Low cardiac output & Mechanical Support

นายแพทย์อรรถภมูิ สูศ่ภุอรรถ

ศลัยศาสตร์หวัใจและทรวงอก

โรงพยาบาล ราชวิถี

Low cardiac output/Cardiogenic Shock

• State of end-organ hypoperfusion due to cardiac failure.

• Hemodynamic parameters:

– Persistent hypotension (SBP 80-90 mm Hg or MAP 30 mm Hg lower than baseline)

– Cardiac index (1.8 L ·min1 · m2 without support or 2.0 to 2.2 L · min1 · m2 with support)

– Adequate or elevated filling pressure (eg, LVEDP18 mm Hg or RVEDP 10-15 mm Hg)

Circulation. 2008;117:686-697

Etiologies

• Acute myocardial infarction/ischemia

• LV failure • Papillary muscle/chordal

rupture- severe MR • Ventricular free wall rupture

with subacute tamponade

• Other conditions complicating large MIs – Hemorrhage – Infection – Excess negative inotropic or vasodilator

medications – Prior valvular heart disease – Hyperglycemia/ketoacidosis – Post-cardiac arrest – Post-cardiotomy – Refractory sustained tachyarrhythmias – Acute fulminant myocarditis – End-stage cardiomyopathyHypertrophic

cardiomyopathy with severe outflow obstruction

– Aortic dissection with aortic insufficiency or tamponade

– Pulmonary embolu – Severe valvular heart disease -Critical

aortic or mitral stenosis, Acute severe aortic or MR

Pathophysiology

Ann Intern Med. 1999;131:47–59.

4 Potential Therapies

• Pressors

• Intra-aortic Balloon Pump (IABP)

• Fibrinolytics

• Revascularization: CABG/PCI

• Refractory shock: ventricular assist device, cardiac transplantation

Pressors do not change outcome

• Dopamine – <2 renal vascular dilation

– <2-10 +chronotropic/inotropic (beta effects)

– >10 vasoconstriction (alpha effects)

• Dobutamine – positive inotrope, vasodilates, arrhythmogenic at higher doses

• Norepinephrine (Levophed): vasoconstriction, inotropic stimulant. Should only be used for refractory hypotension with dec SVR.

• Vasopression – vasoconstriction

• VASO and LEVO should only be used as a last resort

MECHANICAL CIRCULATORY SUPPORT

Intra-aortic balloon pump

Percutaneous assist devices

Surgical assist devices

Intra-Aortic Balloon Pump

• IABP beneficial effects

– Easy to implant

– Improves coronary perfusion

– Myocardial oxygen supply

– After-load reduction

– Improves distal perfusion

– Reduction of myocardial work

– Improvement LV performance

H Thiele Eur Heart J 2007;28:2057 HR Raynolds Circulation 2008;117:686

The Physiology of Counterpulsation

Enhanced coronary blood flow

•Diastolic balloon inflation increases intra-aortic pressure and coronary perfusion •MAP increases from greater increase in diastolic pressure than reduction of systolic pressure •Absolute change in coronary perfusion dependent upon vasoregulation

Left ventricular unloading •Displacement of blood into the periphery •Reduction of SBP •Reduction of LVEDP •Reduced LV wall stress •Reduced LV O2 consumption

Improved cardiac output •Preserved or increased stroke volume •Increased cardiac output as a result of afterload reduction

Rogers, J. Mechanical Devices in Cardiogenic Shock, AHA 2009

Indications for IABP

• Complicated acute myocardial infarction • Cardiogenic shock • Refractory unstable angina • Severe CAD with hemodynamic compromise • Mechanical complications of AMI • Support of high risk coronary intervention • Stabilization of left main disease • Induction and weaning of cardiopulmonary bypass • Bridge to cardiac transplantation • Refractory arrhythmias • Surgery for high risk cardiovascular patients

Contraindications to IABP

• Significant aortic regurgitation

• significant arteriovenous shunting

• Abdominal aortic aneurysm or aortic dissection

• Uncontrolled sepsis

• Uncontrolled bleeding disorder

• Severe bilateral peripheral vascular disease

• Bilateral femoral popliteal bypass grafts for severe peripheral vascular disease.

