Primary angioplasty in patient with shock HF is

Primary angioplasty in patient with shock

• HF is the single largest expense for Medicare – > 7 million hospital days/yr for acute HF – Almost all literature focused on Chronic CHF and not Acute • Cardiogenic Shock: – Serious disorder, high death rate, but treatable with improved outcomes if aggressive, but a 50% death rate persists • 5 -8% of STEMI patient, 2. 5% NSTEMI patients – Approximately 40 -50, 000 cases/year Hunt SA et al. J Am Coll Cardiol. 2001; 38: 2101 Graves EJ, Kozak LJ. Vital and Health Statistics. 1999; Series 13: 1 AHA. Heart Disease and Stroke Statistics— 2005 Update. Available at: http: //www. americanheart. org/downloadable/heart/1105390918119 HDSStats 2005 Update. pdf Reynolds HR, Hachman JS Circulation. 2008; 117: 686 -697.

Death at 30 days (%) In-hospital Mortality 90 80 70 60 50 40 30 20 10 0 USIK 1995, USIC 2000, FAST-MI France National Registry Shock 70 (62 -77) 63 No Shock (56 -70) 51 (44 -59) 8. 7 (7. 5 -10. 0) 1995 4. 2 (3. 4 -5. 1) 2000 3. 6 (3. 0 -4. 4) 2005 Aissaoui et al. Eur Heart J 2012; 33: 2535– 2543

• In STEMI, cardiogenic shock increases mortality from 10% to 50%. • Prompt recognition of CS is very important in STEMI management. • Only 15% of STEMI with CS have CS at admission. In the rest, CS usually develops within 24 hours of admission. Case fatality rate in STEMI with and without cardiogenic shock.

ESC definition of CS in STEMI Hemodynamic Clinical • CI < 2. 2 L/min/m 2 • PCWP > 18 mm Hg • Sys BP < 90 mm Hg (or > 90 mm Hg only with drugs or IABP) • Diuresis < 20 ml/hr.

Once you identify CS in your STEMI patient, try to identify the cause quickly • Causes of cardiogenic shock– Large LV territory involved – RVMI in IWMI – VSR, a/c MR, FWR • Look for factors worsening CS– Arrhythmias – Anemia

• Always do an echo prior to PPCI – Extent of LV involved – RV involvement in IWMI – VSR- missed unless you specifically look for it – Acute MR- not as “impressive” as chronic MR – FWR- you won’t have time to do an echo – Co-existing large pericardial effusion

Cause identified. Now what? Cause Treatment Large part of LV involved PPCI RVMI in IWMI Hydration, PPCI FWR Immediate surgery if pt survives to OT VSR Timing of surgery controversial a/c MR Immediate CABG + MV repair Compounding factors- arrhythmias, anemia Correction This talk deals primarily with the first cause.

Patient presents to an interventional cardiology hospital with STEMI with CS due to large part of LV involved. What to do? A. Immediate primary PCI B. First medical stabilisation. Then PCI once stable. C. Immediate fibrinolysis with medical stabilisation. Then PCI once stable.

The Shock Trial has Been the Most Important Study For Management Guidelines in Patients with Cardiogenic Shock Hochman et al NEJM 1999; 341: 625

SHOCK trial : Randomized and controlled study Acute Myocardial Infarction <= 36 hr Shock <= 12 hr Randomization Emergency Revascularization Initial medical Stabilization IABP/Pharmacological support Possible prior thrombolysis Emergency early PTCA(60%)/CABG(40%)<= 6 hrs IABP/Pharmacological support Thrombolysis unless absolute Contraindication (63%) Delayed revasc. (25%) >54 hr • Primary end point : 30 -day mortality • Secondary end point : 6 mo. mortality Hochman et al, NEJM 1999; 341: 625

