In most patients, exercise or pharmacologic stress testing with echocardiographic or nuclear imaging is an appropriate screening test for heart failure due to coronary artery disease. In this respect, a higher prevalence of excessive alcohol consumption has been reported among individuals diagnosed with DCM than in the general population8. Since those initial descriptions, reports on several isolated cases or in small series of patients with HF due to DCM and high alcohol intake have been published15-17.
Fatty acid ethyl esters: Potentially toxic products of myocardial ethanol metabolism
Dilated cardiomyopathy secondary to alcohol use does not have a pre-defined exposure time. Daily alcohol consumption of 80 g per day or more for more than 5 years significantly increases the risk, however not all chronic alcohol users will develop Alcohol-induced cardiomyopathy. It’s important to note that alcoholic cardiomyopathy may not cause any symptoms until the disease is more advanced. While the overall admissions among patients with AC decreased over time, the proportion of patients with high‐risk characteristics such as smoking, depression, and drug abuse increased. Patients aged 45 and older were largely affected and cardiovascular etiologies predominated among causes for admission. Although the most common cause of heart failure is coronary artery disease, ischemic cardiomyopathy is unlikely in the absence of a clear history of prior ischemic events or angina and in the absence of Q waves on the ECG strip.
Comparison of long-term outcome of alcoholic and idiopathic dilated cardiomyopathy
Alcoholic cardiomyopathy (ACM) is a cardiac disease caused by chronic alcohol consumption. The major risk factor for developing ACM is chronic alcohol use; however, there is no cutoff value for the amount of alcohol consumption that would lead to the development of ACM. This activity describes the pathophysiology of ACM, its causes, presentation and the role of the interprofessional team in its management.ACM is characterized by increased left ventricular mass, dilatation of the left ventricle, and heart failure (both systolic and diastolic). This activity examines when this condition should be considered on differential diagnosis. This activity highlights the role of the interprofessional team in caring for patients with this condition. The majority of the echocardiographic studies performed on asymptomatic alcoholics found only mild changes in their hearts with no clear impairment of the systolic function.
1. The Natural Course of ACM
On physical examination, patients present with non-specific signs of congestive heart failure such as anorexia, generalized cachexia, muscular atrophy, weakness, peripheral edema, third spacing, hepatomegaly, and jugular venous distention. S3 gallop sound along with apical pansystolic murmur due to mitral regurgitation is often heard. Acute can be defined as large volume acute consumption of alcohol promotes myocardial inflammation leading to increased troponin concentration in serum, tachyarrhythmias including atrial fibrillation and rarely ventricular fibrillation.
- These arrhythmias are usually related to episodes of binge drinking 43,62 and are more frequent in established ACM than in subjects with normal cardiac function 52.
- Finally, we analyzed and presented the synthesized literature, along with relevant findings and conclusions from the included studies, in a coherent manner.
- Later and progressively in the course of the disease, around 20% of women and 25% of men with excessive alcohol consumption develop exertion dyspnea and orthopnea, leading to episodes of left-ventricle heart failure 39,46,59.
- Thus, Nicolás et al73 studied the evolution of the ejection fraction in 55 patients with ACM according to their degree of withdrawal.
- Consumption of other drugs such as cocaine or tobacco may interact with ethanol and potentiate the final ethanol-related cardiac damage 22,72.
- Heart remodeling is an adaptive mechanism, susceptible to being modified in ACM by the use of cardiomyokines (FGF21, Metrnl) and growth factors (IGF-1, Myostatin) 112,119.
Clinical Features and Diagnosis of Alcoholic Cardiomyopathy
- Findings from gross examination include an enlarged heart with 4-chamber dilatation and overall increased cardiac mass.
- Finally, only Urbano-Márquez et al24 found a clear decrease in the ejection fraction, in a cohort of 52 alcoholics, which was directly proportional to the accumulated alcohol intake throughout the patients’ lives.
- One of the relevant facts in ACM is the existence of a clear gender difference, women being more susceptible to the toxic effects of alcohol than men at the same level of lifetime ethanol consumption 93,94.
- Most common age population for ACM is males from age with significant history of alcohol use for more than 10 years.
The authors examined the prevalence of cardiomegaly by means of chest x-rays and related it to alcohol consumption among a consecutive series of Japanese males of working age. They found that 2 of the 6 individuals (33%) whose alcohol consumption exceeded 125 mL/d had cardiomegaly. In contrast, an enlarged heart was found in only 1 of 25 subjects with moderate consumption (4%), in 6 of 105 very mild consumers (5.7%), and in 4.5% of non-drinking individuals. However, cardiac apoptosis may also develop independently of the mitochondrial pathway 115 through the extrinsic pathway, which involves cell surface death receptors 116. In addition to inducing apoptosis, ethanol inhibits the effect of anti-apoptotic molecules such as BCL-2 101. Ethanol-induced myocyte apoptosis may be regulated by growth factors 117,118 and cardiomyokines 119.
