Understanding Acute Myocardial Infarction in the Wake of Sushmita Sen's illness

Sushmita Sen, a well-known Bollywood actress and former Miss Universe was born on the 19th of November, 1975. After her reign as Miss Universe, Sushmita Sen became an actress and ruled millions of hearts. She has received numerous awards till date including the IIFA award, the Rajiv Gandhi award, and two Filmfare awards.

Sushmita Sen, in her InstaLive, mentioned her heart attack (myocardial infarction) and how she probably survived it because of her active lifestyle and this was reiterated by her cardiologist. She also spoke about the angioplasty that she underwent. Reports say that she was diagnosed with Addison’s disease in 2014 and was taking steroids to manage the illness. It's worth noting that Satish Kaushik, another well-known actor, recently passed away due to a heart attack.

What is myocardial infarction?

Myocardial infarction is a term used for an event that occurs due to the formation of plaques in the interior walls of the arteries resulting in reduced blood flow to the heart and injuring the heart muscles because of a lack of oxygen supply. An MI results in irreversible damage to the heart muscle due to a lack of oxygen. An MI may lead to impairment in diastolic and systolic function. Acute myocardial infarction is a term used to describe a sudden onset of myocardial infarction symptoms

Unhealthy dietary habits and lifestyle lead to the development of fatty deposits or plaques on the walls of the coronary arteries. As the plaque builds up in the heart over time, it can lead to blockage, preventing blood in the arteries from reaching some parts of the heart muscle. This results in cardiac ischemia, a condition where a portion of the heart is deprived of oxygen. If this is not treated in time, the heart tissues begin to die, leading to a heart attack, or myocardial infarction.

Myocardial infarction is one of the most common causes of fatality worldwide. Globally, the prevalence of the disease approaches three million people. In accordance with the World Health Organization, India accounts for one-fifth of the deaths caused by cardiovascular disease worldwide, especially in the younger population [1].

Myocardial infarction can be classified into 5 types based on etiology and circumstances:

• Type 1: Spontaneous myocardial infarction caused by ischemia due to a primary coronary event (eg, plaque rupture, erosion, or fissuring; coronary dissection). Based on electrocardiogram (ECG) findings, it is further divided into ST‐elevation myocardial infarction (STEMI) and non‐ST‐elevation myocardial infarction (NSTEMI).

• Type 2: Ischemia due to increased oxygen demand (eg, hypertension), or decreased supply (eg, coronary artery spasm or embolism, arrhythmia, hypotension).

• Type 3: Related to sudden unexpected cardiac death.

• Type 4: Associated with percutaneous coronary intervention (signs and symptoms of myocardial infarction with cTn values > 5 × 99th percentile.

• Type 5: Associated with coronary artery bypass grafting (signs and symptoms of myocardial infarction with cTn values > 10 × 99th percentile [2].

Clinical presentation

The medical history and general physical examination are often inconsistent when evaluating for acute myocardial infarction. The history should focus on the onset, quality, and associated symptoms. Recent studies have found that diaphoresis (abnormal sweating) and bilateral arm radiating pain are most often associated with myocardial infarction.

The most common symptoms of myocardial infarction include:

• Chest discomfort/pain usually occurs in the center or on the left side. It usually lasts for a few minutes and feels like pressure, squeezing, or pain. It also can feel like heartburn or indigestion.

• Shortness of breath may sometimes be the only symptom. It may occur while at rest or doing any mild physical activity.

• Discomfort in the upper part of the body may feel like pain or discomfort in one or both arms, the back, shoulders, neck, jaw, or the upper part of the stomach.

• The other associated symptoms are nausea, vomiting, dizziness, lightheadedness, sweating, anxiety, fatigue, weakness, stress, cough, choking sensation, diaphoresis, wheezing, and/or irregular heart rate [3], [4].

The physical examination, most importantly, must be performed to evaluate vital signs and the patient’s appearance, including diaphoresis, as well as lung findings, and cardiac auscultation (listening to the sounds of the heart, usually using a stethoscope).

• Heart rate may reveal tachycardia (a heart rate over 100 beats a minute), atrial fibrillation (irregular and often abnormally fast heart rate), or ventricular arrhythmia (abnormal heartbeats that originate in the lower heart chambers).