SHOCK Trial : Mortality among Study Patients Outcome and Subgroup ERV 30 -day mortality Total Age<75 yr Age>=75 yr 6 -mo. mortality Total Age<75 yr Age>=75 yr Medical Therapy Difference Relative risk P-value percent(number in subgroup) 46. 7(152) 41. 4(128) 75. 0(24) 56. 0(150) -9. 3 56. 8(118) -15. 4 53. 1(32) +21. 9 0. 83 0. 73 1. 41 0. 11 0. 01 50. 3(151) 44. 9(127) 79. 2(24) 63. 1(149) -12. 8 65. 0(117) -20. 1 56. 3(32) +22. 9 0. 80 0. 70 1. 41 0. 027 0. 003 Hochman et al , NEJM 1999; 341: 625

SHOCK Trial: Subgroup analysis, Age less than 75 65% 66. 7% Mortality 56% 41% P=0. 02 CI<1. 0 45% 48. 4% Revasc. Med Rx P=0. 002 CI<1. 0 P<0. 02 CI<1. 0

SHOCK Trial: What to do with Pt. s older than 75 Ø Total no. of Pt. s older than 75 y. o. = 56 (/302) Ø The early revascularization groups had worse outcome at: § 30 days (CI >> 1. 0) § 6 months( CI >> 1. 0) § 12 months, no difference in outcome

What to do with Pt. s older than 75 Ø SHOCK Registry results is in contrast to the SHOCK Trial findings in this subgroup. § Those older than 75 y. o. , selected to undergo ERV had a survival advantage. § Case by case assessment in this population, and not across the board exclusion is called for.

• SHOCK trial- the lesson learned– Direct CAG is better than initial thrombolytic therapy with CAG later. • Proceed for direct CAG- patient should be stabilized in parallel by critical care team. – O 2, CPAP, SOS ventilator – Inotropes

Which inotrope? • Dopamine • Noradrenaline • Dobutamine • Levosimendan • Noradrenaline preferred to dopamine for low BP. • Once BP is > 90 mm Hg systolic- dobutamine or levosimendan.

• What if patient presents with STEMI with CS to a non-interventional centre? – STEMI without cardiogenic shock- Fibrinolytic is to be given unless primary PCI can be done in a nearby hospital very fast. – STEMI with cardiogenic shock- Primary PCI is much better than fibrinolysis, delay is acceptable. (How much delay- grey zone).

• In STEMI with CS, direct admit patients to interventional centre and transfer patients from non-interventional centres have same in hospital mortality (56% Vs. 55%. ) • When patient presents with STEMI with CS to non -interventional centre – Immediate transfer to interventional centre and primary PCI- IHM 41 % – Stabilisation and then transfer if/when stable- IHM 53% (p=0. 02)

Patient presents to non-interventional centre with STEMI with CS. Patient cannot be shifted to interventional centre due to some reason. What to do? A. No fibrinolysis B. Fibrinolysis

• Fibrinolysis is better than no fibrinolysis even in STEMI with CS. So if no option to shift to primary PCI centre, give fibrinolysis.

• Patient with STEMI with cardiogenic shock, PCI to culprit lesion done, should other lesions, if any, be dealt with in the same sitting?

Classical reasons to avoid non-IRA PCI during primary PCI 1. Systemic thrombotic state 2. Vasoconstriction exaggerates non-culprit lesions • Roe et al- STEMI all types – IRA + non culprit PCI increased death, reinfarction, CABG and shock • Corpus et al- STEMI all types – IRA + non culprit PCI cf IRA PCI alone in STEMI • More reinfarction • More revascularization • More MACE

But in STEMI with CS, non-IRA PCI decreases mortality. • Complete revascularization at time of primary PCI decreases in hospital mortality compared to culprit PCI only in STEMI with CS. P= 0. 02 • Complete revasc cf IRA PCI • Less cardiac death (42% vs 15%) • Less MACE (58% vs 25%)

• So non culprit lesion may be done at the time of primary PCI in STEMI with cardiogenic shock if – Both the below conditions are satisfied- • Persistent ischemia after PCI of IRA • Critical lesion (90%) or unstable lesion (thrombus/disrupted lesion) • Preferably by a highly experienced interventionalist. • A procedural complication in non culprit vessel will be catastrophic. • Meticulously analyse coronary anatomy and lesion characteristic. • Preferably avoid if calcified, tortuous, bifurcation, LM or saphenous graft.