Benchmark registry: Indication Total

Populatio

n (n =

16,909)

Diagnostic

Catheterizatio

n (n = 1576)

Catheterization

Only & PCI Only

(n = 3882)

Surgery No

Interventio

n (n =

1186)

CABG (n =

9179)

Non-CABG

(n = 1086)

Support and stabilization (%) 20.6 21.4 54.4 9.7 5.0 7.8

Cardiogenic shock (%) 18.8 33.1 23.7 12.3 23.8 29.4

Weaning from cardiopulmonary

bypass (%) 16.1 0.4 0.1 24.9 31.4 7.1

Preop: high risk CABG (%) 13.0 4.6 0.2 22.1 6.4 1.9

Refractory unstable angina (%) 12.3 15.3 8.3 15.8 2.2 3.0

Refractory ventricular failure (%) 6.5 9.1 2.5 5.9 15.7 12.7

Mechanical complication due to

AMI (%) 5.5 9.8 7.0 4.2 5.2 5.1

Ischemia related to intractable VA

(%) 1.7 1.6 1.5 1.9 1.7 1.6

Cardiac support for high-risk

general surgery (%) 0.9 2.1 0.2 0.5 4.3 1.1

Other (%) 0.8 0.7 0.2 0.8 2.5 2.0

Intraoperative pulsatile flow (%) 0.4 0.1 0.1 0.7 0.5 0.2

Missing indication (%) 3.3 1.8 1.9 1.2 1.5 28.1

Ferguson et al. Am Coll Cardiol 2001;38:1456-62.

• GUSTO-1(1995), 7% (2,972) of pts had CS and IABP was used in 734 pts with a trend towards decreased mortality at 30 days (47% vs 60%, p=0.06)

• International Shock Registry (Hochman 1995) enrolled 251 pts with CS and found unadjusted mortality to be lower in the 173 pts treated with IABP (57% vs 72%, p=0.039)

• SHOCK Trial Registry (Sanborn 2000) looked at 856 pts with LV heart failure and CS, found pts did better with revascularization and IABP when compared with medical management alone (47% vs 77%, p<0.0001)

• In NRMI-2 Registry (Chen 2003) with n=23,138, 31% of CS was treated with IABP and a substantial mortality benefit (49% vs 67%) was seen when IABP was used in conjunction with reperfusion therapy, especially thrombolysis

• There was lower overall mortality in pts underwent primary PCI but not influenced by the use of IABP (45% vs 47%)

IntraAortic Balloon Pump

• Guidelines for STEMI complicated with cardiogenic shock support IABP counterpulsation as the method of choice for mechanical assistance

F Van der Werf Eur Heart J 2008;29:2909

EM Antman J Am Coll Cardiol 2004;44:761

Algorithm for revascularization strategy in cardiogenic shock, from ACC/AHA guidelines.

Whether shock onset occurs early or late after MI, rapid IABP placement and angiography are

recommended.

Reynolds H R , and Hochman J S Circulation 2008;117:686-697 Copyright © American Heart Association

Data from the SHOCK Trial-STEMI and CS • Randomized trial comparing ERV with PCI vs MT

• 185 patients with STEMI and CS were treated with IABP

• Rapid complete reverse of hypoperfusion (CRH) 30 min after IABP implantation was achieved in 68 pts (37%)

30-day mortality: 25% CRH vs 63% non CRH, (p<0.001) After adjustment for age, LVEF and early revascularization

Need for continuous evaluation and if hemodynamic improvement is not achieved at 4-6 hours the implantation of an assist device should be considered

H Thiele Eur Heart J 2007;28:2057 K Ramanathan Am Heart J 2011;162:268

Meta-analysis of IABP therapy in STEMI and CS

• 2 separate meta-analysis – 7 randomized trial (n=1009)

• No 30-day survival benefit • No improved LVEF • Higher stroke and bleeding rates

