All the Patients of Acute Myocardial Infarction (STEMI) may not require Oxygen therapy

Oxygen therapy has been a mandatory requirement for more than 100 years unquestionably, to treat acute heart attack, i.e. Myocardial Infarction, most of the times on the basis of anecdotal evidence, expert opinion, and tradition. Recent compelling evidences have challenged this conventional thinking.

myocardial infarction - Myokardinfarkt - scheme (Photo credit: Wikipedia)

Immediate treatment with Morphine, oxygen, nitrates and antiplatelets (MONA) has become the standard treatment for acute myocardial infarction (AMI) patient. Oxygen is a lifesaving drug. Giving oxygen to patient with impending clinical emergency has become knee-jerk reflex reaction of clinician. At the same time, if not provided immediately, raises many questions from all the quarters including patient and his attendants.

Patient with AMI has compromised myocardial perfusion and event arises due to myocardial hypoxia. It appears quite logical and biologically plausible to give oxygen in such situations to improve the oxygenation of the ischemic myocardial tissue and decrease ischemic pain.
On the other side, oxygen may be harmful for its’ paradoxical effect in decreasing coronary artery blood flow and increasing coronary vascular resistance, evidenced by intra-coronary Doppler ultrasonography. This effect leads to decrease in cardiac output and stroke volume. Excess Oxygen in blood (hyperoxia) causes increase in vascular resistance and reperfusion injury due to increased oxygen free radicals.
A survey among doctors managing AMI cases had showed that oxygen supplementation was given to 96% of their patients with acute coronary syndrome. About 50% of participants believed that oxygen reduces fatality, 25% thought it is helpful in decreasing pain, and 25% thought it has no effect.
Researchers like, Nicholson, Beasley et al. and Wijesinghe et al. have suggested that efficacy and safety of high flow oxygen in MI is not substantial. The existing evidence suggests that the routine use of high flow oxygen in uncomplicated MI can cause greater infarct size and possibly increase the risk of mortality.
Cochrane systemic review by Cabello et al., did not find any conclusive evidence from randomized controlled trials (four parallel-design, randomized controlled trials reported between 1976 and 2012) to support the routine use of inhaled oxygen in patients with acute AMI.
Recently published, Air Verses Oxygen in myocardial infarction study (AVOID Study) suggested routine oxygen supplementation to AMI patients from the ambulance through to the recovery room might actually be hurting their hearts. AVOID was a randomized, controlled, multicenter trial with the aim of comparing oxygen supplementation (6–8 L/min) with no oxygen in STEMI patients with oxygen saturation in the normal range pulse oximetry saturation >94%.
The study found a significant 25% increase in creatine kinase, suggestive of increased myocardial injury and cardiac magnetic resonance imaging (cardiovascular magnetic resonance) at 6 months suggestive of larger infarction size with oxygen therapy. Although, the mortality was similar in both groups, significant increases in recurrent MI and arrhythmias were observed in the oxygen group. Even though, AVOID Study used higher oxygen flow 6–8 L/min (more than usual clinical practice) and study was not powered for hard clinical end points, AVOID trial would really question the current practice of oxygen supplementation to all patients with acute myocardial ischemia and definitely to those with normoxia.
This subject is being further studied by researchers with the Swedish Coronary Angiography and Angioplasty Registry in an open-label randomized trial DETO₂ X-AMI (with more than 5000 enrolled patients in multi centres) with mortality as the primary endpoint. Results are awaited which may have definitive conclusive evidence.
American Heart Association Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care recommends oxygen in patients with dyspnea, hypoxemic, or with signs of heart failure and shock, based on monitoring of oxy-hemoglobin saturation, to ≥94%. However, evidence to support oxygen use in uncomplicated acute coronary syndromes is inadequate.
Oxygen overdose is not a new, but the way we use oxygen in coronary emergency needs reconsideration. Time has come to reassess oxygen treatment in acute coronary syndrome. Clinical practice should be based on proven benefits and safety, not on tradition. Oxygen is a life-saving drug and how much you give the patients, depends on how much they need.
The question of oxygen administration to all patients of AMI remains unanswered until new strong evidence comes.
The original article can be accessed here.

