Myocardial infarction remains a leading cause of mortality and morbidity worldwide


Myocardial infarction (MI), commonly called heart attack, remains a leading cause of mortality and morbidity worldwide, raising an urgent need for novel therapies.

Acute MI provokes an inflammatory response in the heart that removes damaged tissue to promote repair and regeneration.

Overactive and/or prolonged inflammation impedes healing, however, suggesting that reducing inflammation may lead to better outcomes.

Previously Lan Wu, MD, Luc Van Kaer, Ph.D., and colleagues identified a subpopulation of regulatory B lymphocytes in the fat tissue of obese mice that secretes interleukin-10 (IL-10), an anti-inflammatory cytokine which protects against obesity-associated insulin resistance.

Reporting now in the Proceedings of the National Academy of Sciences, they found IL-10-producing B cells in mice also are highly enriched in fat tissue around the heart.

Following MI, the cells increase in number and move to the damaged heart, where they terminate inflammation and protect against further injury and dysfunction.

IL-10-producing B cells thus are novel targets to improve the outcome of MI, the researchers concluded.

Depression has been associated with a higher risk of cardiovascular events and a higher mortality in patients with one or more comorbidities.

This study investigated whether continuative use of antidepressants (ADs), considered as a proxy of a state of depression, prior to acute myocardial infarction (AMI) is associated with a higher mortality afterwards. The outcome to assess was mortality by AD use.

Coronary heart disease (CHD) is the leading cause of mortality worldwide, and ranks among the top six causes of morbidity. Depression accounts for a relevant proportion of the global burden of disease, ranking among the top three causes, despite a low impact on mortality. In high-income countries, acute myocardial infarction (AMI) is the CHD carrying the highest mortality and morbidity rates [1,2,3,4].

In the USA, the age-adjusted hospitalization rates for CHDs decreased constantly between 2002 and 2013.

Detailed data have shown a drop in the hospitalization rates for ST-segment elevation myocardial infarction (STEMI) and a rise in the proportion of hospital admissions for other forms (NSTEMI) in the past decade in both Europe and the United States [5,6,7].

A retrospective observational registry study conducted in Sweden found that the annual incidence rate and prevalence of depression rose steadily from 1991 to 2010, increasing more rapidly in women than in men [8].

For both genders, the incidence of clinically-relevant depressive symptoms increases with age, especially in the case of other ongoing comorbidities or institutionalization [9].

Following an episode of AMI, the incidence of depression ranges widely, from 15 to 30%, for major depressive disorder [10,11,12], and is around 20% for dysthymia (minor depression) or depressive symptoms [13].

Depression has been associated with a higher risk of cardiovascular events and a higher mortality in patients with one or more comorbidities [14].

Depression has been identified as a prognostic risk factor in CHD: the risk of all-cause mortality and the risk of cardiovascular events rise by 22 and 13%, respectively [312].

Another study investigated the impact of depression on mortality after AMI, reporting a mortality risk at one year of 33% in patients previously diagnosed with depression, as opposed to 26% in the others; and at 19 years after the AMI, the mortality risk was 87 and 78%, respectively [15].

The occurrence of depression in patients with CHD substantially increases the likelihood of a worse cardiovascular prognosis [16].

Knowing the time frame of depression in relation to patient outcomes would have important mechanistic and screening implications [17]. Some authors reported that patients with and without a diagnosis of depression prior to their cardiac event had similar survival rates [18].

Others found mortality higher among patients with even mild, clinically insignificant depressive symptoms prior to their AMI than for those with no symptoms of depression [19]. A meta-analysis confirmed that both premorbid and postmorbid depression are of prognostic significance [17].

In the analysis of the fatality rate after hospitalization for AMI, another important factor to take into account is adherence to evidence-based treatment (EBT) for AMI patients after their discharge from hospital.

The international guidelines recommend a combined and continuative use of beta-blockers, aspirin/clopidogrel, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) after a myocardial infarction in order to reduce cardiac morbidity and mortality [20].

The objective of this study was to test the hypothesis of an association between a continuative use of antidepressants, as proxy of a state of depression, prior to the onset of AMI and a higher mortality afterwards, controlling for potential confounders.