• Patient presents in STEMI with cardiogenic shock. Any change in loading drugs compared to usual STEMI cases? – Yes. Until CAG is done, do not give clopidogrel/prasugrel/ticagrelor (ESC recommendation)

Intra-Aortic Balloon Pump Support • Reduces afterload • Augments diastolic perfusion pressure • Improvement in cardiac output and coronary blood flow • No change in myocardial oxygen demand • IABP support was associated with a ↓ in mortality: - NRMI-2 with lysis, from 67% to 49%2 - SHOCK Trial, from 63% to 47% 1 Hollenberg Ann Int Med 1999; 131: 47 -99 2 Barron AHJ 2001; 141: 933

TACTICS q q ST elevation MI patients, presenting within 12 hours of Sx, and Cardiogenic shock 57 Patients were randomized Thrombolytic Therapy alone Thrombolytic Therapy + IABP

TACTICS q q The primary endpoint of 6 month mortality was not statistically significant, P=0. 3 Subgroup analysis: For KILLIP classes III and IV, P=0. 07

NEW JOURNAL The ESTABL IS H ED l. N 1812 Intraaortic ENGLAND of MEDICINE OCTOBE R 4, 2012 VOL. 367 NO. 14 Balloon Support for Myocardial Infarction with Cardiogenic Shocl< Holger Thiele, M. D. , Uwe Zeymer, M. D. , Franz-josef Neumann, M. D. , Miroslaw Ferenc, M. D. , Hans-Georg Olbrich, M. D. , jorg Hausleiter, M. D. , Gert Richardt, M. D. , Marcus Hennersdorf, M. D. , Klaus Empen, M. D. , Georg Fuernau, M. D. , Steffen Desch, M. D. , lngo Eitel, M. D. , Rainer Hambrecht, M. D. , jorg Fuhrmann, M. D. , Michael Bohm, M. D. , Henning Ebelt, M. D. , Steffen Schneider, Ph. D. , Gerhard Schuler, M. D. , and Karl Werdan, M. D. , for the IABP-SHOCK II Trial Investigators*

Is the IABP Indicated in All Patients with Cardiogenic Shock? Thiele et al. N Engl J Med 2012; 367: 1287 -96

IABP SHOCK II: 1 Year Mortality 30 -day mortality 6 -month mortality 12 -month mortality 60% 51. 8%IABP 48. 7% Mortality 50% 41. 3% 40% Control 51. 4% 49. 2% 39. 7% 30% Logrank p = 0. 94 20% RR 1. 02 95% CI 0. 88 -1. 19 10% 0% 0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 Days after randomization No. at risk IABP 301 181 171 165 161 159 154 152 149 147 146 144 136 45 21 Control 299 174 166 165 159 154 152 147 146 144 140 55 29 Thiele et al. Lancet 2013

• STEMI with cardiogenic shock- should IABP be used? – Use only if patient does not quickly stabilize with drugs (ACC & ESC) • ACC- Class II A • ESC- Class II B

BCIS Study: Early Results Do Not Support Prophylactic Use of IABP MACCE at Discharge p=0. 85 15. 2% 16. 0% N= 151 N= 150 Elective IABP Not Planned IABP Perera et al. JAMA 2010 Aug 25; 304(8): 867 -74

BCIS-1 Long Term (5 Year Data) Suggest Benefit to IABP Support in High Risk PCI (hazard ratio, 0. 66; 95% confidence Interval, 0. 44– 0. 98; P=0. 039 Perera D et al. Circulation. 2013; 127: 207 -212

What Constitutes “High Risk PCI? ” • Patients for whom high-risk interventions are considered generally have: • severe diffuse coronary artery disease • a single last patent conduit • Significant unprotected left main disease with large territories of myocardial ischemia • Typically have reduced left ventricular function (ejection fraction <25%– 35%) • Comorbidities that make them high risk for standard coronary artery bypass grafting. O’Neill, et al. Circulation. 2012; 126: 1717 -1727