Until the second part of the 20th century, there was no scientific evidence on alcoholic cardiomyopathy symptoms the direct and dose-dependent effect of ethanol on the heart as cause of ACM 6,38. However, there is a clear personal susceptibility of this effect that creates a wide variability range and supposes significant inter-individual differences 50,66. In fact, ACM is considered to be the result of dosage and individual predisposition 32. Another curious hypothesis from Germany suspected that some ethanol additives, such as anti-foam beer products with arsenic or cobalt content, produced cardiac toxicity and development of ACM 71. Therefore, it is evident that ACM may develop with normal serum thiamine and electrolyte levels 38,66. Consumption of other drugs such as cocaine or tobacco may interact with ethanol and potentiate the final ethanol-related cardiac damage 22,72.
Human Disease-Associated Genetic Variation Impacts Large Intergenic Non-Coding RNA Expression
This is because the ethanol molecule has a small size and is highly reactive, with many cell targets. In addition, ethanol has a widespread diffusion because of the potential for distribution though biological membranes, achieving targets not only in the membrane receptors and channels but also in endocellular particles and at the same nuclear compartment 29,99,100. This induces a variety of effects, since more than 14 different sites in the myocyte can be affected by ethanol 19,98. Specifically, ethanol disturbs the ryanodine Ca2+ release, the sarcomere Ca2+sensitivity 102,103, the excitation–contraction coupling and myofibrillary structure, and protein expression, decreasing heart contraction 86.
Epidemiological studies
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. Evidence of altered bioenergetics or mitochondrial dysfunction has been observed in various investigations of ethanol effect on the heart. Disrupted bioenergetics and oxidative phosphorylation indices and a change in the ultrastructure of the mitochondria may be the cause of such dysfunctions. This can be understood through clinical observations that highlight the mitochondria as the main target of oxidative damage. When reactive oxygen species (ROS) are produced in excessive manners due to heavy alcohol consumption, it damages mitochondrial DNA, resulting in mitochondrial injuries.
- The effect measure for each outcome was conducted using the mean differences effect measure, where the outcomes were assessed in identical units across the various literature reviews used in the study.
- Results from serum chemistry evaluations have not been shown to be useful for distinguishing patients with alcoholic cardiomyopathy (AC) from those with other forms of dilated cardiomyopathy (DC).
- Out of end-stage cases, the majority of subjects affected by ACM who achieve complete ethanol abstinence functionally improve 33,82,135.
- They found that 2 of the 6 individuals (33%) whose alcohol consumption exceeded 125 mL/d had cardiomegaly.
- It is estimated, approximately 21-36% of all non-ischemic cardiomyopathies are attributed to alcohol.
Demakis et al70 in 1974 divided a cohort of 57 ACM patients according to the evolution of their symptoms during follow-up. The sub-group of patients in whom symptoms improved was made up of a larger proportion of non-drinkers (73%), compared to 25% in the group who did not improve, or 17% in the group whose condition worsened. However, a possible confusion factor was identified because the group with clinical improvement also exhibited a shorter evolution of the symptoms and the disease. The first paper to assess the natural history and long-term prognosis of ACM was published by McDonald et al69 in 1971. He recruited 48 patients admitted to hospital with cardiomegaly without a clear aetiology and severe alcoholism.
- However, looking into a big population database might be a good way to study such a difficult to diagnose disease process.
- Post-mortem biopsies from the hearts of human alcoholics revealed that the myocardial mitochondria is enlarged and damaged 1-9.
- Since myocardium requires a high energy supply to maintain persistent sarcomere contractions, it was supposed that alcohol could exert its damaging effect on the mitochondrial energy supply system, with the disruption of oxidative control mechanisms 26,100.
Findings from gross examination include an enlarged heart with 4-chamber dilatation and overall increased cardiac mass. Histologically, light microscopy reveals interstitial fibrosis (a finding that has been shown to be prevented by zinc supplementation in the mouse model), myocyte necrosis with hypertrophy of other myocytes, and evidence of inflammation. Electron microscopy reveals mitochondrial enlargement and disorganization, dilatation of the sarcoplasmic reticulum, fat and glycogen deposition, and dilatation of the intercalating discs.