In our study, the AMI-related hospitalization rate decreased constantly during the period investigated, while among AD users the rate of hospitalization for AMI remained steady. A similar trend has been observed in other high-income countries, presumably due to a marked improvement in the treatment of CHDs in recent decades [24].

The steady rate of AMI-related hospitalization involving AD users could be explained by an improvement in the monitoring of antidepressant medication over the study period too, which may enable a better definition of depressive status.

The AMI-related hospitalization rate in our study was higher for men than for women; and males were younger than females on average.

These results are consistent with the literature, which has drawn attention to gender-related differences in the occurrence of AMI [25,26,27].

About 9% of the patients in our sample had a history of antidepressant use, and they had a higher mortality after AMI than patients without this condition.

Depressive disorders are common among people suffering from cardiovascular diseases and are associated with a broad range of adverse outcomes. In patients with AMI, depressive symptoms have emerged as a prognostic risk factor for a higher cardiovascular-specific mortality, recurrent hospital admissions, worse general health and well-being, and higher costs of care, even in the absence of a clinical diagnosis of depression [2829].

The women in our sample were more likely to use antidepressants before being hospitalized for AMI. This finding is consistent with a multicenter study conducted in Canada, the USA and Switzerland, in which data were collected on patients aged 18–55 years using a self-report questionnaire that included a validated standard tool for assessing depression [30,31,32,33].

Regarding the association between antidepressant use and the risk of CHD among subjects with no history of CHD, the results of a meta-analysis provide no evidence of any association between SSRI or NSMRI use and CHD risk [34]. Although the use of antidepressants in patients with CHD helps to control their depression, their use in this group is controversial.

The results of a meta-analysis nonetheless found that SSRI use in these patients reduces their depression symptoms and may improve their CHD prognosis [16].

Patients hospitalized with AMI are at particularly high risk of mortality, but the mortality rates for patients hospitalized with heart failure can vary significantly, ranging from 5 to 9% [35]. The prognosis after hospitalization for AMI is also reportedly very poor, with a 10-year mortality risk of 48.6% [36].

The 30-day mortality rate of 13.1% seen in our sample could be due to the patients’ advanced age, and associated chronic conditions. In fact, the sample’s long-term survival was consistent with other published reports.

The association seen between chronic physical conditions and depression is common. Depression has been associated with a higher incidence of at least one chronic comorbidity, while people with chronic diseases have been found more prone to suffer from depression than people in good health [3738].

Our study identified a better survival rate for patients hospitalized for AMI with no history of antidepressant treatment. This difference, was confirmed even after adjusting for age, gender, CCI, adherence to EBT for AMI, and type of AMI. Depression in patients who experience AMI remains a severe condition and warrants treatment and care. Patients with a history of moderate-severe depressive symptoms may benefit from adequate treatment, or at least careful clinical follow-up, after they have been hospitalized for AMI, in order to monitor any rapid mood swings and start treatment should symptoms persist.

Patients with depression are less likely to adopt an adequately healthy lifestyle in order to reduce their cardiac risk after an AMI [39], and nonadherence to medication is significantly higher among the depressed [40].

Focusing on the evidence-based treatment as a whole, the proportions of patients adhering to the combined EBT for AMI were much the same as in other studies, and our findings confirm the positive effects of EBT for AMI on survival after AMI [20].

Our results show that it is important to identify AMI patients at high risk of depression, so that they can be targeted for depression screening, and benefit from appropriate treatment in relation to their baseline conditions [18]. In our study, there was no difference in mortality between patients who were or were not given continuative antidepressants after discharge. This finding is consistent with another study that examined the timing of antidepressant prescription vis-à-vis the time of hospital discharge after AMI [19]. It is still by no means clear whether managing any depression can improve survival after AMI, and clinical trials on this issue are obviously needed, also to ascertain the most appropriate treatment for post-AMI depression. Currently-available evidence nonetheless indicates that psychotherapy and psychoactive pharmacological treatments are both safe and effective in reducing depression in patients with cardiovascular diseases [41].

