Myocarditis is the third most common cause of death among young adults with a cumulative incidence rate globally of 1.5 cases per 100,000 persons annually. [ 57 ]  Myocarditis accounts for approximately 20% of sudden cardiac death in a variety of populations, including adults under the age of 40, young athletes, United States Air Force recruits, and elite Swedish orienteers. [ 12 ]   With individuals who develop myocarditis, the first year is difficult as a collection of cases have shown there is a 20% mortality rate. [ 15 ]


Myocarditis can be seen during  COVID-19 , the disease caused by the  SARS-CoV-2  virus; [ 60 ]  with the myocarditis being associated with a spectrum of severities from asymptomatic to fulminant. The symptoms for myocarditis following a COVID-19 infection can present as chest pain, shortness of breath, fatigue, and irregular heartbeats which can make the accurate diagnosis of myocarditis challenging. [ 61 ]  In one cohort study, comparing the autopsy reports of 277 hearts of people who died from COVID-19, clinically significant myocarditis was seen in approximately 2% of hearts. [ 25 ] [ 62 ] [ 63 ]  Other estimates of the incidence of myocarditis in those with COVID-19 range from 2.4 cases of definite/probable myocarditis (based on clinical criteria) per 1,000 people with COVID-19 to 4.1 cases per 1,000 persons in those who are hospitalized with COVID-19. [ 31 ]


Although myocarditis is relatively rare in those with COVID-19, when it is present it is likely to follow a severe and fulminant course for those previously hospitalized with COVID-19. Of those with COVID-19 and myocarditis, 39% presented with severe myocarditis associated with hemodynamic instability, needing mechanical circulation support or other major interventions. [ 31 ]  Severe myocarditis in COVID-19 is also more likely in those who have COVID-19 pneumonia. [ 31 ]


Myocarditis is a rare adverse side effect from mRNA COVID-19 vaccines. [ 64 ] [ 65 ] [ 66 ]


Cases of myocarditis have been documented as early as the 1600s, [ 67 ]  but the term "myocarditis", implying an inflammatory process of the myocardium, was introduced by German physician Joseph Friedrich Sobernheim in 1837. [ 68 ]  However, the term has been confused with other cardiovascular conditions, such as  hypertension  and  ischemic heart disease . [ 69 ]  Following admonition regarding the indiscriminate use of myocarditis as a diagnosis from authorities such as British cardiologist Sir  Thomas Lewis  and American cardiologist and co-founder of the  American Heart Association   Paul White , myocarditis was under-diagnosed. [ 69 ]


Although myocarditis is clinically and pathologically clearly defined as "inflammation of the myocardium", its definition, classification, diagnosis, and treatment are subject to continued controversy, but endomyocardial biopsy has helped define the natural history of myocarditis and clarify clinicopathological correlations. [ 70 ]


Nonbacterial thrombotic endocarditis  ( NBTE ) is a form of  endocarditis  in which small  sterile   vegetations  are deposited on the  valve  leaflets. Formerly known as  marantic endocarditis , which comes from the  Greek   marantikos , meaning "wasting away". [ 1 ]  The term "marantic endocarditis" is still sometimes used to emphasize the association with a wasting state [ 2 ]  such as  cancer . [ 3 ]


Marantic vegetations are often associated with previous  rheumatic fever . Other risk factors include: [ citation needed ]


The disease affects the valves with following predilection:  mitral valve  >  aortic valve  >  tricuspid valve  >  pulmonary valve [ 4 ]


Grossly, vegetations form along lines of valve closure and are generally symmetric with a smooth or  verrucoid  (warty) texture.  Histologically , lesions are composed of  fibrin [ 5 ]  (eosinophilic) and  platelets  but, unlike  bacterial  etiologies, contain little evidence of  PMNs ,  microorganisms  or  inflammation . [ citation needed ]


Due to the non-invasive nature of NBTE, clinical examination may or may not reveal a new  murmur . An embolic stroke may be the first feature to suggest diagnosis of NBTE. An echocardiogram is essential for visualization of the mass. [ citation needed ]


1YPO ,  1YPQ ,  1YPU ,  1YXJ ,  1YXK ,  3VLG


NM_001172632 NM_001172633 NM_002543


NM_001301094 NM_001301096 NM_138648


NP_001166103 NP_001166104 NP_002534


NP_001288023 NP_001288025 NP_619589


Oxidized low-density lipoprotein receptor 1  (Ox-LDL receptor 1) also known as  lectin-type oxidized LDL receptor 1  (LOX-1) is a  protein  that in humans is encoded by the  OLR1   gene . [ 5 ] [ 6 ]


LOX-1 is the main receptor for oxidized LDL on  endothelial cells ,  macrophages ,  smooth muscle cells , [ 7 ]  and other cell types. [ 8 ]  But minimally oxidized LDL is more readily recognized by the  TLR4  receptor, and highly oxidized LDL is more readily recognized by the  CD36  receptor. [ 9 ]


LOX-1 is a receptor protein which belongs to the  C-type lectin superfamily . Its gene is regulated through the cyclic AMP signaling pathway. The protein binds, internalizes and degrades  oxidized   low-density lipoprotein . [ citation needed ]


Normally, LOX-1 expression on endothelial cells is low, but  tumor necrosis factor alpha , oxidized LDL, blood vessel  shear stress , and other atherosclerotic stimuli substantially increase LOX-1 expression. [ 8 ] [ 10 ]


LOX-1 may be involved in the regulation of  Fas -induced  apoptosis .  Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding. [ 7 ]  Other  ligands  for LOX-1 include oxidized  high-density lipoprotein ,  advanced glycation end-products ,  platelets , and apoptotic cells. [ 7 ] [ 10 ]
The binding of platelets to LOX-1 causes a release of vasoconstrictive  endothelin , which induces  endothelial dysfunction . [ 10 ]


This protein may play a role as a scavenger receptor. [ 6 ]


Binding of oxidized LDL to LOX-1 activates  NF-κB , leading to  monocyte  adhesion to enthothelial cells (a pre-requisite for the macrophage  foam cell  formation of atherosclerosis). [ 8 ]  Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized. [ 11 ]  LDL oxidation occurs in the sub-endothelial space, rather than in the circulation. [ 11 ]  But oxidized cholesterol from foods cooked at high temperature can also be a source of  oxysterols . [ 9 ]


Mutations of the OLR1 gene have been associated with  atherosclerosis , risk of  myocardial infarction , and may modify the risk of  Alzheimer's disease . [ 6 ]  When applied to human macrophage-derived foam cells  in vitro , the  dietary supplement   berberine  inhibits the  expression  of the ORL1 gene in response to oxidized  low-density lipoprotein cholesterol , [ 12 ]  but this has not yet been demonstrated in a living animal or human. [ citation needed ]


Ostial disease , namely  coronary   ostial   stenosis , is the occlusion of coronary ostium. Causing factors include  atherosclerosis ,  syphilis ,  Kawasaki disease , and  Takayasu's arteritis , etc. [ 1 ]


A  papillary fibroelastoma  is a  primary tumor of the heart  that typically involves one of the  heart valves . [ 1 ]  Papillary fibroelastomas, while considered uncommon, make up about 10 percent of all primary tumors of the heart. [ 2 ]  They are the third most common type of primary tumor of the heart, [ 3 ]  behind  cardiac myxomas  and cardiac  lipomas .


