Classification of the patients according to the inclusion criteria were carried out based on ECG findings, Troponin T, and medical records.

RESULTS

A total of 496 patients who were admitted in the Department of Cardiology in the hospital during the study period was analyzed according the to the study parameters. Of the total number of patients included in the study, 310 (62%) were males and 186 (38%) were females [Figure 1].

Acute coronary syndrome was established in 278 (56%) patients, 184 (31%) of the patients were with a history of myocardial infarction and 64 (13%) of the patients were with evidence of chronic ischemic heart disease [Figure 2].

Of the patients studied, 19 (3.8%) were under the age of 35, 78 (15.7%) were in the age group 35‑44, 139 (28%) were in the age group 45‑54, 171 (34.4%) were in the age group 55‑64, and 90 (18.1%) were above the age of 65 [Figure 3].

Peak incidence of CAD occurred between the age group 45 and 64, and the incidence of CAD was negligible in females below the age of 44 (9%). From the study, it was seen that in males CAD starts a decade prior to females – more incidence of CAD in males (20%) when compared to females (8.6%) between the age group 35 and 45 and above 45 years male/female ratio for the occurrence of CAD was the same,[12,13] [Figure 3].



A total of 282 (57%) patients in the study gave a positive family history for CAD.[14,15]

Based on the blood pressure monitoring, the patients were classified according to JNC 7 (reviewed) classification for hypertension as normotensive 232 (47%), pre‑hypertensive 17 (14%), stage I hypertensive 52 (10%), stage II hypertensive 82 (17%). Isolated systolic hypertension was found in 60 patients (12%) [Figure 4]. There was no gender difference noted in the occurrence of hypertension.

Diabetes mellitus was found to be a major risk factor in both males and females in the study population. Of the total 496 patients, 284 (58%) had diabetes mellitus, and 102 (21%) were with impaired glucose tolerance. Of the male patients, 166 (54%) were diabetics and 62 (20%) were found with impaired glucose tolerance. For the female group, the values were 118 (54%) and 40 (20%), respectively [Figure 5].

Dyslipidemia was also a major risk factor along with diabetes mellitus for Indian population. In the study group, the fasting lipid profile tests revealed evidence of dyslipidemia in 352 (71%) of the patients: 206 (66%) of the males and 146 (78%) of the females were with dyslipidemia. All the patients (100%) included in the study population reported using saturated oil mainly coconut oil for

cooking purposes. This may be considered a causative factor for the high incidence of dyslipidemia among the study group [Figure 6].

Of the study population, 378 (76%) had never smoked in their lifetime, and only 40 (8%) were current smokers. The number of females who smoked in the study population was 0 (0%).

Considering obesity as the risk factor for CAD, based on the body mass index (BMI), only 50 (16%) of the males had a BMI higher than 30, whereas 102 (55%) of the females had a BMI higher than 30. Only 62 (12%) of the studied population reported walking at least 30 min a day.

DISCUSSION

In this study, it was seen that in males CAD starts a decade prior to females – more incidence of CAD in males (20%) when compared to females (8.6%) between the age group 3545 and above 45 years male/female ratio for the occurrence of CAD was the same. The peak incidence of CAD was seen between 45 years and 64 years. Heart diseases rise in Asian Indians 5‑10 years earlier than in other populations around the world. The mean age for first presentation of acute myocardial infarction in Indians is 53 years.[16] CAD that manifests at a younger age

Figure 3: Distribution of study group based on age groupFigure 4: Distribution of patients based on blood pressure monitoring according to JNC 7 (reviewed) Classification for hypertension

Figure 1: Distribution of study group by gender

Figure 2: Distribution of study group on inclusion criteria and gender



can have devastating consequences for an individual, the family, and society.

A low incidence of hypertension (39%) was seen among the study population. Hence, hypertension was revealed as an insignificant risk factor among the studied population. The prevalence of hypertension in India is low compared to world figures. In India, 23.10% men and 22.6% women over 25 years old suffer from hypertension, says the World Health Organization’s “global health statistics 2012”.[17] Sofia Study and EUROSPIRE III have shown that among the Europeans with advancing age, all forms of CAD increase. In Sofia Study and EUROSPIRE study, hypertension has been seen as a major risk factor for CAD.[18]

A high incidence of Diabetes and impaired glucose were seen among the studied population. Of the total 496 patients, 284 (58%) had diabetes mellitus, and 102 (21%) were with impaired glucose tolerance. Of the male patients, 166 (54%) were diabetics, and 62 (20%) were found with impaired glucose tolerance. For the female group, the values were 118 (54%) and 40 (20%), respectively.

Indians are genetically prone to develop type II diabetes mellitus due to insulin resistance. The hyperinsulinimia in these patients accelerates the atherosclerotic process in the coronary arteries. Diabetes is second only to CAD as a health burden in India. During the past decade, the number of people with diabetes in India increased from 32 million to 50 million, and the projected figure may reach 87 million by 2030.[19] Hyperinsulinemia, insulin resistance, and the higher rate of prevalence of metabolic syndrome in people with type 2 diabetes were attributed to high coronary risk in south Asians.[20,21] In Chennai (formerly Madras), India in an urban population study, the prevalence rates for CAD were 9.1% in normal subjects and 21.4% in those with type 2 diabetes. Attributable risk due to diabetes for myocardial infarction was 9.9% in the Inter‑heart study.[22]

In the study group, the fasting lipid profile tests revealed evidence of dyslipidemia in 352 (71%) of the patients: 206 (66%) of the males and 146 (78%) of the females were with dyslipidemia. The importance of dyslipidemia in the pathogenesis of CAD is well‑known.[21] In a study conducted between 1998 and 2002 in a North Indian population, Mohan et al. showed that CAD occurred at much lower levels of total cholesterol and LDL‑C than other populations, and high triglyceride and low HDL levels were of a universal phenomenon in this population. Our study revealed a high prevalence of dyslipidemia (71%)‑elevated levels of total cholesterol, LDL‑C and high triglycerides with concurrent low HDL‑C values.

Nearly, 57% patients in the study gave a positive family history for CAD. Family history reflects not only genetic susceptibility, but also interactions between genetic, environmental, cultural and behavioral factors. Individuals with genetic susceptibility develop disease at an earlier age. Early detection of CAD in these individuals may help in risk factor modification. Non‑invasive methods, such as coronary calcium scoring, might help predicting CAD in these patients. Some studies indicate that positive family history is a predictor of impaired endothelium – dependent coronary blood flow regulation in human beings.[23]

Enas et al. have shown that Indian emigrants to western states have a high prevalence of dyslipidemia and insulin resistance, thereby increasing the risk for CAD.[16,24] A modest increase in body fat with central distribution has been shown to increase the risk of CAD. Jain et al. have shown that a family history of premature CAD in first‑degree relatives is associated with development of CAD.[13] Gambhir et al. have further demonstrated that low‑molecular‑weight isoforms of lipoprotein (a) were prevalent in Indian subjects with a positive family history of premature CAD. Interleukin‑6 gene polymorphisms have also been described to be important genetic factors in premature CAD, and in the regulation of key atherogenic markers in Asian Indian families.[25] The family history not only indicates

Figure 5: Diabetic status of the study population Figure 6: Dyslipidemia status of the study population



the genetic predisposition to disease, but may also represent the sum total of the interaction of the individual with environment, expressed in the several ways, including diabetes and thrombotic disorders.

Considering obesity as the risk factor for CAD, based on the BMI, only 50 (16%) of the males had a BMI higher than 30, whereas 102 (55%) of the females had a BMI higher than 30. Although most of the co morbidities relating obesity to CAD increase as BMI increases, they also relate to body fat distribution. Long‑term longitudinal studies; however, indicate that obesity as such not only relates to but independently predicts coronary atherosclerosis.