IABP in acute myocardial infarction: When does it make sense? : • large myocardial infarction • ongoing (persistent) ischemia despite successful stenting • whether or not complicated by (pre-)shock In these patients, IABP significantly decreases mortality! Van Nunen et al, Euro. Intervention, september 2014 ( online) In CRISP-AMI and SHOCK 2, benefit of IABP was obscured by including too many patients in whom no effect could be expected anyway and by inadequate statistical methods 21

CRISP-AMI: 30 -day mortality no no. IABP All patients (N=329) no IABP “large” infarction (N=146) ( ST-elevation ≥ 15 mm. Hg) pno<IA 0. B 0 P 5 IABP persistent ischemia ( N=36) (ST resolution ≤ 50%)

Is IABP- therapy a matter of timing?

IABP support: Is it time dependent? In 119 STEMI patients with cardiogenic shock treated with primary PCI, the use of IABP before intervention was associated with a significantly lower incidence of VF, cardiopulmonary arrest, and total catheterization laboratory events compared with no IABP or IABP after intervention Brodie et al, Am J Cardiol 1999; 84: 18 -23

Impact of IABP-Timing in CS Clinical outcomes at 30 days IABP after before PCI (n=49) PCI (n=53) pvalue Mortality 12 (25%) 29 (55%) 0. 002 Emergency CABG 0 (0%) 5 (9%) 0. 027 Cerebrovascular Events 4 (8%) 0. 908 MACCE 15 (31%) 32 (60%) < 0. 001 Bleeding 12 (25%) 14 (26%) 0. 824 Acute renal failure 9 (18%) 14 (26%) 0. 331 Schwarz et al. (submitted for publication)

Dissecting the data for (or against) IABP Conclusions • IABP can be safely applied in shock patients undergoing PCI. • Routine use of IABP in CS, which is not due to mechanical complications is no longer recommended. • IABP-assisted PCI is useful in acute patients with severe shock to support complex interventions.

• LV assist devices

Randomized Trial Tandem Heart vs. IABP in Cardiogenic Shock 30 d Survival p=ns IABP n=14 Tandem Heart n=19 Burkhoff, AHJ 2006; 152: 469.

PROTECT II Trial Design Patients Requiring Prophylactic Hemodynamic Support During Non-Emergent High Risk PCI on Unprotected LM/Last Patent Conduit and LVEF≤ 35% OR 3 Vessel Disease and LVEF≤ 30% R IABP + PCI 1: 1 IMPELLA 2. 5 + PCI Primary Endpoint = 30 -day Composite MAE* rate Follow-up of the Composite MAE* rate at 90 days *Major Adverse Events (MAE) : Death, MI (>3 x. ULN CK-MB or Troponin) , Stroke/TIA, Repeat Revasc, Cardiac or Vascular Operation or Vasc. Operation for limb ischemia, Acute Renal Dysfunction, Increase in Aortic insufficiency, Severe Hypotension, CPR/VT, Angio Failure

PROTECT II MACCE Per Protocol Population, N=427 Death, Stroke, MI, Repeat revasc. IABP IMPELLA Log rank test, p=0. 042 MACCE= Death, Stroke, MI*, Repeat revasc. (*Stone et al, Circulation 2001; 104: 642 -647 )

Pre-Specified Sub-group Analysis (PP) 90 day MAE Relative Risk [95% CI] Overall – Per Protocol (n=425) Group Interaction p-value 0. 79 [0. 64, 0. 97] 0. 023 0. 70 [0. 55, 0. 89] 0. 003 1. 19 [0. 75, 1. 91] 0. 444 Anatomy 0. 82 [0. 53, 1. 25] 0. 351 ULM / Last conduit (n=101) 3 VD (n=324) 0. 78 [0. 61, 0. 99] 0. 039 1. 14 [0. 75, 1. 71] 0. 540 0. 71 [0. 56, 0. 91] 0. 006 0. 92 [0. 62, 1. 38] 0. 697 0. 74 [0. 58, 0. 95] 0. 016 PCI Procedure 0. 087 Without Atherectomy (n=373) With Atherectomy (n=52) STS Mortality Score STS ≥ 10 (n=71) STS < 10 (n=354) Roll in subject =116) 1 st Impella/IABP Pt per site (n After 1 st Impella/IABP Pt (n=309) 0. 0 0. 5 Impella better 1. 0 1. 5 IABP better 2. 0 O’Neill et al, Circulation. 2012; 126(14): 1717 -27 0. 845 0. 092 0. 348 PP= Per Protocol