A papillary fibroelastoma is generally considered pathologically benign, [ 4 ]  however outflow obstruction or embolism can be associated with  syncope , [ 5 ]   chest pain ,  heart attack ,  stroke [ 6 ] [ 7 ]  and  sudden cardiac death .


Symptoms due to papillary fibroelastomas are generally due to either mechanical effects of the tumor or due to embolization of a portion of the tumor to a distal organ. In particular, chest pain or syncope may be due to transient occlusion of the  left main coronary artery  by the tumor, [ 8 ]  while a heart attack or sudden cardiac death may be due to embolization of a portion of the tumor into a coronary artery. [ 9 ]


Papillary fibroelastoma are typically found and accurately diagnosed by  imaging . The  diagnosis  is confirmed by  pathology .  Histologically , papillary fibroelastomas have branching  avascular   papillae , composed of  collagen , that are covered by  endothelium . [ citation needed ]


If the tumor is found incidentally in an asymptomatic person, the treatment approach is controversial. Certainly a conservative approach is warranted in certain individuals. [ 10 ]  If the tumor is large, greater than 1 cm in asymptomatic patients, [ 11 ]  and pedunculated, a case may be made for surgical excision prior to symptoms developing due to the higher risk of embolism. However, this is still considered controversial. [ 12 ]


If the papillary fibroelastoma is associated with symptoms, surgical excision is generally recommended for relief of symptoms. [ 10 ]  A minimally invasive approach may be possible if the tumor involves the  aortic valve [ 13 ]  or right atrium. [ 14 ]  In the case of aortic valve involvement, excision of the tumor is often valve-sparing, meaning that replacement of the valve with a  prosthetic valve  is not necessary. Repair of the native valve with a pericardial patch has been described. [ 15 ]


The main  pathophysiology  of  heart failure  is a reduction in the efficiency of the heart muscle, through damage or overloading. As such, it can be caused by a wide number of conditions, including myocardial infarction (in which the heart muscle is  starved of oxygen  and dies), hypertension (which increases the force of contraction needed to pump blood) and  cardiac amyloidosis  (in which misfolded proteins are deposited in the heart muscle, causing it to stiffen). [ 1 ]  Over time these increases in workload will produce changes to the heart itself:


The heart of a person with heart failure may have a reduced force of contraction due to overloading of the  ventricle . In a healthy heart, increased filling of the ventricle results in increased contraction force (by the  Frank–Starling law of the heart ) and thus a rise in  cardiac output . In heart failure, this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to reduced ability to cross-link  actin  and  myosin  filaments in over-stretched heart muscle. [ 2 ]


A reduced  stroke volume  may occur as a result of a failure of  systole ,  diastole  or both. Increased  end systolic volume  is usually caused by reduced  contractility . Decreased  end diastolic volume  results from impaired ventricular filling; this occurs when the compliance of the ventricle falls (i.e. when the walls stiffen). As the heart works harder to meet normal metabolic demands, the amount cardiac output can increase in times of increased oxygen demand (e.g., exercise) is reduced. This contributes to the exercise intolerance commonly seen in heart failure. This translates to the loss of one's  cardiac reserve , or the ability of the heart to work harder during strenuous physical activity. Since the heart has to work harder to meet the normal metabolic demands, it is incapable of meeting the metabolic demands of the body during exercise. [ citation needed ]


A common finding in those with heart failure is an increased heart rate, stimulated by increased  sympathetic activity [ 3 ]  in order to maintain an adequate cardiac output. Initially, this helps compensate for heart failure by maintaining blood pressure and perfusion, but places further strain on the myocardium, increasing coronary perfusion requirements, which can lead to worsening of ischemic heart disease. Sympathetic activity may also cause potentially fatal  abnormal heart rhythms .  An increase in the physical size  of the heart's muscular layer may occur. This is caused by the terminally differentiated heart muscle fibers increasing in size in an attempt to improve contractility. This may contribute to the increased stiffness and thus decrease the ability to relax during diastole. Enlargement of the ventricles can also occur and contributes to the enlargement and spherical shape of the failing heart. The increase in ventricular volume also causes a reduction in stroke volume due to mechanical and inefficient contraction of the heart. [ 4 ]


The general effect is one of reduced cardiac output and increased strain on the heart. This increases the risk of cardiac arrest (specifically due to abnormal ventricular heart rhythms) and reduces blood supply to the rest of the body. In chronic disease the reduced cardiac output causes a number of changes in the rest of the body, some of which are physiological compensations, some of which are part of the disease process: [ citation needed ]


The increased peripheral resistance and greater blood volume place further strain on the heart and accelerates the process of damage to the myocardium. Vasoconstriction and fluid retention produce an increased hydrostatic pressure in the capillaries. This shifts the balance of forces in favor of  interstitial fluid  formation as the increased pressure forces additional fluid out of the blood, into the tissue. This results in  edema  (fluid build-up) in the tissues. In right-sided heart failure, this commonly starts in the ankles where venous pressure is high due to the effects of gravity (although if the patient is bed-ridden, fluid accumulation may begin in the sacral region). It may also occur in the abdominal cavity, where the fluid buildup is called ascites. In left-sided heart failure  edema  can occur in the lungs – this is called cardiogenic  pulmonary edema . This reduces spare capacity for ventilation, causes stiffening of the lungs and reduces the efficiency of gas exchange by increasing the distance between the air and the blood. The consequences of this are  dyspnea  (shortness of breath),  orthopnea  and  paroxysmal nocturnal dyspnea . [ citation needed ]