Prevalence of an increasing number of risk factors in patients with CAD is also crucial since it has been shown that as the number of cardiovascular risk factors increases, so does the severity of asymptomatic coronary and aortic atherosclerosis.

CONCLUSION

The importance of this study lies in the fact that it revealed a distinct association of diabetes mellitus and dyslipidemia among those suffering from CAD. The study highlighted diabetes mellitus, obesity, and dyslipidemia as potential targets. A large multicenter study can help further substantiate the hypothesis and help devise a scoring system specific for Indian patients at higher risk for CAD. Most of the patients had more than two risk factors. Patient’s need to be managed intensively for the control of multiple risk factors. Early detection of the risk factors and proper management by life‑style modification,[26] and by drugs if needed may play a key role in preventing the progress of the atherosclerotic process.

REFERENCES

1. Lopez AD, Murray CC. The global burden of disease, 1990‑2020. Nat Med 1998;4:1241‑3.

2. Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation 1998;97:596‑601.

3. Reddy KS. Cardiovascular disease in non‑Western countries. N Engl J Med 2004;350:2438‑40.

4. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case‑control study. Lancet 2004;364:937‑52.

5. Gupta R. Burden of coronary heart disease in India. Indian Heart J 2005;57:632‑8.

6. Shah B, Mathur P. Surveillance of cardiovascular disease risk factors in India: The need and scope. Indian J Med Res 2010;132:634‑42.

7. Ajay VS, Prabhakaran D. Coronary heart disease in Indians: Implications of the INTERHEART study. Indian J Med Res 2010;132:561‑6.

8. Goyal A, Yusuf S. The burden of cardiovascular disease in the Indian subcontinent. Indian J Med Res 2006;124:235‑44.

9. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: Part II: Variations in cardiovascular disease by specific ethnic

groups and geographic regions and prevention strategies. Circulation 2001;104:2855‑64.

10. Mackay J, Mensah G. The Atlas of Heart Disease and Stroke. Geneva, Switzerland: World Health Organization, Centers for Disease Control and Prevention; 2004.

11. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA 2003;289:2560‑72.

12. Jackson R, Chambles L, Higgins M, Kuulasmaa K, Wijnberg L, Williams D, WHO MONICA Project, and ARIC Study.) Sex difference in ischaemic heart disease mortality and risk factors in 46 communities: An ecologic analysis. Cardiovasc Risk Fact 1999;7:43‑54.

13. Jain P, Jain P, Bhandari S, Siddhu A. A case‑control study of risk factors for coronary heart disease in urban Indian middle‑aged males. Indian Heart J 2008;60:233‑40.

14. Gambhir JK, Kaur H, Prabhu KM, Morrisett JD, Gambhir DS. Association between lipoprotein(a) levels, apo(a) isoforms and family history of premature CAD in young Asian Indians. Clin Biochem 2008;41:453‑8.

15. Scheuner MT. Genetic evaluation for coronary artery disease. Genet Med 2003;5:269‑85.

16. Enas EA, Garg A, Davidson MA, Nair VM, Huet BA, Yusuf S. Coronary heart disease and its risk factors in first‑generation immigrant Asian Indians to the United States of America. Indian Heart J 1996;48:343‑53.

17. World Health Statistics 2012. Available from: http://www.who.int/gho/publications/world_health_statistics/2012/en.

18. Euroaspire III: lifestyle, risk factor and therapeutic management in people at high risk of developing cardiovascular disease from 12 European regions. Heart 2009;95:4.

19. Mohan V, Radhika G, Vijayalakshmi P, Sudha V. Can the diabetes/cardiovascular disease epidemic in India be explained, at least in part, by excess refined grain (rice) intake? Indian J Med Res 2010;131:369‑72.

20. McKeigue PM, Ferrie JE, Pierpoint T, Marmot MG. Association of early‑onset coronary heart disease in South Asian men with glucose intolerance and hyperinsulinemia. Circulation 1993;87:152‑61.

21. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 2007;125:217‑30.

22. Mohan V, Deepa R, Rani SS, Premalatha G, Chennai Urban Population Study (CUPS No. 5). Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India: The Chennai Urban Population Study (CUPS No. 5). J Am Coll Cardiol 2001;38:682‑7.

23. Schächinger V, Britten MB, Elsner M, Walter DH, Scharrer I, Zeiher AM. A positive family history of premature coronary artery disease is associated with impaired endothelium‑dependent coronary blood flow regulation. Circulation 1999;100:1502‑8.

24. Enas EA, Yusuf S, Sharma S. Coronary artery disease in South Asians. Second meeting of the International Working Group. 16 March 1997, Anaheim, California. Indian Heart J 1998;50:105‑13.

25. Maitra A, Shanker J, Dash D, John S, Sannappa PR, Rao VS, et al. Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease – The Indian Atherosclerosis Research Study. Thromb Haemost 2008;99:944‑50.

26. Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: A statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 2003;107:3109‑16.


Source of Support: Nil Conflict of Interest: no conflict of interest.


Obstructive Sleep Apnea in Patients with Myocardial Infarction: Experience from a Tertiary Care Hospital in South IndiaUma Devaraj, Priya Ramachandran, George A D’souzaDepartment of Chest Medicine, St. John’s Medical College and Hospital, Bangalore, India

Epidemiologic data suggest that OSA is over‑represented in patients with coronary artery disease (CAD).

Some investigators consider OSA to be an independent risk factor for CAD because the incidence of OSA is twofold to threefold higher in patients with CAD relative to age and gender matched healthy individuals, and because OSA is often present in patients who have experienced acute coronary artery events.[3‑5]

Hung et al. reported that in patients with myocardial infarction (MI) OSA was as strong a risk factor as obesity, smoking, and hypertension.[5]

India has a heavy burden of patients with CAD and it occurs in the younger population (age < 50 years) as compared to western population.[6]

OSA is an easily treatable disease and its early identification and treatment in patients with CAD will help to reduce the occurrence of MI. There are no studies on the prevalence of OSA in patients with CAD from India. In this article, we describe our experience with the occurrence of OSA in patients with a recent coronary event in a tertiary care hospital in the South India.

A B S T R A C TAims and Objective: The aim of this study was to describe the occurrence of sleep disordered breathing/obstructive sleep apnea (OSA) in patients admitted with acute myocardial infarction (MI) in a tertiary care hospital. Materials and Methods: All consecutive patients with a recent MI, presenting to the hospital for a period of over 1 year, were administered with a well‑designed questionnaire and subjected to polysomnography (PSG) after obtaining a written informed consent. Results: A total of 55 patients were screened with the questionnaire and 44 patients were subjected to PSG. Of the 55 patients 42 (76.4%) were snorers and 14 (25.5%) were insomniacs. OSA was diagnosed in 12 (28.6%) of the 44 patients. There was no significant difference in the presence of hypertension, diabetes mellitus or hypercholesterolemia among the patients diagnosed with OSA and those without OSA. Conclusions: There is a high prevalence of previously undiagnosed OSA in patients admitted to the hospital with acute MI as compared to the general population. OSA is under‑recognized in India. Early recognition of undiagnosed OSA in this population of patients with coronary artery disease (CAD), and treatment of the same would help in reducing cardiovascular morbidity and mortality. This study reinforces the need for the routine screening of MI/CAD patients for the presence of OSA.

