1. Alcoholic Cardiomyopathy (a.k.a. ACM)
By,
Atman Shah

2. Introduction Epidemiology-incidence Definition Etiology & Pathogenesis
Symptoms
Diagnosis
Research paper: ACE enzyme gene polymorphism may lead to cardiomyopathy

3. Epidemiology
In the U.S., in both sexes and all races, long-term heavy alcohol consumption is the leading cause of dilated cardiomyopathy or ACM.
15% -- 40% of all cases of dilated cardiomyopathy in western countries are related to alcohol abuse.
In all races, deaths due to ACM are greater in males than females.

4. Definition:
Alcoholic cardiomyopathy is a type of nonischemic, dilated cardiomyopathy caused due to long term heavy alcohol consumption.

5. The main pumping chambers of the heart are dilated and contract poorly
The main pumping chambers of the heart are dilated and contract poorly. This results in a low output of the blood from the heart and features of heart failure are seen.

6. Possible Causes of ACM:
Excessive consumption of alcohol
Occasionally occurs as a complication of pregnancy and childbirth
Various infections, mostly viral, lead to an inflammation of the heart muscle (myocarditis)
Toxins (such as cobalt, once used in beers)
Heredity- (current research indicates)

7. Pathogenesis:
Long term alcohol consumption produces a number of histological and cellular changes in:
Myocytes
Intracellular organelles
Contractile proteins
Calcium homeostasis

8. Myocyte Loss Cell death can result from necrosis or apoptosis.
Ethanol-induced apoptosis is believed to play a role in ACM.

9. Intracellular Organelle Dysfunction
Change in mitochodrial structure (degeneration of the cristae)
Changes leading to decreased calcium uptake by mitochodria are thought to effect the cardiac muscle fibers
Decreased sarcoplasmic reticulum calcium binding and uptake

10. Contractile Proteins
Changes in structure and/or function of contractile proteins can affect cross-bridge cycling and force production
Decrease in the number of beta-myosin heavy changes
Leads to a decrease in ATPase activity
Leading to decrease in rate of contraction

11. Calcium Homeostasis
In later stages of ACM, contractile function is depressed due to alteration in the calcium homeostasis
Myocardial contractility is thought to be altered by:
Calcium influx into cell
Myofibrillar sensitivity to calcium

12. Signs & Symptoms Ankle, feet, and leg swelling (Edema)
Pronounced neck veins
Anorexia
Decreased urine output (oliguria)
Pulse may feel irregular or rapid

13. Signs & Symptoms
Shortness of breath, especially with activity (dyspnea)
Breathing difficulty, lying down
Fatigue, weakness, faintness
Decreased alertness or concentration
Cough containing mucus, or pink, frothy material coughed up

14. Diagnosis
Examination and tests are directed at diagnosing and evaluating heart failure.
Heart failure may show on these tests:
Echocardiogram
Chest X-ray
Chest CT
Cardiac catheterization
ECG
Myocardial biopsy

15. Research Paper Purpose of the study
To show that individuals having an Angiotensin-converting enzyme (ACE) gene polymorphism are more vulnerable to developing alcoholic cardiomyopathy (ACM)
Ann Intern Med. 2002;137:

16. Method
2 groups of men were selected who were admitted to a hospital in Barcelona, Spain.
The men were younger than 65 years of age and had chronic alcoholism.
All the men in group 1 showed symptoms of heart failure (LVEF lower than 50%).
And the men in group 2 did not show signs of heart failure (LVEF higher than 60%).

17. Method (Cont.) Other similarities between groups:
Both had a mean age of ~52
Percentage of men who smoked more than 20 cigarettes/day was ~63%
Mean duration of alcoholism ~26 years

18. Method (Cont.) ACE GENE POLYMORPHISMS:
DNA was extracted from peripheral blood leukocytes
The ACE I/D genotype was determined by the polymerase chain reaction (PCR)

19. Method (Cont.) The primer pair in the PCR produced:
I genotype-480 base pairs
D genotype-194 base pairs
I/D heterozygous for insertion (I) and deletion (D)

20. Results
All participants were similar in age and reported similar amounts of alcohol and tobacco consumption.
Patients in both groups were treated according to the (NYHA) New York Health Association functional class.

21. Results (Cont.)-Distribution of ACE genotypes in both groups
Variable
Group 1: with cardiomyopathy
Group 2:normal cardiac function
Mean LVEF
33.6 %
64.7%
ACE Genotypes II
10%
33% ID
59% DD
57% 7%

22. Results (Cont.)
89% of patients with the DD genotype had cardiomyopathy
34% of participants who carried an I allele (II or ID) had impaired cardiac function.
Only 7% of participants in group 2 had the DD genotype

23. Conclusion
Vulnerability to cardiomyopathy among chronic alcohol abusers is partially genetic.
It is related to the PRESENCE OF THE ACE DD genotype.

24. Conclusion
A single copy of the I allele is enough to eliminate the 16.4-fold excess risk associated with the DD genotype.
The findings demonstrate genetic susceptibility to alcohol-induced myocardial damage.

25. Questions???
Questions???
The End
Questions???