Previous WHO criteria [ 7 ]  formulated in 1979 put less emphasis on cardiac biomarkers; according to these, a patient is diagnosed with myocardial infarction if two (probable) or three (definite) of the following criteria are satisfied:


The general appearance of patients may vary according to the experienced symptoms; the patient may be comfortable, or restless and in severe distress with an increased  respiratory rate . A cool and  pale skin  is common and points to  vasoconstriction . Some patients have low-grade fever (38–39 °C).  Blood pressure  may be elevated or decreased, and the  pulse  can become  irregular . [ 8 ] [ 9 ] : 1444


If heart failure ensues, elevated  jugular venous pressure  and  hepatojugular reflux , or swelling of the legs due to peripheral  edema  may be found on inspection. Rarely, a cardiac bulge with a pace different from the pulse rhythm can be felt on  precordial examination . Various abnormalities can be found on  auscultation , such as a third and fourth  heart sound ,  systolic murmurs , paradoxical splitting of the second heart sound, a  pericardial  friction rub and  rales  over the lung. [ 8 ] [ 9 ] : 1450


The primary purpose of the  electrocardiogram  is to detect  ischemia  or acute coronary injury in broad, symptomatic  emergency department  populations. A serial ECG may be used to follow rapid changes in time. The standard 12 lead ECG does not directly examine the  right ventricle , and is relatively poor at examining the posterior basal and lateral walls of the  left ventricle . In particular, acute myocardial infarction in the distribution of the circumflex artery is likely to produce a nondiagnostic ECG. [ 10 ]  The use of additional ECG leads like right-sided leads V3R and V4R and posterior leads V7, V8, and V9 may improve sensitivity for right ventricular and posterior myocardial infarction. [ citation needed ]


The 12 lead ECG is used to classify patients into one of three groups: [ 11 ]


A normal ECG does not rule out acute myocardial infarction. Mistakes in interpretation are relatively common, and the failure to identify high risk features has a negative effect on the quality of patient care. [ 12 ]


It should be determined if a person is at high risk for myocardial infarction before conducting imaging tests to make a diagnosis. [ 13 ]  People who have a normal ECG and who are able to exercise, for example, do not merit routine imaging. [ 13 ]  Imaging tests such as stress radionuclide  myocardial perfusion imaging  or stress  echocardiography  can confirm a diagnosis when a person's history, physical exam, ECG and cardiac biomarkers suggest the likelihood of a problem. [ 13 ]


Cardiac markers or cardiac enzymes are proteins that leak out of injured myocardial cells through their damaged cell membranes into the bloodstream. Until the 1980s, the enzymes  SGOT  and  LDH  were used to assess cardiac injury. Now, the markers most widely used in detection of MI are  MB  subtype of the enzyme  creatine kinase  and cardiac  troponins  T and I as they are more specific for myocardial injury. The cardiac troponins T and I which are released within 4–6 hours of an attack of MI and remain elevated for up to 2 weeks, have nearly complete tissue specificity and are now the preferred markers for assessing myocardial damage. [ 14 ]
 Heart-type fatty acid binding protein  is another marker, used in some home test kits.
Elevated troponins in the setting of chest pain may accurately predict a high likelihood of a myocardial infarction in the near future. [ 15 ]  New markers such as  glycogen phosphorylase isoenzyme BB  are under investigation. [ 16 ]  Note that only the cardiac troponins are used clinically for myocardial infarction as creatine kinase adds little value in diagnosing MI while adding to system cost. [ 17 ] [ 18 ] [ 19 ]


The diagnosis of myocardial infarction requires two out of three components (history, ECG, and enzymes).  When damage to the heart occurs, levels of cardiac markers rise over time, which is why  blood tests  for them are taken over a 24-hour period. Because these enzyme levels are not elevated immediately following a heart attack, patients presenting with chest pain are generally treated with the assumption that a myocardial infarction has occurred and then evaluated for a more precise diagnosis. [ 20 ]


In difficult cases or in situations where intervention to restore blood flow is appropriate, coronary  angiography  can be performed. A  catheter  is inserted into an artery (typically the  radial  or  femoral artery [ 21 ] ) and pushed to the vessels supplying the heart. A radio-opaque dye is administered through the catheter and a sequence of x-rays (fluoroscopy) is performed. Obstructed or narrowed arteries can be identified, and  angioplasty  applied as a therapeutic measure (see below). Angioplasty requires extensive skill, especially in emergency settings. It is performed by a physician trained in  interventional cardiology . [ citation needed ]


Histopathological  examination of the heart may reveal infarction at  autopsy .  Gross examination  may reveal signs of myocardial infarction. [ citation needed ]


Under the microscope, myocardial infarction presents as a circumscribed area of ischemic, coagulative  necrosis  (cell death). On gross examination, the infarct is not identifiable within the first 12 hours. [ 22 ]


Although earlier changes can be discerned using  electron microscopy , one of the earliest changes under a normal microscope are so-called  wavy fibers . [ 23 ]  Subsequently, the myocyte  cytoplasm  becomes more  eosinophilic  (pink) and the cells lose their transversal striations, with typical changes and eventually loss of the  cell nucleus . [ 24 ]  The interstitium at the margin of the infarcted area is initially infiltrated with  neutrophils , then with  lymphocytes  and  macrophages , who  phagocytose  ("eat") the myocyte debris. The necrotic area is surrounded and progressively invaded by  granulation tissue , which will replace the infarct with a fibrous ( collagenous )  scar  (which are typical steps in  wound healing ). The interstitial space (the space between cells outside of blood vessels) may be infiltrated with  red blood cells . [ 22 ]


These features can be recognized in cases where the perfusion was not restored; reperfused infarcts can have other hallmarks, such as  contraction band necrosis . [ 25 ]


These tables gives an overview of the histopathology seen in myocardial infarction by time after obstruction. [ citation needed ]


Differential diagnoses for myocardial fibrosis:


Management of acute coronary syndrome  is targeted against the effects of reduced blood flow to the affected area of the  heart muscle , usually because of a  blood clot  in one of the  coronary arteries , the vessels that supply oxygenated blood to the myocardium. This is achieved with urgent hospitalization and medical therapy, including drugs that relieve  chest pain  and reduce the size of the infarct, and drugs that inhibit clot formation; for a subset of patients invasive measures are also employed ( coronary angiography  and  percutaneous coronary intervention ). Basic principles of management are the same for all types of  acute coronary syndrome . However, some important aspects of treatment depend on the presence or absence of  elevation of the ST segment  on the  electrocardiogram , which classifies cases upon presentation to either  ST segment  elevation  myocardial infarction  (STEMI) or non-ST elevation acute coronary syndrome (NST-ACS); the latter includes  unstable angina  and non-ST elevation myocardial infarction (NSTEMI). Treatment is generally more aggressive for STEMI patients, and  reperfusion therapy  is more often reserved for them. Long-term therapy is necessary for prevention of  recurrent events  and  complications . [ 1 ]


Acute coronary syndromes are caused by sudden and critical reduction of blood flow in one of the coronary arteries, the vessels that supply oxygenated blood to the myocardium (heart muscle), typically by a blood clot. The principal symptom is typically chest pain, known as angina pectoris; people who present with angina must prompt evaluation for possible acute coronary syndrome. [ 2 ]


Acute coronary syndromes are classified to two major categories, according to the patient's electrocardiogram, and specifically the presence or absence of persistent (>20 min)  ST segment elevation  (or  left bundle branch block ). [ 2 ]  Patients with acute coronary syndrome and ST elevation are said to have ST-elevation myocardial infarction (STEMI) and they tend to have one of their coronary arteries totally blocked. [ 3 ]  Damage is reversible for approximately 20 [ 4 ] -30 [ 5 ]  minutes after complete obstruction of blood flow; thereafter myocardial  cell death  ensues and progresses as time passes. Therefore, complete and sustained restoration of blood flow must be as prompt as possible to ensure maximum salvage of functional myocardium, a principle expressed in the maxim "time is muscle". [ 6 ]  This is achieved with reperfusion therapy, which is based on invasive reopening of the affected coronary artery with primary percutaneous coronary intervention, or non-invasive breaking up of the responsible blood clot with a  thrombolytic drug . [ 7 ]


Patients without ST segment elevation are said to have non-ST-elevation acute coronary syndrome and tend not to have full occlusion of a coronary artery. If there is evidence of myocardial cell death (especially elevated  cardiac biomarkers ) they are considered to have a non-ST-elevation myocardial infarction (NSTEMI); otherwise they are classified with unstable angina. [ 8 ]  Their management is based on the estimation of their risk for adverse events. Patients at low risk can be adequately treated with medical therapy, in many ways similar to the one used for STEMI (but excluding thrombolytics). Those at moderate to high risk benefit from an early invasive strategy, which includes  coronary angiography  and, if necessary,  revascularization  with percutaneous coronary intervention or  coronary artery bypass surgery . [ 9 ]


Medical therapy for acute coronary syndromes is based on drugs that act against ischemia and resultant angina and limit the infarct size (i.e., the area of myocardium that is affected), as well as drugs that inhibit clot formation. The latter include  antiplatelet agents , which block the activation and aggregation of  platelets  (cellular blood components that contribute to clot formation), and  anticoagulant agents  (which attenuate the  coagulation cascade ). Long-term therapy in acute coronary syndrome survivors is targeted against recurrence and long-term complications ( secondary prevention ). [ 1 ]


Women are taken less seriously than men when they have a heart attack leading to higher mortality among women. [ 10 ]


Because of the relationship between the duration of myocardial ischemia and the extent of damage to  heart muscle, public health services encourage people experiencing possible  acute coronary syndrome symptoms  or those around them to immediately call  emergency medical services . [ 11 ] [ 12 ] [ 13 ]


Patients with known  coronary artery disease  who have been prescribed  nitroglycerin  should promptly take one dose, and call emergency medical services if their symptoms do not improve within 2–5 minutes. Chewing non−enteric-coated  aspirin  is encouraged (unless there are  contraindications ).


Patients should stay calmed in a comfortable position. In case of heart attack, [ 14 ]  it would not usually be lying down, but sitting down or sitting down with folded knees (but patients would notice the position that fits for them).