Key words: Coronary artery disease, myocardial infarction, obstructive sleep apnea

Address for correspondence: Dr. Uma Devaraj, Department of Chest Medicine, St. John’s Medical College and Hospital, John Nagar, Sarjapur Road, Bangalore ‑ 560 034, India. E‑mail: [email protected]

INTRODUCTION

Obstructive sleep apnea (OSA) is a condition causing abnormal collapse of the pharyngeal airway during sleep, causing repetitive arousals from sleep and excessive daytime sleepiness, disruptive snoring, and nocturnal hypoxemia. Undiagnosed OSA represents a major public health hazard. Various global epidemiologic studies have demonstrated the prevalence of OSA to vary from 5% to 15%.[1] Udwadia et al. have estimated the prevalence of OSA in urban Indian population as 7.5%.[2]

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Devaraj, et al.: Obstructive sleep apnea in myocardial infarction


MATERIALS AND METHODS

We screened all consecutive patients admitted in the cardiology wards with MI over 1 year (i.e. from November 2011 onward) using a carefully designed protocol. Detailed history regarding onset of pain, duration of admission, history of co‑morbid illness, smoking and alcohol history, drug history (including β‑blockers and sedatives) was taken and a brief clinical examination according to the protocol was carried out. A questionnaire regarding snoring, apneic episode during sleep, non‑restorative sleep, nocturia, morning headaches, insomnia, epworth sleepiness score (ESS), and Berlin questionnaire was administered. Required lab investigation reports were also collected.

Patients in congestive cardiac failure (ejection fraction < 35%) were excluded from the study as there is evidence showing the incidence of central sleep apnea in such patients. Hemodynamically unstable patients and patients with a prior diagnosis of OSA were also excluded.

The study was approved by the institutional review board and all patients provided written informed consent.

Sleep studies were performed using a 12‑channel in‑hospital polysomnography (PSG) (Rembrant software) for quantifying sleep‑disordered breathing. The parameters measured included electroencephalogram, electro‑oculogram, chin electromyogram, nasal airflow (nasal cannula), thoracoabdominal movements (induction respiratory bands), arterial oxygen saturation (pulse oximetry), snoring episodes, limb movement, and electrocardiography.

Respiratory events were defined according to the revised American Academy of Sleep Medicine (AASM) criteria. An apnea was defined as cessation of airflow of >10 s, and hypopnea as a >50% reduction of airflow lasting >10 s. An event was also considered to be a hypopnea when there was a reduction in airflow that did not reach the 50% criteria, but was associated with an arterial oxygen desaturation of >4%. Apneas are classified as obstructive if there was thoracoabdominal movement and as central if there was no thoracoabdominal movement. The apnea‑hypopnea index (AHI) was calculated as the number of apneas and hypopneas per hour of recording time in bed, with the start of recording at stage 1 NREM sleep. The end of the recording time was the waking time recorded by the subject.

An AHI of 15 events/h was considered clinically significant for the purpose of this study.

Statistical analysisThe data are presented in a descriptive fashion as the mean (SD) or the median (range). Univariate association between (MI) and OSA‑positivity as well as other patient‑related risk

factors (e.g., diabetes and hypertension), which were recorded as categorical variables were evaluated using the Fisher exact test.

For continuous risk factors, the t‑test or the Wilcoxon rank sum test was used. Data were statistically analyzed using the Statistical Package for the Social Sciences (SPSS for Microsoft Windows, package version 14; SPSS Inc.; Chicago, IL, USA). Assuming a two‑sided test, the statistical significance was pegged at a P < 0.05.

RESULTS

During the study period, a total of 55 patients who were admitted with acute MI were screened [Figure 1]. Eight patients met the exclusion criteria. An overnight sleep study was done in 44 patients and completed in 42 patients. The sleep study was not satisfactory for analysis in the remaining two patients as they had slept for less than 3 hours.

The mean (±SD) age was 57.5 ± 10.44 years and the majority of patients were males (n = 47, males = 37, 78.7%) [Table 1].

Twenty three patients (48.9%) were smokers, significantly higher than seen in the general population and 11 (23.4%) patients gave a history of alcohol abuse.

Cardiovascular disease characteristicsThe most common type of MI seen in these patients was anterior wall MI seen in 24 patients (51.1%). The next most common type of MI was the non‑ST elevation MI seen in 12 patients (25.5%) [Figure 2].

A total of 17 patients (36.1%) gave a history of nocturnal chest pain leading to infarction. There were no significant differences between the OSA‑positive and the OSA‑negative groups with regard to the percentage of patients presenting with nocturnal chest pain (P = 0.763).

Figure 1: Study flow

15



Most of them had single (18 patients, 38.3%) and two vessel disease (16 patients, 34%). Six patients (12.7%) had triple vessel disease. Eight patients (17.02%) were managed conservatively and did not undergo coronary angiogram. The pattern of involvement of coronary arteries was similar in the OSA‑positive and the OSA‑negative group.

A total of 11 patients (23.4%) gave family history of CAD. The distribution of patients with family history of CAD was comparable in OSA‑positive and the OSA‑negative group.

Sleep characteristicsA statistically significant number of patients ‑ 25 (53.2%) were snorers with P value of 0.001. The percentage of snorers in this population was twice more than the 25.8% of habitual snorers reported in the general population by Sharma et al.[7]

The other sleep disturbances noted in this patient population were insomnia in 14 subjects (24.5%), sleep talking in 1 subject, and symptoms suggestive of restless leg syndrome in two subjects.

Seventeen patients had an ESS of >10 out of whom 7 were confirmed to have OSA and 7 patients were negative for OSA. Three subjects did not undergo PSG. ESS was significantly higher in patients with OSA (P value −0.03).

A total of 12 (28.6%) of the 42 patients had OSA with an AHI of > 15. The median AHI for the OSA‑positive group was 19.8 events/h. The prevalence of OSA was significantly higher as compared to the general population (P value −0.001).

Lab investigationsThe mean blood sugar was 170.58 mg ± 86.12 (95% confidence interval [CI] of 142.03‑197.12 mg). The mean total cholesterol was 195.23 ± 58.5 (95% CI of 176.5‑213.94 mg) Table 2.

Occurrence of OSAAmong the 42 patients who completed the overnight sleep study, AHI ranged from 1.0 to 41.5 events/h. AHI was > 15 events/h in 12 patients, giving an occurrence of OSA of 28.6% in this population.

The occurrence increased to 16 (38.1%) and 27 (64.2%) when the cut‑off for OSA was lowered to AHI of 10 and 5/h respectively. The median AHIs for the OSA‑positive and OSA‑negative groups were 19.8 and 4.9 events/h respectively (P < 0.001).

Udwadia et al.[2] reported the prevalence of OSA and OSAS as 19.5% and 7.5% respectively, in urban Indian males, using a cut off of AHI 5 or more per hour. The prevalence of OSA and OSAS in the population based‑study done by Sharma et al.,[7] were estimated to be 13.7% and 3.6%, respectively.

The present study showing an OSA occurrence of 64.2% using the same criteria and is comparatively much higher.

Table 1: Patients demographic and clinical characteristicsCharacteristics Overall

N=42OSA‑

positive group N=12

OSA‑ negative

group N=30

P value

Age (years) 57.5 58.1 57.1 0.261Number of males 33 8 25 0.534Smoking 20 7 13 0.392Snoring 27 10 17 0.158Hypertension 26 6 21 0.292Diabetes mellitus 23 6 17 0.742Hypercholesterolemia 22 6 16 0.697Family history of coronary artery disease

19 10 9 0.117

Body mass index (kg/m2) (mean)

24.7 25.8 24.2 0.204

OSA: Obstructive sleep apnea

Table 2: Patients lab characteristicsCharacteristics Overall

N=42OSA‑

positive group N=12

OSA‑ negative

group N=30

P value

Random blood sugar

170.58 163.8 173.46 0.75

Serum creatinine 1.17 0.95 1.26 0.57Total cholesterol 195.23 201.1 192.9 0.68Triglycerides 155.9 (75.9) 171.4 150.0 0.43HbA1c 7.55 (2.44) 6.55 7.85 0.25CRP 4.18 (9.2) 2.1 5.08 0.39ECHO‑ejection fraction %

49.29 (8.34) 52.17 48.13 0.16

Apnea hypopnea index

10.91 (9.8) 23.86 5.7 0.001

Time spent in <90% saturation

4.7 (10.42) 6.9 3.8 0.39

OSA: Obstructive sleep apnea, CRP: C‑Reactive protein, ECHO: Echocardiogram

Figure 2: Type of myocardial infarction. AWMI: Anterior wall myocardial infarction, NSTEMI: Non‑ST elevation myocardial infarction, IWMI: Inferior wall myocardial infarction, IN + PWMI: Inferior wall and posterior wall myocardial infarction

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DISCUSSION

Evidence has accumulated over the last 10‑15 years of a possible causal link between OSA and cardiovascular disease. OSA is linked strongest with hypertension, but has been implicated as a causal factor in atherogenesis leading to stroke and MI, secondary to exposure to chronic hypoxia. In patients with MI, depending AHI cutoff, relative odds of OSA ranges from 0.4 to 23.3.[3‑5,8‑10]

In India, the prevalence of IHD and cardiovascular morbidity is high. It is hence important to identify factors that may be associated with this increased risk. The prevalence of OSA in the general population ranges from 3.6% to 7.5% in Indian studies.

