Myocardial injury
Synonyms and keywords: Acute myocardial injury, Chronic myocardial injury, Myocardial ischemia, troponin concentration, systemic illness

# Overview
Myocardial injury is defined as elevated troponin concentrations without sign and symptom indicating overt myocardial ischemia and is the most common cause of increased troponin level. Traditionally, elevated troponin level was eqaul to myocardial infarction. Diagnosis of myocardial injury is a challange for clinicians. By improving the laboratory method for detecting high sensitive troponin and clinical approach to diagnosis of myocardial ischemia, patients with myocardial injury due to underlying diseases were excluded and treated. Evaluation and treatment of  percipitant factors of myocardial injury including sepsis, anemia, chronic kidney disease, cardiomyopathy are practically indicated. However,  patients with evidence of myocardial injury and myocardial ischemia both have poor short and long term outcome.

# Historical Perspective
- Troponin  was first discovered by setsuro ebashi, a Japanese physiologist, in 1963 as a component of muscle contraction. 
- In 2000, use of troponin  was established as the biomarker of choice in diagnosis of myocardial infarction by European Society of Cardiology (ESC) and American College of Cardiology (ACC).

# Classification
- Myocardial injury may be classified into acute and chronic based upon the pattern of troponin concentration.
- Acute myocardial injury is considered when there is a rise and/or fall of cardiac troponin concentrations exceeding the biological and/or analytical variation.
- Chronic myocardial injury may occur when cardiac troponin is greater than 99th-percentile URL without a rise and/or fall over a period of serial measurements ( more than 8 hours) in the conditions such as structural heart disease (hypertensive heart disease, ischemic cardiomyopathy, dilated cardiomyopathy) or secondary to non-cardiac causes such as chronic renal failure.
- Table below shown the classification of myocardial injury and also different types of myocardial infarction:

# Pathophysiology
- The pathogenesis of myocardial injury depends on increased cardiac troponin released by myocardial strain, inflammation, apoptosis, and cell injury, or  decreased clearance of cardiac troponin.
- It is thought that increased troponin level in  patients with advanced kidney disease is caused by either decreased clearance of cardiac troponin, underlying coronary artery disease and the presence of a left ventricular hypertrophy.
- The presence of chronic myocardial injury and cardiac troponin in valvular heart disease such as aortic stenosis  may be associated with cardiac mass, replacement fibrosis, and prognosis.

# Causes
- Common causes associated with myocardial injury include:
- Cardiovascular causes of chronic myocardial injury:
- Chronic heart failure
- Infiltrative cardiomyopathies (amyloidosis, hemochromatosis, sarcoidosis)
- Hypertrophic cardiomyopathy
- Stable coronary artery disease
- Hypertension
- Valvular heart disease
- Persistent arrhythmias (atrial fibrillation)
- Noncardiovascular causes of chronic myocardial injury:
- Chronic renal disease
- Pulmonary hypertension
- Toxins 
- Diabetes mellitus
- Cardiovascular causes of acute myocardial injury:
- Myocardial infarction 
- Pulmonary embolism
- Myocarditis
- Myopericarditis
- Aortic dissection
- Cardiac surgery or procedures (cardioversion or ablation)
- Hypertension
- Arrhythmias
- Acute heart failure
- Acute valvular heart disease (aortic regurgitation or mitral regurgitation)
- Takotsubo cardiomyopathy
- Cardiac contusions ( chest compressions)
- Noncardiovascular causes of acute myocardial injury:
- Acute renal failure
- Sepsis
- Anemia 
- Hypotension
- Hypoxia
- Noncardiac  surgery 
- Critical illness
- Rhabdomyolysis
- Drug-induced causes (chemotherapy)
- Stroke
- Extreme exertion

# Differentiating myocardial injury from other Diseases
- Myocardial injury must be differentiated from myocardial ischemia based on the troponin concentration changes, ECG changes and clinical approach.

# Epidemiology and Demographics
- The prevalence of myocardial injury is approximately 12,400 per 100,000 individuals presented in emergency department.
- Between 2010 to 2011, the incidence of myocardial injury was approximately 29,000 per 100,000 individuals with a mortality rate of 39%.
- The incidence of myocardial injury increases with age.
- There is no racial predilection to myocardial injury.
- women are more commonly affected by myocardial injury than men.

# Risk Factors
Common risk factors in the development of myocardial injury include:
- older age
- Hypertension
- Diabetes mellitus
- Cardiovascular disease

# Screening
- According to the Canadian Cardiovascular Society,cardiac troponin screening   for myocardial injury in noncardiac surgery (stayed at least 1 night in hospital ) is indicated for patients with history of:
- Age >45 years old with known cardiovascular disease such as coronary artery disease, cerebral vascular disease, peripheral arterial disease, congestive heart failure,
- Age between 18-64 years old with significant cardiovascular disease scheduled for urgent or semi-urgent surgery (hip fracture)
- Age at least 65 years old
- A Revised Cardiac Risk Score Index (RCRI>1)

# Natural History, Complications, and Prognosis
- 60% of cases of abnormal troponin concentrations , and 1 in 8 patients presenting to the hospital will have evidence of myocardial injury.
- Evidence of myocardial injury in chronic heart failure disease was associated with increased all-cause mortality, cardiovascular death, cardiovascular hospitalization.
- Increases in cTnI concentrations in patients undergoing high-dose chemotherapy for aggressive malignant conditions have been correlated with future decreases in left ventricular ejection fraction.
- In patients with chronic kidney disease and end stage renal disease, amyloidosis, pulmonary embolism, increased level of troponin was associated with increased  all-cause mortality.
- Among patients admitted in emergency department, evidence of acute myocardial injury  was associated with higher rate of all cause mortality and heart failure compared with chronic myocardial injury.
- Prognosis is generally poor especially in non-cardiac causes of myocardial injury which have higher in-hospital mortality rate ( compared with cardiac causes of chronic myocardial injury).
- The 5-year mortality rate of patients with myocardial injury is approximately 70%.

