Author: Alex Thompson

Alcoholic Cardiomyopathy: Overview, Cardiac Effects of Alcohol, Quantity of Alcohol Intake in Cardiac Disease

Measuring blood alcohol concentration in an acute intoxication gives baseline information but does not permit deductions to chronic misuse. Markers for chronic alcohol consumption rely on liver enzymes such as gamma-glutamyltransferase (GGT) 119, glutamic oxalacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT). Elevations of the transaminases (GOT, GPT), especially a ratio of GOT/GPT higher than 2 might be indicative of alcoholic liver disease instead of liver disease from other etiologies 120, 121. An excellent marker is carbohydrate deficient transferrin (CDT), which best detects chronic alcohol consumption alone 122, 123 or in combination with the other markers such as GGT 8, 124. Markers such as ethyl sulphate, phosphatidyl ethanol, and fatty acid ethyl esters are not routinely done.

Hypertension due to alcohol may be a confounding comorbidity in that it may contribute to LV dysfunction; therefore, LV dysfunction due to hypertension must be differentiated from pure AC. The subject with excessive alcohol consumption, after more than 10 years of high ethanol consumption, usually develops subclinical heart functional changes before symptom appearance or signs of heart failure 55,56. These may be detected with echosonography in around one-third of high-dose chronic consumers with preliminary evidence of subclinical left-ventricle (LV) diastolic dysfunction before progression to subclinical LV systolic dysfunction 57.

Abstinence is the preferred goal, although controlled drinking may still improve cardiac function. New strategies are addressed to decrease myocyte hypertrophy and interstitial fibrosis and try to improve myocyte regeneration, minimizing ethanol-related cardiac damage. Cardiac transplantation is the final measure in end-stage ACM but is limited to those subjects able to achieve abstinence. The cardiovascular system is, after the liver and gastrointestinal system, the second most affected system by global ethanol toxicity 1,33,34.

The final damage is an equilibrium between the intensity of damaging effects and the possibility of defense, plasticity, regeneration, and adaptation for every specific organ 29,30,31. Thus, alcohol-dilated cardiomyopathy (ACM) is the result of dosage and individual predisposition 32. We reviewed the effects of ethanol on the cardiovascular system in 1996 15, including aspects of inflammation 16, rhythm disturbances 17, and hypertension 18. In 2001 we updated the data on the ambivalent relationship between alcohol and the heart 19 and in 2008 added new evidence on a larger cohort of patients with different forms of cardiomyopathy and increased alcohol intake from the German competence network on heart failure 20.

Arrhythmias and stroke

The effect of a low dose of alcohol consumption on the cardiovascular system has been also extensively evaluated with evidence of a dual effect, beneficial for coronary artery disease at low doses 44 but reversing to a damaging effect at moderate to high doses 19. Although there is beneficial potential in some patients, the coexistence of increased risk of cancer, neurological brain damage, and the high risk of ethanol addiction makes it necessary to discourage this low-dose consumption in the general population 19,41,45. Specific caution should be recommended regarding children or adolescents 4 and women 46, who are more susceptible to the damaging effects of ethanol at the same doses of consumption as men.

Laboratory Studies

Although up to 81% of ACM patients received an ACEI, none received beta-blockers and the use of spironolactone was not specified, although it was probably quite low. Also, current common cardiac therapies such as ICD and CRT devices were not used because of the period when the study was conducted. After a follow-up period of 47 mo, a significantly higher survival rate was observed among patients with DCM compared to patients with ACM.

TREATMENT

In fact, mitochondrial structural changes have been described in chronic alcohol consumers, with swollen megamitochondria and the distortion of inner cristae 107,108. Functionally high ethanol produces disruptions in the myocyte oxidative pattern and decreases in Complex I, II, and IV of the mitochondrial respiratory chain 100,109,110. As a reflection of this metabolic derangement, cytoplasmic lipid droplets and glycogen deposits appear. This ethanol misuse at high consumption rates causes a variety of health problems, ethanol being the sixth most relevant factor of global burden of disease and responsible for 5.3% of all deaths 5. Despite this clear epidemiological evidence of ethanol’s unsafe consumption and increased health risk, results of consumption policies are not effective enough.

4. The dose-Related Effect of Ethanol and Beverage Types on the Heart

1. In the second study, Gavazzi led a multicentre study in which, from 1986 to 1995, 79 patients with ACM and 259 patients with DCM were recruited10.
2. Chronic ethanol misuse clearly depresses protein synthesis and degradation, involving both structural and non-structural heart proteins 104,128.
3. For tens of years, the literature has documented many clinical cases or small series of patients who have undergone a full recovery of ejection fraction and a good clinical evolution after a period of complete alcoholic abstinence.
4. Excessive intake of alcohol may result in increased systemic blood pressure in a dose-response relationship, and this may contribute to chronic myocardial dysfunction.
5. Cardiac remodeling is a global process that myocardium establishes as a result of different aggressions 31,132.

Conversely, those whose consumption remained in excess of 80 g/d showed an average decline of 3.8% in their ejection fraction. Other findings may include cool extremities with decreased pulses and generalized cachexia, muscle atrophy, and weakness due to chronic heart failure and/or the direct effect of chronic alcohol consumption. Physical examination findings in alcoholic cardiomyopathy (AC) are not unique compared with findings in dilated cardiomyopathy from other causes. Elevated systemic blood pressure may reflect excessive intake of alcohol, but not AC per se. Alcoholic cardiomyopathy (ACM) is a disease in which the long-term consumption of alcohol leads to heart failure.1 ACM is a type of dilated cardiomyopathy.

Prompt treatment can help prevent the disease from getting worse and developing into a more serious condition, such as congestive heart failure (CHF). Before recognizing that ethanol itself is the etiological factor of ACM, different theories and hypotheses emerged 1,66. It was suspected that malnutrition, frequently related to chronic alcohol misuse, was the origin of ACM 6,67.

New strategies to improve the natural course of ACM have been proposed as promising agents in this field 112,147. Since ethanol has multiple cell targets with different pathological mechanisms implicated, those different strategies to directly target alcohol-induced heart damage are only partially effective and can only be used as support medication in a multidisciplinary approach 112. They try to control myocardial remodeling to avoid the progression of myocyte hypertrophy 39,148 or fibrosis 149 and ventricle dysfunction and dilatation, as well as to increase the degree of myocyte regeneration 150. Recently, new cardiomyokines (FGF21, Metrnl) and several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCKs inhibitors) have been described as being able to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms 112,119. They aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis, and persistent apoptosis. Pharmacological restoration of autophagic reflux by inhibition of soluble epoxide hydrolase has been described to ameliorate chronic ethanol-induced cardiac fibrosis in an in vivo swine model 151.

Despite the key clinical importance of alcohol as a cause of DCM, relatively few studies have investigated the effects of alcohol on the heart and the clinical characteristics of DCM caused by excessive alcohol consumption (known as alcoholic cardiomyopathy). Daily consumption of low to moderate amounts of alcohol has beneficial effects on cardiovascular health among both ischemic and non-ischemic patients1-3. In contrast, chronic and excessive alcohol consumption could lead to progressive cardiac dysfunction and heart failure (HF)3. The signs and symptoms of alcoholic cardiomyopathy (ACM) can vary depending on the severity of the condition.6 In the early stages, people with ACM may not experience any symptoms. However, as the condition progresses, they may experience symptoms such as fatigue, shortness of breath, palpitations, and swelling of the legs and ankles.6 They may also experience chest pain, dizziness, and fainting.