Connections Between Hepatic and Cardiovascular Disease,Diagnostic criteria for cirrhotic cardiomyopathy 2005 and 2019.New CCM criteria based on contemporary CV imaging parameters LV Systolic Function. LV Diastolic Dysfunction.cardiac evaluation algorithm for liver transplant candidates

1. Magdy El-Masry
Prof. of Cardiology
Tanta University

2. 1.Introduction
2.Definition
3.Epidemiology
4.Pathophysiology
5.Clinical effects
6.Diagnostic criteria
7.Treatment
How to see the big picture is not as easy as you'd think.
Today’s talk will include:

3. Introduction

4. In their clinical practice, physicians can face heart diseases (chronic or acute
heart failure) affecting the liver and liver diseases (liver cirrhosis, NAFLD/NASH )
affecting the heart. Systemic diseases (e.g., alcohol abuse, drugs, inflammation,
autoimmunity, infections) can also affect both heart and liver.
Cardiologist and Hepatologist Crosstalk

5. Interactions between the heart and the liver
The heart as a cause of liver disease*
The liver as a cause of heart disease**
Conditions affecting both the
liver and the heart***
*Chronic or acute heart failure→ congestive hepatopathy (cardiac cirrhosis)
and ischemic hepatopathy (acute cardiogenic liver injury)
**Liver cirrhosis→ cirrhotic cardiomyopathy
***Alcoholism→alcoholic cardiomyopathy & alcoholic liver cirrhosis

6. The scope of the presentation
How does the heart react when the liver is diseased?
The heart matters when the liver shatters !
Cirrhotic Cardiomyopathy

7. Arterial vasodilatation leads to redistribution of the blood volume with development of
central hypovolaemia, hyperdynamic circulation, and cardiac dysfunction.
AVP: vasopressin, CBV: central blood volume, ET: endothelin, RAAS: renin–angiotensin–aldosterone
system, SNS: sympathetic nervous system, SVR: systemic vascular resistance.
Role of hepatocellular dysfunction and portosystemic shunting in the
development of extrahepatic vasodilatation in cirrhosis.

8. Definition

9. Working definition of cirrhotic cardiomyopathy
as defined by the expert consensus committee at the World Congress of
Gastroenterology in Montreal, Canada in 2005.
Cirrhotic patient with
Abnormal
contractile
response to
stress
Diastolic
dysfunction
Absence of
another
clinically
significant
cardiac disease

10. Epidemiology

11. CCM is a condition easily tolerated, remaining asymptomatic for months to years because of the near-
normal cardiac function at rest, manifesting only under conditions of physical or pharmacological
stress.
So , the diagnosis of CCM is difficult →Therefore, the exact prevalence cannot be defined
There is only
very limited data
about
epidemiology, as
well as actual
prevalence of this
condition at
present time. No Data

12. Pathophysiology

13. Liver cirrhosis and
portal hypertension
Splanchnic vasodilatation
Central hypovolemia
Hyperdynamic circulation
Cirrhotic cardiomyopathy
The sequence in development of cirrhotic
cardiomyopathy in liver cirrhosis.

14. The figure reviews the most important cellular and molecular pathogenic
mechanisms involved in cirrhotic cardiomyopathy
European Heart Journal(2013)34,2804
Down-regulation
Up-regulation
Increased
inhibitory effects
of cardio
depressant
substances
such as
haemoxygenase
(HO), carbon
monoxide (CO),
nitric oxide
synthase (NOS)-
induced nitric
oxide (NO)
release, and
tumour necrosis
factor-a (TNF-a).
Altered function
Inhibition
Increased fluidity
Alterations
Decreased content of G-protein
Alterations

15. Clinical effects

16. Cirrhosis is a progressive liver disease characterized by diffuse fibrosis, which evolution is
divided in compensated and decompensated cirrhosis, where its development shows variceal
hemorrhage, jaundice, ascites and hepatic encephalopathy.
 As the disease develops, reactive oxygen species increase as well as inflammation.
 A second insult is a trigger for acute-on-chronic liver failure (ACLF) to occur, leading the
patient to multi-organ failure or even death if he does not receive a liver transplant.
Upwards arrows indicated ‘an increase’. ROS, reactive oxygen species.Clin Mol Hepatol Vol26 No1 Jan 2020
The clinical course of cirrhosis.
Cirrhotic cardiomyopathy is independent of the etiology
of the liver cirrhosis but related to severity and survival.

