Myocardial regeneration

•Potential cells for repair:–Skeletal muscles.–Fetal cardiomyocyte.–Embryonic stem cells.–Bone marrow stromal cells.–Endothelial progenerator cells.

Skeletal myoblasts transplantation in animal model - rats

Taylor et al, Nature Medicine 1998;4:929

Infarction After transplantation

Myocardial regeneration

•Bodo E. Strauer et al: Circ 2002;106:1913:–20 patients with AMI 5-9 days. –IC infusion of Autologous, mononuclear BMCs via

a balloon catheter.–The main cells infused: AC 133, and CD 34 positive

cells.

Syringe containingAdult stem cells

LAD

Balloon Catheter

Border Zone

Infarcted Zone

Bodo E. Strauer et al: Circ 2002;106:1913

Cell transplantation into infarcted myocardium

Bodo E. Strauer et al: Circ 2002;106:1913

Improved myocardial perfusion 3 months after intra-coronary cell transplantation by 201Thallium scintigraphy

Pre

Post

Myocardial regeneration

•Bodo E. Strauer et al: Circ 2002;106:1913:

–Results:•Decreased infarct size. 30% to 12% . P=0.005.•Improved myocardial perfusion.•Improved wall motion. 2 to 4 cm/sec. P=0.028.

Myocardial preservation

Myocardial preservation•Drowning in cold water improves survivals

compared to warm water.

•In cardiac arrest, induced hypothermia reduces neurological injury (NEJM 2002;346:557)

•COOL MI ( Radiant medical)•ICE-IT (Innercool therapies)

Reprieve TM Endovascular Temperature Therapy System

CONCLUSION-1Acute Coronary Syndromes are clinical entities with

significant morbidity and mortality.

Coronary artery plaque disruption and thrombosis are pathognomonic features of ACS.

Early risk stratification is an important step in the management of ACS.

CONCLUSION-2Acute reperfusion therapy with thrombolytic agent

or primary angioplasty is the standard of care for STEMI patients .

The key to successful reperfusion lies more in the efficiency of delivery than in the choice of modality

In the Developed and more in the developing countries significant under-utilization and delays of

reperfusion strategies have been identified.

CONCLUSION-3Door to Needle time should not exceed 30 minDoor to Balloon time should not exceed 90 min

Tools and means:Media campaign, patient educationAdequate EMS transport systemWell established Emergency Department chest pain

protocolPartnership between ED and cardiology personnelInstitution of pre-hospital rapid assessment, EKG and

thrombolytic therapy protocolPre-arrival alert to ED/cardiology

CONCLUSION-4Aggressive Clopidogrel loading and a longer duration of therapy

have been suggested with clear efficacy and safety Enoxaparin is preferable to UFH as an anticoagulant in patients

with ACS.

Newer Agents: Bivalirudin, Fondaparinux have shown benefit in the management of ACS, with significant safety.

An early invasive approach with PCI is favored over initial conservative management.

Above all aggressive risk factors’ modifications are CRITICAL.

Thank you

REFERENCES:1 .Braunwald E. Shattuck lecture-cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 1997; 337:1360-9.2 .White HD, Van de Werf FJ. Thrombolysis for acute myocardial infarction. Circulation 1998; 97: 1632-46.3 .Gersh BJ, Anderson JL. Thrombolysis and myocardial salvage: results of clinical trials and the animal paradigm-paradoxic or predictable? Circulation 1993; 88: 296-306.4 .DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980; 303:897-

902.5 .Gersh B, Antoniucci D, Bolognese L, Santoro, GM: Optimal management of acute myocardial infarction at the dawn of the next millennium. Am Heart J, Volume 138(2,

Part 2) Supplement. August 1999.S188-S2026 .Williams SC, Schmaltz SP, Morton DJ, et al. Quality of care in U.S. Hospitals as reflected by standardized measures, 2002-2004. N Engl J Med. 2005; 353:255-264.7 .Jha AK, Li Z, Orav EJ, Epstein AM. Care in U.S. hospitals – the Hospital Quality Alliance program. N Engl J Med. 2005; 353:265-274.8 .Williams DO. Treatment delayed is treatment denied. Circulation.2004;109:1806-1808.9 .Barron HV, Bowlby LJ, Breen T, et al. Use of reperfusion therapy for acute myocardial infarction in the United States: data from the National Registry of Myocardial

Infarction 2. Circulation. 1998;97:1150-1156.10 .Rogers WJ, Canto JG, Lambrew CT, et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999:

the National Registry of Myocardial Infarction 1, 2 and 3. J Am Coll Cardiol. 2000;36:2056-2063.11 .Eagle KA, Goodman SG, Avezum A, et al. Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: findings from the

Global Registry of Acute Coronary Events (GRACE). Lancet. 2002;359:373-377.12 .Newby LK, Rutsch WR, Califf RM, et al. Time from symptom onset to treatment and outcomes after thrombolytic therapy. GUSTO-1 Investigators. J Am Coll Cardiol

1996;1646-55.12 .Hasdai D, Behar S, Wallentin L, et al. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and

the Mediterranean basin, the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur Heart J. 2002;23:1190-1201.13 .Nallamothu BK, Blaney ME, Morris SM, Parsons L, Miller DP, Canto JG, Barron HV, Krumholz HM. Acute reperfusion therapy in ST-Elevation Myocardial Infarction from

1994-2003. The American Journal of Medicine, Vol 120, No. 8, August 2007-09-1614 .Berger PB, Ellis SG, Holmes DR, Jr., Granger CB, Criger DA, Betriu A, Topol EJ, Califf RM. Relationship between delay in performing direct coronary angioplasty and

early clinical outcome in patients with acute myocardial infarction: results from the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb)trial.Circulation. 1999;100:14-20.