Why Cardiac Troponin Test need to be Repeated Several Times in a case of Suspected Acute Coronary Syndrome (ACS)

Importance:
Cardiac Troponin (cTn) I or T need to be repeated at least once after 12 hours of onset of the symptoms, if patient is seen within 12 hours and the initial result is negative to exclude the diagnosis of Myocardial Infarction. Highly sensitive cTn may be repeated 2-3 hourly for two to three times for the same purpose.
Normal Values ¹
Cardiac troponin levels are normally so low they cannot be detected with most blood tests. Troponins are found only in skeletal muscles and heart muscles; smooth muscle cells do not contain troponins.
Test results are usually considered normal if the results are:

• Troponin I : less than 10 µg/L
  
• Troponin T : 0–0.1 µg/L
  

Normal troponin levels after 12 hours of chest pain mean a heart attack is unlikely.
What abnormal results mean:
An increase in the troponin level, even a slight one, usually means there has been some damage to the heart. Significantly high levels of troponin are a sign that a heart attack has occurred.
Most patients who have had a heart attack have increased troponin levels within 6 hours. After 12 hours almost everyone who has had a heart attack will have raised levels.
Troponin levels may remain high for 1 to 2 weeks after a heart attack.
Increased troponin levels may also be due to:

• Abnormally fast heart beat
  
• High blood pressure in lung arteries (pulmonary hypertension)
  
• Blockage of a lung artery by a blood clot, fat, or tumor cells (pulmonary embolus)
• Congestive heart failure
  
• Coronary artery spasm
  
• Inflammation of the heart muscle usually due to a virus (myocarditis)
  
• Strenuous exercise (for example, due to marathons or triathlons)
  
• Trauma that injures the heart such as a car accident
  
• Weakening of the heart muscle (cardiomyopathy)
  

Increased troponin levels may also result from certain medical procedures such as:

• Cardiac angioplasty/stenting
  
• Heart defibrillation or electrical cardioversion (purposeful shocking of the heart by medical personnel)
  
• Open heart surgery
  
• Radiofrequency ablation of the heart
  

The Changing Scenario:
Previously, clinicians often had to wait an average of 6 hours with the lower-sensitivity, lower-precision cTn assays to see a conclusive increase in plasma cTn levels after the first troponin measurement, but today's high-sensitivity cTn tests that are separated by a mere 2 to 3 hours, can be highly informative.
Given the urgent need for early diagnosis of ACS and appropriate emergency intervention, as well as the ease of performing this relatively inexpensive assay, clinicians do not need to wait 6 to 8 hours before ordering a second troponin test to rule in ACS.
It is recommend to collect a second specimen for cTn testing within 2 to 3 hours from the collection of the blood sample at presentation to help confirm the diagnosis of MI.
Why dynamics of Troponin is Important:
The most common cause of cardiac injury is myocardial ischemia, ie, acute myocardial infarction. To be detectable, Troponin T takes 2 to 4 hours after the onset of myocardial necrosis, attends peak after about 12 hours and can remain elevated for up to 14 days.
In patients with MI, there is a lag before troponin elevations can be detected.Thus, the markers should be serially monitored upon suspicion for acute coronary syndrome (ACS). The initial recommendations were to check the markers every 6 hours until the expected peak was reached. However, with the more sensitive assays now available, very low concentrations of elevated cardiac markers can be detected, and evidence has demonstrated that checking troponins 3-4 hours after the initial draw can help in early diagnosis of ACS.

The safest rule of thumb is that a single negative test result for troponin does not exclude AMI in a patient with current or very recent symptoms, nor does it exclude clinically significant coronary artery disease.

Let us go here to recapitulate the physiological Role of Troponin in cardiac muscle contraction to appreciate it

 
Importance of the Dynamics of Troponin:
The dynamics of troponin levels (rise and/or fall over time) help distinguish AMI from non-AMI conditions, thus serial troponin testing is the standard approach recommended for assessing patients with suspected acute coronary syndrome (ACS).
The safest rule of thumb is that a single negative test result for troponin does not exclude AMI in a patient with current or very recent symptoms, nor does it exclude clinically significant coronary artery disease.
About acute myocardial infarction (AMI)

1. AMI is part of a group of conditions collectively known as acute coronary syndrome (ACS), which includes both ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI), and unstable angina.
   