17. Compensated
cirrhosis
Decompensated
cirrhosis
Liver transplant
or death
 Vasodilatation
 Hyper- dynamic state
 ↑ Cardiac output
 ↓Cardiac output
The clinical course of cirrhosis.
 Clinical Heart failure
 Normal/Increased LVEF
 LV diastolic dysfunction
 Clinically Silent
(Oligo symptomatic
or even asymptomatic)
 Decreased LVEF
 LV diastolic dysfunction
Furthermore,
cirrhotic
cardiomyopathy is
an important cause
of perioperative
morbidity and
mortality for liver
transplant recipients

18. Diagnostic
criteria

19. CCM : a diagnostic challenge
Lack of universally accepted diagnostic criteria.
CCM remains an ill-defined entity among cardiologists

20. Diagnostic criteria for cirrhotic cardiomyopathy ,
as defined by the expert consensus committee at the World Congress of
Gastroenterology in Montreal, Canada in 2005.

21. Diagnostic criteria for cirrhotic cardiomyopathy , as defined by the expert consensus
committee at the World Congress of Gastroenterology in Montreal, Canada in 2005.
2005

22. The Cirrhotic Cardiomyopathy Consortium
is a multidisciplinary
( hepatology , anesthesia , and cardiology )
international group whose focus is to improve the
understanding of cirrhotic cardiomyopathy, its
management and outcomes.
2019

23. The Cirrhotic Cardiomyopathy Consortium
CCM in the
spectrum of HF
New CCM
criteria based on
contemporary
CV imaging
parameters
Potential additional
markers of CCM
The group met in October 2018 at the Mayo Clinic (Minnesota) and
subsequently worked together to develop this document (2019)

24. CCM in the spectrum of HF

25. Symptomatic HF
Cirrhotic Cardiomyopathy in the Spectrum of HF
Based on this classification,
patients with ESLD or
metabolic syndrome and its
components without
structural heart disease might
be classified as stage A,
whereas those considered
to have CCM on the basis
of LV remodeling and/or
systolic or diastolic
dysfunction in the absence
of clinical HF symptoms
might be classified as
stage B HF.
However, identification
of stage C HF due to
CCM in ESLD may be
complicated by the fact
that symptoms of HF
may be masked or
confounded by those of
advanced cirrhosis,
which can also limit
functional capacity.
Asymptomatic HF
The 4 Stages of Heart Failure (AHA/ACC)

26. Stage A
HF.
Stage B
HF.
Symptomatic
HF.
Majority of cirrhotic patients have LVDD
 LVDD is an early manifestation f cardiac dysfunction in patients with liver cirrhosis.
 LVDD predicts poor prognosis in patients with decompensated liver cirrhosis
ESLD LVDD

27. New CCM criteria based
on contemporary CV imaging parameters
• LV Systolic Function.
• LV Diastolic Dysfunction.

28. Redefining CCM Criteria :
Alignment with Contemporary Metrics for Assessing Cardiac Dysfunction
 LV Systolic Function : LVEF / GLS
Global longitudinal strain (GLS) can identify myocardial
contractile dysfunction in those with preserved LVEF
Affected by LV
loading conditions
In adults, GLS < -16% is abnormal,
GLS > -18% is normal,
and GLS -16% to -18% is borderline.
Liver cirrhosis
“ESLD”
The vasodilatory
state
results in
decreased
afterload
and
consequently
normal or even
increased LVEF
Oligo symptomatic
or even asymptomatic
Diminished LVEF or diminished GLS in the absence of known cardiac disease (e.g., other
cardiomyopathies such as ischemic, rheumatic, etc.) should be considered diagnostic of CCM