Patients should not be transported to hospital by private vehicles instead of an ambulance, unless evacuation by land or air ambulance is impossible (e.g., dangerous weather in a very remote area), and if they must be, it should be done if possible with someone trained in cardiac first aid.  [ 15 ]


Health care professionals are responsible for teaching their patients at risk of acute coronary syndrome what the symptoms of this condition are, and that it is imperative to seek urgent medical attention in case they present. [ 16 ]


Emergency Medical Services (EMS) Systems vary considerably in their ability to evaluate and treat patients with suspected acute myocardial infarction. Some provide as little as first aid and early defibrillation. Others employ highly trained paramedics with sophisticated technology and advanced protocols. [ 17 ]  Paramedic services are capable of providing  oxygen , IV access, sublingual  nitroglycerine ,  morphine , and  aspirin .  Some advanced paramedic systems can also perform 12-lead ECGs. [ 18 ]   If a STEMI is recognized the paramedic may be able to contact the local PCI hospital and alert the emergency room physician, and staff of the suspected AMI. Some Paramedic services are capable of providing  thrombolytic therapy  in the prehospital setting, allowing reperfusion of the myocardium. [ 19 ] [ 20 ]


With  primary PCI  emerging as the preferred therapy for ST-segment elevation myocardial infarction,  EMS  can play a key role in reducing  door-to-balloon  intervals (the time from presentation to a hospital  ER  to the restoration of coronary artery blood flow) by performing a 12-lead  ECG  in the field and using this information to triage the patient to the most appropriate medical facility. [ 21 ] [ 22 ] [ 23 ] [ 24 ]  In addition, the 12-lead ECG can be transmitted to the receiving hospital, which enables time saving decisions to be made prior to the arrival of the patient. This may include a "cardiac alert" or "STEMI alert" that calls in off duty personnel in areas where the  cardiac cath lab  is not staffed 24 hours a day. [ 25 ]   Even in the absence of a formal alerting program, prehospital 12-lead ECGs are independently associated with reduced door to treatment intervals in the emergency department. [ 26 ]


In patients with symptoms typical of myocardial ischemia an electrocardiogram must be immediately obtained - e.g., within 10 minutes from first contact with medical or paramedical personnel, including  prehospital  setting; the  electrocardiographic findings  will guide the subsequent management. Patients with  elevation of the ST segment  (or presumed new  left bundle branch block ) are treated based on guidelines for  ST elevation myocardial infarction  (STEMI) and must undergo reperfusion therapy as soon as possible. Serum  cardiac biomarkers  are routinely obtained and their elevation is necessary for confirming diagnosis of myocardial infarction; [ 27 ]  however, reperfusion must not be delayed by waiting for the results. Patients without the above findings are initially classified with non ST elevation  acute coronary syndrome , and subsequent cardiac biomarker results will differentiate between true  non ST elevation myocardial infarction  (NSTEMI) and  unstable angina . [ 28 ] [ 29 ] [ 30 ]


Relief of the pain of angina is of paramount importance, not only for humane reasons but because the pain is associated with  sympathetic activation  that causes  vasoconstriction  and increases the workload of the heart. [ 28 ]  The pain of myocardial ischemia is likely to respond to any intervention that improves the relationship between oxygen demand and supply, like  nitrates ,  beta blockers  and  oxygen . [ 31 ]


Nitrates, like  nitroglycerin , dilate blood vessels, which is beneficial against myocardial ischemia in two ways: By increasing blood flow in the coronary arteries and the amount of oxygen that arrives to heart muscle; and by relaxing all blood vessels in the body, thereby reducing the workload that heart needs to produce against them and the oxygen it consumes. The preferred mode of administration is  sublingually . By relaxing blood vessels nitrates also reduce blood pressure, which must be carefully  monitored ; they must not be used if  hypotension  is present. They must also be avoided in patients who have taken  sildenafil  or other  phosphodiesterase type 5 inhibitors  (used for  erectile dysfunction ) within the previous 24–48 hours, as the combination of the two could cause a serious drop in blood pressure. [ 31 ] [ 32 ] [ 33 ]   Intravenous  nitrates are useful in patients with hypertension or  pulmonary edema . [ 34 ]


By reducing  sympathetic  stimulation of the heart,  beta blockers  decrease heart rate, blood pressure and  cardiac output , and hence heart oxygen consumption. Beta-blockers alleviate ischemic pain, and have also been proved to reduce the size of infarcted heart muscle, the risk of  arrhythmias , and the proportion of patients with acute coronary syndrome who actually evolve STEMI. However, they have also been shown to increase the risk of  acute heart failure . Their early use is contraindicated if there are signs of  congestive heart failure  (e.g.,  Killip class  II or above) or hypotension, along with other  contraindications to beta blockers  ( slow heart rate ,  atrioventricular block ); in the absence of contraindications beta blocker therapy should begin in the first 24 hours. It may be prudent to prefer oral rather than intravenous forms. [ 35 ]


Initial administration of oxygen to all patients with acute coronary syndrome is common practice; however, there is no evidence to support or refute that supplemental oxygen might be harmful or beneficial for cardiac patients who do not need it. [ 36 ]  It is currently recommended to give oxygen only to breathless patients or when  blood oxygen saturation  is low, e.g. <90%. [ 31 ] [ 37 ]


Analgesic agents that are most commonly used are  opioids , and especially  morphine , which is considered the analgesic of choice in patients with ST elevation. Along with its pain-controlling properties, morphine also reduces the work of breathing, alleviates breathlessness, reduces anxiety and has favorable action on  hemodynamic  parameters and cardiac oxygen consumption. [ 31 ] [ 38 ] [ 39 ]  However, in patients presenting without ST elevation, morphine has been shown to have adverse events potential, and its use is considered acceptable only after inadequate pain relief by medication specific against  angina . [ 40 ]   Non-steroidal anti-inflammatory drugs  are contraindicated for both categories of patients. [ 40 ] [ 41 ]


All patients with acute coronary syndrome must immediately receive  antiplatelet therapy , including aspirin and generally a second oral antiplatelet agent. [ 42 ]  Bleeding is the most important side-effect of antiplatelets. [ citation needed ]


Aspirin inhibits  platelet  aggregation and formation of blood clots. It is effective across the entire spectrum of acute coronary syndromes; it has been shown to reduce the  rate of death  in patients with STEMI and in patients presenting without ST elevation.  Aspirin is contraindicated in patients with documented allergy or known platelet disorder. Patients who have had gastrointestinal symptoms while on long-term aspirin therapy are usually able to tolerate aspirin in the short term. For patients with true intolerance to aspirin  clopidogrel  is recommended. Lower doses need days to achieve full antiplatelet effect, therefore a  loading dose  is necessary for patients who are not already on aspirin. [ 43 ]


Aside from aspirin, three antiplatelet agents taken by mouth have been approved for use in acute coronary syndromes, clopidogrel,  ticagrelor  and  prasugrel ; all reduce platelet aggregation by inhibiting the  P2Y 12  receptor , a type of  adenosine phosphate  receptor, on the surface of platelets. Not all three of them are equally indicated in all types of acute coronary syndromes. In patients with ST elevation the choice of P2Y 12  inhibitor depends on reperfusion strategy; for patients undergoing primary  percutaneous coronary intervention  ticagrelor and prasugrel are considered superior to clopidogrel, as they are more potent and have more rapid onset of action, at the cost of some increase in bleeding risk; for STEMI patients who are treated with  fibrinolysis  and those who do not undergo reperfusion treatment only clopidogrel is indicated. Prasugrel must not be given to patients with a history of  ischemic stroke  or aged 75 years or older. In patients with non-ST elevation acute coronary syndrome current guidelines also recommend immediate administration of dual antiplatelet therapy upon diagnosis; clopidogrel and ticagrelor are indicated in this setting, with ticagrelor considered superior for patients undergoing early invasive strategy (see later). However, emerging evidence questions this strategy. [ 44 ]  As with aspirin, it is necessary to administer a loading dose. [ 45 ] [ 46 ]


Glycoprotein IIb/IIIa inhibitors  are a class of intravenous antiplatelet agents used in patients undergoing percutaneous coronary intervention, consisting of  abciximab ,  eptifibatide  and  tirofiban . Patients presenting with ST elevation that will be reperfused with percutaneous coronary intervention may receive one of the above agents at the time of  catheterization , or perhaps before. Administering eptifibatide or tirofiban may also be reasonable in patients presenting with NST-ACS who are considered of intermediate or high risk and are treated with early invasive strategy. [ 47 ] [ 48 ]


Anticoagulants in acute coronary syndrome are targeted against the coronary blood clot, as well as towards prevention of thrombotic complications, like formation of blood clots in the  ventricles ,  stroke ,  pulmonary embolism  or  deep vein thrombosis . [ 49 ]  Patients undergoing PCI also need an anticoagulant to prevent  catheter  thrombosis. Options include  unfractionated heparin ,  enoxaparin  (a  low molecular weight heparin ),  fondaparinux  (a  pentasaccharide  antagonist of  factor Xa ) and  bivalirudin  (a  direct thrombin inhibitor ); all the above agents are given  parenterally  (subcutaneously or  intravenously ). Unfractionated heparin has the disadvantage of requiring dose adjustment based on a laboratory exam,  activated partial thromboplastin time  (APTT). In STEMI patients choice depends on the reperfusion strategy used (see below); bivalirudin is used when PCI is employed only, while in the same case fondaparinux is not preferred. [ 50 ]  Similarly, in Non-STE ACS bivalirudin too is only used when an early invasive strategy is chosen. [ 51 ]


The concept of reperfusion has become so central to the modern treatment of acute myocardial infarction, that we are said to be in the reperfusion era. [ 53 ] [ 54 ]  Patients who present with suspected acute myocardial infarction and ST segment elevation (STEMI) or new bundle branch block on the 12 lead  ECG  are presumed to have an occlusive thrombosis in an epicardial coronary artery. They are therefore candidates for immediate reperfusion, either with  thrombolytic therapy ,  percutaneous coronary intervention  (PCI) or when these therapies are unsuccessful,  bypass surgery . [ citation needed ]


Individuals without ST segment elevation are presumed to be experiencing either unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI). They receive many of the same initial therapies and are often stabilized with  antiplatelet drugs  and  anticoagulated . If their condition remains ( hemodynamically ) stable, they can be offered either late  coronary angiography  with subsequent restoration of blood flow (revascularization), or  non-invasive   stress testing  to determine if there is significant ischemia that would benefit from revascularization.  If hemodynamic instability develops in individuals with NSTEMIs, they may undergo urgent coronary angiography and subsequent revascularization. The use of thrombolytic agents is contraindicated in this patient subset, however. [ 55 ]


The basis for this distinction in treatment regimens is that ST segment elevations on an ECG are typically due to complete occlusion of a coronary artery. On the other hand, in NSTEMIs there is typically a sudden narrowing of a coronary artery with preserved (but diminished) flow to the distal myocardium. Anticoagulation and antiplatelet agents are given to prevent the narrowed artery from occluding. [ citation needed ]


At least 10% of patients with STEMI do not develop myocardial necrosis (as evidenced by a rise in cardiac markers) and subsequent Q waves on EKG after reperfusion therapy. Such a successful restoration of flow to the infarct-related artery during an acute myocardial infarction is known as "aborting" the myocardial infarction. If treated within the hour, about 25% of STEMIs can be aborted. [ 56 ]