2. These conditions are associated with common symptoms but have different underlying pathologies; STEMI is usually associated with a relatively large amount of damage (Transmural) to the myocardium (heart muscle) caused by a major blockage in the coronary artery, and can be detected with ST-elevation on an ECG trace. By comparison, NSTEMI is associated with relatively less damage to myocardium (Sub-endocardial) caused by partial blockage of the coronary artery or blockage of a smaller artery, and does not produce ST-elevation on ECG.
   
3. Acute coronary syndromes arise from an obstruction in the coronary arteries, usually caused by atherosclerosis and build-up of plaque which ruptures. When blood flow to the heart is reduced or blocked for a significant length of time (around 30-60 minutes) damage to cardiomyocytes (heart muscle cells) occurs, a pathological change which distinguishes an AMI from unstable angina.
   
4. Patients with ACS generally present with chest pain, a symptom which is responsible for around 700,000 emergency department attendances per year in England and Wales and 253,765 emergency admissions per year.
   
5. During 2011/12, the Myocardial Ischaemia National Audit Project (MINAP) reported 79,433 admissions with AMI recorded in England and Wales, 32,439 (41%) of which were categorised as STEMI, and 46,994 (59%) were categorised as NSTEMI.
   
6. The incidence of acute myocardial infarction increases with age, with the average age of first STEMI being 65 years, and of first NSTEMI 70 years. The incidence is also greater amongst men, with men being twice as likely to have an AMI as women.
   

^{Why Troponin test is preferred to Creatine Kinase MB}

The skeletal and cardiac muscle troponin T and troponin I are immunologically distinct entities. Separate sets of genes code for these proteins. Thus, the cardiac troponin assays, which rely on antigen antibody interaction, are specific for cardiac troponins and can be used to differentiate between the skeletal and cardiac troponins.
Cardiac troponin levels do not rise in the presence of skeletal damage without cardiac myocyte damage. However, this is not the case for creatine kinase MB, which, being present to some extent in skeletal muscle and several other tissues such as the intestines, tongue, diaphragm, uterus, and prostate, may be elevated upon injury to these tissues, potentially resulting in false-positive results. Because of this, troponin testing is superior to creatine kinase MB testing.
Status of Electrocardiography (ECG) as a single mode of diagnosis of AMI:
Electrocardiography (ECG) was one of the earliest diagnostic modalities introduced to evaluate ischemic injury to the heart. Despite its usefulness, ECG continues to be nonsensitive in diagnosing ischemic cardiac events, as ECG findings are normal in many patients with ischemic injury.
The introduction of various markers of cardiac injury, such as creatinine kinase MB, troponins, and myoglobins, has revolutionized the diagnosis of myocardial injury. The cardiac troponins, by virtue of being the most sensitive and specific, have become the preferred biomarker for evaluation of patients with suspected MI.

Determining infarct size:
Peak troponin values can provide an estimate of the infarct size and the severity of myocardial damage. These values are more sensitive in the setting of transmural infarction (ST-segment–elevation MI [STEMI]) than in subendocardial infarctions (NSTEMI). This correlation holds true for both troponin T and troponin I (peak or values at 72-96 hours). Higher values generally correlate with a larger infarct
Significance of degree of troponin elevation
The degree of troponin elevation correlates well with both the 30-day mortality and long-term mortality. Various clinical trials have evaluated the degree of elevation of both troponin I and troponin T and found that higher elevations at presentation and peak are associated with worse long-term outcomes. The absolute values have been used to guide treatment decisions and to identify patients who are at an increased risk of death.
Prognostic value of the timing of elevation
Patients who present with elevated troponin levels at baseline tend to have worse outcomes than those in whom troponin levels are elevated at 8 hours. Outcomes are best in patients in whom troponin levels never elevate.
In both STEMI and NSTEMI, elevated levels of troponin T and troponin I at presentation are associated with a worse prognosis in terms of both short-term and long-term mortality. 
 
How often to perform troponin testing and the need for serial testing

In patients with MI, there is a lag before troponin elevations can be detected.Thus, the markers should be serially monitored upon suspicion for acute coronary syndrome (ACS). The initial recommendations were to check the markers every 6 hours until the expected peak was reached. However, with the more sensitive assays now available, very low concentrations of elevated cardiac markers can be detected, and evidence has demonstrated that checking troponins 3-4 hours after the initial draw can help in early diagnosis of ACS.