29.  LV Diastolic Dysfunction.
4 Criteria
3 Criteria
Application of these modern criteria should supersede the 2005 Montreal CCM criteria, which rely on parameters that
are impacted both by loading conditions and by heart rate, which can vary significantly in patients with ESLD

30. Evaluation of diastolic function in patients with end-stage liver disease
*In this algorithm, only medial annulus velocity is recommended. After applying the modified criteria, filling
pressure is first assessed, then diastolic function is graded based on E/A ratio.
**For values of PV, IVRT, and strain assessment in patients with indeterminate diastolic function, refer to next Fig.
Advanced diastolic dysfunction (grade 2 or 3) in patients with ESLD in the absence of known heart disease is
diagnostic of cirrhotic cardiomyopathy. It is critical to exclude coexisting comorbidities : DM,HTN,CAD
Abbreviations: LA, left atrium; PV, pulmonary vein; IVRT, isovolumetric relaxation time.

31. Additional assessment to reclassify patients with indeterminate diastolic function
based on previous Fig. into normal versus different grades of diastolic dysfunction.
Pictured are still frames of pulmonary vein pressures, values of isovolumetric relaxation
(IVRT), Left atrial systolic strain (LAS), and LV global longitudinal strain (LVS) for normal
and different stages of diastolic function.

32. Echocardiographic evaluation of cirrhotic cardiomyopathy.
Grade 3 of LVDD.
LA dilatation.
high LVFP
LV sys dysf

33. Potential additional markers of CCM

34. Methods Markers
Echo There are suggestions to improve diagnostic criteria
considering dysfunction of right ventricle , biventricular
diastolic dysfunction at rest, large left and right atria,
higher systolic pulmonary arterial pressure and left
ventricular mass and evaluate systolic function
assessment using tissue strain imaging .
Dobutamine Stress
Echo
Abnormal or blunted contractile reserve
Cardiopulmonary
Exercise Testing
(CPET)
Exercise limitation and low pVO₂ (peak oxygen
consumption)
Cardiac Biomarkers Elevated levels of BNP/NT-proBNP (+imaging-based
markers)
ECG :of limited value Prolonged QT interval (>440 milliseconds)
CMRI More sensitive than DSE at detecting subclinical LV
dysfunction in CCM
Potential Additional Markers of CCM

35. Treatment

36. CCM : a therapeutic challenge
Specific therapies for cirrhotic cardiomyopathy
are lacking .

37. There’s
still
a gap of
knowledge
regarding
management
of cirrhotic
cardiomyopathy

38. AHA/ACC and ESC guidelines→no specific strategies to manage cirrhotic
cardiomyopathy→ follow the HF guidelines for the treatment of cirrhotics affected by
cardiomyopathy, with consideration for special conditions in patients with markedly
reduced SVR
At present there are no therapeutic guidelines with regards to
the management of cirrhotic cardiomyopathy

39. Treatment Optimization in Heart Failure
Cardiologists :
Taking responsibility in optimizing patient
care in heart failure
Placement of a transjugular intrahepatic
portosystemic shunt (TIPS) is a minimally invasive
procedure for the treatment of the major
complications of portal hypertension
Liver transplantation (LT) is thought to be
the only treatment for CCM.

40. Volume 13, 2019 - Issue 5
Liver transplantation
ameliorates most of the
abnormalities seen in
cirrhotic
cardiomyopathy, but no
specific treatment can
yet be recommended.
The outcome of invasive
procedures and liver
transplantation is influenced
by the presence of cardiac
dysfunction.
Therefore, a cautious cardiac
evaluation should be included in the
patient evaluation prior to liver
transplantation.
Expert commentary