– 9 cohorts (n=10529) • Pt w thrombolysis- IABP decrease

30 day mortality • Pt w PCI-IABP increase 30 day

mortality

• Non-randomized studies • IABP may have been preferentially

given to patients in worse condition • Reflect a longer ischemic time if it

was implanted for transfer the patient

Sjauw K D et al. Eur Heart J 2009;30:459-468

IABP-SHOCK II: Randomized comparison of intraaortic balloon

counterpulsation versus optimal medical therapy in addition to early revascularization in acute myocardial infarction complicated by cardiogenic

shock • Multi-center, open-label, parallel

group, randomized, control trial

• N=600 patients with acute MI complicated by cardiogenic shock – IABP (n=301)

– Control (n=299)

• 37 centers in Germany

• Enrollment: 2009-2012

• Follow-up: 30 days

N Engl J Med. 2012 Oct 4;367(14):1287-96.

IABP showed no improvement in 30-day mortality, blood pressure no reduction in treatment time in the intensive care unit no decrease in the duration or dose of drugs prescribed no improvement in organ perfusion did not induce complications, and was shown to be a safe device.

• Based upon results from the IABP-SHOCK

• the new 2012 ESC STEMI guidelines downgraded the use of IABP in STEMI patients from 1C to 2B.

• And AHA/ACC STEMI 2013 downgraded from 1B to 2A

Percutaneous MCS Devices

• Potential Clinical Utility of Percutaneous VADS

– Acute cardiogenic shock

– Chronic decompensated heart failure

– Post-cardiotomy

– Hemodynamically assisted high risk coronary interventions

– Supported percutaneous valve repair/replacement

– Supported ventricular arrhythmia ablation

Percutaneous Mechanical Support

• TandemHeart pVAD

• Percutaneous insertion

– 21 F venous cannula passes to left atrium via a transseptal puncture

– 15-17 F arterial cannula

– Centrifugal flow pump that can provide 3.5-4 L/min at 7500 RPM

• Systemic anticoagulation required

• Approved for short-term support

Impella

•Miniaturized rotary blood pump (axial flow) •Provides up to 2.5 (percutaneous) or 5.0 (surgical) L/min at maximum speed of 50,000rpm •Inserted retrograde across the aortic valve to unload the LV •No extracorporeal blood •Required heparin

Percutaneous MCS

H Thiele Eur Heart J 2007;28:2057

Impella microaxial flow pump

TandemHeart Centrifugal pump

Surgical MCS

• ECMO: extracorporeal membrane oxygenation – External blood pump connected to a

membrane oxygenator similar to the cardiopulmonary bypass system used in cardiac surgery

– Short duration (<1 month)

– CS associated with severe respiratory insufficiency

Surgical MCS • Patients on CS are too sick for permanent

LVAD. Therefore stabilization using a temporary system is considered the best option

• In some patients in whom recovery of ventricular function is not expected a long-term VAD can be implanted

• BiVAD should be considered if there is right ventricular dysfunction

• VAD should be implanted before irreversible multi-organ failure is present

Kirklin JK JHLT 2011;30:115

Patient stabilized with MCS

• Bridge to recovery

– AMI+Stunning myocardium

– Fulminant myocarditis

– Postcardiotomy

• Bridge to Heart Transplantation

– No contraindication for HT

– Non-revascularized AMI

– Chronic ischemic and non-ICM

• Bridge to long term LVAD or Destination therapy

M Slaughter J Heart Lung Transplant 2010 L Lund Eur J Heart Fail 2010;12:434

Concerns for VAD implantation

• Severe aortic insufficiency should be corrected with a bioprosthesis • Mechanical aortic valve should be replaced with a bioprosthesis