The symptoms of heart failure are largely determined by which side of the heart fails. The left side pumps blood into the systemic circulation, whilst the right side pumps blood into the  pulmonary circulation . Whilst left-sided heart failure will reduce cardiac output to the systemic circulation, the initial symptoms often manifest due to effects on the pulmonary circulation. In systolic dysfunction, the ejection fraction is decreased, leaving an abnormally elevated volume of blood in the left ventricle. In diastolic dysfunction, the end-diastolic ventricular pressure will be high. This increase in volume or pressure backs up to the left atrium and then to the pulmonary veins. Increased volume or pressure in the pulmonary veins impairs the normal drainage of the alveoli and favors the flow of fluid from the capillaries to the lung parenchyma, causing pulmonary edema. This impairs gas exchange. Thus, left-sided heart failure often presents with respiratory symptoms: shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea. [ citation needed ]


In severe cardiomyopathy, the effects of decreased cardiac output and poor perfusion become more apparent, and patients will manifest with cold and clammy extremities, cyanosis, claudication, generalized weakness, dizziness, and  fainting . [ citation needed ]


The resultant  low blood oxygen  caused by pulmonary edema causes vasoconstriction in the pulmonary circulation, which results in pulmonary hypertension. Since the right ventricle generates far lower pressures than the left ventricle (approximately 20 mmHg versus around 120 mmHg, respectively, in the healthy individual) but nonetheless generates cardiac output exactly equal to the left ventricle, this means that a small increase in pulmonary vascular resistance causes a large increase in amount of work the right ventricle must perform. However, the main mechanism by which left-sided heart failure causes right-sided heart failure is actually not well understood. Some theories invoke mechanisms that are mediated by neurohormonal activation. [ 10 ]  Mechanical effects may also contribute. As the left ventricle distends, the intraventricular septum bows into the right ventricle, decreasing the capacity of the right ventricle.


Heart failure caused by systolic dysfunction is more readily recognized. It can be simplistically described as a failure of the pump function of the heart. It is characterized by a decreased ejection fraction (less than 45%). The strength of ventricular contraction is attenuated and inadequate for creating an adequate stroke volume, resulting in inadequate cardiac output. In general, this is caused by dysfunction or destruction of cardiac myocytes or their molecular components. In congenital diseases such as  Duchenne muscular dystrophy , the molecular structure of individual myocytes is affected. Myocytes and their components can be damaged by inflammation (such as in  myocarditis ) or by infiltration (such as in amyloidosis). Toxins and pharmacological agents (such as  ethanol ,  cocaine ,  doxorubicin , and  amphetamines ) cause intracellular damage and oxidative stress. The most common mechanism of damage is ischemia causing infarction and  scar formation . After myocardial infarction, dead myocytes are replaced by scar tissue, deleteriously affecting the function of the myocardium. On echocardiogram, this is manifest by abnormal wall motion (hypokinesia) or absent wall motion (akinesia). [ citation needed ]


Because the ventricle is inadequately emptied, ventricular end-diastolic pressure and volumes increase. This is transmitted to the atrium. On the left side of the heart, the increased pressure is transmitted to the pulmonary vasculature, and the resultant hydrostatic pressure favors extravasation of fluid into the lung parenchyma, causing pulmonary edema. On the right side of the heart, the increased pressure is transmitted to the systemic venous circulation and systemic capillary beds, favoring extravasation of fluid into the tissues of target organs and extremities, resulting in dependent  peripheral edema . [ citation needed ]


Heart failure caused by diastolic dysfunction is generally described as the backward failure of the ventricle to adequately relax and typically denotes a stiffer ventricular wall. The "stiffness" and contractility of the ventricular walls in diastole was first described by Pierre-Simon Laplace. This causes inadequate filling of the ventricle and therefore results in an inadequate stroke volume (SV). SV is a mathematical term amenable to manipulation of many variables. The failure of ventricular relaxation also results in elevated end-diastolic pressures, and the end result is identical to the case of systolic dysfunction (pulmonary edema in left heart failure, peripheral edema in right heart failure). [ citation needed ]


Diastolic dysfunction can be caused by processes similar to those that cause systolic dysfunction, particularly causes that affect cardiac remodeling. [ citation needed ]


Diastolic dysfunction may not manifest itself except in physiologic extremes if systolic function is preserved. The patient may be completely asymptomatic at rest. However, they are exquisitely sensitive to increases in heart rate, and sudden bouts of tachycardia (which can be caused simply by physiological responses to exertion, fever, or dehydration, or by pathological tachyarrhythmias such as  atrial fibrillation with rapid ventricular response ) may result in  flash pulmonary edema . Adequate rate control (usually with a pharmacological agent that slows down AV conduction such as a calcium channel blocker or a beta-blocker) is, therefore, of key importance to preventing acute decompensation. [ citation needed ]


Left ventricular diastolic function can be determined through echocardiography by measurement of various parameters such as the  E/A ratio  (early-to-atrial left ventricular filling ratio), the E (early left ventricular filling) deceleration time, and the  isovolumic relaxation time . [ citation needed ]


Postpericardiotomy syndrome  (PPS) is an immune phenomenon that occurs days to months (usually 1–6 weeks [ 1 ] ) after surgical incision of the  pericardium  (membranes encapsulating the human heart). [ 2 ]  PPS can also be caused after a trauma, a puncture of the cardiac or  pleural  structures (such as a bullet or stab wound), after  percutaneous coronary intervention  (such as  stent  placement after a  myocardial infarction  or heart attack), or due to pacemaker or pacemaker wire placement. [ 1 ]


The typical signs of post-pericardiotomy syndrome include  fever ,  pleuritis  (with possible  pleural effusion ),   pericarditis  (with possible  pericardial effusion ), occasional but rare pulmonary infiltrates, and fatigue. [ 1 ] [ 2 ]  Cough,  pleuritic  or retrosternal chest pain, joint pain and decreased oxygen saturation can also be seen in some cases. [ 1 ]


Other signs include  arthritis , together with  petechiae  on the skin and palate. [ 3 ] : 827


Complications include  pericarditis , pericardial effusion,  pleuritis , pulmonary infiltration, and very rarely  pericardial tamponade . Of these cardiac tamponade is the most life-threatening complication. The pericardial fluid increases intra-pericardial pressure therefore preventing complete expansion of the atria and the ventricles upon the diastole. This causes equilibration of the pressure in all four heart chambers, and results in the common findings of the tamponade which are  pulsus paradoxus ,  Beck's triad  of hypotension, muffled heart sounds, and raised  jugular venous pressure , as well as EKG or Holter monitor findings such as  electrical alternans . Physically the patients who progress to severe pericardial tamponade obtundate, become mentally altered, and lethargic. If left untreated, severe decrease in cardiac output, vascular collapse, and hypoperfusion of body including the brain results in death. [ citation needed ]


The cause is believed to be an autoimmune response against damaged cardiac tissue.  This is supported by excellent response to immunosuppressive (steroid) therapy. [ 4 ]


