Type A Ao Dissection – Evolution in understanding

Type A Ao Dissection – Evolution in understanding of the Great Masquerader & assessing the

underlying Silent Killer

Dept. of Critical Care Medicine Grand RoundsUniversity of Calgary

March 21, 2018

Jehangir AppooDivision of Cardiac Surgery

On behalf of the Calgary Thoracic Aortic Program

aorta.ca

Audience for this talk:

Intensivists

Diverse backgrounds – Internal Medicine, Neurology, Pulmonary, Surgery, Anaesthesia….

Highly educatedInsightful, v. bright

Take care of the sickest patients in the hospital

What can I tell this group about Aortic Dissection that matters to them?

what we know what we don’t knowevolution

Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing

- Voltaire (1694 – 1778)… (or was it T. Godinez? )

Case – June 2017

57yo male collapsed with Abdo Pain on soccer field around 8pm

EMS called and taken to RGH

PMHx : HealthyKnown for a 4.3cm ascending aorta

FHx: Mother had 2 sisters with aortic dissection

Case

8pm onwards - ongoing abdo pain in ER4:15 am CT abdo followed by CT chest

Collapse of thoraco-abdominal true lumen

True Lumen

FL

Collapse of thoraco-abdominal true lumen

Pneumotosis Intestinalis on pre-op CT !

Renal Malperfusion

R renal artery off collapsed true lumen

Upon transfer to CVICU –10 -12 hours post collapse on soccer field

BP “stable”

Tender abdomenLactate 5pH 7.1K+ 6.9

Intraop TEESevere AINormal LV/RV FunctionNo significant pericardial effusion

Our patient’s acute problems secondary to Aortic Dissection:

Impending rupture of ascending aorta

Severe Aortic Insufficiency

Collapse of true lumen in thoraco-abdominal aorta

Visceral malperfusion with cell death/lysis Dead gut vs viable bowel ?

Renal malperfusion

11% 47% 11% 7% 4% 20%(n=157) (n=673) (n=161) (n=98) (n=58) (n=280)

• 1427 patients • 954 male• mean age 61.7 years

Contemporary Classification of Aortic Dissection

IRAD – Ann Thorac Surg 2016

Intraop view of Type A Dissection

Great Masquerader

Signs and symptoms of Aortic Dissection other than chest pain

RCA more commonly involved

SBP difference >20mmHg

All First Order branches of aorta can be involved

You cannot deceive everybody all of the time

- Abraham Lincoln

Great Masquerader

Country # of pts Misdiagnosed Misdiagnosedas ACS

Canada 66 39% 80%

Japan 109 16% 59%

Singapore 68 38%

China 361 14% 47%

Hansen et al. American J of Cardiology 2007Kurabayashi et al. J of Cardiology 2011Chu et al. American J of Emerg Med 2012Zhan et al. J Clin Hypertens 2012

Great Masquerader - Misdiagnosis of Aortic Dissection in ER

Predictors of misdiagnosis:

Walk in Mode of presentation

Absence of pulse deficit

Absence of widened mediastinum

Presenting symptoms of Aortic Dissection

How to attempt to distinguish from ACS:

PAIN:

Abrupt onset of CPMaximal intensity at time of onsetCP more often “sharp” than “tearing”CP radiating to back or abdomen

Can be painless!

Consequences of Misdiagnosis:

Delayed diagnosis of lethal pathology of variable urgency

Inappropriate treatment antiplatelet agents anti-thrombin agentsfibrinolytics

Initial Medical Treatment of Aortic Dissection

Anti-impulse therapy 60/100 rule : HR 60bpmSBP 100mmHgIV B-blockers and Nipride

Pearl #1



Pain control narcotics

Arterial line in arm with higher blood pressure



Pain control narcotics

Arterial line in arm with higher blood pressure

Type B dissections: close observation in ICU for complications secondary to branch vessel involvement Remember the Great Masquerader

If Hypotensive:

Role of pericardiocentesis in ER ?