This study found a high prevalence of previously undiagnosed OSA in patients with acute MI as compared to general population. The occurrence of OSA was 28.6% using an AHI of 15 events/h as the cutoff. The occurrence increased to 38.1% and 64.2% when the cutoff was lowered to AHI of 10 and 5/h respectively.

This is comparatively lower than the prevalence of 65.7% (AHI cutoff ≥ 15) reported by Lee et al.[11] In a study of Japanese patients admitted to the hospital with acute MI, Nakashima et al.[12] reported a prevalence of 43%. However, in their study, the sleep study was done 14‑21 days after hospital admission, whereas in ours, it was done 5‑7 days after hospital admission.

Skinner et al.[13] reported the prevalence of sleep disordered breathing of 50% and OSA of 46% in 26 patients admitted with acute coronary syndrome using a portable sleep study. The prevalence of OSA dropped to 28% when the sleep study was repeated at or more than 6 weeks after discharge. In two other studies done by Mehra et al.[14] and Yumino et al.[15] using a lower AHI cutoff of 10, the prevalence of OSA in patients with acute coronary syndrome ranged from 57% to 66.4%. A lower threshold in our study also increases the number of patients with OSA to 64.2%.

Differences in the prevalence of OSA between current and the previous studies may be due to: (1) Differences in the timing of sleep studies (PSG after number of days following MI), (2) diagnostic criteria applied (revised AASM criteria used in this study), (3) diagnostic device used (lab vs. portable sleep studies), and (4) characteristics of the study population (South Indians vs. patients from New Zealand and Singapore) as compared to the studies quoted above. These factors have affected the measurement of prevalence of OSA in our study, resulting in lower estimation. In addition, a large number have refused to participate in the study and could have affected the outcome. Despite this limitation, the prevalence of OSA is higher in patients with MI as compared to the general population.

Predominantly males were diagnosed with OSA in this study. This is probably because more males consented to the study. Significant number of study subjects was smokers and gave

history of habitual snoring, even though no difference in smoking history or snoring was noted on subgroup analysis between OSA positive and negative group.

Higher percentage of patients had diabetes, hypertension and hypercholesterolemia as compared to general population, but the prevalence was comparable between the OSA positive and negative group.

CRP was significantly high in the study patients, but was comparable between the OSA positive and negative group.

Certain markers of inflammation are known to decrease with treatment in patients with OSA. Thus OSA may be an additional reversible risk factor and hence needs to be looked into while evaluating patients with CAD.

CONCLUSIONS

The occurrence of undiagnosed OSAHS (28.6%) is high in patients admitted with acute MI. This is significantly high as compared to 3.6% prevalence of OSA in Indian general population.

Early recognition of undiagnosed OSA in this population of patients with CAD, and treatment of the same would help in reducing cardiovascular morbidity and mortality.

Limitations of the studyThis study was carried out on a small number of patients with MI and hence does not have enough statistical power to translate prevalence of OSA in all patients with MI. Larger number of patients are required to establish the association or causal relationship between OSA and MI.

In the general population, the ratio of male to female patients with OSA is estimated to be about 2:1‑3:1. The study group predominantly comprised of males. There could be a selection bias as many female patients interviewed denied consent for PSG.

REFERENCES

1. Parish JM, Somers VK. Obstructive sleep apnea and cardiovascular disease. Mayo Clin Proc 2004;79:1036‑46.

2. Udwadia ZF, Doshi AV, Lonkar SG, Singh CI. Prevalence of sleep‑disordered breathing and sleep apnea in middle‑aged urban Indian men. Am J Respir Crit Care Med 2004;169:168‑73.

3. Mooe T, Rabben T, Wiklund U, Franklin KA, Eriksson P. Sleep‑disordered breathing in women: Occurrence and association with coronary artery disease. Am J Med 1996;101:251‑6.

4. Mooe T, Rabben T, Wiklund U, Franklin KA, Eriksson P. Sleep‑disordered breathing in men with coronary artery disease. Chest 1996;109:659‑63.

5. Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261‑4.

6. Sharma M, Ganguly NK. Premature coronary artery disease in Indians and its associated risk factors. Vasc Health Risk Manag 2005;1:217‑25.

7. Sharma SK, Kumpawat S, Banga A, Goel A. Prevalence and risk factors of obstructive sleep apnea syndrome in a population of Delhi, India. Chest 2006;130:149‑56.

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8. Saito T, Yoshikawa T, Sakamoto Y, Tanaka K, Inoue T, Ogawa R. Sleep apnea in patients with acute myocardial infarction. Crit Care Med 1991;19:938‑41.

9. Andreas S, Schulz R, Werner GS, Kreuzer H. Prevalence of obstructive sleep apnoea in patients with coronary artery disease. Coron Artery Dis 1996;7:541‑5.

10. Dincer HE, O’Neill W. Deleterious effects of sleep‑disordered breathing on the heart and vascular system. Respiration 2006;73:124‑30.

11. Lee CH, Khoo SM, Tai BC, Chong EY, Lau C, Than Y, et al. Obstructive sleep apnea in patients admitted for acute myocardial infarction. Prevalence, predictors, and effect on microvascular perfusion. Chest 2009;135:1488‑95.

12. Nakashima H, Katayama T, Takagi C, Amenomori K, Ishizaki M, Honda Y, et al. Obstructive sleep apnoea inhibits the recovery of left ventricular function in patients with acute myocardial infarction. Eur Heart J 2006;27:2317‑22.

13. Skinner MA, Choudhury MS, Homan SD, Cowan JO, Wilkins GT,

Taylor DR. Accuracy of monitoring for sleep‑related breathing disorders in the coronary care unit. Chest 2005;127:66‑71.

14. Mehra R, Principe‑Rodriguez K, Kirchner HL, Strohl KP. Sleep apnea in acute coronary syndrome: High prevalence but low impact on 6‑month outcome. Sleep Med 2006;7:521‑8.

15. Yumino D, Tsurumi Y, Takagi A, Suzuki K, Kasanuki H. Impact of obstructive sleep apnea on clinical and angiographic outcomes following precut aneous coronary intervention in patients with acute coronary syndrome. Am J Cardiol 2007;99:26‑30.



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The Vanishing Right Ventricular MassesSudarshan Kumar Vijay, Bhuwan Chandra Tiwari, Mukul Misra, Lalit Mohan Joshi1

Departments of Cardiology, and 1Cardiothoracic and Vascular Surgery, Dr. Ram Manohar Lohia Institute of Medical Sciences, Gomti Nagar, Lucknow, Uttar Pradesh, India

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A B S T R A C TThe mural endocarditis is a rare cause of intracardiac masses, which is difficult to diagnose and usually requires surgery to prevent embolization and intracardiac complications. We herein present an unusual case of right ventricular mural endocarditis in a patient with rheumatic heart disease, in which presence of multiple mural vegetations was visualized on two‑dimensional transthoracic echocardiography and better delineated with three‑dimensional echocardiography. There was complete resolution of vegetations with antibiotic therapy.