A limitation of our study lies in that patients were identified as AD users (considered as a proxy for a state of depression) on the basis of their having purchased antidepressants for more than 24 consecutive weeks prior to their hospitalization for AMI, not on the grounds of a clinical diagnosis. The threshold of 24 weeks has been adopted by several clinical practice guidelines as an indication of treatment for chronically depressed patients, however [42]. A clinical assessment of the severity of AMI was also lacking in our study. The main strength of our study, on the other hand, concerns the AMI population analyzed, which was numerically large, well defined, and followed up for several years after discharge from hospital.


Myocardial infarction (MI), colloquially known as “heart attack,” is caused by decreased or complete cessation of blood flow to a portion of the myocardium.

Myocardial infarction may be “silent” and go undetected, or it could be a catastrophic event leading to hemodynamic deterioration and sudden death.[1]

 Most myocardial infarctions are due to underlying coronary artery disease, the leading cause of death in the United States.

With coronary artery occlusion, the myocardium is deprived of oxygen. Prolonged deprivation of oxygen supply to the myocardium can lead to myocardial cell death and necrosis.[2] 

Patients can present with chest discomfort or pressure that can radiate to the neck, jaw, shoulder, or arm. In addition to the history and physical exam, myocardial ischemia may be associated with ECG changes and elevated biochemical markers such as cardiac troponins.[3][4]


As stated above, myocardial infarction is closely associated with coronary artery disease. INTERHEART is an international multi-center case-control study which delineated the following modifiable risk factors for coronary artery disease:[5] [6]

  1. Smoking
  2. Abnormal lipid profile/blood apolipoprotein (raised ApoB/ApoA1)
  3. Hypertension
  4. Diabetes mellitus
  5. Abdominal obesity (waist/hip ratio) (greater than 0.90 for males and greater than 0.85 for females)
  6. Psychosocial factors such as depression, loss of the locus of control, global stress, financial stress, and life events including marital separation, job loss, and family conflicts
  7. Lack of daily consumption of fruits or vegetables
  8. Lack of physical activity
  9. Alcohol consumption (weaker association, protective)

The INTERHEART study showed that all the above risk factors were significantly associated with acute myocardial infarction except for alcohol consumption which showed a weaker association.

Smoking and abnormal apolipoprotein ratio showed the strongest association with acute myocardial infarction.

The increased risk associated with diabetes and hypertension were found to be higher in women, and the protective effect of exercise and alcohol were also found to be higher in women.[5]

Other risk factors include a moderately high level of plasma homocysteine, which is an independent risk factor of MI. Elevated plasma homocysteine is potentially modifiable and can be treated with folic acid, vitamin B6, and vitamin B12.[7]

Some non-modifiable risk factors for myocardial infarction include advanced age, male gender (males tend to have myocardial infarction earlier in life), genetics (there is an increased risk of MI if a first-degree relative has a history of cardiovascular events before the age of 50).[6][8] 

The role of genetic loci that increase the risk for in MI is under active investigation.[9][10]


The most common cause of death and disability in the western world and worldwide is coronary artery disease.[11] Based on 2015 mortality data from the National Health Interview Survey (NHIS-CDC), MI mortality was 114,023, and MI any-mention mortality (i.e., MI is mentioned as a contributing factor in the death certificate) was 151,863.

As per the National Health and Nutrition Examination Survey (NHANES)-CDC data from 2011 to 2014 an estimated 16.5 million Americans older than 20 years of age have coronary artery disease, and the prevalence was higher in males than females for all ages. As per the NHANES 2011 through 2014, the overall prevalence of MI is 3.0% in US adults older than 20 years of age.

Prevalence of MI in the US Sub-Populations

Non-Hispanic Whites

  • 4.0% (Male)
  • 2.4% (Female)

Non-Hispanic Blacks

  • 3.3% (Male)
  • 2.2% (Female)


  • 2.9% (Male)
  • 2.1% (Female)

Non-Hispanic Asians

  • 2.6% (Male)
  • 0.7% (Female)

Based on the Atherosclerosis Risk in Communities Study (ARIC) performed by National Heart, Lung and Blood Institute (NHLBI) collected between 2005 and 2014, the estimated annual incidence is 605,000 new MIs and 200,000 recurrent MIs.[12]

The ARIC study also found that the average age at first MI is 65.6 years for males and 72.0 years for females. In the past decades, several studies have shown a declining incidence of MI in the United States.[12]


The acute occlusion of one or multiple large epicardial coronary arteries for more than 20 to 40 minutes can lead to acute myocardial infarction. The occlusion is usually thrombotic and due to rupture of a plaque formed in the coronary arteries.