Fluid Resuscitation

Pearl #2

Nov 2017

59 y.o male presented to MHH with leg pain & weakness

Trop positive Fundoparinux & PlavixDiagnosed with “pneumonia” Transferred to FMC ICU with sepsisMental confusionMRI hypoxic strokeHypoxic resp failure requiring intubationCreat 300Murmur appreciated? Endocarditis TTE severe AI

TEE severe AIdissection flap in descending aortadiagnosed ̴ 36 hrs post presentation

Great Masquerader - Challenging Diagnosis

Even more true for the Great Masquerader

March 2016

20 y.o male abdo pain

Lap Appendectomy at Rural Hospital

Repeat CT POD4 for CP/unwell

Died prior to transfer

In retrospect, root dilatation and abdo aortic dissection could be appreciated on preop CT at time of abdo pain presentation

Questions:What kind of systematic screening program can identify him early?

How did aorta get to 8cm in young man without rupturing?

March 2016

Type A Aortic Dissection

Variable acuity 1%/hr

Variable presentation “Great Masquerader”

Sept 2016

46y.o Type A and GI bleedRapid diagnosisDied prior to transfer from RGH

Variable acuity

Why is Aorta Aneurysm challenging?

SILENT KILLER

LethalAneurysm disease top 20 causes of death of human beingsActual number likely underestimated

Asymptomatic95% are asymptomatic prior to catastrophic event

“Any aneurysm of the aorta is a hopeless condition” - William Osler, 1903

Etiology of the Silent Killer

Tracking a Silent Killer

Elefteriades et al. Guilt by association: paradigm for detecting a Silent Killer (thoracic aortic aneurysm). Open Heart Journal 2015

SyndromicFamilial

Sporadic

High risk genetic variants

Low risk genetic variants

Genetic-------------------------------------------------------------Environmental

Slide courtesy of Dr. Ouzounian

Genetic Causes of Aortic Dissection:

Marfan’s

Loeys-Dietz

Vascular Ehler’s Danlos

Turner’s Syndrome

In our experience, identifiable genetic causes are uncommon

Role of Hypertension in Etiology of Aortic Dissection

easy/intuitive blames patient

however, severe pre-op HTN not the norm

Need to look harder as to why aortas break

Conventional Operation

Tear specific operationResect Intimal Entry Site

“Standard of care” for acute Type A Dissection – when I started in 2005


Tear specific operationResect Intimal Entry SiteProximal arch reconstruction

“Standard of care” for acute Type A Dissection


Tear specific operationResect Intimal Entry SiteProximal arch reconstructionCirculatory arrest with cerebral perfusion

“Standard of care” for acute Type A Dissection


Tear specific operationResect Intimal Entry SiteProximal arch reconstructionCirculatory arrest with cerebral perfusionAscending aortic replacement

Proximal ComplicationsRoot/Valve/CoronaryPericardial effusions

“Standard of care” for acute Type A Dissection – when I started in 2005

526 pts 1996 – 2001

Operative Mortality 25%

GERAADA German Registry for Acute Aortic Dissection Type A

52 European Centres

>2100 patients from 2006-2010JACC 2015

Mortality 17% (10-35% based on age quartile)

Post op Neurodeficits 17% (includes 7% with preop deficit)

Operative mortality increases 10% from baseline with each organ system involved with malperfusion

In addition to world wide high periop mortality (17-25%)....long term outcome for survivors is questionable

Double dagger of Type A Dissection Surgery

Example of possible outcome of conventional surgery

51 y.o. Male Distal Arch TearConventional Surgery Spring 2014– Asc/Open Distal

Pre-op 2 weeks post op 3 months post op

Intimal tear in distal arch

3.8cm descending aorta

Presents with CP/Back Pain

5.3cm distal arch/descending aorta

Given known CT disorder, rapid rate of growth, residual dissected arch, 4 branch arch with dominant left vertebral, redo sternotomy setting

Progressed to urgent thoracotomy & resection of distal arch and descending aorta

Profound HypothermiaL chest circ arrestCSF drain for Safi type C aneurysm

Outcomes for survivors of surgery for Type A dissection is unclear

Long-term survival ~ 50% at 10 years

Patent false lumen up to 80% of patientsmore reoperation

~ 20% at 10 yrs~ 50% at 10 yrs for age <45y.o

worse survival at 10 yrs

Mortality from distal operation up to 30%

Geirrson Ann Thorac Surg 2007Fattouch Ann Thorac Surg 2009

Conventional OperationCurrent “standard of care” for acute Type A Dissection

Good operation

Addresses proximal complications of aortic insufficiency and ascending aortic rupture

Saves many lives in distressful times

Conventional OperationCurrent “standard of care” for acute Type A Dissection

But, is it enough in all cases?

Does it satisfactorily treat the aorta and side branches at risk?