Additional objectives are to prevent life-threatening arrhythmias or conduction disturbances. This requires monitoring in a  coronary care unit  and protocolized administration of  antiarrhythmic agents .  Antiarrhythmic agents are typically only given to individuals with life-threatening arrhythmias after a myocardial infarction and not to suppress the  ventricular ectopy  that is often seen after a myocardial infarction. [ 57 ] [ 58 ] [ 59 ]


Cardiac rehabilitation  aims to optimize function and  quality of life  in those affected by a heart disease. This can be with the help of a physician, or in the form of a cardiac rehabilitation program. [ 60 ]


Physical exercise  is an important part of  rehabilitation  after a myocardial infarction, with beneficial effects on cholesterol levels, blood pressure, weight,  stress  and  mood . [ 60 ]  Some patients become afraid of exercising because it might trigger another infarct. [ 61 ]  Patients are encouraged to exercise, and should only avoid certain exerting activities. Local authorities may place limitations on  driving   motor vehicles . [ 62 ]  In most cases, the advice is a gradual increase in physical exercise during about 6–8 weeks following an MI. [ 63 ]  If it doesn't feel too hard for the patient, the advice about exercise is then the same as applies to anyone else to gain health benefits, that is, at least 20–30 minutes of moderate exercise on most days (at least five days per week) to the extent of getting slightly short of breath. [ 63 ]


Some people are afraid to have  sex  after a heart attack. Most people can resume sexual activities after 3 to 4 weeks. The amount of activity needs to be dosed to the patient's possibilities. [ 64 ]


Cocaine  associated myocardial infarction should be managed in a manner similar to other patients with acute coronary syndrome, except that  beta blockers  should not be used and  benzodiazepines  should be administered early. [ 65 ]   The treatment itself may have complications. If attempts to restore the blood flow are initiated after a critical period of only a few hours, the result may be a  reperfusion injury  instead of amelioration. [ 66 ]


In  wilderness first aid , a possible heart attack justifies  evacuation  by the fastest available means, often meaning the initiation of a  MEDEVAC . The suspicion or provisional diagnosis of an MI means that it is inappropriate for the patient to walk out of the wilderness setting and will require them to be carried or conveyed in a vehicle.  Aspirin, nitroglycerin, and oxygen can all be given with relative ease in a wilderness setting and should be administered as soon as possible in suspected cases of MI.  Wilderness management of  cardiac arrest  differs slightly from that carried out in an urban setting in that it is generally considered acceptable to terminate a resuscitation attempt after 30 minutes if there has been no change in the patient's condition. [ citation needed ]


Certified personnel traveling by commercial aircraft may be able to assist an MI patient by using the on-board  first aid kit , which may contain some cardiac drugs (such as  glyceryl trinitrate  spray,  aspirin , or  opioid  painkillers), an  AED , [ 67 ]  and  oxygen . Pilots may divert the flight to land at a nearby airport.  Cardiac monitors  are being introduced by some airlines, and they can be used by both on-board and ground-based physicians. [ 68 ]


Percutaneous coronary intervention  ( PCI ) is a minimally invasive non-surgical procedure used to treat  narrowing  of the  coronary arteries  of the  heart  found in  coronary artery disease . [ 2 ]  The procedure is used to place and deploy  coronary stents , a permanent wire-meshed tube, to open narrowed coronary arteries. PCI is considered 'non-surgical' as it uses a small hole in a peripheral artery (leg/arm) to gain access to the arterial system; an equivalent surgical procedure would involve the opening of the chest wall to gain access to the heart area. The term ' coronary angioplasty  with stent' is synonymous with PCI. The procedure visualises the blood vessels via  fluoroscopic  imaging and  contrast dyes . PCI is performed by an  interventional cardiologists  in a  catheterization laboratory  setting. [ 3 ]


Patients who undergo PCI broadly fall into two patient groups. Those who are suffering from a  heart attack  and are in a critical care emergency room setting and patients who are clinically at a high risk of suffering a heart attack at some future point. PCI is an alternative to the invasive surgery  coronary artery bypass grafting  ( CABG , often referred to as "bypass surgery"), which bypasses narrowed arteries by grafting vessels from other locations in the body. Coronary angioplasty was first introduced in 1977 by  Andreas Gruentzig  in Switzerland. [ 4 ]


PCI is used to open a blocked coronary artery/arteries and to restore arterial blood flow to heart muscle, without requiring open-heart surgery. In patients with acute coronary syndromes, PCI may be appropriate; guidelines and best practices are constantly evolving. [ 5 ]  Heart attack 'onset to treatment time' is important and significantly influences clinical outcomes of PCI procedures. The rapid  reperfusion  of heart muscle is critical in preventing further heart muscle damage caused by heart attacks, this time is often referred to as 'Onset-to-Door' and ' Door-to-balloon'  time, shortening this time is an important goal within an emergency care/ hospital setting. A number of initiatives have been active sponsored by a variety of organizations and hospital groups since the late 1990s to reduce this time to treatment. [ 6 ]


The use of PCI in addition to  anti-angina medication  in stable angina  may reduce the number of patients with angina attacks for up to 3 years following the therapy, [ 7 ]  but does not reduce the risk of death, future myocardial infarction or need for other interventions. [ 8 ]


PCI is widely practiced and has a number of risks; [ 9 ]  however, major procedural complications are uncommon. PCI is performed using minimally invasive  catheter-based procedures  by an interventional cardiologist, a medical doctor with special training in the treatment of the heart. [ 10 ]


For most patients who are not receiving primary PCI (not having PCI to treat a heart attack) the patient is usually awake during PCI, and chest discomfort may be experienced during the procedure.  Bleeding from the insertion point in the groin (femoral artery) or wrist (radial artery) is common, in part due to the use of  antiplatelet drugs . Some  bruising  is common, but occasionally a  hematoma  may form. This may delay hospital discharge as flow from the artery into the hematoma may continue (pseudoaneurysm) which requires surgical repair. Infection at the skin puncture site is rare and  dissection  (tearing) in the interior wall of an arterial blood vessel is uncommon.  Allergic reaction  to the contrast dye used is possible, but has been reduced with the newer agents. [ 11 ]  Deterioration of kidney function can occur in patients with pre-existing kidney disease, but kidney failure requiring dialysis is rare. Vascular access complications are less common and less serious when the procedure is performed via the radial artery. [ 12 ]


The most serious risks are  death ,  stroke ,  ventricular fibrillation  (non-sustained  ventricular tachycardia  is common),  myocardial infarction  (heart attack, MI), and  aortic dissection . A heart attack during or shortly after the procedure occurs in 0.3% of cases; this may require emergency  coronary artery bypass surgery . [ 13 ]  Heart muscle injury characterized by elevated levels of  CK-MB ,  troponin I , and  troponin T  may occur in up to 30% of all PCI procedures. Elevated enzymes have been associated with later clinical outcomes such as higher risk of death, subsequent MI, and need for repeat revascularization procedures. [ 14 ] [ 15 ]  Angioplasty carried out shortly after an MI has a risk of causing a  stroke , but this is less than the risk of a stroke following thrombolytic drug therapy. [ 16 ]


As with any procedure involving the heart, complications can sometimes, though rarely, cause death. The mortality rate during angioplasty is 1.2%. [ 17 ]  Sometimes chest pain can occur during angioplasty because the balloon briefly blocks off the blood supply to the heart.
The risk of complications is higher in: [ 18 ]


Balloon angioplasty  is the inflation of a balloon (often part of an integrated medical device combining a balloon, guidewire, and stent) within the coronary artery to 'crush' the plaque causing the occlusion into the walls of the artery. Balloon angioplasty is still often performed as a part of PCI procedure, it is rarely the only activity performed. Procedures commonly associated with PCI are:


PCI consists of preparation of the skin area to be accessed (groin or arm), by shaving and swabbing the area with a bacteriostatic agent, usually a  chlorhexidine  based product. An introducer needle is inserted into the target artery. Once the access is gained, a "sheath introducer" is inserted to keep the artery open. This procedure is termed  percutaneous  access. As of 2023, catheter systems used in PCI procedures are often fully integrated medical devices. They are usually referred to as "over the wire" or OTW catheters. [ 19 ]  Typically having two lumen paths (a cavity within any tubular structure), the larger one for the navigating highly flexible guidewire and the smaller one for inflating and deflating the balloon or balloon/catheter assembly. The guidewire lumen extends the total length of the catheter. A balloon-stent is often part of the assembled device, other features may also be part of the medical device design depending on the nature of the procedure. [ 20 ]


The interventional cardiologist uses the entry point created during the percutaneous access step, to introduce the catheter system and guides it to the  occluded  area of the coronary artery being treated, using  fluoroscopy  and  radiopaque  dyes as an imaging tool. The device and its balloon/stent components can be inflated to open the  stenotic  diseased artery area. When a stent is used, the stent tube mesh is initially collapsed onto the balloon component of the catheter. In this collapsed state, it is small enough to be passed though relatively narrow peripheral arteries and then inflated by the underlying balloon and pressed firmly against the diseased coronary artery wall. It  is expanded by pressure introduced by injecting physiological saline into the device through the lumen of the still attached catheter. Inflation time and pressure used are recorded during this placement procedure. After the balloon inflation/deflation or the deposition of the stent, the placement device/deflated balloon are removed leaving the stent in place. [ 21 ] [ 22 ]


The interventional cardiologist decides how to treat the blockage in the best way during the PCI/stent placement, based on real-time data. The cardiologist uses imaging data provided by both  intravascular ultrasound  (IVUS), and  fluoroscopic  imaging (combined with a  radiopaque  dye) during the procedure. The information obtained from these two sources enables the cardiologist to track the path of the catheter-device as it moves through the arterial vessels. This information also helps determine both the location and physical characteristics of plaque(s) causing narrowing in the arteries. Data from these two techniques is used to correctly position the stent and to obtain detailed information relating to the coronary arterial anatomy. This anatomy varies greatly among individuals, having this information becomes crucial for effective treatment. The obtained data is recorded on video and is of value in cases when future treatment is needed. [ 23 ] [ 24 ] [ 25 ] [ 26 ]


Older  bare-metal  stents (BMS) provide a mechanical framework that holds the artery wall open, preventing stenosis, or narrowing, of coronary arteries. Newer  drug-eluting stents  (DES) are traditional stents with a polymer coating containing drugs that prevent cell proliferation. The antiproliferative drugs are released slowly over time to help prevent tissue growth.