Reference:
http://emedicine.medscape.com/article/2073935-overview#a30
Jaffe AS: 2001-A biomarker odyssey. Clin Chim Acta 1999;284:197-211

More Sensitive Troponin 1 Assay to Screen for Possible Heart Attack in Future

Typical Changes in CK-MB and Cardiac Troponin In MI

Currently, troponin is measured on admission and 12 hours after the onset of symptoms of heart attack as recommended in the UK. However,
Troponin levels actually rise quickly after an MI but may not reach higher thresholds until six to 12 hours after symptom onset. The cut off level to diagnose myocardial infarction at present is more than 0.20ng/ml of plasma.
More sensitive troponin assay can detect levels as low as 0.05ng/ml of plasma. Symptomatic patients having level between 0.05ng/ml and 0.20ng/ml frequently had heart attack within following 12 months; observed by the researchers. But they are being conveniently reassured not to have myocardial infarction(MI) at that time; but may have high risk of another MI within following 12 months.
In the new study, published in the March 23/30, 2011 issue of the Journal of the American Medical Association, the researchers found that the introduction of the more sensitive assay to the clinic led to a halving in death/MI at 12 months in patients who had troponin levels between 0.05 and 0.20 ng/ml.
These more sensitive troponin tests have been available since 2008 and are more widely used in Europe than in the US. By lowering the diagnostic threshold, more patients will be referred to specialists and be investigated. Interestingly, the researchers identified only one patient in a study who was given an inappropriate diagnosis of acute coronary syndrome after the sensitive assay was introduced, and she turned out to have a pulmonary embolism. So false positive diagnosis is not an alarming problem.
False positives could be more of a problem with the new assays, if they were used inappropriately as a screening test in patients who don't have chest pain. This needs to be discouraged. But the study shown that in patients with chest pain, there is little doubt that sensitive troponin tests will improve diagnostic accuracy and outcomes.
From the enrolled 2092 patients with chest pain, 1340 (64%) had plasma troponin assay concentrations of less than 0.05 ng/mL, 170 (8%) had levels of 0.05 to 0.19 ng/ml, and 582 (28%) had levels of 0.20 ng/ml or more.
During the validation phase, at 12 months, a greater proportion of patients with troponin assay concentrations of 0.05 to 0.19 ng/ml had died or been re-admitted with an MI compared with those with troponin levels less than 0.05 ng/ml or 0.20 ng/ml or more; the study concludes.
During the implementation phase, lowering the diagnostic threshold to 0.05 ng/ml was associated with a lower risk of death and recurrent MI in patients with troponin concentrations of 0.05 to 0.19 ng/ml--from 39% to 21%; the study says.
This study was conducted by Dr Nicholas Mills (British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Scotland).

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More Evidence that PPIs Blunt Antiplatelet Activity

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This link is all about the warning of FDA in concomitant use of some proton pump inhibitors (PPI) with clopidogrel; a blood thinning agent usually prescribed after stent placements and other cases of coronary artery disease treatment. It has been seen by the researchers that pantaprazole a PPI prescribed to reduce adverse effect of aspirin, which is also co-prescribed along with clopidogrel may interfere with the action of clopidogrel, adversely affecting the task of blood thinning.

clipped from www.medpagetoday.com The risk of rehospitalization for myocardial infarction (MI) almost doubled in patients treated with both a proton pump inhibitor (PPI) and clopidogrel (Plavix) after acute MI or coronary stent deployment, data from a retrospective cohort study showed. PPIs are frequently used to reduce the risk of gastrointestinal bleeding in patients treated with clopidogrel. However, a growing volume of evidence has suggested that PPIs might reduce clopidogrel's efficacy, the authors wrote. In one recent study, patients treated with omeprazole (Prilosec) in addition to aspirin and clopidogrel had a significantly higher platelet reactivity index score after seven days of treatment than patients who didn't get the PPI (J Am Coll Cardiol 2008; 51: 256-60). However, a subgroup analysis of a large clinical trial showed no increased risk of adverse events in patients who received clopidogrel with or without a PPI (Circulation 2008; 118(suppl 2): Abstract 3999).