Does it address issue of distal aortic aneurysm formation?

Good operation

Addresses proximal complications of aortic insufficiency and ascending aortic rupture

Saves many lives in distressful times

Extended Arch operations for Acute Type A Aortic Dissectionincreases complexity of operation with high mortality ratefew centers world wide

Japan

China

Europe

USA

http://www-ncbi-nlm-nih-gov.ezproxy.lib.ucalgary.ca/pmc/articles/PMC3791186/figure/f2/

http://www-ncbi-nlm-nih-gov.ezproxy.lib.ucalgary.ca/pmc/articles/PMC3791186/figure/f2/

Pooled hospital mortality = 8.6%

Might be feasible to do more surgery and even decrease periop mortality

2018

Early Feasibility FDA Study: Acute Type A

5 sites in US enrolling

Technology is here….and future generations will improve on shortcomings...

Endovascular Treatment of Type A Aortic Dissections:

Evolution

Case reports and small case series published

For the right case, we are ready to try this in Calgary

Back to our patient with ATAAD:

Impending rupture of ascending aorta

Severe Aortic Insufficiency

Collapse of true lumen in thoraco-abdominal aorta

Visceral malperfusion with cell death/lysis Dead gut vs viable bowel ?

Renal malperfusion

Surgical Strategy:

Pre op emergency Gen Surgery consultation re bowel viability and plan

Surgical Strategy:


Rapid perfusion of bowel by accessing true lumen for cardiopulmonary bypass inflow prior to start of long operation

TL expansion but low flow due to small sizeBoth TL & FL cannulated and flows regulated based on TEE expansion of respective lumens

Surgical Strategy:

Pre op emergency Gen Surgery consultation re bowel viability and planRapid perfusion of bowel by accessing true lumen for cardiopulmonary bypass inflow

Replace Ascending aorta, total arch and bypass all 3 head vessels

Treat collapsed distal true lumen with TEVAR

Surgical Strategy:


Rapid perfusion of bowel by accessing true lumen for cardiopulmonary bypass inflow

Replace Ascending aorta, total arch and bypass all 3 head vessels

Treat collapsed distal true lumen with TEVAR

On table laparotomy after perfusion to bowel restored from aortic sidesegment of infarcted small bowel resectedasc colon dusky but appeared viableabdomen left open

Post op course:

Complications of ischemic gut GI bleedsStroke with hemiplegiaSepsisHITTIschemic strictures requiring laparotomy 3 months post op

6 months post op:

CVA sequelae: unilateral arm weaknesswalking independently

Tolerating full diet

….residual aorta looks stable

Big team effort needed to survive these complicated devastating presentations: Gen Surgery, ICU, Interventional Radiology, Cardiac Anaesthesia, Cardiac Surgery

Example of a Silent Killer (6cm ascending aortic aneurysm) and Great Masquerader (presentation with abdo pain)

Share with you our research/evolution on:

I. Why/When do Aortas Dissect?II. Stroke Complication of Aortic DissectionIII. What type of operation should be performed ?

Why is Aorta challenging?

SILENT KILLER

LethalAneurysm disease top 20 causes of death of human beingsActual number likely underestimated

Asymptomatic95% are asymptomatic prior to catastrophic event

Natural History of Thoracic Aortic AneurysmsSilent Killer

Why understanding aortic behaviour is important?

Dilemma:

Young patients with small aneurysms can dissectvs.

Denominator is very large – many patients have large aortic aneurysms that are stable for prolonged periods of time

Intervention is invasive – has some risks

If we operated on every dilated aorta, we may do more harm than benefit

Summary of 2014-2016 ESC, AHA & CCC Guidelines for Prox Ao Intervention:

Asc Ao > 5.5cm

Asc Ao > 5.0cm with some risk factors (rate of growth, family history of dissection, hypertension, patient preference…)

Asc Ao 4.5 – 5.0cm for Connective Tissue Disease

Probably don’t need to be more aggressive if bicuspid valve

Summary of 2014-2016 Guidelines on Prox Aortic Intervention:

Level of scientific evidence is poor

no randomized data

no large non randomized studies

small, retrospective studies

consensus opinions

Lots of room for flexible interpretation including patient preference, aortic shape, rate of growth, patient size

How robust are the natural history data of Ascending Aortic Aneurysms?