This condition is a febrile illness caused by immune attack of the  pleura  and the  pericardium . Possible cell mediated immunity led by Helper T-cells and Cytotoxic T-cells is postulated to be important in the pathogenesis of this condition. [ 1 ]  There is also possibility of anti-cardiac antibodies created idiopathically, or due to concurrent cross-reactivity of the antibodies produced against viral antigens, however the latter assumption is not fool-proof or completely reliable due to conflicting studies. [ 1 ]


A chest X-ray might depict pleural effusion, pulmonary infiltration, or pericardial effusion. [ 2 ]


During medical doctor examination, a  pericardial friction rub  can be auscultated indicating pericarditis. Auscultation of the lungs can show  crackles  indicating pulmonary infiltration, and there can be retrosternal/pleuritic chest pain worse on  inspiration  (breathing in). Patient can also depict sweating ( diaphoresis ) and agitation or anxiety. [ citation needed ]


Colchicine  has been used effectively to prevent  pericarditis , and inflammation that follows surgery of the pericardium. [ 5 ]  Although no current drug on the market prevents post-pericardiotomy syndrome, colchicine seems to provide an effective and safe way to treat pericarditis by reducing inflammation. [ 6 ]  Colchicine is a natural product extracted from plants, and is a secondary metabolite (an organic compound not directly related to growth and development in an organism). [ 5 ]


Colchicine interferes with the inflammatory process by altering several important steps in the pathway.  Microtubules are structural components of the cytoskeleton that lengthen and shrink for important cell functions.  Colchicine binds to β- tubulin and forms tubulin-colchicine complexes. [ 5 ] [ 6 ]  These complexes interfere with microtubule formation microtubules. Low doses of colchicine can inhibit the formation of microtubules, while high doses depolymerize or break down a polymer to a monomer. [ 7 ]  Therefore, any process involving cytoskeleton change, including mitosis and motility of white blood cells, is highly impacted. [ citation needed ]


Microtubule disruption decreases neutrophil adhesion, an important step for inflammation. [ 7 ]   Neutrophils are recruited to the target location of inflammation via signals from the endothelium where they adhere and play a role in the inflammatory response.  Colchicine diminishes neutrophil adhesion by decreasing expression of selectins, a family of cell adhesion molecules. [ 7 ]  In addition, colchicine prevents the movement and secretion of intercellular granules, substances, proinflammatory enzymes from neutrophils, thus making a significant impact on inflammatory processes within the body. [ 6 ]  The high concentration of colchicine in neutrophils, sixteen times greater compared the plasma levels, can account for the positive therapeutic effects. [ 6 ]


Many mediators are altered to assist neutrophils during inflammation, including the monokine tumor necrosis factor-alpha (TNFα). [ 8 ]  Cytokines help stimulate the acute phase reaction in response to inflammation.  Colchicine inhibits macrophage production of TNFα, leading to the interference between TNFα and neutrophil interaction. [ 8 ]  There are many more effects of colchicine that are currently under research, and some aspects of this metabolite are not fully understood. [ citation needed ]


There was great hope that colchicine could be a primary preventive measure in treating post-pericardiotomy syndrome due to its anti-inflammatory effects. [ 6 ]   In the COPPS-2 trial, however, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. Thus colchicine is not likely going to be the ideal way to prevent this problem. [ 9 ]


More common in children and often common in patients receiving cardiac operations that involve opening the pericardium. [ 1 ]   CABG  surgery is a common culprit.


Progressive cardiac conduction defect   (PCCD)  is a hereditary cardiac condition marked by a progressive delay in impulse conduction via the His-Purkinje system, resulting in right or left  bundle branch block  (RBBB or LBBB),  syncope , and occasionally  sudden cardiac death . [ 1 ]


When progressive conduction abnormalities in people under 50 with structurally normal hearts are present but skeletal  myopathies  are absent, progressive cardiac conduction defect is primarily diagnosed, particularly if there is a family history of PCCD. [ 2 ]


At the moment, implanting an implantable  pacemaker  is the only proven treatment for PCCD, regardless of the underlying cause. [ 3 ]


The electrical axis of the heart is the net direction in which the wave of  depolarization  travels. It is measured using an  electrocardiogram (ECG) . Normally, this begins at the  sinoatrial node  (SA node); from here the wave of depolarisation travels down to the apex of the heart.  The hexaxial reference system can be used to visualise the directions in which the depolarisation wave may travel.


On a hexaxial diagram  (see figure 1):


RAD is an ECG finding that arises either as an anatomically normal variant or an indicator of underlying pathology.


There are often no symptoms for RAD and it is usually found by chance during an ECG. Many of the symptoms exhibited by patients with RAD are associated with its different causes. The table below displays the four most common causes and the signs, symptoms and risk factors associated with it. [ citation needed ]


Chest pain


Fatigue


Shortness of breath [ 1 ]


Obesity


Gender


Hypertension


Diabetes


Physical inactivity


Age


Alcohol


Dizziness


Fainting


Pulmonary hypertension


Mitral stenosis


Pulmonary embolism


Congenital heart disease


Arrythmogenic right ventricle cardiomyopathy


Palpitations [ 3 ]


Drug toxicity (e.g. tricyclic antidepressants [ 5 ] )


Hyperkalaemia


Blockage of the  left posterior fascicle  would lead to activation of the anterior portion of the left ventricle followed by activation of the rest of the ventricle in a superior to inferior direction and directed towards the right. This would lead to right axis deviation findings on an ECG. [ 6 ]
Bifascicular block is a combination of right bundle branch block and either left anterior fascicular block or left posterior fascicular block. Conduction to the ventricle would therefore be via the remaining fascicle. The ECG will show typical features of RBBB plus either left or right axis deviation. [ 7 ] [ 8 ]


The lateral wall of the left ventricle is supplied by branches of the  left anterior descending (LAD)  and  left circumflex (LCx) arteries . [ 8 ]  Infarction of the lateral wall will thus lead to deviation of the axis away from the site of infarction. [ 9 ]


Increased thickness of the right ventricle leads to right axis deviation  [ citation needed ]


Pre-excitation refers to early activation of the ventricles due to impulses bypassing the AV node via an accessory pathway. [ 10 ]
Accessory pathways are abnormal conduction pathways formed during cardiac development. An example of pre-excitation syndromes is  Wolff Parkinson White syndrome . Here, the presence of a left lateral accessory pathway leads to right-axis deviation. [ 11 ]


Fascicular tachycardia usually arises from the posterior fascicle of the left bundle branch. They produce QRS complexes of relatively short durations with a right bundle branch block pattern. Tachycardias originating in the anterior left fascicle would lead to right axis deviation. [ citation needed ]