• Role of LVAD in STEMI with cardiogenic shock? – Only if there is refractory shock – Class II B (ACC & ESC) • No advantage for LVAD cf. IABP.

Hemodynamic support A. In patients with cardiogenic shock there is no evidence that routine use of IABP reduces 30 day mortality B. In patients undergoing high risk PCI, the Impella 2. 5, compared to IABP, allows more complete revascularization but does not reduce the incidence of irreversible events C. A hemodynamic support device is recommended for patients with cardiogenic shock after STEMI who do not quickly stabilize with pharmacologic therapy

What TIMI flow is needed in STEMI with cardiogenic shock? • Always aim for TIMI 3 flow as in any primary PCI – SHOCK trial- STEMI with cardiogenic shock- in hospital mortality • TIMI 3 - 26% • TIMI 0/1 - 47%

• Should GP II b III a inhibitors be routinely used for primary PCI in STEMI with cardigenic shock?

q SHOCK Trial: Revascularization Medical Treatment (N=152) (N=150) IIb/IIIa Antagonist Stent Placement 41. 7% 25% 35. 7% 52. 3%

q Retrospective subgroup analysis from the PURSUIT trial Hassade, et. al. , JACC, 2000 • Randomization to eptifibatide did not affect the incidence of shock • Patients randomized to eptifibatide who developed shock had a significantly reduced incidence of death at 30 days • A possible mechanism of benefit is relief of microvascular obstruction

Long-Term Mortality Benefit With the Combination of Stents and Abciximab for Cardiogenic Shock Complicating Acute Myocardial Infarction [Coronary Artery Disease] Chan, Albert W. MD, MS; Chew, Derek P. MBBS; Bhatt, Deepak L. MD; Moliterno, David J. MD; Topol, Eric J. MD; Ellis, Stephen G. MD STEMI with cardiogenic shock- abciximab increased chance of TIMI 3 flow (87% vs 58%) and decreased chance of no reflow (9% vs 37%).

Role of IIb/IIIa Inhibitors and Stents in Cardiogenic Shock At 30 months Use of Stents • 29% Absolute mortality reduction • 1 additional life saved for each 3 -4 treated Patients. Abciximab +Stenting • 10% Absolute mortality reduction • 1 additional life saved for each 10 patients treated.

Role of IIb/IIIa Inhibitors and Stents in Cardiogenic Shock Results of Primary Percutaneous Transluminal Coronary Angioplasty Plus Abciximab With or Without Stenting for Acute Myocardial Infarction Complicated by Cardiogenic Shock[Coronary Artery Disease]Giri, Satyendra MD, MPH, MRCP; Mitchel, Joseph DO; Azar, Rabih R. MD, MSc; Kiernan, Francis J. MD; Fram, Daniel B. MD; Mc. Kay, Raymond G. MD; Mennett, Roger MSc; Clive, Jonathan Ph. D; Hirst, Jeffrey A. MD, MS AJC, 15 January 2002 .

Role of IIb/IIIa Inhibitors and Stents in Cardiogenic Shock Ø This was a nonrandomized, prospective observational study. Ø 113 (13. 9%) were diagnosed with cardiogenic shock from 8/95 to 8/99.

Role of IIb/IIIa Inhibitors and Stents in Cardiogenic Shock No Reopro With Reopro

Role of IIb/IIIa Inhibitors and Stents in Cardiogenic Shock Multivariate Analysis

Role of IIb/IIIa Inhibitors and Stents in Cardiogenic Shock Speculation: Greater use of Abxicimab, and Stents in the SHOCK Trial may well have resulted in a positive primary endpoint. The age cutoff of 75 may or may not have retained its significance vis-à-vis increased mortality.