Common Knowledge

Figure 1. Flowchart

Studies Identified: • By primary search:

• Medline: 3859 • Embase: 6088

• 2 by reference search • Total: 9949

Abstract Reviewed: 7198

Duplicated Studies Removed: 2749

Excluded by Title & Abstract: 7136 Eliminated by Full Text Review Based on Exclusion Criteria: 42

• 14 considered TAA as a single entity

• 7 analyses from aortic dissection database

• 6 biomechanical studies 5 studies from the same centre

• 4 studies on BAVs without AsAA

• 2 studies on natural history of aortic root/SoV after AsAA replacement

• 1 genetic study • 1 mathematic modelling

study • 1 population-based study • 1 study on arch

aneurysm only

Studies Included in Systematic Review: 20

AsAA with TAV with or without previous AVR: 6

AsAA with BAV: 8 AsAA with unspecified valve type: 5

Full Text Reviewed: 62

AsAA with mixed TAV & BAV: 4

Examining the Risk of Ascending Aortic Aneurysm: A Systematic Review and Meta-analysisMing Hao Guo, MD1, Jehangir J. Appoo, MDCM2, Richard Saczkowski, CPC, CCC3, Holly N. Smith, MD2, Maral Ouzounian, MD, PhD4, Alexander J. Gregory, MD5, Eric J. Herget, MD6, Munir Boodhwani, MD, MSc1

NY Aortic Symposium, May 2018In submission JAMA

Linearized rate of dissection, rupture, or death:

Conclusions and Relevance: The growth rate of AsAA is slow and the risk of

dissection, rupture, and death may be lower than previously understood. A

randomized control trial may be required to understand the benefit of surgical

intervention compared to surveillance for patients with moderately dilated ascending

aorta.

Examining the Risk of Ascending Aortic Aneurysm: A Systematic Review and Meta-analysisMing Hao Guo, MD1, Jehangir J. Appoo, MDCM2, Richard Saczkowski, CPC, CCC3, Holly N. Smith, MD2, Maral Ouzounian, MD, PhD4, Alexander J. Gregory, MD5, Eric J. Herget, MD6, Munir Boodhwani, MD, MSc1

“Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing” – Voltaire, 1694-1778

Is there a knowledge gap in understanding of ascending aortic aneurysm?

Do we as surgeons understand the NNT to save a life at one year?

What happens when endovascular repair of ascending aorta is feasible?

Anyone who isn’t confused doesn’t really understand the situation

Edward R. Morrow – TV News Anchor

On Research:

Sturgeon’s Law: “90% of everything is crap”

….so if you are going to critique/question, go after the good stuff or leave it alone

TITAN SvS: Treatment In Thoracic Aortic aNeurysm: Surgery vs. Surveillance

Multicentre Randomized Study of surgery vs surveillance for ascending aortic aneurysms 5.0-5.4cm

Munir Boodhwani, Ming Guo, Vamshi Kotha, Eric Herget, Alex Gregory, George Wells, Akash Fichadiya, & Jehangir Appoo

Libin Cardiovascular Insitiute, University of CalgaryEFW Radiology, University of Calgary

Ottawa Heart Institute, University of Ottawa

TITAN: SvSTreatment In Thoracic Aortic aNeurysm: Surgery vs. Surveillance

Primary Outcome:

Impact of Early Surgery vs. Surveillance strategy on all cause mortality and incidence of acute aortic syndrome at follow up


Secondary Outcomes:1. 30 day mortality of ascending aortic repair2. Incidence of elective ascending aortic surgery3. Incidence of CVA4. Annual ascending aortic growth rate 5. Quality of Life Assessment at 1 year and 3 years6. Non diameter related assessment of risk of acute aortic syndrome

1. Biobank of blood sample2. Biomedical Engineering Analysis

First trial to randomize ascending aortic aneurysms to surgery vs. medical therapy…evolution


Steps Accomplished 2016-2018

Raised Seed Funding $200,000Libin, Cumming School of Medicine, EFW, Ottawa Heart Institute

Ethics submitted in Ottawa & Calgary

Letter of Intent 12 Canadian sites

CIHR grant application $1M submitted March 2018


Next Steps:

Set up online database

Enroll first patients June 2018

Await result of CIHR grant application

Gradual roll out to all participating sites Fall 2018


I. Why/When do Aortas Dissect? – TITAN SvSII. Stroke Complication of Aortic DissectionIII. What type of operation should be performed ?