DES stents have been shown to help prevent  restenosis  of the artery through mechanisms that rely upon the suppression of tissue growth at the stent site and local modulation of the body's inflammatory and immune responses. The first two drug-eluting stents to be utilized were the  paclitaxel -eluting stent and the  sirolimus -eluting stent, both of which have received approval from the U.S. Food and Drug Administration. Most current FDA-approved drug-eluting stents use sirolimus (also known as rapamycin),  everolimus  and  zotarolimus . Biolimus A9-eluting stents, which utilize biodegradable polymers, are approved outside the U.S. [ 27 ]


Newer-generation PCI technologies aim to reduce the risk of late stent thrombosis or other long-term adverse events. Some DES products market a biodegradable polymer coating with the belief that the permanent polymer coatings of DES contribute to long-term inflammation. Other strategies: A more recent study proposes that in the case of population with diabetes mellitus—a population particularly at risk—a treatment with paclitaxel-eluting balloon followed by BMS may reduce the incidence of coronary restenosis or myocardial infarction compared with BMS administered alone. [ 28 ]


After placement of a stent or scaffold, the patient needs to take two antiplatelet medications (aspirin and one of a few other options) for several months to help prevent blood clots. The length of time a patient needs to be on dual antiplatelet therapy is individualized based risks of ischemic events and bleeding risk. [ 29 ]


In primary PCI,  angiography  may demonstrate  thrombus  (blood clots) inside the coronary arteries. Various studies have been performed to determine whether aspirating these clots (thrombus aspiration or manual thrombectomy) is  beneficial. At the moment there is no evidence that routine clot aspiration improves outcomes. [ 30 ]


Lesions with a high degree of calcium deposition within the vessel wall, especially if the calcium is circumferential, are considered to be hard to dilate in regards to balloon  angioplasty . Complex lesions are one of the key predictors of poor outcome in percutaneous coronary intervention (PCI), [ 31 ]  hence calcium lesion modification is needed before implantations of stents. The aim is to create cracks in the calcium within the vessel wall in order to increase the likelihood of successful expansion of the stenosis and delivery of the final stent. [ 32 ] [ 33 ]  This is traditionally achieved by balloon  angioplasty  or debulking strategies including rotational, orbital and laser atherectomy. However, coronary intravascular  lithotripsy  using acoustic shockwaves is a novel approach for treating superficial and deep calcium in the vessel wall. [ 34 ]


For many patients the stenting procedures does not require an in-hospital stay. Much of the time spent in immediate recovery post stenting is to ensure the access site is not bleeding. The patient is generally monitored using ECG etc. Medications to prevent a blood clots from forming generally and in the stent are given directly after the stenting procedure, commonly in the form of an immediate loading dose of the potent anticoagulant (blood thinner)  Plavix  administered as a tablet. Other anticoagulant medicines are also used and the combination of aspirin and Plavix is a typical anticoagulant practice. For patients who have had a heart attack, the length of hospitalization is largely dependent on the muscle damage caused by the event. [ 35 ]


If a stent has been placed as part of the PCI procedure, the patient will be given a 'medical device card' (US) with information about the implanted stent such as a medical device serial number, this is important as it informs clinicians performing future potential medical procedures, this is also the case with arterial closure systems which are also medical devices. [ 36 ]


There is usually significant soreness at the point of entry into the arterial system, and fairly large  hematomas  (significant bruising) are very common, this soreness usually improves after a week or so. Patients are generally advised to 'take it easy' for a week or two and are instructed to be cautious not to lift any substantial weight, this is primarily to ensure the access site heals. Follow up appointments within a week or two of the procedure with a cardiologist or primary care provider/GP are a standard global practice. [ 3 ]


It is a standard practice to have further follow-up examinations every three to six months for the first year, though these practices do vary by region and practitioners. Further diagnostic  coronary angiography  is not routinely indicated after coronary stent implantation. If progression of heart disease is suspected, a stress test will be performed; patients who develop symptoms or show evidence of ischemia in a stress test may undergo diagnostic cardiac re-catheterization. [ 35 ]


Physical examinations play an important role after PCI-stenting procedures. Those patients at high risk of suffering from complications and those with more complexed coronary issues, angiography may be indicated regardless of the findings of non-invasive stress tests. [ 36 ]


Cardiac rehabilitation  activities are dependent on many factors, but largely are connected to the degree of heart muscle damage prior to the PCI/DES procedure. Many patients who undergo this procedure have not had a heart attack, and may have no notable damage to their hearts. Others may have had a serious heart attack and the amount of damage to their heart's ability to supply the body with oxygenated blood might be impaired. Rehabilitation activities are prescribed to fit each individuals needs. [ 37 ]


Percutaneous coronary angioplasty is one of the most common procedures performed during U.S. hospital stays; it accounted for 3.6% of all operating room procedures performed in 2011. [ 38 ]  Between 2001 and 2011, however, its volume decreased by 28%, from 773,900 operating procedures performed in 2001 to 560,500 procedures in 2011. [ 39 ]


Conflicting data exists relating to clinical outcomes comparing PCI/Stenting and CABG surgery. The preponderance of studies do suggest that CABG offers advantages in reducing death and myocardial infarction in people with multivessel blockages compared with PCI. [ 40 ]  The assessments are complicated by considerations such as the fact that PCI is a minimally invasive procedure and CABG is significant surgery. [ 41 ]  Different modeling studies have come to opposing conclusions on the relative cost-effectiveness of PCI and CABG in people with myocardial ischemia that does not improve with medical treatment. [ 42 ] [ 43 ] [ 44 ]


Coronary angioplasty, also known as  percutaneous  transluminal coronary angioplasty (PTCA), because it is done through the skin and through the lumen of the artery, was first developed in 1977 by  Andreas Gruentzig . The first procedure took place Friday Sept 16, 1977, at  Zurich ,  Switzerland . [ 45 ]  Adoption of the procedure accelerated subsequent to Gruentzig's move to  Emory University  in the United States. Gruentzig's first fellow at Emory was  Merril Knudtson , who, by 1981, had already introduced it to  Calgary ,  Alberta ,  Canada . [ 46 ]  By the mid-1980s, many leading medical centers throughout the world were adopting the procedure as a treatment for  coronary artery disease . [ 47 ]


Current concepts recognize that after three months the artery has adapted and healed and no longer needs the stent. [ 48 ]  Complete revasculariztion of all stenosed coronary arteries after a STEMI is more efficacious in terms of major adverse cardiac events and all-cause mortality, while being safer than culprit-vessel-only approach. [ 49 ]


In 2007 the  New England Journal of Medicine  published the results of a trial called COURAGE. [ 50 ]  The study compared stenting as used in PCI to medical therapy alone in symptomatic stable  coronary artery disease  (CAD). [ 50 ]  This showed there was no mortality advantage to stenting in stable CAD, though there was earlier relief of symptoms which equalized by five years. After this trial there were widely publicized reports of individual doctors performing PCI in patients who did not meet any traditional criteria. [ 51 ]  A 2014 meta-analysis showed there may be improved mortality with second generation  drug-eluting stents , which were not available during the COURAGE trial. [ 52 ]  Medical societies have since issued guidelines as to when it is appropriate to perform percutaneous coronary intervention. [ 53 ] [ 54 ]  In response the rate of inappropriate stenting was seen to have declined between 2009 and 2014. [ 55 ]  Statistics published related to the trends in U.S. hospital procedures, showed a 28% decrease in the overall number of PCIs performed in the period from 2001 to 2011, with the largest decrease notable from 2007. [ 39 ]


The 2017 ORBITA study [ 56 ]  has also caused much controversy, in that it found that following percutaneous coronary intervention there was no statistically significant difference in exercise time compared with medical therapy. The study authors believe that angina relief by PCI is largely a placebo effect. [ 57 ]  Others have noted the small sample size with insufficient power to detect outcome differences and the short 6 week duration of the trial. [ 58 ]  85% of patients in the medical therapy arm elected to have PCI at the end of the trial. [ 59 ]


The 2019 ISCHEMIA trial [ 60 ]  has confirmed that invasive procedures (PCI or CABG) do not reduce death or heart attacks compared to medical therapy alone for stable angina. Patients with angina experienced improved quality of life with PCI compared to medical therapy. [ 61 ]


Precordial thump  is a  medical procedure  used in the treatment of  ventricular fibrillation  or pulseless  ventricular tachycardia  under certain conditions. The procedure has a very low success rate, but may be used in those with witnessed, monitored onset of one of the "shockable"  cardiac rhythms  if a  defibrillator  is not immediately available. [ 1 ] [ 2 ]  It should not delay  cardiopulmonary resuscitation  (CPR) and defibrillation, nor should it be used in those with unwitnessed out-of-hospital  cardiac arrest . [ 1 ] [ 3 ]


In a precordial thump, a provider strikes at the middle of a person's  sternum  with the  ulnar  aspect of the fist. [ 4 ]  The intent is to interrupt a potentially life-threatening rhythm. The thump is thought to produce an electrical  depolarization  of 2 to 5  joules . [ citation needed ]


The precordial thump may only be effective if administered within seconds of the onset of  ventricular fibrillation  or pulseless  ventricular tachycardia . [ 5 ]  It is not helpful for treating ventricular fibrillation if too much time has passed. [ 6 ]  It also has very low effectiveness for treating  ventricular arrhythmia [ 7 ]  (possibly even making it worse), [ 4 ] [ 7 ]  and ventricular tachycardia, [ 2 ]  especially when compared to CPR and defibrillation as alternatives.


Historically, it was recommended as the initial action to take when addressing such witnessed and monitored cardiac arrests in a hospital setting. [ 5 ]  More recently, European guidelines recommend it should no longer be routinely used with available evidence suggesting it does not improve survival to hospital discharge. [ 8 ]  However, American guidelines continue advocating its use by healthcare professionals. [ 9 ]


There are concerns that the precordial thump can result in worsening of a person's heart rhythm more often than it improves it. [ 2 ]


The use of the precordial thump technique has sometimes been shown in famous  movies  and  television , such as in  The Good Doctor  Season 2 episode 5 in which it is performed by Dr. Brown, and  The Resident  Season 1 episode 2 in which it is performed by Conrad Hawkins, usually in passing without any explanation.  Untrained laypersons have been known to attempt it, and sometimes cause additional injury to the person as the blow must be carefully aimed. If applied incorrectly it may cause further injury, for instance inducing  cardiac arrest by blunt trauma , or breaking  the tip of the sternum , risking fatal damage to the  liver  or other abdominal organs. [ citation needed ]


At one time, the technique was also taught as part of standard CPR training with the requirement that it must be administered within 60 seconds of the onset of symptoms.  That time restriction, combined with a number of injuries caused by improper technique, [ citation needed ]  resulted in the procedure being removed from CPR training.