41. Patients Cirrhotics without cardiomyopathy Cirrhotics with cardiomyopathy
After TIPS • Clinical findings:
1. Heart failure (rare, and mild)
2. Ascites (rare)
3. Liver and renal failure (rare)
4. Death (extremely rare)
• Clinical findings:
1. Heart failure (more frequent)
2. Ascites (more frequent)
3. Liver and renal failure (more frequent)
4. Death (more frequent)
5. Further prolongation QT interval
After liver
transplant
• Clinical findings:
1. Normalization of portal-hepatic
hemodynamics
2. Amelioration of cardiac
autonomic function after 12
postoperative months
• ECG:
Normalizaton of QT prolungation in
50 % of subjects within 12 months
• Clinical findings:
1. Normalization of portal-hepatic
hemodynamics
2. Early myocardial depression
3. Early drop in cardiac index and oxygen
delivery
4. Normalization of cardiac structure and
function by 9–12 postoperative months
• ECG:
Normalization of QT prolongation in 50 % of
subjects within 12 months
Clinical and diagnostic comparison between cirrhotics with and without
cardiomyopathy after TIPS & after liver transplant
Kathirvel Subramaniam Tetsuro Sakai ,Editors, 2017

42. Cardiologists may be asked to help
hepatologists and surgeons in the diagnosis and treatment
of this syndrome before and after liver transplantation.
 Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure
after TIPS and liver transplantation (these interventions generate a sudden increase in the preload
and, consequently, a rise in LVFP → acute pulmonary edema)
CVD is a common cause of morbidity and
mortality after liver transplantation.

43. Published in Current opinion in organ transplantation 2019
Risk factors and prevention of cardiovascular disease in liver transplant recipients

44. Liver transplant waiting list
E.M. Zardi et al. / Journal of Cardiology 67 (2016) 125–130
Consider therapy with :
 Furosemide
 Spironolactone
 B-blockers
 ACEI/ARB
 Optimize and monitor volume status
and hemodynamics
 Monitor ECG

45. Loop-diuretics →to treat hypervolemia
Aldosterone antagonists →to reduce the frequency of
hospitalization and mortality & to reduce the hepatic-venous
pressure(HVP) gradient, the LV wall thickness, and the LVEDV
Beta-blockers → to reduce the prolonged QT interval & to reduce
the hyperdynamic load
Carvedilol is a potent agent to reduce portal pressure
( Low dose : 12.5 mg.)
ACE-Is /ARBs (and vasodilators in general) →are not useful in
conditions of severe systemic vasodilation such as those observed
in cirrhotics with cardiomyopathy
( They should be used in the early phases of cirrhosis because of the
risk of hypotension and hepatic-renal syndrome in later phases )
However, there are still some issues that deserve to be addressed.

46. Take home figure

47. Redefining Criteria for CCM
(Manhal Izzy et al , Hepatology, VOL. 0, NO. 0, 2019 on behalf of The Cirrhotic Cardiomyopathy Consortium)
b. Proposed criteria by the Cirrhotic Cardiomyopathy Consortium (2019)
Systolic Dysfunction Advanced Diastolic Dysfunction† Areas for Future Research Which
Require Further Validation
Any of the following
•LV ejection fraction ≤50%
•Absolute* GLS <18% or
>22%
≥3 of the following
•Septal e′ velocity
<7 cm/second
•E/e′ ratio ≥15
•LAVI >34 mL/m2
•TR velocity >
2.8 m/second‡
•Abnormal chronotropic
or inotropic response§
•Electrocardiographic
changes
•Electromechanical
uncoupling
•Myocardial mass change
•Serum biomarkers
•Chamber enlargement
•CMRI||
* GLS is reported as a negative value in echocardiography reports. Changes in GLS should be described as changes in the
absolute value.† Refer to Fig. for echocardiographic changes in early diastolic dysfunction. They were not included in this
table given their decreased specificity as they can occur due to aging.‡ In the absence of evidence of primary pulmonary
hypertension or portopulmonary hypertension.§ Examples include absence of or blunted contractile or diastolic reserve
on exercise stress testing, dobutamine stress testing, or at rest on CMRI.|| Myocardial extracellular volume as a
surrogate for myocardial fibrosis can be assessed using this modality.
Abbreviation: e′, early diastolic mitral annular velocity.

48. Proposed cardiac evaluation algorithm for liver transplant candidates
Current Transplantation Reports (2019) 6:328–337