The occlusion leads to a lack of oxygen in the myocardium which results in sarcolemmal disruption and myofibril relaxation.[2] These changes are one of the first ultrastructural changes in the process of MI which are followed by mitochondrial alterations. The prolonged ischemia ultimately results in liquefactive necrosis of myocardial tissue.

The necrosis spreads from sub-endocardium to sub-epicardium. Sub-epicardium is believed to have increased collateral circulation which delays its death.[2] Depending on the territory affected by the infarction, the cardiac function is compromised.

Due to negligible regeneration capacity of the myocardium, the infarcted area heals by scar formation, and often, the heart is remodeled characterized by dilation, segmental hypertrophy of remaining viable tissue and cardiac dysfunction.[13]Go to:

History and Physical

The imbalance between oxygen supply and the demand leads to myocardial ischemia and can sometimes lead to myocardial infarction.

The patient’s history, electrocardiographic findings, and elevated serum biomarkers are helpful in identifying ischemic symptoms. Myocardial ischemia can present as chest pain, upper extremity pain, mandibular or epigastric discomfort that occurs during exertion or at rest.

Myocardial ischemia can also present as dyspnea or fatigue which are known to be ischemic equivalents.[14] 

The chest pain is usually retrosternal and is sometimes described as the sensation of pressure or heaviness. The pain often radiates to the left shoulder, neck or arms with no obvious precipitating factors and it may be intermittent or persistent. The pain usually lasts for more than 20 minutes.[15] It is usually not affected by positional changes or active movement of the region. Additional symptoms such as sweating, nausea, abdominal pain, dyspnea, and syncope may also be present.[14][16][17] 

The MI can also present atypically with subtle findings such as palpitations, or more dramatic manifestations, such as cardiac arrest. The MI can sometimes present with no symptoms.[18]


The three components in the evaluation of the MI are clinical features, ECG findings, and cardiac biomarkers.


The resting 12 lead ECG is the first-line diagnostic tool for the diagnosis of an acute coronary syndrome (ACS). It should be obtained within 10 minutes of the patient’s arrival in the emergency room.[17] Acute MI is often associated with dynamic changes in the ECG waveform. Serial ECG monitoring can provide important clues to the diagnosis if the initial EKG is non-diagnostic at initial presentation.[14] Serial or continuous ECG recordings may be helpful in determining reperfusion or re-occlusion status. A large and prompt reduction in ST-segment elevation is usually seen in reperfusion.[14]

ECG findings suggestive of ongoing coronary artery occlusion (in the absence of left ventricular hypertrophy and bundle branch block):[19]

ST-segment elevation in two contiguous lead (measured at J-point) of

  1. Greater than 5 mm in men younger than 40 years, greater than 2 mm in men older than 40 years, or greater than 1.5 mm in women in leads V2-V3 and/or
  2. Greater than 1 mm in all other leads

ST-segment depression and T-wave changes

  1. New horizontal or down-sloping ST-segment depression greater than 5 mm in 2 contiguous leads and/or T inversion greater than 1 mm in two contiguous leads with prominent R waves or R/S ratio of greater than 1

The hyperacute T-wave amplitude, with prominent symmetrical T waves in two contiguous leads, may be an early sign of acute MI that may precede the ST-segment elevation. Other ECG findings associated with myocardial ischemia include cardiac arrhythmias, intraventricular blocks, atrioventricular conduction delays, and loss of precordial R-wave amplitude (less specific finding).[14]

ECG findings alone are not sufficient to diagnose acute myocardial ischemia or acute MI as other conditions such as acute pericarditis, left ventricular hypertrophy (LVH), left bundle branch block (LBBB), Brugada syndrome, Takatsubo syndrome (TTS), and early repolarization patterns also present with ST deviation.