Right ventricular outflow tract tachycardia originates from the outflow tract of the right ventricle or the tricuspid annulus. As it arises from the right ventricle, the impulse spreads inferiorly from beneath the pulmonary valve, and there right axis deviation. [ 12 ]


Ventricular ectopy is when the heartbeat is an  abnormal heartbeat  where the QRS complex is significantly wider. When the origin of the ectopic heartbeat is in the anterior fascicule then there is right axis deviation. [ 13 ]


The pathophysiology depends on the specific cause of right axis deviation. Most causes can be attributed to one of four main mechanisms. [ 14 ] [ 15 ]  These include  right ventricular hypertrophy , reduced muscle mass of left ventricle, altered conduction pathways and change in the position of the heart in the chest. [ citation needed ]


Enlargement of right ventricular myocardial mass can result in right axis deviation. There are 2 main reasons for this mechanism. [ 15 ]  Firstly, more muscle mass will result in greater amplitude of depolarisation of that side of the heart. [ 15 ]  Secondly, depolarisation of the heart will be slower through the right ventricle relative to the left, and therefore the effects of the right ventricle on the axis of the heart will be dominant. [ 15 ]


Decrease in myocardial mass of the left ventricle will shift the balance of depolarisation towards the right. For example, scarring and atrophy caused by ischaemia of the left ventricle will cause depolarisation of the left side of the heart to be less forceful. [ 15 ]  Hence, depolarisation of the right ventricle will be greater in amplitude than left, shifting the axis to the right. [ citation needed ]


Changes in the conduction pathways of the heart can result in right axis deviation. For example, an accessory pathway from the left atrium to the left ventricle, as in Wolff-Parkinson-White Syndrome, will result in the left ventricle finishing depolarisation earlier than the right. [ 16 ]  Hence, the right ventricle will have more of an effect on the axis of the heart. [ citation needed ]


The apex of the heart is normally orientated towards the left. A more vertical orientation of the heart, shifts the axis to the right. Physiologically, this can occur in tall and thin individuals. [ 16 ]  Pathologically, conditions such as a left-sided  pneumothorax  and lung hyperinflation (e.g.  COPD ) [ 17 ]  can cause rightwards displacement of the heart. The congenital condition of  dextrocardia  results in right axis deviation.


In general, a positive (upwards) deflection of an ECG trace demonstrates an electrical activity that moves towards the measuring electrode, whereas a negative (downwards) deflection of an ECG trace demonstrates an electrical activity that moves away from the measuring electrode. The electrical heart axis can be estimated from the ECG by using the quadrant method or degree method. [ 18 ]


A simple tool to quickly identify axis deviation (Figure 3) is the popular mnemonic;  R eaching for  R ight Axis Deviation and  L eaving for  L eft Axis Deviation. This refers to the appearance of leads I and II. If the QRS complex is negative in lead I and positive in lead II, the QRS complexes appear to be "reaching" to touch each other. This signifies right axis deviation. Conversely, if the QRS complex is positive in lead I and negative in lead II the leads have the appearance of "leaving" each other. If the QRS complex in lead II is also negative, this confirms a left axis deviation. [ citation needed ]


Right ventricular hypertrophy   ( RVH ) is a condition defined by an abnormal enlargement of the cardiac muscle surrounding the  right ventricle . The right ventricle is one of the four chambers of the heart. It is located towards the right lower chamber of the heart and it receives deoxygenated blood from the right upper chamber (right atrium) and pumps blood into the lungs.


Since RVH is an enlargement of muscle it arises when the muscle is required to work harder. Therefore, the main causes of RVH are pathologies of systems related to the right ventricle such as the  pulmonary artery , the  tricuspid valve  or the airways.


RVH can be benign and have little impact on day-to-day life or it can lead to conditions such as  heart failure , which has a poor prognosis.


Although presentations vary, individuals with right ventricular hypertrophy can experience symptoms that are associated with  pulmonary hypertension ,  heart failure  and/or a reduced  cardiac output . These include: [ 1 ] [ 2 ]


People may rarely present with the symptoms of  Ortner's syndrome , which include cough, haemoptysis and hoarseness. [ citation needed ]


On physical examination, the most prominent features are due to the development of right-sided heart failure. These can include a raised  jugular venous pressure ,  ascites , left  parasternal heave  and a tender, enlarged  liver  on palpation. [ 3 ]
On inspection, patients may be chronically ill,  cyanotic ,  cachectic  and occasionally  jaundiced . [ citation needed ]


On  auscultation , an accentuated second pulmonary sound (S2), a third heart sound termed a ‘right ventricular gallop’, as well as a  systolic murmur  over the  tricuspid  area accentuated by inspiration may be present. On occasion, the systolic murmur can be transmitted and auscultated over the liver. Less typically,  diastolic murmur  may also be heard as a result of pulmonary insufficiency. [ 3 ]


RVH usually occurs due to chronic lung disease or structural defects in the heart. One of the most common causes of RVH is  pulmonary hypertension  (PH), [ 3 ]  defined as increased  blood pressure  in the vessels supplying blood to the lungs. PH leads to increased pulmonary artery pressure. The  right ventricle  tries to compensate for this increased pressure by changing its shape and size. Hypertrophy of individual  myocytes  results in an increase in right ventricular wall thickness. [ 3 ]  The worldwide incidence of PH is 4 per million people. [ 4 ]  RVH occurs in approximately 30% of these cases. [ citation needed ]


PH is broadly split into five categories by the  World Health Organization , based on the underlying cause. The incidence of RVH varies between the groups. Common causes of PH include  chronic obstructive pulmonary disease  (COPD),  pulmonary embolism , and other restrictive lung diseases. RVH often occurs as a result of these disorders. RVH is seen in 76% of patients with advanced COPD and 50% of patients with restrictive lung disease. [ 3 ]


RVH also occurs in response to structural defects in the heart. One common cause is  tricuspid insufficiency . This is a disorder where the  tricuspid valve  fails to close properly, allowing backward flow of blood. Other structural defects which lead to RVH include  tetralogy of Fallot ,  ventricular septal defects ,  pulmonary valve stenosis , and  atrial septal defects . [ medical citation needed ]  RVH is also associated with  abdominal obesity , elevated fasting blood glucose, high  systolic blood pressure , and fractional shortening of the left ventricular mid-wall. [ medical citation needed ]


Other risk factors for RVH include smoking,  sleep apnea , and strenuous activity. These increase the risk of heart and lung disease and hence RVH. [ 5 ]