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Salt Restriction Can Lower Mortality

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The first advice to a hypertensive patient is to lower dietary salt intake. There has been a number of publications in support of salt restriction in diet. The below is a published article in Medpagetoday; will be interesting to read.

clipped from www.medpagetoday.com Health Group Asks for Lower Salt Limits A New York City-based health organization is proposing that restaurants and packaged food manufacturers lower sodium levels by 25% over five years to greatly reduce preventable health risks. The National Salt Reduction Initiative (NSRI) request would cut the nation's salt intake by 20%, helping prevent a variety of health complications, including hypertension, myocardial infarction, stroke, and ultimately mortality, a statement from the group said. Salt intake is a major contributor to hypertension, which can lead to a MI or stroke and is a leading cause of preventable death, killing more than 800,000 people annually, the government estimates. Many national and international health organizations support the proposal, including the American Heart Association, which added in a release that the group would like to see sodium levels on packaged and prepared foods halved in 10 years.

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New Biomarker Tests For Cool Diagnising Heart Attack

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Copeptin a newer test for myocardial infarction alone is more sensitivity than the conventional troponin test ,and in combination the sensitivity rises to 99%, researchers found.

clipped from www.mims.com Testing for stress marker copeptin, meanwhile, can exclude MI with 99 percent certainty, thus saving many patients from unnecessary further testing. New biomarker tests could slash heart attack diagnosis time Professor Christian Müller, reviewing the data, said that the new tests could answer an unmet clinical need in the assessment of chest pain, since current troponin tests have an undetectable “blind interval” of 3-4 hours after the onset of MI. Even if patients follow recommendations and present within 2 hours of chest pain, the test will be negative and electrocardiography monitoring will be required for 6 to 8 hours. “The current-generation troponin tests are important but have important limitations in [making an] early diagnosis. There seem to be two approaches to solve this problem: either use troponin in combination with copeptin, or perhaps the approach now favored by many is the use of sensitive troponin assays,” said Müller, of the University Hospital Basel, Switzerland.

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A PANACEA CALLED ASPIRIN

Molecule of Aspirin

Aspirin appeared and used fro treatment of headache alone or in combination with paracetamol and caffeine long time back .It was very much an effective remedy.But is notorious to cause stomach problem in form of gastritis, ulcers and bleeding.Then it was not used for many years till its beneficial effect in myocardial ischaemia and infarction was rediscovered.In low doses, as low as 75 mgs per day is prescribed to myocardial infarction patients to keep their blood more fluid i.e. to prevent thrombosis.It is also prescribed in combination with other thrombolytic agents.The advantage it has is low cost and easy availability. It is said that if heart attack is suspected and nothing is found a tablet of aspirin will prevent much damage to heart muscle.The potential side effect ,gastrointestinal bleeding can be prevented by other anti-ulcerogenic drugs. 
Researchers also say that aspirin helps in early diagnosis of colon cancer.The hall mark of colon cancer is painless  bleeding per anus besides other symptoms.the bleeding tendency is probably facilitated by aspirin.
It is still the drug of choice for a very important disease called Rheumatic arthritis having much dreaded sequelae  of rheumatic heart disease.
So in right doses and judicious combination it is a panacea for health.

1) Blocked Coronary Artery,2)Ischaemic heart muscle.

Headache ???

Distribution Of Pain Of Heart Attack.

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WORNING SYMPTOMS OF HEART ATTACK

Generally speaking heart attack means assault on it's muscles.Heart can be thought as a muscular pump,maintaining blood circulation throughout the body providing nutrition and oxygen .The heart also get supply from it's own blood vessels to survive and function.Due to various reasons importantly blockade to it's blood vessels, may be partial or complete, deprives it of the oxygen and other things.This blocked most commonly occurs due to deposition of bad fat on it's wall called atherosclerosis . This causes heart muscles to scream for oxygen and nutrition and may progress to death of a portion it, called myocardial infarction.The symptoms experienced are in form of some sort of squeegeeing sensation of chest more towards left,severe to milder pain in left lower chest which may seem traveling to neck,arm, upper abdomen and right side of chest.Patient may be sweating, fainting,vomiting and laboring to take respiration.Patient may go to immediate shock and even death instantaneously.More often patient becomes breathless on accustomed exertion, a common warning sign not to be ignored.Immediate rush to the local doctor in the first place instead of searching for expert may save life and lessen the damage .

The message is that the local doctor is the savior