15 .Antman Em, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, Ornato JP. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice

Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). J Am Coll Cardiol.2004;44:E1-E211.16 .Krumholz HM, Anderson JL, Brooks NH, Fesmire FM, Lambrew CT, Landrum MB, Weaver WD, Whyte J, Bonow RO, Bennett SJ, Burke G, Eagle KA, Linderbaum J,

Masoudi FA, Normand SL, Pina IL, Radford MJ, Rumsfeld JS, Ritchie JL, Spertus JA. ACC/AHA clinical performance measures for adults with ST-elevation and non-ST elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to

Develop Performance Measures on ST-elevation and Non-ST Elevation Myocardial Infarction). J AM Coll Cardiol.2006;47:236-265.

REFERENCES:17 .Centers for Medicare and Medicaid Services and the Joint Commission on Accreditation of Healthcare Organizations: Specifications Manual for National Hospital

Quality Measures. Baltimore, Md: Centers for Medicare and Medicaid Services and the Joint Commission on Accreditation of Healthcare Organizations; 2006 .18 .Williams SC, Schmaltz SP, Morton DJ, Koss RG, Loeb JM. Quality of care in U.S. hospitals as reflected by standardized measures, 2002-2004 N Engl J Med.

2005;353:255-264.19 .Magid DJ, Wang Y, Herrin J, McNamara RL, Bradley EH, Curtis JP, Pollack CV Jr, French WJ, Blaney ME, Krumholz HM. Relationship between time of day, day of week,

timelines of reperfusion, and in-hospital mortality for patients with acute ST-segment elevation myocardial infarction. JAMA.2005;294:803-812.20 .Nallamothu BK, Bates ER, Herrin J, Wang Y, Bradley EH, Krumholz HM. Times to treatment in transfer patients undergoing primary percutaneous coronary

intervention in The United States: National Registry of Myocardial Infarction (NRMI)-3/4 analysis. Cirulation. 2005;111:761-767.21 .McNamara RL, Herrin J, Bradley EH, Portnay EL, Curtis JP, Wang Y, Magid DJ, Blaney M, Krumholz HM. Hospital improvement in time to reperfusion in patients with

acute myocardial infarction, 1999 to 2002. J Am Coll Cardiol. 2006;47:45-51.22 .Bradley EH, Herring J,Wang Y, Barton BA, Webster TR, Mattera JA, Roumanis SA, Curtis JP, Nallamothu BK, Magid DJ, McNamara RL, Parkosewich J, Loeb JM, Krumholz

HM. Strategies for reducing the door-to-balloon time in acute myocardial infarction. N Engl J Med. 2006;355:2308-2320.23 .The Atlas of Heart Diseases and Stroke www.who.int/cardiovascular_diseases/resources/atlas/en./24 .Murray CJL, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet 1997;349:1498-504.25 .George E, Hunsberger S, Savitha D, et al. Treatment of acute myocardial infarction: does the type of hospital make a difference?PPAMI Study Group. Indian Heart J

1999;51(2):161-6.26 .Zornoff LA, Paiva SA, Assalin VM, et al. Clinical profile, predictors of mortality, and treatment of patients after myocardial infarction, in an academic medical center

hospital. Arq Bras Cardiol 2002;78(4):396-405.27 .Dakik HA, Koubeissi Z, Kleiman N, et al. Acute myocardial infarction: clinical characteristics, management and outcome in a university medical centre in a developing

Middle Eastern country. Can J Cardiol 2004;20(8):789-93.28 .Lupi Herrera E, National Registry of Acute Ischemic Coronary Syndromes (RENASICA). Mexican Cardiology Society. The RENASICA Cooperative Group. Arch Cardiol

Mex 2002;72(Suppl. 2):S45-64.29 .Samad Z, Rashid A, Khan MA, et al. Acute myocardial infarction: profile and management at a tertiary care hospital in Karachi. J Pak Med Assoc 2002;52(1):45-50.30 .Malhotra S, Gupta M, Chandra KK. Prehospital delay in patients hospitalized with acute myocardial infarction in the emergency unit of a North Indian tertiary care

hospital. Indian Heart J 2003;55(4):349-53.31 .Abba AA, Wani BA, Rahmatullah RA, et al. Door to needle time administering thrombolytic therapy for acute myocardial infarction. Saudi Med J 2003;24(4):361-4.32 .Loke YK, Hwang SL, Tan MH. Delays in thrombolytic therapy in acute myocardial infarction: an audit from the East Coast of peninsular Malaysia. Ann Acad Med

Singapore 1997;26(3):285-9.33 .Levy D, Thom TJ. Death rates from coronary disease – progress and a puzzling paradox. N Engl J Med 1998;339:915-7.34 .Ramani A, Bilgrami NL, Kumar S. Mortality and morbidity of acute myocardial infarction in and around Aligarh. J Indian Med Assoc 1990;88(7):192-5.35 .Passos LC, Lopes AA, de Souza CA, et a. Predictors of hospital mortality in the thrombolytic era for acute myocardial infarction in Salvador, State of Bahia, Brazil. Arq

Bras Cardiol 1997;68(4):249-55.36 .Siwach SB, Singh H, Sharma D, et al. Profile of young acute myocardial infarction in Harayana. J Assoc Physicians India 1998;46(5):424-6.37 .Abdallah MH, Arnaout A, Karrowni W, Dakik HA. The management of acute myocardial infarction in developing countries. International Journal of Cardiology 111

(2006) 189 – 194