Right ventricular hypertrophy can be both a physiological and pathophysiological process. It becomes pathophysiological (damaging) when there is excessive hypertrophy. The pathophysiological process mainly occurs through aberrant signalling of the neuroendocrine hormones;  angiotensin II ,  endothelin-1  and the catecholamines (e.g.  noradrenaline ). [ citation needed ]


Angiotensin-II and endothelin-1 are hormones that bind to the angiotensin (AT) and endothelin (ET) receptors. These are  G-protein  coupled receptors that act via internal signalling pathways. Through several intermediates, these pathways directly or indirectly increase  reactive oxygen species  (ROS) production causing accumulation in  myocardial cells . This can subsequently induce necrotic cell death,  fibrosis , and mitochondrial dysfunction. [ 6 ]


This has been demonstrated in animal studies.  Protein Kinase C  (PKC) is an intermediate molecule in the signalling pathway and mice lacking PKC shown resistance to heart failure compared to mice overexpressing PKC which shown heart dysfunction. [ 7 ]


Targeting the  renin–angiotensin (RAAS) system  (using angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers) are a well-recognized clinical approach for reversing maladaptive cardiac hypertrophy independently of blood pressure. [ citation needed ]


Catecholamines  levels increase due to increased sympathetic nervous system activity. Catecholamines can act on the alpha-adrenergic receptors and beta-adrenergic receptors which are G-protein coupled receptors. This binding initiates the same intracellular signalling pathways as angiotensin and endothelin. There is also activation of cAMP and an increase in intracellular Ca2+ which leads to contractile dysfunction and fibrosis. [ 6 ]


Hormones are not the only cause of RVH. Hypertrophy can also be caused by mechanical forces, mTOR pathways,  nitric oxide  and  immune cells . Immune cells can cause hypertrophy by inducing inflammation. [ 6 ]


The two main diagnostic tests used to confirm right ventricular hypertrophy are electrocardiography and echocardiography. [ citation needed ]


The use of  electrocardiogram  (ECG) to measure cardiac chamber hypertrophy is well established but since the left ventricular activity is dominant on the ECG a large degree of RVH is often required for any detectable changes. Nonetheless, the ECG is used to assist with the diagnosis of RVH. A  post mortem  study on 51 adult male patients concluded that anatomical RVH may be diagnosed using one or more of the following ECG criteria: [ 8 ]


However, the American Heart Association recommended the use of additional diagnostic tests to diagnose RVH because no single criteria or set of criteria were considered sufficiently reliable. [ 9 ]


Echocardiography  can be used to directly visualise right ventricular wall thickness. The preferred technique is the trans-oesophageal approach giving a view of 4 chambers. The normal thickness of a right ventricular free wall ranges from 2-5 millimetres, with a value above 5 mm considered to be hypertrophic. [ 10 ]


Right ventricular hypertrophy in itself is not the main issue, but what right ventricular hypertrophy represents is. Right ventricular hypertrophy is the intermediate stage between increased right ventricular pressure (in the early stages) and right ventricle failure (in the later stages). [ 11 ]  As such, management of right ventricular hypertrophy is about either preventing the development of right ventricular hypertrophy in the first place, or preventing the progression towards right ventricle failure. Right ventricular hypertrophy in itself has no (pharmacological) treatment. [ 5 ]


Since the main causes of right ventricular hypertrophy is tricuspid regurgitation or pulmonary hypertension (discussed above), management involves treatment of these conditions. [ 3 ]
Tricuspid regurgitation is typically treated conservatively by aiming to treat the underlying cause and following up the patient regularly. [ 12 ]  Surgery is considered in more serious situations where the patient is severely symptomatic. Surgical options include either: replacement of the valve or repair of the valve (termed annuloplasty). [ 3 ]   When it comes to replacement, there is a choice between a bioprosthetic valve or a mechanical valve, depending upon the specific patient characteristics. Mechanical valve has greater durability, but requires anti-coagulation to reduce the risk of thrombosis. [ 3 ]
Treatment of pulmonary hypertension will depend on the specific cause of the pulmonary hypertension. On top of this, the following may also be considered: diuretic, oxygen and anti-coagulant therapy. [ 3 ]


After a prolonged period, the right ventricle fails to adapt sufficiently to pump against increased right ventricle pressure, which is termed right ventricular failure. This right ventricular failure is the main complication of right ventricular hypertrophy. The mechanisms underlying the progression from hypertrophy to failure is not well understood, [ 11 ]  and the best management approach involves reducing/minimising the risk factors of progression. Lifestyle changes can often help to reduce the risk of this progression. Lifestyle changes include: eating less salty food as salt consumption leads to greater fluid retention by the body; smoking cessation; avoiding excessive alcohol consumption as alcohol reduces the force of heart contractions.
Once right ventricular hypertrophy progresses to right ventricular failure, the treatment becomes that of heart failure. Briefly, this includes the use of: [ citation needed ]


Roemheld syndrome  ( RS ), or  gastrocardiac syndrome , [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  or  gastric cardiac syndrome [ 6 ]  or  Roemheld–Techlenburg–Ceconi syndrome [ 7 ]  or  gastric-cardia , [ 7 ]  was a medical syndrome first coined by  Ludwig von Roemheld  (1871–1938) describing a cluster of cardiovascular symptoms stimulated by gastrointestinal changes. Although it is currently considered an obsolete medical diagnosis, recent studies have described similar clinical presentations and highlighted potential underlying mechanisms. [ 3 ] [ 8 ] [ 9 ] [ 5 ]


Symptoms can be as follows. [ 10 ] [ 11 ]  They are periodic, and occur only during an "episode", usually after eating.


Mechanically induced Roemheld syndrome is characterized by  pressure  in the epigastric and left  hypochondriac  region. Often the pressure is in the  fundus  of the stomach, the  esophagus  or distention of the bowel. It is believed this leads to elevation of the  diaphragm , and secondary displacement of the heart. This reduces the ability of the heart to fill and increases the  contractility of the heart  to maintain homeostasis.


The cranium dysfunction mechanical changes in the gut can compress the  vagus nerve  at any number of locations along the vagus, slowing the heart. As the heart slows, autonomic reflexes are triggered to increase blood pressure and heart rate.


This is complemented by gastro-coronary reflexes [ 12 ]  whereby the coronary arteries constrict with "functional  cardiovascular  symptoms" similar to chest-pain on the left side and radiation to the left shoulder, dyspnea, sweating, up to angina pectoris-like attacks with  extrasystoles , drop of blood pressure, and tachycardia (high heart rate) or sinus bradycardia (heart rate below 60 bpm). Typically, there are no changes/abnormalities related in the  EKG  detected. This can actually trigger a heart attack in people with cardiac structural abnormalities i.e.  coronary bridge , missing coronary, and  atherosclerosis .