Key words: Infective endocarditis, mural vegetations, three‑dimensional echocardiography, two‑dimensional echocardiography

known case of rheumatic heart disease with severe mitral regurgitation and had a history of hospitalization for heart failure 6 month back. On physical examination, her pulse rate was 110/min with the blood pressure of 100/70 mmHg. The jugular venous pressure was raised and mild pallor and splenomegaly was present. The chest examination revealed the presence of bilateral fine crepitations and cardiovascular examination showed the presence of a harsh grade IV/VI pansystolic murmur with radiation to axilla and a loud third heart sound at the apex with an early diastolic murmur at the left third intercostal space and loud pulmonic component of the second heart sound. Her blood examination showed leukocytosis and raised erythrocyte sedimentation rate. The chest X‑ray Posteroanterior (PA view) showed left ventricular type of cardiomegaly with signs of pulmonary congestion. Two‑dimensional transthoracic echocardiography examination in apical four chamber view showed the presence of dilated left atrium and left ventricle with a circular 16 mm × 18 mm mobile mass attached to the basal right ventricular wall just above the lateral tricuspid annulus [Figure 1a, Movie clip 1]. Tilted right ventricular inflow view showed multiple balls like opacities in the right ventricular cavity [Figure 1b, Movie clip 2]. The color Doppler examination revealed severe mitral regurgitation and moderate aortic regurgitation and mild tricuspid regurgitation. Subsequent three‑dimensional transthoracic examination in the parasternal short axis view showed two masses of size 14 mm × 16 mm and 16 mm × 1 mm, attached to the basal right ventricular wall [Figure 1c, Movie clip 3]. The blood cultures from the patient revealed growth of methicillin resistant Staphylococcus aureus. The final diagnosis of right ventricular mural infective endocarditis was made and the patient was treated with intravenous vancomycin along with

Address for correspondence: Dr. Sudarshan Kumar Vijay, Department of Cardiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar, Lucknow ‑ 226 012, Uttar Pradesh, India. E‑mail: [email protected]

INTRODUCTION

Intracardiac infection involving mural endocardium and non valvular structures is uncommon in infective endocarditis. The mural endocarditis is usually associated with valvular vegetations, high velocity regurgitant jets, pacing leads and other artificial devices and congenital shunts. It can be seen in all cardiac chambers and may result from hematogenous seeding or direct spread of infection. If not diagnosed early, it usually causes significant cardiac morbidity and mortality.

CASE REPORT

A 10‑year‑old female presented to us with the 4 months history of continuous fever and increasing dyspnea New York Heart Association (NYHA class‑IV) for last 1 month. She was a


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Vijay, et al.: The vanishing right ventricular masses


after 4 weeks of antibiotic therapy and medical stabilization showed disappearance of one vegetation and reduction in size of the other vegetation [Figure 2a and b respectively, Movie clips 4 and 5]. The antibiotic therapy was continued for 6 weeks and final two‑dimensional and three‑dimensional transthoracic echocardiogram at 6 week showed complete disappearance of vegetations [Figure 3a and b respectively, Movie clip 6]. The patient is doing well after 6 months of follow‑up with no recurrence of fever.

DISCUSSION

Mural vegetations are very rare findings during the course of infective endocarditis. The diagnosis of infective endocarditis by the presence of mural vegetations without valvular involvement is difficult. Mural vegetations are commonly seen in patients with congenital heart diseases because of impact of the jet stream leading to endocarditis, like in the ventricular septal defect.[1] Chronic debilitating illness, immunosuppression, and indwelling catheters are common risk factors for mural endocarditis.[1] Cardiac tumors, thrombi and metastasis should be considered in the differential diagnosis of mural vegetations.[2] The organisms commonly associated with mural endocarditis include staphylococci, viridans streptococci, enterococci, and fungi.[1,3] Urgent surgical treatment carries the advantage of preventing embolization of large vegetations and intracardiac complications, but with the increased risk of uncontrolled sepsis. Three‑dimensional echocardiography can better delineate mural vegetations and other intracardiac masses.[4] Our case is a rare case of right ventricular mural endocarditis, where the presence of multiple vegetations was confirmed with two‑dimensional and three‑dimensional transthoracic echocardiography with unusual and successful response to

other measures to treat heart failure. Her fever subsided and a repeat two‑dimensional and three‑dimensional echocardiogram

Figure 1: (a) Two‑dimensional transthoracic echocardiogram (apical four chamber view) showing dilated left atrium and ventricle with a 16 mm × 18 mm mass attached at the basal right ventriclular wall just above the tricuspid annulus. (b) Tilted right ventricular inflow view revealed multiple rounded vegetations mimicking cardiac tumors. (c) Three‑dimensional transthoracic echocardiogram in parasternal short axis view showing two well‑defined vegetations attached to the right ventricular wall just above the lateral tricuspid annulus. RA ‑ right atrium, RV ‑ right ventricle, LA ‑ left atrium, LV ‑ left ventricle, A ‑ aorta

cba

Figure 3: After 6 weeks of antibiotic therapy: (a) Two‑dimensional transthoracic echocardiogram (apical four chamber view) showing complete resolution of vegetations and (b) three‑dimensional transthoracic echocardiogram (parasternal short axis view) was showing disappearance of vegetations. RA ‑ right atrium, RV ‑ right ventricle, LA ‑ left atrium, LV ‑ left ventricle

ba

Figure 2: After 4 weeks of antibiotic therapy: (a) Two‑dimensional transthoracic echocardiogram (tilted apical four chamber view) showing partial resolution of vegetations and (b) three‑dimensional transthoracic echocardiogram (parasternal short axis view) was showing the presence of only single small vegetation. RA ‑ right atrium, RV ‑ right ventricle, LA ‑ left atrium, LV ‑ left ventricle

ba

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Vijay, et al.: The vanishing right ventricular masses




intravenous antibiotic resulting in complete disappearance of large vegetations.

REFERENCES

1. Kearney RA, Eisen HJ, Wolf JE. Nonvalvular infections of the cardiovascular system. Ann Intern Med 1994;121:219‑30.

2. Yu PJ, Fordyce M, Srichai MB, Zinn A, Losada M, El‑ftesi S, et al. Giant right atrial wall vegetation mimicking cardiac tumor. J Am Soc Echocardiogr 2007;20:1315.e9‑11.

3. Ak K, Adademir T, Isbir S, Arsan S. Right ventricular mural

endocarditis presenting as an isolated apical mass in a non‑addict patient with congenital deafness and aphasia. Interact Cardiovasc Thorac Surg 2009;8:498‑500.

4. Zaragoza‑Macias E, Chen MA, Gill EA. Real time three‑dimensional echocardiography evaluation of intracardiac masses. Echocardiography 2012;29:207‑19.

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A Rare Case of Double Orifice Mitral Valve with Multiple Muscular Ventricular Septal DefectShamsher Singh, Ratna Pandey, Alok Kumar Singh, Ajay Kumar PandeyDepartment of Cardiology, Heritage Hospital, Varanasi, Uttar Pradesh, India

Address for correspondence: Dr. Ajay Kumar Pandey, Department of Cardiology, Heritage Hospital, Varanasi ‑ 221 005, Uttar Pradesh, India. E‑mail: [email protected]

CASE REPORT

A 25‑year‑old boy with a history of progressive breathlessness for 2 year referred to Heritage Hospital echocardiography lab on 16th March 2012 for echocardiography examinations by local physician. Physical examination was unremarkable except for grade 4 pansystolic murmur in the left parasternal area and spo2 by pulse oxymeter was 95%. His 2D Echocardiography (ECHO) shows multiple muscular Ventricular Septal Defect (VSD) with bidirectional flow (predominant left to right shunt) and double orifice mitral valve (DOMV) [Figures 1‑3]. Mitral valve is functionally normal without stenosis and regurgitation and there was no tricuspid regurgitation jet visible. He was advised for cardiac catheterization, but patient refused for the same. He was on frusemide 20 mg twice daily. We are reporting this case because of rare combination of muscular VSD with DOMV.