• Uncertain neurologic status after surviving a cardiac arrest • High risk of bleeding (pre-operative abnormal coagulation) • Severe thrombocytopenia (Heparin-induced antibodies) • Active sepsis • Advanced inflammatory systemic response syndrome (SIRS) • Correct evaluation of irreversible end-organ failure is still a

challenge • Advanced age or severe comorbidities may contraindicate VAD

JL Brown Current Treat Options Cardiovasc Med 2011

CLINICAL EVIDENCE OF ITS IMPACT ON IMPROVING THE PT’S CONDITION

Improving Survival with LVAD Therapy

Percutaneous VAD: TandemHeart

• 117 patients with refractory CS, (48%) underwent CP resuscitation

Mortality at 30-day was 40% B Kar JACC 2011;57:688

Hemodynamic and metabolic parameters

Randomized Trial IABP vs TH

• 41 AMI and CS

• IABP 20 pts vs TandemHeart 21 pts

• 95% of pts underwent primary PCI

• The primary endpoint was hemodynamic improvement within 2 h after device insertion

The median duration of support was not different between the two systems H Thiele Eur Heart J 2005;26:1276

Adverse events comparing IABP and TH IABP VAD-TH p

Limb ischemia 0 7 0.009

Transfusion 8 19 0.002

Fresh frozen plasma and platelets

4 15 0.003

Fever 10 17 0.08

H Thiele Eur Heart J 2005;26:1276

Despite higher hemodynamic stability with TH, 30-day mortality was not reduced

IABP mortality 45% TH mortality 43%

ISAR-SHOCK trial: Impella LP 2.5 vs IABP Cardiogenic shock caused by AMI

• Randomized trial two centers: 25 pts

• IABP (13) vs Impella (12) implanted after revascularization therapy

• The primary endpoint was hemodynamic improvement within 30 min after device insertion

The increase in CI was greater with the Impella than IABP +0.49±0.46 vs +0.11±0.31 (p=0.002) Serum lactate were lower

M Seyfarth J Am Coll Cardiol 2008;52:1584

6 patients died in each group

Impella Trials

• PROTECT II: Prospective, randomized trial of Impella vs IABP in patients undergoing non-emergent high-risk PCI

• RECOVER II: Prospective, randomized trial of Impella vs IABP in patients with post-MI hemodynamic instability

Meta-analysis IABP vs P-AD

• Despite higher hemodynamic stabilization with PAD, the higher rate of complications and the presence of more advanced inflammatory syndrome might explain the lack of improvement in 30-day mortality

Randomized studies

Cheng JM Eur Heart J 2009;30:2108

Surgical LVAD/HT Retrospective study of 130 pts with STEMI and cardiogenic shock All treated with inotropics and IABP • 43 pts conservative therapy • 95 pts aggressive therapy:

– 77 pts PCI (47%) or CABG (43%) – 18 (19%) LVAD/HT (ECMO+LVAD 14, 1 LVAD, primary HT 3)

5-year mortality

BTT was successful in 72% W Tayara L Heart Lung Transplant 2006;25:504

In-hospital mortality

BiVAD as a bridge to HT in CS

• Retrospective study of 80 patients,

• All were in critical CS with emergency implantation of biVAD

Alive(71%) Death(29%)

BTT was successful in 57 pts (71%) 20 pts (87%) died of MODS

J Morigushi J Heart Lung Transplant 2011

So, Which device for my patient?

• Amount of support needed?

– Impella5.0, TandemHeart> Impella2.5> IABP

• Duration of support?

• Other issues (e.g., PVD, active bleeding)

• Local expertise?

Chronic end-stage HF Acute Cardiogenic shock

Long-term VAD

ECMO

Short-term VAD

Cardiac recovery?

Cardiopulmonary failure?

Isolated pulmonary recovery

Sustained VT, multiorgan dysfunction, or RV failure

BVAD •TandemHeart •CentriMag •Biomedicus •Abiomed VADs

LVAD •Impella •TandemHeart •CentriMag •Biomedicus

Device Explantation

Sustained VT, multiorgan dysfunction, or RV failure

LVAD BVAD/ATH

BTT BTT DT DT

Thoratec devices Investigational devices

Thoratec devices Investigational devices

Abiocor TAH

Syncardia TAH Thoratec PVAD

Contraindication to transplant?

Conclusions

• IABP continue to be the first choice of MCS in pts with CS. More studies are needed in pts with an AMI undergoing primary PCI to establish the best approach.