If the heart rate drops too low for too long,  catecholamines  are released to counteract any lowering of blood pressure. Catecholamines bind to  alpha receptors  and  beta receptors , decreasing  vasodilation  and increasing  contractility of the heart . Sustaining this state causes  heart fatigue  which can lead to a decline in systolic and  diastolic function , resulting in fatigue and chest pain.


There is significant scope of misdiagnosis of Roemheld syndrome. Diagnosis of Roemheld syndrome usually begins with a cardiac workup, as the gastric symptoms may go unnoticed, and the cardiac symptoms are frightening and can be quite severe. After an  EKG ,  Holter monitor ,  tilt table test ,  cardiac MRI ,  cardiac CT ,  heart catheterization ,  electrophysiology study ,  echocardiogram , and extensive blood work, and possibly a  sleep study , a cardiologist may rule out a heart condition.


Often a  psychiatric evaluation  may follow, as conversion disorder may be suspected in the absence of heart disease or structural heart abnormalities.


In the absence of heart abnormalities, the diagnosis is often made on the basis of symptoms. A  gastroenterologist  will perform a  colonoscopy ,  endoscopy , and  abdominal ultrasound  to locate or rule out problems in the abdomen.


Determining the cause of Roemheld syndrome is still not an exact science. If you have an ultrasound or sleep study, ensure that you know how to reproduce the symptoms, as it is difficult to detect any abnormalities when symptoms have subsided.


Treatment of the primary gastroenterological distress is the first concern, mitigation of gastric symptoms will also alleviate cardiac distress.


Roemheld syndrome is characterized strictly by abdominal maladies triggering reflexes in the heart. There are a number of pathways through which cardiac reflexes can occur: hormones, mechanical, neurological and immunological. [ citation needed ]


Ludwig Roemheld characterized this particular syndrome shortly before his death; one of his research topics around this time was the effects of calorie intake on the heart. In  Elsevier  publications, there is no current research or publishing under the name Roemheld syndrome, and as a result, many cases go undiagnosed. German publishing on the subject remains untranslated as of 2009.


sCAR-Fc  ( Soluble Receptor Analogue ) is an experimental prophylactic treatment against  coxsackievirus  B3 (CVB) infections. Coxsackievirus B3 can cause cardiac damage, eventually resulting in a weakened and enlarged heart that is termed  dilated cardiomyopathy . [ 1 ]  While many other treatments inhibit viral proliferation in  myocytes , sCAR-Fc prevents the virus entering the cell by competitively binding to  coxsackie virus and adenovirus receptors  (CAR) on the membrane of myocytes.


Coxsackievirus B3 is a single-stranded RNA  enterovirus  and a member of the  Picornavirdae  family. [ 1 ] [ 2 ]  Once the virus penetrates the host's systemic circulation via contaminated water or food, it can travel and infect the heart and cause myocarditis.  Myocarditis  is an inflammation of the heart, most commonly cause by viral infections. Amongst the viruses capable of causing myocarditis, CVB3 is a common agent identified in inducing cardiac damage. Internalization of the virus into myocytes occurs by binding to coxsackievirus-adenovirus receptors (CAR) located in  tight junctions  on cell membranes. [ 1 ] [ 3 ]  Once inside the cytoplasm, the virus can use the host's ribosomal machinery to proliferate and replicate progenies for further infection. [ 4 ]  Extensive cardiac  necrosis  can occur by day three after infection as incubated viruses lyse myocytes, resulting in severe and rapid cardiac decompensation. With loss of cardiac cells increasing progressively, infected individual will experience abnormalities in left ventricular systolic and diastolic function, as well as electrical conduction defects manifesting as  cardiac dysrhythmias . [ 5 ]  As a result,  ejection fraction  decreases substantially. [ 5 ]  The cytolytic destruction of heart cells can lead to dilated cardiomyopathy if not treated appropriately. [ citation needed ]


The role of the immune system in response to the presence of a virus has both beneficial and detrimental effects on the cardiac system. [ 1 ]  The arrival of  natural killer cells  (NK cells) at the site of infection limits viral proliferation in myocytes. Conversely, while certain cytokines released from immune cells have protective effects, others such as  tumor necrosis factor-alpha  (TNFα) have deleterious effects on heart cells. Moreover, peak concentrations of  T cells  in the myocardium during days 7-14 play important roles in both viral clearance and immune mediated cardiac damage. T-cells not only lyse and destroy infected myocytes, but due to molecular mimicry, they also destroy normal, healthy cardiac cells, further driving the heart towards dilated cardiomyopathy. [ 6 ]


A synthetic and soluble form of CAR (sCAR) has been created to prevent viral infection with CVB3. Attaching Fc domain of  immunoglobulin   IgG1  to sCAR (sCAR-Fc) enhances solubility and extends its  half-life . [ 1 ] [ 7 ]  Furthermore, once sCAR-Fc binds the virus,  macrophages  and other phagocytic immune cells with Fc receptor recognition bind to the sCAR-Fc-viral complex to eliminate the virus. Essentially, sCAR-Fc mimics CAR receptors on cardiac cells, competitively inhibiting viral attachment and entry into myocytes. Decreased lesions in cardiac tissues, reduced cell necrosis, and diminished inflammatory responses are observed in sCAR-Fc treated cells (CITE). This suggests protective effects against myocardial damage by CVB3. [ citation needed ]


Conformational changes in a viral particle (A-particle) with sCAR-Fc-virus binding causing the loss of the virus’ internal  capsid  protein, VP4. [ 2 ]  This irreversible reaction prevents the virus from interacting with cellular receptors (CAR) on cardiac cells, decreasing infectivity of CVB3. [ 8 ]


Administration of sCAR-Fc beyond three days after initial exposure to the virus does not have any beneficial effects as cardiac damage is too severe. [ 2 ]  As such, the use of sCAR-Fc is currently limited to prophylactic treatments. [ citation needed ]


Shone's syndrome  is a rare  congenital heart defect  described by Shone in 1963. In the complete form, four left-sided defects are present: [ 1 ]


Of these four defects, supravalvular mitral membrane (SVMM) is the first to occur and triggers the development of the other three defects. Partial complexes, or  forme fruste , have also been described. [ 1 ]  The definition is often expanded to include  lesions  of the left side of the  heart  not originally ascribed to Shone's  syndrome , including mitral and  aortic  valvular lesions and supravalvular  aortic stenosis . [ 2 ]


The term  parachute mitral valve  stems from the  morphological  appearance of the valve; that is to say, the mitral valve leaflets appear as the  canopy  of the  parachute , the  chordae  as the strings and the  papillary muscle  as the harness.