DOMV is a rarely reported anomaly was first described by Greenfield in 1876.[1] This anomaly is characterized by a mitral valve with a single fibrous annulus with two orifices that open into the left ventricle. In most cases (85%), a larger orifice is accompanied by a small eccentric accessory orifice known as eccentric variety of DOMV, and second uncommon type

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Figure 1: Parasternal short axis view showing double orifice mitral valve

Figure 2: An apical four chamber view showing double orifice mitral valve

of DOMV is concentric DOMV (15%) in which both mitral orifices are equal. Embryologically the lesion results from persistence of the left part of the common atrio‑ventricular canal and abnormal leaflet fusion. In about 50% of DOMV

22

Singh, et al.: A rare case of double orifice mitral valve with multiple muscular vsds


Figure 3: An apical chamber view showing multiple muscular ventricular septal defects

cases, valvular function is normal, others present with stenosis or regurgitation.[2] Definitive management of most of the DOMV patients is surgical replacement of mitral valve.

REFERENCES

1. Greenfield WS. Double mitral valve. Trans Pathol Soc 1876;27:128‑9.2. van Buuren F, Faber L, Bogunovic N. Double orifice mitral valve

with normal function: An echocardiography and MRI study of a rare finding. Eur Heart J 2011;32:137.



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presenting with chest pain. The superiority of these new assays, particularly in the early phase of pain onset, was prospectively demonstrated.[2,3] The negative predictive value for MI with a single test on admission is 95% and by including a second sample within 3 h of presentation the sensitivity for MI approaches 100%. The waiting time in Emergency Department can be reduced with a rapid rule put protocol. The new ESC guidelines for the management of ACS in patients presenting without persistent ST‑segment elevation, 2011 now recommend a rapid rule‑out protocol (0 and 3 h) when highly sensitive troponin tests are available.[4] The guidelines also emphasize the role for prompt withdrawl of blood for troponins and recommend point‑of‑care tests for troponins should be implemented when a central laboratory cannot consistently provide test results within 60 min.

Coronary computed tomography (CT) angiographyMultidetector computed tomography (CT) is a promising technique for direct visualization of the coronary arteries. Owing to its high negative predictive value reported in various studies[5‑7] CT angiography, can be useful to exclude ACS or other causes of chest pain. The ESC 2011 guidelines for non ST segment elevation myocardial infarction (NSTEMI) recommend Coronary CT angiography as an alternative to invasive angiography to exclude ACS when there is a low to intermediate likelihood of CAD and when troponins and ECG are inconclusive (Class IIa).

In the CT‑STAT trial, Goldstein et al.[8] randomly assigned patients with acute chest pain in the Emergency Department to Coronary computed tomography angiography (CCTA) and to single‑positron emission computed tomography myocardial perfusion imaging (MPI). The CCTA strategy resulted in a 54% reduction in time to diagnosis compared with MPI (2.9 h vs. 6.3 h), and costs of care were 38% lower for the CCTA group. The two strategies showed no difference in freedom from major adverse cardiac events (MACE) at 6 months of follow‑up.

Antiplatelet therapyPlatelet activation and subsequent aggregation play a dominant role in the propagation of arterial thrombosis and consequently are the key therapeutic targets in the management of ACS. New adenosine diphosphate (ADP) receptor blockers prasugrel and

Management of Coronary Artery Disease in 2013: Recent Insights (Journal Scan)Akshyaya Kumar PradhanInterventional Cardiologist, Shekhar Heart and Lung Centre, Indira Nagar, Lucknow, Uttar Pradesh, India

Address for correspondence: Dr. Akshyaya Kumar Pradhan, Interventional Cardiologist, Shekhar Heart and Lung Centre, Indria Nagar, Lucknow ‑ 226 016, Uttar Pradesh, India. E‑mail: [email protected]

JOURNAL SCAN

DEFINING MYOCARDIAL INFARCTION

The recently updated European Society of Cardiology (ESC) consensus statement on “third universal definition of myocardial infarction” released in 2012 has emphasized the central role of cardiac biomarker 6 in diagnosis of acute coronary syndromes.[1] The term acute MI should be used when there is evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. Hence detection of an rise and/or fall of cardiac biomarker values preferably cardiac troponin with at least one value above the 99th percentile upper reference limit needed along with at least one of the following:1. Symptoms of ischemia.2. New or presumed new significant ST‑segment–T wave

(ST–T) changes or new left bundle branch block.3. Development of pathologica l Q waves in the

electrocardiogram (ECG).4. Imaging evidence of new loss of viable myocardium or new

regional wall motion abnormality.5. Identification of an intracoronary thrombus by angiography

or autopsy.

High sensitive troponinsRecently, high‑sensitivity or ultrasensitive assays have been introduced that have a 10 to100 fold lower limit of detection and fulfill the requirements of analytical precision. Therefore, MI can now be detected more frequently and earlier in patients


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ticagrelor have a more rapid onset of action and greater potency and have been proven superior to clopidogrel in large outcome trials.

In the TRITON‑TIMI 38 trial,[9] prasugrel (60 mg loading dose followed by 10 mg) was compared to clopidogrel (300 mg loading dose and then 75 mg daily) in clopidogrel naive patients undergoing percutaneous coronary angioplasty (PCI). The composite primary endpoint (cardiovascular death, non‑fatal MI, or stroke) occurred in 11.2% of clopidogrel‑treated patients and in 9.3% of prasugrel treated patients (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.73‑0.93; P = 0.002), mostly driven by a significant risk reduction for MI. In the whole cohort, the rate of definite or probable stent thrombosis (as defined by the academic research consortium (ARC)) was significantly reduced in the prasugrel group compared to the clopidogrel group (1.1% vs. 2.4%, respectively; HR 0.48; 95% CI 0.36‑0.64; P = 0.001). Prasugrel is contraindicated in patients with prior stroke/transient ischaemic attack. Its use is generally not recommended in patients aged ≥75 years or in patients with lower body weight (<60 kg) as it was not associated with net clinical benefit in these subsets.

In the PLATelet inhibition and patient Outcomes (PLATO) trial,[10] ticagrelor reduced the composite primary endpoint (cardiovascular death, non‑fatal MI, or stroke) and also reduced cardiovascular mortality in clopidogrel naive or pretreated patients with either ST segment elevation myocardial infarction (STEMI) ‑(planned for primary PCI) or moderate‑to‑high risk NSTEMI (planned for either conservative or invasive management). Although there was no significant difference in overall PLATO defined major bleeding rates between the clopidogrel and ticagrelor groups, PLATO‑defined and TIMI‑defined major bleeding that was unrelated to coronary artery bypass grafting (CABG) surgery was increased with Ticagrelor. The new ESC 2012 guidelines for STEMI recommend prasugrel and ticagrelor as first line ADP receptor blockers.[11] Clopidogrel should be used preferably when prasugrel or ticagrelor are either not available or contraindicated.