Should GP II b III a inhibitors be used for STEMI with cardiogenic shock? Ø GP II b III a inhibitors are not routinely recommended in primary PCI. Ø Since TIMI 3 flow is very important for STEMI with cardiogenic shock- should GP IIb IIIa use have a lower threshold in STEMI with CS than in usual STEMI PCI? Open for discussion.

Case no… 1

Story so far • Admitted with acute MI in another hospital in november 2014, primary angioplasty done • Stent thrombosis in LAD resulting in acute MI again in the same hospital after 10 days. Angioplasty and stenting done again. • Evaluated in amrita hospital after 24 hours, for one week and discharged • After one week admitted with vague discomfort in lower jaw and mild fever

Interesting clinical features • ESR , , 24 mm/hr in the first hospital , 45 mm/hr in AIMS, 130 mm/hr in our hospital • Mild fever present in AIMS , continue to be in our hospital • Mild swelling in parotid region from AIMS onwards , which patient and relatives are accounting as parotitis • Patient is a police officer who is involved in a major criminal case. So the relatives and police people are surrounding the hospital premises and making problems for our hospital and doctors

• Admitted and evaluated for fever and chest pain? ? ? • Leukocytosis, high ESR, altered liver function, mild renal impairment. • No fresh ECG changes and Echo showed AWMI, mild LV dysfunction • No organo megaly and no evident focus of infection • Culture sent and combination of higher antibiotics started • Severe chestpain in the night at 12. 30 am after 2 days with ECG changes suggestive of LMCA disease

• BP is low, relatives are” very good”, asking for guarantee…… • O 2 saturation very low • Echo … severe MR which is new event • Impression. . Post stenting twice in last month, re-MI, acute severe MR, cardiogenic shock • CAG. . TVD, new occlusion of CX , swelling in the overlapping junction. . Aneurysm? ? , /abscess? ? ?

7 F XB 3. 5 FC into CX and galeo to LAD thrombus aspiration tried. Failed. IC eptifibatide, nikoran are ineffective

• Done very well in the next 24 hours. Discussed about the possibility of stent thrombosis and aneurysm enlargement / abscess …… • High dose of triple antibiotics started because of mild fever • Discussed about surgical possibility with surgeon. • He agreed. Relatives wanted a guarantee and transferred to AIMS. Underwent CABG after 10 days.

Case … 2 • Young fellow admitted with pulmonary edema and low BP in our hospital • ECG shows ST depression of > 4 mm in all leads except in Avr • Patient is struggling and managing with diuretics and BIPAP, loaded with clopidogrel and asprin. • Echo. . Suggestive of global LV dysfunction and mild MR. EF … 30% • Patient has angina for more than 9 months and evaluated with an ECG only and told to him as normal.

• RCA CTO with bridging collaterals proximally • LAD occluded …. Acute or chronic ? ? ? • CX. . Normal • Approach ……. . • LAD angioplasty … •

• In dilemma … • What to do • Doing something in RCA will be disastrous if I could not open RCA • So tried once again LAD before call it a day

• Decided to open diagonal if possible…. . • If LAD and RCA are CTOs, why there is a deterioration now. Probably a new lesion or acute on chronic lesion in LAD which I could not open……

• Patient became alright in another 10 minutes • Angina disappeared immediately after stenting. • Referred for surgery after 4 weeks. • Graft to LAD and RCA done. . LAD was intramyocardial • Patient doing very well. EF improved to 54%

Take home messages Ø CS dramatically increases mortality in STEMI. Ø Always prefer primary PCI to fibrinolytic therapy in CS. Ø Interhospital transfer patients have same benefit with primary PCI as direct admission patients. Ø Aim for TIMI 3 flow. Ø Load clopidogrel/ticagrelor/prasugrel only after CAG. Ø IABP/LVAD only if no stabilisation with noradrenaline. Ø Non IRA lesions may be opened in specific circumstances.

Thank you