# Diagnosis

## Diagnostic Study of Choice
- There are no established criteria for the diagnosis of myocardial injury. However, in patients with increased level of cardiac troponin, after evaluation about myocardial ischemia, diagnosis and treating the underlying disorders is considered.

## History and Symptoms
- The initial workup includes an evaluation about myocardial ischemia.
- If myocardial infarction is ruled out, further assessment involves a detailed history, physical examination, laboratory testing, a 12-lead electrocardiogram, and an echocardiogram.
- Medical history should be taken about:
- Recent procedures (cardiac and non-cardiac)
- Use of cardiotoxic medications ( chemotherapy and substance abuse)
- Activity ( intense exercise regimens)
- Life stressors (takotsubo cardiomyopathy)
- Recent travel
- Comorbidities (specifically cardiovascular, pulmonary, renal )
- The most practical approach is identifying and treating the underlying causes of myocardial injury.
Common symptoms associated with underlying causes of myocardial injury include:
- Pleuritic chest pain may suggest pulmonary embolism, pneumonia, or myocarditis.
- Chest discomfort radiating to the back may suggest aortic dissection.
- Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema may suggest  heart failure disease
- Syncope, angina, dyspnea may suggest  valvular heart disease
- Palpitations, syncope may be seen in patients with cardiac  arrhythmias
- Fevers, chills may suggest infection

## Physical Examination
- There are no specific physical examination findings associated with myocardial injury. However, cardiovascular evaluation and systemic organs assessment is warranted as follows:
- Check of vital signs
- Cardiovascular system: heart rate and rhythm, murmurs, presence of congestion
- Pulmonary system: wheezing, rhonchi, crackles
- Detecting origin of infection

## Laboratory Findings
Laboratory investigation consistent with the diagnosis of myocardial injury include: 
- Serial cardiac troponin measurement
- Renal function testing (chronic kidney disease)
- Natriuretic peptide (heart failure)
- Complete blood cell count (anemia or infection)
- D-dimer (pulmonary embolism, aortic dissection)
- C-reactive protein (infectious and inflammatory markers)
- Serial cardiac troponin samples should be obtained for differentiating between acute or chronic myocardial injury.
- In patients suspected MI, given a third sample of troponin without the pattern of rising and falling (in 26% of patients) and also ECG changes may be helpful to differentiate from myocardial injury.

## Electrocardiogram
There are no specific ECG findings associated with myocardial injury. Findings on an ECG suggestive of myocardial injury may include:
- Evidence of ischemia, infarction
- Arrhythmias
- Acute right ventricular strain
- Conduction disease
- Structural disease ( left ventricular hypertrophy).

## X-ray
There are no x-ray findings associated with myocardial injury.

## Echocardiography or Ultrasound
Echocardiography  may be helpful in the diagnosis of underlying causes of myocardial injury.
- Findings on an echocardiography associated with myocardial injury include:
Assessment of   systolic and diastolic function
Left ventricular hypertrophy
Regional wall motion abnormalities
Valvular abnormalities.

## CT scan
There are no CT scan findings associated with myocardial injury. However, a CT scan may be helpful in suspicion of  pulmonary thromboembolism or aortic dissection.

## MRI
Cardiac MRI may be helpful when there is clinically suspicion of myocarditis or infiltrative cardiomyopathy as the underlying causes of myocardial injury.

## Other Imaging Findings
There are no other imaging findings associated with myocardial injury.

## Other Diagnostic Studies
There are no other diagnostic studies associated with myocardial injury.

# Treatment

## Medical Therapy
- There is no established consensus regarding the routine management of myocardial injury. However, treating the underlying precipitant factors such as heart failure, chronic kidney disease is recommended.
- WOSCOPS study showed that pravastatin reduced hs-cTnI in patients without previous MI by the means of 13%  leading to reduced future risk of MI .However, the role of pravastatin in acute phase of nonischemic myocardial injury is uncertain.
- Use of dabigatran in patients with myocardial injury after noncardiac surgery  was associated with reduced risk of major vascular event rate. However, this trial was terminated early and medication discontinuation rates were high. 
- The efficacy of Sodium-glucose cotransporter 2 inhibitors such as canagliflozin in patients with diabetes mellitus type 2 and myocardial injury was a delay of the rise in troponin over 2 years as well as diuresis, reduce blood pressure, and improve left ventricular remodeling.

## Surgery
Surgical intervention is not recommended for the management of myocardial injury.

## Primary Prevention
There are no established measures for the primary prevention  of myocardial injury.

## Secondary Prevention
There are no established measures for the secondary prevention of myocardial injury.