ECG changes associated with prior MI (in the absence of left ventricular hypertrophy and left bundle branch block):

  1. Any Q wave in lead V2-V3 greater than 0.02 s or QS complex in leads V2-V3
  2. Q wave > 03 s and greater than 1 mm deep or QS complex in leads I, II, aVL, aVF or V4-V6 in any two leads of contiguous lead grouping (I, aVL; V1-V6; II, III, aVF)
  • R wave > 0.04 s in V1-V2 and R/S greater than 1 with a concordant positive T wave in the absence of conduction defect

Biomarker Detection of MI

Cardiac troponins (I and T) are components of the contractile apparatus of myocardial cells and expressed almost exclusively in the heart. Elevated serum levels of cardiac troponin are not specific to the underlying mode of injury (ischemic vs. tension)[14] [20]. The rising and/or falling pattern of cardiac troponins (cTn) values with at least one value above the 99 percentile of upper reference limit (URL) associated with symptoms of myocardial ischemia would indicate an acute MI. Serial testing of cTn values at 0 hours, 3 hours, and 6 hours would give a better perspective on the severity and time course of the myocardial injury. Depending on the baseline cTn value the rising/falling pattern is interpreted. If the cTn baseline value is markedly elevated, a minimum change of greater than 20% in follow up testing is significant for myocardial ischemia. Creatine kinase MB isoform can also be used in the diagnosis of MI, but it is less sensitive and specific than cTn level.[4][21]


Different imaging techniques are used to assess myocardial perfusion, myocardial viability, myocardial thickness, thickening and motion, and the effect of myocyte loss on the kinetics of para-magnetic or radio-opaque contrast agents indicating myocardial fibrosis or scars.[14] Some imaging modalities that can be used are echocardiography, radionuclide imaging, and cardiac magnetic resonance imaging (cardiac MRI). Regional wall motion abnormalities induced by ischemia can be detected by echocardiography almost immediately after the onset of ischemia when greater than 20% transmural myocardial thickness is affected. Cardiac MRI provides an accurate assessment of myocardial structure and function.[14]

Treatment / Management

Acute Management

Reperfusion therapy is indicated in all patients with symptoms of ischemia of less than 12-hour duration and persistent ST-segment elevation. Primary percutaneous coronary intervention (PCI) is preferred to fibrinolysis if the procedure can be performed < 120 minutes of ECG diagnosis. If there is no immediate option of PCI (> 120 minutes), fibrinolysis should be started within 10 minutes of STEMI after ruling out contraindications. If transfer to a PCI center is possible in 60 to 90 minutes after a bolus of the fibrinolytic agent and patient meets reperfusion criteria, a routine PCI can be done, or a rescue PCI can be planned.[19][17] If fibrinolysis is planned, it should be carried out with fibrin-specific agents such as tenecteplase, alteplase or reteplase (class I).[19]

Relief of pain, breathlessness, and anxiety: The chest pain due to myocardial infarction is associated with sympathetic arousal which causes vasoconstriction and increased workload for the ischemic heart. Intravenous opioids (e.g., morphine) are the analgesics most commonly used for pain relief (Class IIa).[19] The results from CRUSADE quality improvement initiative has shown that the use of morphine may be associated with a higher risk of death and adverse clinical outcomes.[22] The study was done from the CIRCUS (Does Cyclosporine Improve outcome in STEMI patients) database which showed no significant adverse events associated with morphine use in a case of anterior ST-segment elevation MI.[23] A mild anxiolytic (usually a benzodiazepine) may be considered in very anxious patients (class IIa). Supplemental oxygen is indicated in patients with hypoxemia (SaO2 < 90% or PaO2 < 60mm Hg) (Class I).[19]

Nitrates: Intravenous nitrates are more effective than sublingual nitrates with regard to symptom relief and regression of ST depression (NSTEMI). The dose is titrated upward until symptoms are relieved, blood pressure is normalized in hypertensive patients, or side effects such as a headache and hypotension are noted.[17]

Beta-blockers: This group of drugs reduces myocardial oxygen consumption by lowering heart rate, blood pressure, and myocardial contractility. They block beta receptors in the body including the heart and reduce the effects of circulating catecholamines. Beta-blockers should not be used in suspected coronary vasospasm or cocaine use.