Stroke and Aortic Dissection

Underappreciated problem

Cause ? Dissection extends to head vessels?Hypoperfusion during surgery?Emboli from surgical manipulation? Clot on dissection flap? Other?

Stroke and Aortic Dissection

Complicated problem

Needed expertise from other specialties

Formed a group including DI, Neuro Rads, Stroke Neurology, Anaesthesia & Surgery

Meta-analysis of the literature

Retrospective review of FMC cases

Meta Analysis of Stroke and Dissection identified:

Inconsistent definitions for stroke

Inconsistent ascertainment of stroke

Limited brain imaging

Limited assessment of nature and severity of stroke

Small sample size

8% incidence – likely under reported

Alex Gregory, Bijoy Menon et al…

Retrospective review of FMC Stroke and Ao Dissection :

38/189 (20%) incidence of stroke with Ao Dissection

87% had moderate stroke severity vs. only 5% with mild stroke92% had some neurological deficits at discharge10.5% died in hospital, 60% needed rehabilitationMortality at 30 days: 23.7%

=> Worked with DI & NeuroRads to change local protocol so that CTA H&N done at time of diagnosis of Aortic Dissection while patient still on CT table

Ericka Teleg, Bijoy Menon, Alex Gregory et al…

ASSIST : Aortic diSSection & stroke Imaging Study – Ericka Teleg et al.

Prospective study to identify mechanism of stroke in Aortic Dissection

Pre-operative neurovascular imaging in patients with ATAAD

Early post-operative imaging assessment of neuro-vasculature and physiology

Early detailed clinical neurological assessment of all patients with Aortic Dissection

Plan a prospective study nationally to address pending questions using a larger sample size


I. Why/When do Aortas Dissect? => TITAN SvSII. Stroke Complication of Aortic Dissection =>ASSISTIII. What type of operation should be performed ?

Problem:

Long term survival is compromised

Distal aortic problems may be higher than we appreciate

Immediate op mortality is high:

IRAD (2005) 25%GERAADA(2014) 17%US Registry Data (Oct.2014) 21%CTAC 18%

Question:Can extended distal aortic repair decrease long term mortality?

Can increase complexity be accomplished without increased periop morbidity?

Goal: Decrease both long term and short term mortality

HEMIARCH EXTENDED ARCH

P value

n 67 28

In-hospitalmortality

12% 7% 0.73

New post-op stroke 15% 21% 0.52

Permanent neurologic deficit

12% 7% 0.73

Calgary Experience 2011- 2015In submission

HEMIARCH EXTENDED ARCH

P value

Early prox FL obliteration 9% 58% <0.01

Mean prox aortic growth rate (mm/yr)

2.66 0.66 0.095

Redo thoracotomy 18% 0%

Calgary Experience 2011- 2015In submission

HEADSTART: Hemiarch vs Extended arch in Aortic Dissection - a SystemaTic Analysis by Randomized Trial

Vamshi Kotha, Francois Dagenais, Eric Herget, Alex Gregory, Akash Fichadiya, Jehangir Appoo

Multicenter trial randomizing patients to standard Hemiarch vs. Extended arch operation at time of acute Type A Dissection

Protocol, Ethics close to completionInterest from 7 US & 5 Canadian centersFundraising stage

For Trainees:

Lots of new Programs Developed

My definition of a “Program” in Medicine:

1. Clinical work – new therapies to take care of patients2. Education

i. Colleaguesii. Traineesiii. Referring physiciansiv. Patients

3. Innovation4. Research/Evolve

i. Start locallyii. Collaborate nationally/internationally

Summary

Aortic Aneurysms are Silent Killershigh index of suspicion required to track & identifyrisk of rupture/dissection process in evolution

Summary

When Silent Killer presents, it is a Great Masquerader

Variable presentation & acuity

Misdiagnosis is not unusual

60/100 Rule

Summary

Novel therapies evolving

Extended arch & Endovascular therapies

Summary

Type B Aortic Dissection

topic for another time

It’s now clear to me that my purpose, your purpose and the purpose of everything else is to evolve and to contribute to evolution in some small way

Ray Dalio, Principles 2017

“Experience is what you got when you didn’t get what you wanted.”— Howard Marks

Evolution of Understanding and Therapy

Acknowledgements

“Life if too short to do business with people you don’t like”- Charlie Munger

www.aorta.ca

Aortic Program clinicalteachingresearchinnovation

Documents

Type A Ao Dissection – Evolution in understanding