James E. Pennington and  Bernard Lown  at  Harvard University  are credited with formalizing this technique in the medical literature. They published their report in the  New England Journal of Medicine  in the early 1970s.  Richard S. Crampton  and George Craddock, at the  University of Virginia  helped to promote the  paramedic  use of chest thump through a curious accident. In 1970, the Charlottesville-Albemarle Rescue Squad (VA) was transporting a patient with an unstable  cardiac rhythm  in what was then called a  Mobile Coronary Care Unit . When the vehicle inadvertently hit a speed bump in a shopping center parking lot, the patient's normal heart rhythm was restored. Further research confirmed that chest thumping patients with life-threatening  arrhythmias  could save lives. [ 10 ]


Percussion pacing or fist pacing was proposed as a method of delivering  mechanical pacing  to someone in cardiac arrest. There is little evidence to support its use. [ 11 ]  In 1920, German physician Eduard Schott originally described percussion pacing, and a 2007 BJA article describes good benefit to this technique. [ 12 ]


quantium Medical Cardiac Output  ( qCO ) uses  impedance cardiography  in a simple, continuous, and non-invasive way to estimate the  cardiac output  (CO) and other hemodynamic parameters such as the  stroke volume  (SV) and  cardiac index  (CI). The CO estimated by the qCO monitor is referred to as the "qCO". The  impedance plethysmography  allows determining changes in volume of the body tissues based on the measurement of the  electric impedance  at the body surface. [ 1 ] [ 2 ] [ 3 ]


The assessment of cardiac output (CO) is important because it reveals the main cardiac function: the supply of blood to tissues. CO reflects the hemodynamic flow and hence the transport of oxygen; its clinical applications by non-invasive continuous  hemodynamic monitoring  are especially useful for some medical specialties like  anaesthesiology ,  emergency care  and  cardiology , for example to prevent  hypoperfusion  and to guide fluid administration.


Several authors advocate the high reliability and good correlation of cardiography impedance compared to others techniques more established. [ 4 ] [ 5 ] [ 6 ]  Nevertheless, some detractors complain about the sensitivity of the technique to artefacts such as the  electromyography  or breathing movements. [ 7 ] [ 8 ]


The Impedance Cardiography (ICG or Ztot) signal represents the changes in the thoracic impedance due to variations in the blood flow. In practice, the raw Ztot signal (in O) is transformed to the –dZ/dt waveform (filtered negative  first derivative , in O x s-1) by using the first derivative to remark the  inflection points  of the raw Ztot signal. The most important characteristic points of the –dZ/dt waveform are B, C, and X points (see figure 2). All these points are associated with distinct physiological events within the systolic part of the  cardiac cycle , i.e., located after the  QRS complex  onset. In that sense, the R wave from the  ECG  signal can be an important reference for detecting such events. [ citation needed ]


The ICG signal is extremely sensitive to artifacts due to movements and respiration. Baseline variations can considerably alter the dZ/dtmax point and the dependent hemodynamic parameters. High-frequency interferences also can affect the  accuracy  in estimating some characteristics points, essentially the B point, affecting the LVET dependent parameters. The qCO's algorithm uses classical and advanced adaptive filtering techniques to minimize such problems with good results. The algorithm applies a  band-pass filtering stage , which attenuates both the baseline drifts (due to movement or respiration) and the high-frequency signal. Also, it features  Adaptive Neuro-Fuzzy Inference System (ANFIS) , for higher accuracy, which is able to obliterate even artifacts such as the electrosurgical noise. [ 9 ]


Since its discovery, the use of CO monitoring has been restricted to certain kinds of patients because of the risk of the classical procedures. Lately, new kinds of methods and devices have been developed. Nowadays, in practice, the method election is determined mainly by the features of the patients and the possibilities of the hospital to accede to this technology.
Different CO monitor methods can be characterized by their invasiveness or their ability to measure continuously. The most ideal should be reliable, continuous, non-invasive, easy to use, and cost-effective. [ 10 ]  The invasive methods like the still gold standard method  Swan-ganz catheter  ( pulmonary artery catheter ), based on transcardiac thermodilution, are being replaced by its invasiveness; hence these systems will not be inspected in this document.
The minimally invasive methods also require catheterization, but less harmful. One of them is the  Thermodilution Transpulmonary (TDTP) , developed in the late 1990s, which presents risk of  iatrogenic effect  effects such as  pneumothorax ,  Bleeding ,  infection ,  thrombosis  or  vascular ischemia , inherent to the requirement of both  arterial and central venous catheter . As a calibrating method, this system performs a thermodilution curve by measuring the changes in blood temperature due to the injection of cold serum and calculates the CO intermittently through a modified equation of Stewart-Hamilton. [ 11 ]  Furthermore, this method lets a continuous reading of the CO through the analysis of the  arterial Pulse Pressure  (PP) wave.
Admittedly, these systems have some limitations, related for example to the thermodilution, such as thermic artifacts due to the injection of another serum or during the extracorporeal purification treatment (this therapy is required by approximately the 5% of patients in critical areas). [ 12 ]  Most of the monitors able to provide a continuous measure of the CO, are based on the analysis of the  arterial blood pressure (BP) curve, called pulse contour methods. [ 13 ]  They are founded by the fact that the pulse pressure is proportional to the ejection volume; however, this is only true when aortic resistance remains constant, hence, these methods have some limitations such as  obesity , which affects the arterial distensibility, or  aortic regurgitation . Furthermore, the values may be modified in patients with  Intra-Aortic Balloon Pumps (IABP)  or unstable arterial signal as in cases of severe arrhythmias or  ventricular extrasystolia . The signal can be altered also by shock or hypothermia states because of the peripheral vasoconstriction or arterial spasm. Usually, for calculating the stroke volume, the methods based on pulse wave analysis need previous and periodic calibrations that must be done in the same patient, which is a drawback.
The main non-invasive methods can be classified into two groups. The first group is formed by different variations of the echocardiography and  echo-Doppler techniques  and the second group is comprised by the aortic bioimpedance and bioreactance.  [ citation needed ]


Doppler or echocardiography systems cannot assess the CO continuously. The continuous assessment capability is the major advantage of the qCO device. This is especially important to predict if the patient is fluid responsive in cases of hemodynamic instability or circulatory shock, which can be assessed with a simple test named  Passive Leg Raising  (PLR, described in detail below), for which, the quick variations in the CO should be detected.
Another benefit is the fact that qCO is fully non-invasive, thus avoiding risks for the patient. Further, it does not need to be calibrated, which allows accelerating and simplifying the monitoring, thereby, providing a large benefit for both the patients and clinicians.
The Pulse Pressure Variation (PPV) method is influenced by mechanical ventilation, due to changes in the pleural pressure, hence, such monitoring should not be recommended for patients who are not being mechanically ventilated with a regular tidal volume. [ 14 ]


The average resting CO is 5.6 L/min for a healthy male and 4.9 L/min for a female, decreasing with age and increasing with Body Surface Area (BSA).
Changes in the CO can be determined by  Heart rate  (HR) and Stroke Volume (SV). The SV in turn, depends on three general factors:  pre-load ,  post-load  and  myocardial contractility . [ citation needed ]


In the field of anesthesia, the main reason for CO monitoring during surgery are complications that can arise after the immediate postoperative period (such as hypoxemia, tachycardia, or oliguria) and also, if the therapeutic intervention becomes complex. Despite some clinicians believe that the CO monitor can be introduced only when complications emerge, it is recommended to monitor since before the induction in order to have a baseline.
Fluid administration in the intraoperative period is part of the daily practice in anesthesiology. Several studies have demonstrated that the time of administering fluid therapy can be more important than the volume dispensed; thus the treatment guided by BP is primitive, whereas the functional parameters CO and SV can detect easily and quickly the preload variations
In the branch of medical intensive care, the CO and other related parameters may be useful for the differential diagnosis of shock states such as hypovolemic shock, cardiogenic or septic.


The rise of volume is the main therapy elected to improve oxygen delivery. However, approximately, only 50% of subjects respond to fluids by increasing SV. The treatment of non-responsive patients can promote deleterious effects in the pulmonary system due to the increase in extravascular fluid. Hence it is important to have a tool to determine this condition.
It is called SVV to the physiological variations, due to changes in intra-thoracic pressure of spontaneous breathing, which diminish the arterial pulse pressure during inspiration and increase it during inspiration; however if the SVV decreases too much, it can be termed paradoxical pulse and can be related to different pathologies such EPOC or pericarditis.
In mechanically ventilated patients, the same process takes place in reverse, due to the positive pressure. Therefore, the normal values of SVV depend on the ventilation mode, and it can be calculated through the SV with the formula:

 S
 V
 V
 =
 (
 S

 V

 m
 a
 x

 −
 S

 V

 m
 i
 n

 )

 /

 S

 V

 m
 e
 a
 n

 {\displaystyle SVV=(SV_{max}-SV_{min})/SV_{mean}}

 , by a respiratory cycle or other period of time.
During mechanical ventilation the goal is to maintain SVV between 10 and 15%, higher values along with a low SV may indicate the need for volume resuscitation.  [ citation needed ]


SVV may be fairly sensitive and specific used as a dynamic indicator of the volume status to answer the question: “Is your patient fluid responsive?”, compared to the conventional parameters. However, using the SVV should not be recommended to interpret the situation of patients with arrhythmias or vasodilator therapy. Also, to avoid natural variations, the patients must be under mechanical ventilation. [ citation needed ]


A critical point for fluid management in some medical specialties is to adjust the intravascular volume replacement. An incorrect practice can seriously affect the organ function and hence the outcome. Guiding fluid management using standard physiologic variables such as BP and HR, because of their regulated nature, is usually insensitive to changes in intravascular volume and may be misleading for example occulting a hypo-perfusion state. Therefore, optimizing the cardiac preload with fluid administration guided by BP is not reliable. [ citation needed ]


With the formula to achieve objectives, called Goal-Directed Therapy (GDT), Rivers (2001) demonstrated how to reduce mortality in patients with severe sepsis and septic shock through the optimization of different hemodynamic variables for a dynamic and individualized view, instead of maintaining only an adequate Arterial Pressure (AP). Later publications support that the intraoperative GDT, used to maintain adequate systemic oxygenation, can safeguard organs especially sensible from perioperative hypo-perfusion. High-risk patients or even less pernicious patients to major surgery could profit from GDT by reducing the incidence of postoperative complications, thus, improving and accelerating the outcome.  [ citation needed ]


The CO measurement in cardiology provides rewarding diagnostic and prognostic information for the management of patients with left- and right-sided cardiac dysfunction. Pulmonary Arterial Hypertension (PAH) may diminish the CO and promote right-sided heart failure, which untreated could be fatal. A simultaneous measurement of the preload also enables to assay the blood flow levels to discard states of hypovolemia or hypervolemia. [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ]


For the fluid responsiveness evaluation, a small amount of solution can be previously administered as a tester, though this method is not recommended because it is irreversible. Another option is the passive leg raising test, which consists of inducing a fast and transient hemodynamic challenge without fluid infusion. By modifying the patient's position, a volume of venous blood from the lower body toward the right heart it is transferred, simulating an infusion of approximately 300 ml. [ citation needed ]