Platelet inhibition: Aspirin is recommended in both STEMI and NSTEMI in an oral loading dose of 150 to 300 mg (non-enteric coated formulation) and a maintenance dose of 75 to 100 mg per day long-term regardless of treatment strategy (class I).[17] Aspirin inhibits thromboxane A2 production throughout the lifespan of the platelet.[24]

Most P2Y12 inhibitors are inactive prodrugs (except for ticagrelor which is an orally active drug which does not require activation) that require oxidation by hepatic cytochrome P450 system to generate an active metabolite which selectively inhibits P2Y12 receptors irreversibly. Inhibition of P2Y12 receptors leads to inhibition of ATP induced platelet aggregation. The commonly used P2Y12 inhibitors are clopidogrel, prasugrel, and ticagrelor.

The loading dose for clopidogrel is 300 to 600 mg loading dose followed by 75 mg per day.

Prasugrel, 60 mg loading dose, and 10 mg per day of a maintenance dose have a faster onset when compared to clopidogrel.[19]

Patients undergoing PCI should be treated with dual antiplatelet therapy (DAPT) with aspirin + P2Y12 inhibitor and a parenteral anticoagulant. In PCI, use of prasugrel or ticagrelor is found to be superior to clopidogrel. Aspirin and clopidogrel are also found to decrease the number of ischemic events in NSTEMI and UA.[17]

The anticoagulants used during PCI are unfractionated heparin, enoxaparin, and bivalirudin. The bivalirudin is recommended during primary PCI if the patient has heparin-induced thrombocytopenia.[19]

Long-Term Management

Lipid-lowering treatment: It is recommended to start high-intensity statins which reduce low-density lipoproteins (LDLs) and stabilize atherosclerotic plaques. High-density lipoproteins are found to be protective.[19]

Anti-thrombotic therapy: Aspirin is recommended lifelong, and the addition of another agent depends on the therapeutic procedure done such as PCI with stent placement.

ACE inhibitors are recommended in patients with systolic left ventricular dysfunction, or heart failure, hypertension or diabetes.

Beta-blockers are recommended in patients with LVEF less than 40% if no other contraindications are present.

Anti-hypertensive therapy can maintain a blood pressure goal less than 140/90 mm Hg.

Mineralocorticoid receptor antagonist therapy is recommended in a patient with left ventricular dysfunction (LVEF less than 40%).

Glucose lowering therapy in diabetics to achieve current blood sugar goals. [19]

Lifestyle Modifications

Smoking cessation is the most cost-effective secondary measure to prevent MI. Smoking has a pro-thrombotic effect which has a strong association with atherosclerosis and myocardial infarction.[6]

Diet, alcohol and weight control: A diet low in saturated fat with a focus on whole grain products, vegetables, fruits and, the fish is considered cardioprotective. The target level for body weight is body mass index of 20 to 25 kg/m2  and waist circumference of < 94 cm for the men and < 80 cm for the female.[25]Go to:

Differential Diagnosis

  1. Angina pectoris
  3. STEMI
  4. Pulmonary Embolism
  5. Pneumothorax


Type and Manifestation

I: Ischemic

  • Reinfarction
  • Extension of infarction
  • Angina

II: Arrhythmias

  • Supraventricular or ventricular arrhythmia
  • Sinus bradycardia and atrioventricular block

III: Mechanical

  • Myocardial dysfunction
  • Cardiac failure
  • Cardiogenic shock
  • Cardiac rupture (Free wall rupture, Ventricular septal rupture, papillary muscle rupture)

IV: Embolic

  • Left ventricular mural thrombus,
  • Peripheral embolus

V: Inflammatory

  • Pericarditis (Infarct associated pericarditis, late pericarditis or post-cardiac injury pericarditis).
  • Pericardial effusion

Enhancing Healthcare Team Outcomes

The key to management of MI is time until treatment. Thus, healthcare professionals including nurses who work in the emergency department must be familiar with the symptoms of MI and the importance of rapid triage. A cardiology consult should be made immediately to ensure that the patient gets treated within the time frame recommendations. Because MI can be associated with several serious complications, these patients are best managed in an ICU setting.

More information: Lan Wu et al. IL-10–producing B cells are enriched in murine pericardial adipose tissues and ameliorate the outcome of acute myocardial infarction, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1911464116

Journal information: Proceedings of the National Academy of Sciences
Provided by Vanderbilt University


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