Antithrombotics for PCIIntravenous unfractionated heparin (UFH) titrated to an appropriate activated clotting remains the mainstay and time tested strategy for anticoagulant therapy at the time of PCI. Enoxaparin and fondaparinux have been studied less extensively in this setting. The ATOLL (acute STEMI treated with Primary PCI and IV enoxaparin or UFH to lower ischemic and bleeding events at short‑ and long‑term follow‑up) trial comparing intravenous enoxaparin with UFH for primary PCI failed to meet its primary, composite endpoint.[12]

Fondaparinux, the only selective activated factor X (factor Xa) inhibitor available for clinical use is inhibits coagulation factor Xa by binding reversibly and non‑covalently to antithrombin,

with a high affinity. In the OASIS‑5 (the fifth organization to assess strategies in acute ischemic syndromes investigators) study, fondaparinux was non inferior to enoxaparin with respect to primary efficacy outcome of death, MI, or refractory ischemia in patients of NSTEMI.[13] At the same point, major bleeds were halved with fondaparinux (2.2% vs 4.1%). At 6 months the composite endpoint of death, MI, or stroke was significantly lower with fondaparinux vs. enoxaparin (11.3% vs. 12.5%). In the population submitted to PCI, catheter thrombus was observed more frequently with fondaparinux (0.9%) than with enoxaparin (0.4%), but was abolished by injection of an empirically determined bolus of UFH at the time of PCI.

The FUTURA/OASIS‑8 trial[14] compared a low dose i.v. bolus of UFH (50 IU/kg) and a standard dose UFH, namely 85 IU/kg (reduced to 60 U/kg in the case of the use of GP IIb/IIIa receptor inhibitors), in patients pretreated with fondaparinux, submitted to PCI within 72 h following initiation of therapy. There was no significant difference between the two groups in terms of the primary composite endpoint (major bleeding, minor bleeding, or major vascular access site complications) at 48 h after PCI (4.7% vs. 5.8%, low vs. standard dose group; OR 0.80; 95% CI 0.54‑1.19; P = 0.27).

The practical implications of these data are that a standard UFH bolus should be recommended at the time of PCI in patients pre‑treated with fondaparinux on the basis of a more favorable net clinical benefit and lower risk of catheter thrombosis compared to low dose UFH. The new ESC guidelines of NSTEMI 2011 list Fondaparinux (2.5 mg subcutaneously daily) as having the most favorable efficacy–safety profile with respect to anticoagulation (Class I recommendation).[15‑16] If the initial anticoagulant is fondaparinux, a single bolus of UFH (85 IU/kg adapted to ACT, or 60 IU in the case of concomitant use of GP IIb/IIIa receptor inhibitors) should be added at the time of PCI. However it is not recommended in setting of primary PCI for STEMI.

Novel oral anticoagulantsIn ATLAS ACS 2‑TIMI 51 study,[17] rivaroxaban in patients with a recent ACS, reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke compared to placebo (hazard ratio in the rivaroxaban group, 0.84; 95% CI, 0.74 to 0.96; P = 0.008). The twice‑daily 2.5‑mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P = 0.002) and from any cause (2.9% vs. 4.5%, P = 0.002), a survival benefit that was not seen with the twice‑daily 5‑mg dose. Interestingly, stent thrombosis was reduced by one third. This was associated with 3 fold increase in non‑CABG‑related major bleeding, and intracranial haemorrhage. However, apixaban in APPRAISE‑2,[18] darexaban in RUBY‑1[19] and dabigatran in REDEEM[20] trial,



caused dose‑dependent increases in major bleeding but no signal of added efficacy when adding anticoagulant therapy to antiplatelet therapy in this setting of ACS. Hence the verdict on novel oral anticoagulants in ACS is still not out, but low dose rivaroxaban reducing mortality in ACS as an add on therapy on aspirin and clopidogrel is interesting.

Glycoprotein IIb/IIIa antagonistsINFUSE‑AMI trial showed that local delivery of abciximab reduced the 30‑day infarct size, evaluated by magnetic resonance imaging, but did not improve abnormal wall motion score, ST‑segment resolution, post‑PCI coronary flow or myocardial perfusion.[21]

The large abciximab intracoronary vs. intravenously drug application 4 (AIDA‑STEMI) randomized trial, found no clinical benefit (but also no harm) in this route of administration in terms of the composite of death, reinfarction and heart failure, and found a borderline reduction in the secondary endpoint of heart failure.[22] Therefore, the intracoronary route may be considered but the i.v. route should remain the standard of care for administration of GP IIb/IIIa inhibitor.

PCI without on site CABGThe Atlantic CPORT investigators randomized,[23] in a non‑inferiority design, nearly 19,000 patients undergoing PCI to a hospital with or without on‑site surgery in a ratio of. Six‑week mortality was virtually identical (1.0 vs. 0.9%) and 9‑month MACE were also similar (11.2 vs. 12.1%); however, target vessel revascularization (TVR) was higher without on‑site surgery (6.5 vs. 5.4%, P ¼ 0.01). This difference was seen regardless of the definition of TVR and regardless of stent type and may reflect a more conservative approach or a lower initial success rate without on‑site surgery.

Multi vessel diseaseThe FREEDOM trial randomized 1900 diabetic patients with multi‑vessel disease to PCI using drug‑eluting stents (DESs) vs. CABG. At 5 years, the primary outcome of death, MI, or cerebrovascular accident occurred more commonly in the PCI group (26.6 vs. 18.7%, P = 0.005). The benefit of CABG was driven by differences in rates of both MI (P < 0.001) and death from any cause (P = 0.049). However, stroke was more frequent in the CABG group (5‑year rates of 2.4% in PCI Vs 5.2% with CABG). Hence, patients with diabetes and advanced coronary artery disease, CABG should definitely offered to as a first line therapy.[24]

In the SYNTAX trial, investigators compared PCI to CABG in patients with left main or three‑vessel CAD. The previously reported 1‑year results showed similar rates of death and MI with both procedures, more strokes with CABG, and more repeat revascularization procedures with PCI.[25] The recently presented 5 year results of SYNTAX study demonstrate that outcomes were

similar with coronary artery bypass grafting and percutaneous coronary intervention in the lowest tertile of SYNTAX score, whereas CABG outcomes were superior in the highest tertile. Longer follow‑up now suggests that CABG beats PCI in the intermediate‑risk group as well.[26]

However, a meta‑analysis of 19 randomized trials of over 10,000 patients found a 30‑day rate of stroke of 1.2% after CABG and 0.34% after PCI (P = 0.0001) This equates to an excess of seven strokes for every 1000 patients treated with CABG rather than PCI. Similar results were observed after a median follow‑up of 1 year and in an analysis of nearly 34,000 patients from 27 observational studies.[27]

StentsIn primary PCI, drug‑eluting stents (DES) reduce the risk of repeated TVR, compared with bare‑metal stents (BMS).[28] There have been concerns about increased risks of very late stent thrombosis and reinfarction with DES, compared to BMS. However, HORIZONS AMI a randomized study of DES versus. BMS in STEMI patients, did not reveal any safety concerns, whereas a consistent reduction of restenosis and unplanned repeat revascularization was found after DES implantation even on long‑term follow up.[29] An issue with the routine use of DES in this setting is that it is often difficult to determine reliably the ability of patients to comply with or tolerate the protracted use of dual antiplatelet therapy (DAPT).