An increase in the CO (of = 10%) and AP within the next 60–90 seconds after leg elevation indicates a positive result, suggesting that the patient is fluid responsive and might benefit from additional fluid. By contrast if the test is negative, the patient should not be treated as it would be harmful. The fluid overload can raise extravascular water causing deleterious side effects in lungs. [ 22 ]


The basic mechanisms for the hemodynamic regulation are: [ citation needed ]


The explanation why the heart is capable of adapting to growing volumes of blood flow is called 'Frank-Starling's mechanism', which says that the more distended is the muscle during the filling, the more strength of contraction and quantity of blood pumped by the left ventricle to the aorta. When the heart reaches a physiological limitation, then blood pumping cannot increase, although the venous return is further increased. The SVV contributes to knowing the state of euvolemia in ventilated patients and designates the point on the Frank-Starling curve where the patient is. [ 23 ]


In addition to cardiac function, the qCO also evaluates indirectly other related fields as is the  parasympathetic nervous system  (PNS), through the evaluation of the R-R intervals and Heart Rate Variability (HRV or beat-to-beat variation). Since 1960 the HRV has been analyzed. Nowadays, it has become a widely used tool for study the ANS modulation in clinical areas such as cardiology. Even though, its utility is not well known yet. The interest lies in its profound relationship with breathing, ANS, and cardiac autonomic regulation.  [ citation needed ]


The most relevant and validated capacity is to prognosticate the coronary heart disease patients, accordingly, a reduced HRV is related to a high risk of mortality after myocardial infarction. Another important point is the fact that Inflammation is stimulated by the effect of the parasympathetic nervous system and inhibited by the sympathetic, thereby, could also be measured through the R-R intervals to guide the physician. [ citation needed ]


Several reports maintain that the HRV analysis is a highly accurate indicator of the autonomic dysfunction in alcoholic and diabetic subjects. Also, it is growing interest in applying the HRV to evaluate a neurologic function, and the best results have been found out in psychiatric patients. Regarding the anesthesia and critical care fields, the ANS dysfunction should be considered because it is related to high morbidity and mortality in patients undergoing surgery under the general anesthesia effect. Naturally, events as the tracheal intubation and inhalation agents can produce quick variations in ANS. Also, should be regarded in critical patients who may show a worse outcome when it is added to certain illnesses such as sepsis [24,25]. [ 24 ] [ 25 ]


The HRV depends on the age, sex, and also other physiological variations such as hormonal components, genetics, exercise, environmental factors, thermoregulation, etc. A controlled recording could explain variations in ANS due to physiology, pharmacology or pathology [ 26 ]


There exist several systems for quantifying the HRV, nevertheless, none of them have shown better result than others. [ 27 ]  The most widely used methods for the HRV analysis can be grouped under time-domain and frequency-domain, the qCO offers the following values:


The  Relative Atrial Index (RAI)  is a numeric parameter used to assess for  cardiac shunt  defects.  It is calculated from the  standard transthoracic Doppler  echocardiogram  measurements of the right atrial area divided by the left atrial area.  RAI = right atrial area / left atrial area. [ 1 ]  These measurements are made from the apical four chamber view. [ citation needed ]


Large validation studies [ 2 ]  in patients with known atrial septal defects showed that the RAI > 1.0 in the majority of cases. This is in contrast to matched and population controls, where the RAI was significantly below 1.0.  This simple numeric parameter has found a role in the diagnostic work-up for possible shunt defects on standard tranthorcaic  echocardiograms . The RAI rapidly normalizes within 24 hours of percutaneous closure [ 3 ]  of atrial septal defects. [ 4 ]  Secondary validation studies have confirmed the data in discrete patient populations. [ 5 ]   This parameter has been shown to predict long-term survival after acute pulmonary embolism. [ 6 ]


The RAI was conceptualized in response to observed clinical inadequacies of standard transthoracic echocardiography in some shunt conditions. The same author [ 7 ]  had developed several Doppler echocardiographic  numeric parameters  over the last two decades to assess cardiac diastolic function. [ 8 ] [ 9 ]


Remote ischemic conditioning  (RIC) is an experimental medical procedure that aims to reduce the severity of  ischaemic injury  to an organ such as the heart or the brain, most commonly in the situation of a  heart attack  or a  stroke , or during procedures such as heart surgery when the heart may temporary suffer ischaemia during the operation, by triggering the body's natural protection against tissue injury. [ 1 ] [ 2 ]  Although noted to have some benefits in experimental models in animals, this is still an experimental procedure in humans and initial evidence from small studies have not been replicated in larger clinical trials. Successive clinical trials have failed to identify evidence supporting a protective role in humans. [ 3 ]


The procedure involves repeated, temporary cessation of blood flow to a limb to create  ischemia  (lack of  oxygen  and  glucose ) in the tissue. This "conditioning" activates the body's natural protective physiology against  reperfusion injury  and the tissue damage caused by low oxygen levels [ 4 ] —a protection present in many mammals. [ 5 ]  RIC essentially mimics the cardio-protective effects of exercise; [ 6 ]  in fact, exercise can be considered a form of RIC in which the stimulus is distant from the organ being protected. RIC has been termed "exercise in a device", especially suited for patients who are unable or unwilling to work out. [ 7 ]


The phenomenon of  ischemic preconditioning  (IPC) was discovered in 1986 by C. E. Murry and colleagues, [ 8 ]  who observed that repeated, temporary cross-clamping of the  left anterior descending artery  (LAD) in  dogs  protected the LAD territory of the heart against a subsequent prolonged ischemic event, reducing  infarct  size by 75%. This was thought to be a local effect and was termed local ischemic preconditioning. The phenomenon was confirmed by other researchers in dogs,  pigs ,  mice , and  rats . [ citation needed ]


In 1993, Karin Przyklenk and colleagues began using the term "remote" when they observed that cross-clamping on the right side of the heart ( right circumflex artery ) protected the left side of the heart (LAD territory) from ischemia: that is, the protective trigger was remote from the observed effect. [ 9 ]  Other researchers confirmed this remote effect and found that performing the preconditioning protocol on  kidney  or  gastrointestinal  tissue also provided protection to the heart. [ 10 ]


In 2002, Raj Kharbanda and Andrew Redington, working at the  Hospital for Sick Children  in  Toronto , showed that non-invasively stopping and starting blood flow in the arm provided the same protection as invasive preconditioning of the heart. [ 11 ]  This adaptation of the RIC protocol significantly improved its safety and applicability, and resulted in a surge of clinical interest in the technique. [ citation needed ]


More than 10,000 patients worldwide have completed clinical trials involving RIC, and another 20,000 are enrolled in ongoing trials. [ citation needed ]  The first human clinical trial of RIC was conducted by Dr. Redington in pediatric patients undergoing  heart surgery  at the Hospital for Sick Children. [ 12 ]  The patients treated with RIC prior to surgery exhibited less heart damage, as measured by the biomarker  troponin , as well as less need for supportive drugs. This trial was followed by others measuring the effects of RIC on rates and outcomes of  heart attacks ,  heart failure ,  stroke , and cardiothoracic intervention. [ 13 ]


In multiple  randomized controlled trials , [ which? ]  remote ischemic conditioning reduced infarct size in  ST-elevation  myocardial infarction (STEMI) patients when used in the ambulance [ 14 ]  or  emergency department [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ]  as an adjunct therapy to primary  percutaneous coronary intervention  (PCI), or when used with  thrombolytic drugs . [ 20 ]  In seven trials comprising 2,372 STEMI patients, infarct size—a measure of damage to the heart—was reduced by 17–30% on average, and the reduction was greatest (~60%) in the largest infarcts. Further analysis of a Danish study (CONDI-1), in which patients were treated in the ambulance, [ 21 ]  showed that those who received RIC did not show a decline in myocardial salvage index (a measure of a healthy heart) when they experienced a delay in treatment, while the  control group  experienced a significant decline in salvage index. [ 22 ]  The RIC treatment therefore resulted, effectively, in an extension of the " golden hour ", the period in which medical treatment for heart attacks is most effective. [ citation needed ]


Infarct size is a predictor of future cardiovascular events as well as mortality, [ 23 ]  and researchers doing long-term follow-up on STEMI patients treated with RIC found that the reduction in heart damage at the time of the heart attack resulted in clinical improvement four years later: MACCE ( m ajor  a dverse  c ardiovascular and  c erebrovascular  e vent) rates were reduced by 47% (13.5% vs. 25.6%, p=0.018). [ 24 ]  This improvement resulted in mean cumulative cardiovascular medical care costs that were €2,763 lower in the RIC-treated group than in the control group (€12,065 vs. €14,828) [ 25 ] —savings of approximately 20%.


There are currently two large randomized controlled trials of RIC treatment in STEMI patients ongoing in Europe, [ 26 ] [ 27 ]  both of which will examine the effects of RIC treatment on coronary death and hospitalization for heart failure after one year. [ citation needed ]


Remote ischemic conditioning significantly reduced heart damage (as measured by troponin elevations) in four randomized controlled trials involving 816 elective (non-emergency) PCI patients. [ 28 ] [ 29 ] [ 30 ] [ 31 ]  The myocardial damage and troponin elevations seen in elective PCI patients are less than that in emergency STEMI patient, because there is less acute reperfusion injury in elective PCI, and damage instead results from distal embolization and side-branch occlusion. [ 32 ]  Nevertheless, myocardial damage during elective PCI remains a significant predictor of morbidity and mortality, as patients exhibiting any increase in troponin are at a significantly increased risk of future cardiovascular events. [ 33 ]


Researchers at  Papworth Hospital  in  Cambridge  conducted the first large study of RIC in elective PCI patients (the CRISP study) [ 28 ]  and found that patients treated with RIC prior to  stenting  showed a 62% reduction in troponin levels, less chest discomfort, and reduced six-month hospitalization rates. Long-term follow-up of the CRISP [ 34 ]  study showed that this single RIC treatment resulted in a 35% reduction in six-year MACCE rates. [ 35 ]


RIC has been shown to reduce  Contrast-induced nephropathy  (CIN) and contrast-induced  acute kidney injury  (CI-AKI), two serious complications that can occur when patients are given  contrast media  during imaging or invasive procedures such as angioplasty or  percutaneous aortic valve replacement . The incidence of CIN is 13% in an unselected population and can be as much as 57% in patients with poor kidney function and congestive heart failure. [ 36 ]  The development of CIN after percutaneous coronary intervention is independently associated with an increased risk of short- and long-term ischemic and hemorrhagic events. [ 37 ]


RIC provided a statistically significant benefit in five randomized clinical trials comprising 480 patients. The first report was in an observational study of patients in the United States, [ 38 ]  and the first randomized clinical trial to show a benefit in patients at extremely high risk of injury (those with Stage 3 or 4 kidney disease,  diabetes , or heart failure) was done in Germany. [ 39 ]  The German study showed a reduced incidence of CIN (a 70% reduction, from 40% to 12%, p=0.002), with no patients in the treated arm needing in-hospital  dialysis  (compared with 14% in the control group), and reduced six-week readmission rates (a 60% reduction, from 36% to 14%). Similar protection was seen in cancer patients undergoing contrast-enhanced  computed tomography  (CECT): Researchers found a 35% reduction in CIN across the population, [ 40 ]  and the patients at highest risk benefited the most, with a 60% reduction.