• Blood pressure is usually high, but hypotension (low blood pressure) may be present if the patient is in shock.

• Neck veins may be distended indicating right ventricular failure.

• The heart may indicate lateral displacement of apical impulse, soft S1, palpable S4, and new mitral regurgitation murmur. A loud holosystolic murmur radiating to the sternum may be indicative of ventricular septal rupture.

• Wheezing may be present if the patient has developed pulmonary edema.

• Extremities may show edema or cyanosis and will be cold.

The clinical examination is followed by imaging which includes a chest radiograph, ECG, and/or echocardiography based on the requirement in the acute clinical setting.

Diagnosis

Some imaging modalities used in the diagnosis of acute myocardial infarction are:

• Echocardiography

• Radionuclide imaging

• Angiogram

• Cardiac magnetic resonance imaging (cardiac MRI)

The routine lab investigations required are:

• Complete blood count

• Lipid profile

• Electrolytes

• Renal function tests

• Liver function tests

• C - reactive protein

The diagnosis is based on the risk factors, patient’s history, associated symptoms, clinical presentation, serial changes in ECG, and serologic markers. Further echocardiography often plays a critical role in the early diagnosis and management of patients. Importantly, when a patient’s symptoms and ECG are clearly indicative of an ongoing acute MI, there is no need to obtain an echo in the acute setting, when the focus should be on progression towards definitive therapy. In patients with abnormal symptoms and nondiagnostic ECG, an echocardiogram may be necessary at an early stage when there is sufficient suspicion [4].

The diagnostic criteria for diagnosing myocardial infarction are the detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th percentile of the upper reference limit, together with evidence of myocardial ischemia with at least one of the following:

• Symptoms of ischemia.

• ECG changes indicative of new ischemia (new ST-T changes or new left bundle branch block).

• Development of pathological Q-wave changes in the ECG.

• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.

• Identification of an intracoronary thrombus by angiography or autopsy.

Biomarkers & special tests

Acute chest pain with persistent ECG changes is the key determinant of acute myocardial infarction diagnosis. However, the sensitivity and specificity of ECG changes in diagnosing acute myocardial infarction are not very accurate, meaning that they may miss some cases of acute myocardial infarction or wrongly identify acute myocardial infarction in some cases. Additionally, around 90% of patients who come with chest pain do not have acute myocardial infarction.

So, a need for additional diagnostic criteria and cardiac biomarkers has come to light as the most logical solution. Detection of the levels of cardiac biomarkers was first used only as an additional method to confirm the diagnosis of acute myocardial infarction. But slowly, their significance has increased, and cardiac biomarker alterations are now considered an important diagnostic criterion for acute myocardial infarction [5]. The biomarkers that are frequently required to be evaluated in acute myocardial infarction patients are:

• Initial indicators - Myoglobin, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and creatinine kinase (CK).

• Historically, AST and LDH are the first biomarkers that get elevated in AMI. But their application as a cardiac biomarker is restricted due to their widespread expression in numerous organs which restricts their impact on myocardial damage specificity.

• Cardiac Troponin is the current gold standard biomarker in acute myocardial infarction. The diagnosis of acute myocardial infarction has been significantly altered by the introduction of this biomarker, enabling earlier therapeutic interventions in acute myocardial infarction patients. It is of two types- Troponin I which is unique to the heart muscle and Troponin T which is seen in other muscles also but in limited proportions [6].

• So, the preferred special laboratory tests for the diagnosis of acute myocardial infarction are cardiac Troponin I or cardiac Troponin T, which are both extremely sensitive and specific. In order to confirm or rule out a change in this biomarker concentration, serial testing is advised [7].

• When combined with clinical or ECG signs suggestive of acute myocardial infarction, a rise or fall in Troponin with at least one value over the population's 99th percentile is indicative of this disease.

• Microarray technology has advanced and been used extensively in recent years in the field of bioinformatics. With the advent of this technology, many other new biomarkers, including matrix metalloproteinase (MMP9), toll-like receptor (TLR2), and interleukin (ILB1) were also used as acute myocardial infarction diagnostic and prognostic test tools. Moreover, according to the literature, a multi-biomarker strategy may also significantly improve the diagnostic precision for AMI. But the only limitation is their complicated genetic structure.