The EXAMINATION trial presented at ESC Congress 2012, randomized 1500 patients with STEMI to everolimus DESs and BMSs.[30] The primary endpoint of death, recurrent MI, or revascularization was similar in the two groups. However, TVR rates were lower with the everolimus stent (3.7 vs. 6.8%), as was sub acute stent thrombosis (SAT) (0.9 vs. 2.5%). Biolimus eluting biodegradable polymer stents were compared the BMS in a 1100‑patient randomized COMFORTABLE ‑AMI trial.[31] 1‑year MACE was lower with the biolimus stent, a difference driven mainly by a reduction in re‑infarction and TLR. The ESC 2011 guidelines for NSTEMI recommend that owing to the lack of randomized trials in NSTE‑ACS, the choice between the use of a BMS or a DES should be based on an individual assessment of benefit versus risk. The new American College of Cardiology/American Heart Association STEMI 2013 guidelines say that lowest rates of stent thrombosis have been reported with cobalt‑chromium everolimus‑eluting stents.[32,33]

In the setting of stable angina, a meta‑analysis of 72 randomized trials (>117, 000 patients) looked at comparative outcomes of different DESs compared with BMSs. Everolimus DESs seemed to have the lowest TVR. Reassuringly, there was no increased risk of any long‑term safety outcomes with DESs compared with BMSs; in fact, DESs were associated with reduced MI and SAT rates.[34]

26



The RESET trial found that everolimus DES was non inferior sirolimus DES at 1 year for the primary endpoint of TLR (4.3 vs. 5.0%).[35] The TWENTE trial randomized 1391 patients to zotarolimus (Resolute) versus everolimus (Xience) stents in a non‑inferiority design. The primary endpoint of target vessel failure (TVF) was similar in the two groups (8.2 vs. 8.1%), and stent thrombosis rates were low and similar.[36] SORT OUT IV also compared these two different DESs (sirolimus and everolimus) in a non‑inferiority design but with a composite primary endpoint of safety and efficacy. The composite endpoint was similar in the two groups at 9 and 18 months, but definite stent thrombosis was higher at 18 months with the sirolimus stent (0.9 vs. 0.2%).[37] Even in the subset of left main reduced 1‑year MACE, TVF, and restenosis was shown with everolimus DESs.[38]

Stent thrombosisIn Bern Rotterdam Cohort study, Raber et al. reported that everolimus eluting stent (EES) use is associated with a lower risk of very late stent thrombosis compared to early‑generation DESs.[39] The overall incidence rate of definite stent thrombosis with EES was (1.4 per 100 person‑years) compared to SES (2.9; HR, 0.41; P < 0.0001) and PES (4.4; HR, 0.33; P < 0.0001). The incidence rate per 100 person‑years of early (0‑30 days), late (31 days–1 year), and very late stent thrombosis was significantly lower among everolimus DES‑treated patients when compared to sirolimus and paclitaxel eluting DESs. Differences in favor of EES were most pronounced beyond 1 year, with a HR of 0.33 (EES versus SES; P = 0.006) and 0.34 (EES versus PES; P < 0.0001).

In a pooled analysis of ISAR‑TEST 3 and 4 and LEADERS trials, the risk of SAT at 4 years with biodegradable polymer DESs was compared with that with a cypher stent (a durable polymer); biodegradable polymer was associated with lower TLR and SAT (HR: 0.56), driven mainly by a reduction in very late SAT.[40] In a meta‑analysis of 50, 000 patients, 1‑year SAT was the lowest with everolimus DESs compared with BMSs, zotarolimus, paclitaxel, or sirolimus DESs.[32]

Duration of dual antiplatelet therapy after PCIThe PRODIGY trial compared a 6 month versus 24‑month dual Antiplatelet (DAPT) strategy following a variety of BMSs or DESs implantation.[41] The study failed to show that prolonging DAPT for 24 months is superior to 6 month duration of therapy in reducing composite primary endpoint of death, MI or stroke in patients receiving 1st or 2nd generation DES.

The PROTECT trial compared zotarolimus with sirolimus (cypher) stents in nearly 9,000 patients with duration of DAPT left to the discretion of the operator and showed no difference between the two stents in the primary endpoint of stent thrombosis at 3 years.[42]

In the EXCELLENT non‑inferiority randomized study of 6 months versus 12‑month DAPT after DESs, 1‑year TVF occurred in 4.8 vs. 4.3%, respectively. A further study of 2000 patients compared 3‑12‑month DAPT following zotarolimus DESs and found no difference in SAT (0.2 vs. 0.3%) at 1 year.[43]

Physiological lesion assessment guidance for PCIThe FAME 2 trial assessed fractional flow reserve (FFR) in stable patients and those who had at least one significant lesion (FFR < 0.8) were randomized to FFR‑guided PCI or optimal medical therapy (OMT).[44] The primary endpoint of death, MI, or urgent revascularization was 4.3% in the PCI group and 12.7% in the OMT group (P < 0.001); this difference was due to higher urgent revascularization in the OMT group. The 2011 ACC/AHA Guidelines for PCI recommend FFR to assess angiographic intermediate coronary lesions (50% to 70% diameter stenosis) and to guide revascularization in patients with Stable Ischemic Heart Disease (class IIa).[45]

Hemodynamic supportThe counter‑pulsation to reduce infarct size pre‑PCI‑acute myocardial infarction (CRISP AMI) trial showed no benefit from a routine intra‑aortic balloon pump (IABP) in anterior myocardial infarction without shock, and did show increased bleeding, which is consistent with data available regarding the role of IABPs in patients with acute myocardial infarction without cardiogenic shock.[46]

The IABP‑SHOCK II trial showed that the 30 ‑day mortality was very similar in the two groups (39.7 vs. 41.3%, respectively).[47] However, in the IABP group, only 13% were inserted pre‑PCI. However the 5‑year follow data of BCIS‑1 trial reported a significant mortality advantage favoring upfront IABP insertion (HR: 0.66, 95% CI: 0.44‑0.98, P = 0.039), although the potential mechanisms of this remain unclear.[48]

Access site for PCIThe STEMI‑RADIAL presented at transcatheter therapeutics (TCT) randomized 700 patients to either a radial or femoral approach.[49] The primary endpoint of bleeding or access‑site complications was dramatically lower with the radial approach and MACE was equivalent. Also the radial approach was associated with less contrast use and shorter ICU stay. In the radial versus femoral (RIVAL) access for coronary intervention trial, using radial rather than femoral access actually reduced mortality in the subset of STEMI patients.[50] Similar findings were also observed in the RIFLE STEACS trial.[51] In RIVAL there was, however, an interaction between benefit of the radial access route and operator experience, suggesting that the benefit of radial access over femoral depends upon the radial expertise of operators.



High dose statinsCurrent guidelines suggest early and aggressive low‑density lipoprotein (LDL) cholesterol lowering therapy with high dose statins in patients with acute coronary syndrome. ESC guidelines for STEMI 2012 state that, the strongest trial data available so far favors atorvastatin at a dose of 80 mg daily.[11]

The LUNAR study compared the efficacy of high dose rosuvastatin with that of atorvastatin in decreasing LDL cholesterol in patients with ACS. Results from the LUNAR study show that rosuvastatin 40mg more effectively decreased LDL cholesterol, increased high density lipoproteins (HDL) cholesterol, and improved other blood lipid parameters than atorvastatin 80 mg.[52] It would not be long before rosuvastatin makes inroads into major guidelines for secondary prevention in ACS.

Biodegradable stentsBioabsorbable stent promise important theoretical advantages over conventional DES including shorter antiplatelet duration, restored vasomotion and abolished late stent thrombosis risk. The ABSORB B Cohort tested revision 1.1 version of the everolimus‑eluting bioabsorbable vascular scaffold (BVS, Abbott vascular) in patients, with up to 2 de novo native coronary artery.[53] In the first 45 patients of ABSORB Cohort B, in‑stent late loss was 0.19 mm at 6‑month angiographic follow‑up. The 6‑month major adverse cardiac event rate (defined as cardiac death, MI, or ischemia‑driven TLR) was 4.4%. Furthermore, no stent thrombosis had occurred at 6 months. The everolimus BVS (Absorb) demonstrated a similar neointimal response as the everolimus DES (xience).[54]

CONCLUSION

The management of coronary artery disease is evolving rapidly. The use of high sensitive troponin assays and coronary CT angiography in emergency department promises to be a boon for early and accurate diagnosis of acute MI. With the addition of more powerful ADP receptor antagonists and novel anticoagulant, the medical management of ACS has been revamped. Everolimus DES have been promising with low rates of stent thrombosis and TVR. Biodegradable vascular scaffolds are also now being implanted with ease. In addition a shorter duration of DAPT following PCI is on the anvil. FFR and the Radial route have been positive developments in reducing mortality associated with PCI. Future holds bright for biodegradable vascular scaffolds and gene therapy.

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