These results, confirmed in subsequent clinical trials involving cardiac patients, [ 41 ] [ 18 ] [ 42 ]  show that RIC can protect the kidneys as well as the heart.


Yetgin and colleagues conducted a systematic review and analysis of RIC in cardiac surgery, [ 43 ]  examining thirteen trials involving 891 patients, and found that RIC treatment reduced troponin levels by 21% to 49%. In addition, they concluded that trials in which the primary measure was a validated biomarker (e.g., 72-hour cardiac troponin  AUC ) [ 44 ]  showed a benefit from RIC treatment, while trials in which a non-validated biomarker (e.g., 24-hour troponin AUC) was the primary measure did not show a benefit. [ citation needed ]


In the first prospectively designed trial to examine the effect of RIC on clinical outcomes in  coronary artery bypass grafting  (CABG), Thielmann and colleagues showed that RIC treatment reduced troponin levels and improved long-term morbidity and mortality. [ 45 ]  However, while patients who received the anesthetic  isoflurane  benefited from the treatment, the anesthetic  propofol  blocked the effects of RIC. [ 46 ]  Investigations in Dr. Gerd Heusch's lab showed that propofol abolishes the  phosphorylation  of  STAT5 , [ 47 ]  a key survival molecule that is activated by RIC. Two other trials in CABG surgery (ERICCA [ 48 ]  and RIP-HEART [ 49 ] ) reported neutral results for the clinical benefit of RIC, but both of these trials used propofol as the initiating anesthetic. In a viewpoint letter that followed the publication of the ERICCA and RIP-HEART trials, Heusch and Dr. Bernard Gersh wrote that the use of propofol rather than  volatile anesthesia  appeared to be a common denominator in all studies that failed to find protection with RIC. [ 50 ]


A 2015 trial in high-risk CABG patients showed a reduced incidence of surgical acute kidney injury in RIC-treated patients (37.5% vs. 52.5%, p=0.02), a reduced need for dialysis, and shorter stays in the  intensive care unit . [ 51 ]  This study did not use propofol, and a three-month follow-up found that RIC treatment improved clinical outcomes. [ 52 ]


Researchers are working to expand the clinical applications of RIC beyond cardiovascular indications. Because RIC modifies the  expression of genes  involved in  inflammation ,  coagulation , and  complement pathways , [ 53 ]  researchers believe repeated treatments (chronic conditioning) could aid recovery or prevent disease progression in a variety of chronic conditions. The areas of research that are most advanced are in heart failure and stroke recovery. [ citation needed ]


Despite advances in the treatment of heart attacks, survivors are at a significant risk of heart failure and death within five years because of adverse remodeling processes in the heart. [ 54 ] [ 55 ]  The acute inflammatory process that occurs soon after a heart attack is necessary for healing and scar formation, [ 56 ]  but can be harmful if it continues for an extended period of time. Continued  oxidative stress  results in inflammation, death of heart cells,  fibrosis of the ventricles , and  hypertrophy  (enlargement) of the heart, [ 57 ]  progressing to heart failure. Studies show that repeated daily RIC treatments lead to significant  downregulation  of  neutrophil  activation and proinflammatory responses in humans, [ 58 ]  and could reduce post-heart-attack inflammation.


In rodent models of post-heart-attack heart failure, daily RIC treatment for 28 days resulted in reduced markers of inflammation (including  TGF-b ), improved ventricular function, and improved survival over 100 days, in a dose-dependent manner. [ 59 ]  This study provided the scientific rationale for the CRIC-RCT clinical trial ( NCT01817114 ). There are two other ongoing randomized controlled trials of chronic conditioning in heart-failure patients:  NCT01664611  and  NCT02248441 .


In addition to its efficacy in cardiological settings, RIC is thought to remotely recruit neuroprotective pathways, and its safety, feasibility, and low cost give it high potential in a wide variety of neurological conditions. [ 7 ]  Like the heart, the brain has self-protective abilities and can adapt to stress and injury (e.g.,  hypoxia  or ischemia) by activating cellular protective pathways. [ 60 ]  RIC not only confers protection against ischemia-reperfusion injury, but also increases cerebral blood flow, which may contribute to the neuroprotective effect. [ 61 ]


The first randomized trial of RIC in acute stroke patients was done by Hougaard and colleagues in Denmark. [ 62 ]  Compared with standard treatment, RIC increased tissue survival after one month and reduced the risk of infarction in high-risk tissue. [ citation needed ]


Two randomized trials of RIC have also been conducted in patients with intracranial atherosclerotic stenosis (ICAS), a significant risk factor for stroke with a high risk of recurrence. The first—which included 68 Chinese patients under the age of 80 who had intracranial arterial stenosis of 50–99% and had experienced a stroke or  transient ischemic attack  (TIA) within the previous 30 days [ 63 ] —evaluated the effects of 300 days of brief, repetitive, bilateral arm ischemic conditioning on stroke recurrence. It found that the conditioning reduced the incidence of recurrent stroke from 23.3% to 5% at 90 days, and from 26.7% to 7.9% at 300 days; it also improved the rate of recovery (measured with the  modified Rankin scale ) and cerebral  perfusion . The second trial examined the effect of 180 days of RIC on symptomatic ICAS in Chinese people aged 80–95 years, as invasive stenting is not always suitable for elderly patients, and less-invasive methods are needed. RIC safely prevented stroke and TIA recurrence and reduced inflammation in these patients. [ 64 ]


Delayed  cerebral infarction  after  subarachnoid hemorrhage  is a major cause of morbidity. Two Phase I clinical trials have shown that RIC after subarachnoid hemorrhage is feasible, safe, and well tolerated, and can prevent delayed neurological deficits. [ 65 ] [ 66 ]


Traumatic brain injury  (TBI) shares many pathophysiological pathways with acute stroke, and ischemic preconditioning increases the brain's resistance to injury. [ 67 ]  Animal models of stroke (both open-skull and closed-skull models) [ 68 ]  show that RIC improves cerebral blood flow; reduces ischemic injury,  edema , and cell death; and improves functional outcomes. A small randomized clinical trial in severe TBI also showed that patients who received RIC had lower levels of brain injury biomarkers. [ 69 ]


Reduced cerebral blood flow is an early finding in  vascular cognitive impairment  (VCI). Cardiovascular risk factor control is currently the only management option for VCI, but observational studies suggest that exercise slows down cognitive decline. [ 70 ]  In a mouse model that reproduced the damage seen in patients with VCI ( white matter  damage, cerebral hypoperfusion, inflammation,  blood–brain barrier  damage, and cognitive deficits), daily RIC for two weeks increased cerebral blood flow, and this increase persisted for one week after cessation of conditioning. Moreover, mice that underwent RIC had less inflammation, less white and  gray matter  damage, less  β‑amyloid  deposition, and improved cognition. [ 71 ]


In  laparoscopic procedures , CO2  pneumoperitoneum  is essential for adequate visualization but can lead to elevated intra-abdominal pressure, potentially causing splanchnic hypoperfusion and capillary microcirculation impairment. This scenario predisposes to  ischemia-reperfusion injury , characterized by an upsurge in  reactive oxygen species  (ROS), culminating in a spectrum of peritoneal pathologies, including mesothelial cell damage, inflammatory cascades, and adhesion formation.


Ischemic preconditioning (IPC), entailing transient ischemic episodes prior to prolonged ischemia, has emerged as a prophylactic strategy to ameliorate such iatrogenic oxidative insults. In vitro and in vivo studies elucidate that IPC augments cellular anti-oxidative defenses and modulates inflammatory mediators, potentially attenuating  peritoneal  injury sequelae. [ 72 ] [ 73 ]  Despite the theoretical mechanistic plausibility and encouraging preclinical data, the translatability of these findings to human laparoscopy remains tentative. Human trials in laparoscopic contexts have shown IPC's potential in modulating biomarkers associated with oxidative stress and alleviating clinical symptoms. Notably, a study involving remote ischemic conditioning applied to the upper arm exhibited enhanced skin microcirculation in the lower extremities, suggesting systemic microcirculatory benefits. [ 74 ]  Furthermore, in a trial involving patients undergoing laparoscopic surgery, those subjected to IPC demonstrated notable improvements in systemic antioxidant capacity, as evidenced by elevated  glutathione  levels. Additionally, these patients reported a significant reduction in pain intensity, highlighting IPC's potential in enhancing patient comfort and recovery. [ 75 ]  These findings, while preliminary, underscore IPC's promise in laparoscopic surgery, suggesting its role in reducing oxidative stress and improving postoperative outcomes.


The RIC stimulus can be applied to different tissues in the body. Either the upper limb (arm) or the lower limb (leg) may be used; however, because it is easier and more comfortable, most clinical trials use the upper limb. [ 76 ]  Researchers investigating the optimal dosing for the RIC stimulus have concluded that the upper limb is superior to the lower limb, [ 76 ]  that RIC on one limb generates an equivalent response to RIC on two limbs, [ 77 ]  and that maximal benefit occurs at 4–6 cycles. [ 77 ]


The non-invasiveness and ease of application of RIC have allowed it to be studied in more situations than the original, invasive ischemic preconditioning, which was only realistically applicable in elective surgery. Studies have examined the effects of RIC applied at different times:  [ citation needed ]


The term "post-conditioning" is used to describe short, intermittent inflations of an intra-coronary balloon at the time of reperfusion, and does not refer to RIC on a limb. Delayed post-conditioning is synonymous with chronic conditioning. [ 78 ]


Remote ischemic conditioning on the limb is mostly done by healthcare professionals, using a manual  blood-pressure cuff  and a stopwatch. The standard RIC protocol, used in the majority of clinical trials, consists of four cycles of five minutes of inflation at 200mmHg, followed by five minutes of deflation. This is the original conditioning protocol described by Murry et al. [ 79 ]  based on examinations of energetic depletion of the cell.