Is early prediction possible in acute myocardial infarction?

Acute myocardial infarction is preventable if its modifiable risk factors are managed. Some such risk factors are smoking, high blood pressure, high cholesterol level, diabetes, sedentary lifestyle, stress, and obesity. So, early detection of acute myocardial infarction by any means will help in the proper diagnosis and better management.

The newly developed blood test measures levels of a biomarker known as cardiac myosin-binding protein C (cMyC). The test could potentially rule out any hidden myocardial infarction that is not clinically manifested immediately since the concentrations of this protein increase more quickly and to a greater extent after myocardial infarction as compared to Troponin levels. So it helps in the early detection of acute myocardial infarction as compared to the specific Troponin test used in acute myocardial infarction [8].

To overcome the limitations of the complex genetic structure of a few biomarkers which are hindering their ability to aid accurately in acute myocardial infarction detection, technologies like random forest (RF) artificial neural networks have also been used in biomarker discovery. These are machine learning techniques used to solve problems so that they help in the rapid discovery of acute myocardial infarction biomarkers along with its prediction [9].

Therapeutics

Blood flow to the damaged heart muscle must be restored as soon as possible as part of the treatment for acute myocardial infarction. This can be accomplished in several ways, which include surgery and a medicinal approach. Treatment for acute myocardial infarction includes aspirin, clot busters (thrombolytics or fibrinolytics), blood-thinning medications (heparin), nitroglycerin, morphine, beta-blockers, ACE inhibitors, statins, and reperfusion therapy. For STEMI, emergency reperfusion is achieved by fibrinolytic drugs, percutaneous intervention, or rarely, bypass surgery. For NSTEMI, reperfusion is accomplished through percutaneous intervention or bypass surgery. Following are the other therapies used along with these medications:

• Supplementary oxygen

• Balloon angioplasty

• Stent placement

• Bypass surgery

• Stem cells transplantation

• Biomaterial-based in situ implantations [10], [11]

Supplementary oxygen

Supplemental oxygen is frequently given along with other heart attack therapies to patients who have breathing difficulties or have low blood oxygen levels. A mask that covers the nose and mouth or a tube that lies just below the nose are both options for the patient to breathe in oxygen. This eases the strain on the heart and increases the amount of oxygen flowing in the blood [11].

Balloon angioplasty

If necessary, balloon angioplasty can be carried out during cardiac catheterization. A balloon-tipped catheter (thin, hollow tube) is placed into the blocked artery in the heart. The balloon is gradually inflated to push the plaque against the arterial walls outward to widen the artery and increase blood flow [12].

Stent placement

In this technique, a catheter is used to insert a tiny tube into a blocked artery to "prop" the artery open. The stent is typically permanent and made of metal. It might also be made from a substance that the body gradually absorbs. Some stents include drugs that help keep the artery from being blocked again [12].

Bypass surgery

This procedure is frequently referred to as open heart surgery, bypass surgery, or Coronary artery bypass surgery (CABG). People with severe blockages of coronary arteries may undergo bypass surgery. It involves rerouting of blood flow around one or more blocked arterial segments, usually using a blood vessel from the chest, arm, or leg. It could be done as an emergency procedure right after a heart attack, or it might be done a few days later after the heart has recovered to a certain extent [12].

Stem cells transplantation

Stem cells have the potential to become a successful cardiovascular therapy by promoting tissue regeneration. After an acute myocardial infarction, stem cell transplantation has been said to restore heart function. Nevertheless, this therapy is still limited to experimental research and clinical trials. Early, unblinded research suggested that stem cell therapy after an acute myocardial infarction could be beneficial. More recent blinded randomized trials have yielded conflicting findings; notably, the most recent and largest pan-European clinical trial. However, it is unclear how prospective benefits may work [13].