• Percutaneous VAD achieve faster and higher hemodynamic stability. However, this did not translate into improved 30-day survival

• Percutaneous or surgical VAD implant should not be delayed in patients without initial stabilization with IABP or presenting with profound CS

Conclusions

• Despite the rapid hemodynamic stabilization achieved with VAD, the high rate of complications or advanced inflammatory syndrome and ongoing multi-organ failure may explain the high mortality

• How to apply this expensive technology in the “real world” and how to define when ongoing efforts are futile is still a challenge (J TallaJ JACC 2010)

• In very selected patients with cardiogenic shock, LVAD can be successfully bridge to HT

IABP as an Adjunct to Thrombolytic Therapy

J Thromb Thrombolysis 2005; 19:33-9

Meta-analysis of randomized clinical trials of IABP therapy in STEMI. All meta-analyses show

effect estimates for the individual trials, for each type of reperfusion therapy and for the

overall analysis.

Sjauw K D et al. Eur Heart J 2009;30:459-468

IABP SHOCK Trial in STEMI and CS

• 40 pts were randomized before coronary angiography and PCI

• 19IABP, 21 standard therapy without PCI

TandemHeart

• Randomized trial of 42 patients with cardiogenic shock – 70% ACS – 30% Decompensated HF

• 71% with shock despite IABP • Centers implanting first patient

were allowed to implant the TandemHeart in the “Roll In” phase (non-randomized).

• Mean support duration=2.5 days

Burkhoff et al. Am Heart J 2006;152:469

TandemHeart Results

• 42 patients with cardiogenic shock randomized to IABP or TandemHeart

Am Heart J 2006;152:469

TandemHeart

• No difference in 30 day survival rates (IABP 64% vs. TandemHeart 53%)

• No difference in frequency of adverse events

Am Heart J 2006;152:469

LVADs currently in use

Cardiology research and practice 2012

ADVANCED MECHANICAL SUPPORT

Indications for VAD Therapy

Bridge to Recovery/ Explantation

Device intended for short term support for a condition that is anticipated to reversible

Bridge to Bridge Device intended for short term support (typically inserted in an emergent situation) until a more permanent device can be implanted

Bridge to Transplant Device typically intended for short-to intermidiate-term support in patients actively listed for transplantation

Bridge to Decision Device inserted to support a patient in whom the ultimate therapy is not able to be determined at the time of implantation. Device may be used for short or long-term support.

Destination Therapy Device inserted with the intention of long-term support in patients who are not candidates for transplantation

Choices of Device

• Choices continue to evolve with changing technology • Percutaneous

– Intra-aortic balloon pump – Impella – Tandem-heart – ECMO

• Surgically implanted – Centrimag – Abiomed AB5000 – Thoratec pVAD – Long term VADs (e.g., HeartMate II)

Heartmate II

Heartware

Circulite Synergy

• Surgical or percutaneous implant

• Partial cardiac assist

• Flow 2-3 L/min

• Modeling suggests reduction of LVEDP 7-10 mmHg

• 8-12 hours of untethered support

Outline

• Which Patients?

• Which Device?

• What Next?

Clinical Profiles in AHF: Data from Euro Heart Failure Survey II

N=3580

Decomp. HF

Pulm. Edema

HTN HF

Cardiogenic shock

Nieminen, M et al Eur Heart J 2006

Mortality in AHF by Clinical Classification

Nieinen MS et al. Eur Heart J 2006

SBP in AHF: Higher is Better?

Gheorghiade M et al JAMA 2007

ADHERE CART: Predictors of Mortality

Fonarow et al. JAMA 2005

Outline

• Which Patients?

• Which Device?

• What Next?

Surgically Implantable Temporary MCSD

Where to Next?

Summary and Conclusions

• Percutaneous mechanical circulatory support devices are growing in capability and complexity

• Patient selection remains the most critical component of success with these devices

• Randomized data is sparse and complicated by the critical acute illness of many of these patients

• It is likely that centers invested in percutaneous circulatory support will require> 1 device to satisfy the needs of the entire population

• Conceptually we are moving from total cardiac output replacement to partial hemodynamic support