One automated device is approved in Europe and Canada for the delivery of remote ischemic conditioning: the autoRIC Device, [ 80 ]  which delivers four cycles of five minutes of inflation at 200mm Hg followed by five minutes of deflation to the upper limb. In a comparative study of this device and manual conditioning, the autoRIC Device was shown to be much easier to use. [ 81 ]


Reperfusion therapy  is a medical treatment to restore blood flow, either through or around, blocked arteries, typically after a heart attack ( myocardial infarction  (MI)). Reperfusion therapy includes  drugs  and  surgery . The drugs are  thrombolytics  and  fibrinolytics  used in a process called  thrombolysis . Surgeries performed may be  minimally-invasive   endovascular procedures  such as a  percutaneous coronary intervention  (PCI), which involves  coronary angioplasty . The angioplasty uses the insertion of a  balloon  and/or  stents  to open up the artery. [ 1 ]  Other surgeries performed are the more invasive  bypass surgeries  that graft arteries around blockages.


If an MI is presented with  ECG  evidence of an  ST elevation  known as  STEMI , or if a  bundle branch block  is similarly presented, then reperfusion therapy is necessary. In the absence of an ST elevation, a non-ST elevation MI, known as an  NSTEMI , or an  unstable angina  may be presumed (both of these are indistinguishable on initial evaluation of symptoms). ST elevations indicate a completely blocked artery needing immediate reperfusion. In NSTEMI the blood flow is present but limited by  stenosis . In NSTEMI, thrombolytics must be avoided as there is no clear benefit of their use. [ 2 ]  If the condition stays stable a  cardiac stress test  may be offered, and if needed subsequent  revascularization  will be carried out to restore a normal blood flow. If the blood flow becomes unstable an urgent angioplasty may be required. In these unstable cases the use of thrombolytics is contraindicated. [ 3 ]


At least 10% of treated cases of STEMI do not develop  necrosis  of the  heart muscle . A successful restoration of blood flow is known as aborting the heart attack. About 25% of STEMIs can be aborted if treated within the hour of symptoms onset. [ 4 ]


Thrombolytic therapy  is indicated for the treatment of STEMI – if it can begin within 12 hours of the onset of symptoms, and the person is eligible based on exclusion criteria, and a  coronary angioplasty  is not immediately available. [ 5 ]  Thrombolysis is most effective in the first 2 hours. After 12 hours, the risk of  intracranial bleeding  associated with thrombolytic therapy outweighs any benefit. [ 3 ] [ 6 ] [ 7 ]  Because irreversible injury occurs within 2–4 hours of the infarction, there is a limited window of time available for reperfusion to work. [ citation needed ]


Thrombolytic drugs are contraindicated for the treatment of unstable angina and NSTEMI [ 3 ] [ 8 ]  and for the treatment of individuals with evidence of  cardiogenic shock . [ 9 ]


Although no perfect thrombolytic agent exists, ideally it would lead to rapid reperfusion, have a high sustained patency rate, be specific for recent thrombi, be easily and rapidly administered, create a low risk for  intracerebral bleeding  and systemic bleeding, have no  antigenicity , adverse  hemodynamic effects , or clinically significant  drug interactions , and be  cost effective . [ 10 ]  Currently available thrombolytic agents include  streptokinase ,  urokinase , and  alteplase  (recombinant  tissue plasminogen activator , rtPA).  More recently, thrombolytic agents similar in structure to rtPA such as  reteplase  and  tenecteplase  have been used. These newer agents boast efficacy at least as well as rtPA with significantly easier administration. The thrombolytic agent used in a particular individual is based on institution preference and the age of the patient.


Depending on the thrombolytic agent being used, additional  anticoagulation  with  heparin  or  low molecular weight heparin  may be of benefit. [ 11 ] [ 12 ]  With tPa and related agents (reteplase and tenecteplase), heparin is needed to keep the coronary artery open. Because of the anticoagulant effect of fibrinogen depletion with streptokinase [ 13 ]  and urokinase [ 14 ] [ 15 ] [ 16 ]  treatment, it is less necessary there. [ 11 ]


Thrombolytic therapy to abort a myocardial infarction is not always effective. The degree of effectiveness of a thrombolytic agent is dependent on the time since the myocardial infarction began, with the best results occurring if the thrombolytic is used within two hours of the onset of symptoms. [ 17 ] [ 18 ]  Failure rates of thrombolytics can be as high as 50%. [ 19 ]  In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the person is then either treated conservatively with anticoagulants and allowed to "complete the infarction" or  percutaneous coronary intervention  (and coronary angioplasty) is then performed. [ 20 ]   Percutaneous coronary intervention in this setting is known as "rescue PCI" or "salvage PCI". Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic. [ citation needed ]


Intracranial bleeding (ICB) and subsequent  stroke  is a serious  side effect  of thrombolytic use. The  risk factors  for developing intracranial bleeding include a previous episode of intracranial bleed, advanced age of the individual, and the thrombolytic regimen that is being used. In general, the risk of ICB due to thrombolytics is between 0.5 and 1 percent. [ 11 ]


The benefit of prompt,  primary angioplasty over thrombolytic therapy for acute STEMI is now well established. [ 21 ] [ 22 ] [ 23 ]  When performed rapidly, an angioplasty restores flow in the blocked artery in more than 95% of patients compared with the reperfusion rate of about 65% achieved by thrombolysis. [ 21 ]  Logistic and economic obstacles seem to hinder a more widespread application of angioplasty, [ 24 ]  although the feasibility of providing regionalized angioplasty for STEMI is currently being explored in the United States. [ 25 ]  The use of a coronary angioplasty to abort a myocardial infarction is preceded by a primary  percutaneous coronary intervention . The goal of a prompt angioplasty is to open the artery as soon as possible, and preferably within 90 minutes of the patient presenting to the emergency room. This time is referred to as the  door-to-balloon  time. Few hospitals can provide an angioplasty within the 90 minute interval, [ 26 ]  which prompted the  American College of Cardiology  (ACC) to launch a national Door to Balloon (D2B) Initiative in November 2006. Over 800 hospitals have joined the D2B Alliance as of March 16, 2007. [ 27 ]


One particularly successful implementation of a primary PCI protocol is in the  Calgary Health Region  under the auspices of the  Libin Cardiovascular Institute of Alberta .  Under this model,  EMS  teams responding to an emergency can transmit the ECG directly to a digital archiving system that allows emergency room staff to immediately confirm the diagnosis. This in turn allows for redirection of the EMS teams to those facilities that are ready to conduct time-critical angioplasty. This protocol has resulted in a median time to treatment of 62 minutes. [ 28 ]


The current guidelines in the United States restrict angioplasties to hospitals with available emergency bypass surgery as a backup, [ 5 ]  but this is not the case in other parts of the world. [ 29 ]


A PCI involves performing a coronary  angiogram  to determine the location of the infarcting vessel, followed by  balloon angioplasty  (and frequently deployment of an intracoronary stent) of the  stenosed  arterial segment.  In some settings, an extraction catheter may be used to attempt to aspirate (remove) the thrombus prior to balloon angioplasty.  While the use of intracoronary  stents  do not improve the short term outcomes in primary PCI, the use of stents is widespread because of the decreased rates of procedures to treat  restenosis  compared to balloon angioplasty. [ 30 ]


Adjuvant therapy  during an angioplasty includes intravenous  heparin ,  aspirin , and  clopidogrel .   Glycoprotein IIb/IIIa inhibitors  are often used in the setting of primary angioplasty to reduce the risk of ischemic complications during the procedure. [ 31 ] [ 32 ]   Due to the number of antiplatelet agents and anticoagulants used during primary angioplasty, the risk of bleeding associated with the procedure is higher than during an elective procedure. [ 33 ]


Emergency bypass surgery for the treatment of an acute myocardial infarction (MI) is less common than PCI or thrombolysis. From 1995 to 2004, the percentage of people with  cardiogenic shock  treated with primary PCI rose from 27.4% to 54.4%, while the increase in  coronary artery bypass graft surgery  (CABG) was only from 2.1% to 3.2%. [ 34 ]   Emergency CABG is usually undertaken to simultaneously treat a mechanical complication, such as a ruptured papillary muscle, or a ventricular septal defect, with ensuing cardiogenic shock. [ 35 ]  In uncomplicated MI, the  mortality rate  can be high when the surgery is performed immediately following the infarction. [ 36 ]  If this option is entertained, the patient should be stabilized prior to surgery, with supportive interventions such as the use of an  intra-aortic balloon pump . [ 37 ]  In patients developing cardiogenic shock after a myocardial infarction, both PCI and CABG are satisfactory treatment options, with similar survival rates. [ 38 ] [ 39 ]


Coronary artery bypass surgery involves an artery or vein from the patient being implanted to bypass  narrowings  or occlusions in the coronary arteries. Several arteries and veins can be used, however  internal mammary artery  grafts have demonstrated significantly better long-term patency rates than  great saphenous vein  grafts. [ 40 ]  In patients with two or more coronary arteries affected, bypass surgery is associated with higher long-term  survival rates  compared to percutaneous interventions. [ 41 ]  In patients with single vessel disease, surgery is comparably safe and effective, and may be a treatment option in selected cases. [ 42 ]  Bypass surgery has higher costs initially, but becomes  cost-effective  in the long term. [ 43 ]  A surgical bypass graft is more  invasive  initially but bears less risk of recurrent procedures (but these may be again  minimally invasive ). [ 42 ]


Accelerated idioventricular rhythm  which looks like slow  ventricular tachycardia  is a sign of a successful reperfusion. [ 44 ]   No treatment of this rhythm is needed as it rarely changes into a more serious rhythm. [ 45 ]


Transcatheter aortic valve replacement  ( TAVR ) is the implantation of the  aortic valve  of the  heart  through the blood vessels without actual removal of the native valve (as opposed to the aortic valve replacement by  open heart surgery , surgical  aortic valve replacement , AVR). The first TAVI was performed on 16 April 2002 by  Alain Cribier , which became a new alternative in the management of high-risk patients with severe aortic stenosis. [ 2 ] [ 3 ]  The implantated valve is delivered via one of several access methods: transfemoral (in the upper leg), transapical (through the wall of the heart), subclavian (beneath the collar bone), direct aortic (through a minimally invasive surgical incision into the aorta), and transcaval (from a temporary hole in the aorta near the navel through a vein in the upper leg), among others.


Severe symptomatic  aortic stenosis  carries a poor prognosis. At present, there is no treatment via medication, making the timing of aortic valve replacement the most important decision to make for these patients. [ 4 ]  Until recently,  surgical aortic valve replacement  was the standard treatment for adults with severe symptomatic aortic stenosis. However, the risks associated with surgical aortic valve replacement are increased in elderly patients and those with concomitant severe systolic  heart failure  or  coronary artery disease , as well as in people with comorbidities such as  cerebrovascular  and  peripheral arterial disease ,  chronic kidney disease , and chronic respiratory dysfunction.