Biomaterial-based in situ implantations

Cardiac function declines as a result of physical damage caused by cardiovascular disease. To improve patient outcomes, it is important to treat the underlying cause by rebuilding damaged tissues rather than just masking symptoms with medication. Cardiovascular surgeons employ a range of techniques to repair the ventricular septal wall and valves. Repair and restoration of damaged cardiac tissues involve the use of several biomaterials. The two primary types of these biomaterials are synthetic (polymers and metals) and natural (derived from biological sources such as human donors or harvested animal tissues) [14].

Quality of life

Acute myocardial infarction negatively impacts the quality of life (QOL) of the patient with multiple studies suggesting that those experiencing a myocardial infarction have a significantly worse quality of life than the general population [15]–[17]. These patients often face significant challenges in carrying out their day-to-day tasks and participating in activities they once enjoyed, which can be distressing and debilitating. Patients also suffer from a variety of long-term complications such as heart failure, arrhythmias, cardiogenic shock, pericarditis, ventricular aneurysm, and thromboembolism. Additionally, the emotional challenges that come with the diagnosis of acute myocardial infarction, such as anxiety and depression, can exacerbate the negative impact on QOL. However, as time passes, the quality of life seems to get better.

The extent of the impact on QOL following an acute myocardial infarction can vary based on several factors, including sex, comorbidities, and lifestyle choices. For example, males tend to have better QOL than females, and patients with comorbidities such as diabetes mellitus, hypertension, kidney disease, and ischemic heart disease (IHD) tend to have worse QOL [18]. Patients may need to make significant lifestyle changes, such as quitting smoking and adopting a heart-healthy diet to effectively manage their condition and improve their QOL.

Furthermore, the negative impact of acute myocardial infarction on QOL can extend beyond physical limitations, affecting emotional and social well-being as well. Factors such as lack of confidence, social exclusion, and physical restrictions can further contribute to a decreased quality of life. Women, in particular, have reported lower HRQoL compared to men, and several studies have linked dysfunctional eating and lower education levels to poor QOL.

To improve QOL in the early post-acute myocardial infarction period, a range of interventions is available, including psychological and physical counseling, rehabilitation programs, and medications. These interventions aim to not only improve clinical outcomes but also help patients recover physically and emotionally. Patients who have negative coping mechanisms, unhealthy lifestyles, and limited access to social resources tend to have a lower quality of life scores.

Lifestyle modifications such as quitting smoking, adopting a heart-healthy diet, exercising regularly, and maintaining a healthy weight are essential for managing the condition and improving QOL. Patients may also need to limit their intake of alcohol and caffeine, as these substances can exacerbate symptoms. Cardiac rehabilitation programs can also play a vital role in improving QOL by providing exercise training, nutrition counseling, education, and emotional support.

Upon returning to work, patients who have undergone effective treatments and rehabilitation are likely to experience significant recovery in body function, physical role, and overall health [19]. The alleviation of symptoms can make it easier for patients to perform their job responsibilities, and they may choose work that is suitable for their physical abilities to ensure their safety. Overall, a multifaceted approach that encompasses lifestyle modifications, psychological and physical counseling, and rehabilitation can significantly improve the quality of life for patients with acute myocardial infarction.

Clinical trials

​Title	​Intervention	​Summary	​Location	​NCT	​Dates
​EMPACT-MI: A Study to Test Whether Empagliflozin Can Lower the Risk of Heart Failure and Death in People Who Had a Heart Attack (Myocardial Infarction) [20]	Empagliflozin	​This is a phase 3 clinical trial to evaluate the efficacy of empagliflozin in MI in terms of lowering the chances of having to go to the hospital and lowering the chances of death. It is currently recruiting and the number of estimated participants is 6500.	​449 locations worldwide including 14 in India; all of which are currently recruiting.	​NCT04509674	Start date: December 2020 Completion date: August 2023

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20. Boehringer Ingelheim, “EMPACT-MI: A Streamlined, Multicentre, Randomised, Parallel Group, Double-blind Placebo-controlled Superiority Trial to Evaluate the Effect of EMPAgliflozin on Hospitalisation for Heart Failure and Mortality in Patients With aCuTe Myocardial Infarction,” clinicaltrials.gov, Clinical trial registration NCT04509674, Mar. 2023. Accessed: Mar. 13, 2023.