Shone’s syndrome is a rare  disorder  that is often detected in very young children. The children tend to show symptoms like  fatigue ,  nocturnal cough , and reduced  cardiac output  by the age of two years. They also develop  wheezing  due to the  exudation  of fluid into the lungs. [ 1 ]


In the normal human heart, there are two mitral valve leaflets, each with its own set of chordae. However, in the case of the parachute mitral valve, the chordae insert on only one papillary muscle instead of two distinct  papillary muscles . Often, the chordae are short and thick, which can cause restricted movement of the  mitral valve  leaflets and obstruct the blood flow into the left  ventricle . [ 1 ]


The supramitral ring is a  connective tissue  ring at the base of the atrial surfaces of the  mitral valve  leaflets. They may protrude into the orifice of the mitral valve, leading to fixed obstruction of blood flow from the left atria to the  left ventricles . [ 1 ]


Subaortic stenosis  has been observed in both muscular and  membranous  forms. In either case, a variable degree of obstruction may be observed at the  ventricular  surface of the aortic valve. [ 1 ]  This presents an obstruction of flow of blood from the ventricle to the  aorta .


Coarctation  of the aorta which is, narrowing of a section of the aorta may also be observed. [ 1 ]  Again this presents an  obstruction  to blood flow out from the  left ventricle. [ 3 ]


Since there is obstruction of flow into and out of the left  ventricle , the  prognosis  depends on the degree of obstruction and its effect on  blood flow .


Cardiac magnetic resonance imaging  is best suited to evaluate patients with Shone's syndrome. [ 4 ]  Routine blood tests should be done prior to  cardiac catheterization . The surgeons will repair the mitral valve and partially remove the supramitral ring. [ 5 ]  This surgical method is preferred to a valve replacement procedure.


Classifying cardiac lesions in infants is quite difficult, and accurate diagnosis is essential. The diagnosis of Shone’s syndrome requires an  ultrasound  of the heart ( echocardiogram ) and a cardiac catheterization procedure, that is, insertion of a device through  blood vessels  in the groin to the heart that helps identify heart anatomy. [ 3 ]


When treated early, that is, before the onset of  pulmonary hypertension , a good outcome is possible in patients with Shone’s syndrome. However, other surgical methods can be employed depending upon the patient’s medical background. The single most important determinant of poor outcome during the  surgical  management of patients with Shone's syndrome is the degree of involvement of the  mitral valve  and the presence of secondary pulmonary  hypertension . [ 6 ]


In  electrocardiography , a  strain pattern  is a well-recognized marker for the presence of anatomic  left ventricular hypertrophy  (LVH) in the form of  ST depression  and  T wave  inversion on a resting ECG. [ 1 ]  It is an abnormality of  repolarization  and it has been associated with an adverse prognosis in a variety heart disease patients.  It has been important in refining the role of ECG LVH criteria in cardiac  risk stratification . It is thought that a strain pattern could also reflect underlying  coronary heart disease . [ citation needed ]  Floyd strain includes T-wave inversion "Floyd.".


Structural heart disease , also known as  structural cardiac disease , is a collection of  heart diseases  that includes  heart failure ,  coronary artery disease ,  hypertrophic cardiomyopathy , and  congenital heart disease . [ 1 ]


Subacute bacterial endocarditis , abbreviated SBE, is a type of  endocarditis  (more specifically,  infective endocarditis ). [ 5 ]  Subacute bacterial endocarditis can be considered a form of  type III hypersensitivity . [ 6 ]


Among the signs of subacute bacterial endocarditis are: [ 1 ]


It is usually caused by a form of  Viridans group streptococcus  bacteria that normally live in the mouth [ 3 ]  ( Streptococcus mutans , mitis, sanguis  or  milleri ). [ 2 ]


Other strains of streptococci can cause  subacute  endocarditis as well. These include  streptococcus intermedius , which can cause
acute or subacute infection (about 15% of cases pertaining to infective endocarditis). [ 7 ]


Enterococci  from urinary tract infections and  coagulase negative staphylococci  can also be causative agents. [ 5 ]


The mechanism of subacute bacterial endocarditis could be due to malformed stenotic valves which, in the company of bacteremia, become infected via adhesion and subsequent colonization of the surface area. This causes an inflammatory response, with recruitment of matrix metalloproteinases and destruction of collagen. [ 8 ]


Underlying structural  valve  disease is usually present in patients before developing subacute endocarditis, and is less likely to lead to  septic   emboli  than is  acute  endocarditis, but subacute endocarditis has a relatively slow process of  infection  and, if left untreated, can worsen for up to one year before it is fatal. [ medical citation needed ]  In cases of subacute bacterial endocarditis, the causative organism (streptococcus viridans) needs previous heart valve disease to colonize. [ 9 ]  On the other hand, in cases of acute bacterial endocarditis the organism can colonize on the healthy heart valve, causing the disease. [ 10 ]


Subacute bacterial endocarditis can be diagnosed by collecting three blood culture specimens over a 24-hour period for analysis, [ 4 ]  also it can usually be indicated by the existence of:


The standard treatment is with a minimum of four weeks of high-dose intravenous  penicillin  with an  aminoglycoside  such as  gentamicin .
The use of high-dose antibiotics is largely based upon animal models. [ 2 ]


Leo Loewe of  Brooklyn Jewish Hospital  was the first to successfully treat subacute bacterial endocarditis with penicillin. Loewe reported at the time seven cases of subacute bacterial endocarditis in 1944. [ 14 ]


It remains a difficult medical challenge to prevent the  sudden cardiac death of athletes , typically defined as natural, unexpected death from  cardiac arrest  within one hour of the onset of collapse symptoms, excluding additional time on mechanical life support. [ 1 ]  (Wider definitions of sudden death are also in use, but not usually applied to the athletic situation.) Most causes relate to  congenital  or acquired  cardiovascular disease  with no symptoms noted before the fatal event. The  prevalence  of any single, associated condition is low, probably less than 0.3% of the population in the athletes' age group, [ citation needed ]  and the  sensitivity and specificity  of common screening tests leave much to be desired. The single most important predictor is  fainting  or near-fainting during exercise, which should require detailed explanation and investigation. [ 2 ]  The victims include many well-known names, especially in professional association football, and close relatives are often at risk for similar cardiac problems.


The sudden cardiac deaths of 387 young American athletes (under age 35) were analyzed in a 2003 medical review: [ 3 ]


While most causes of sudden cardiac death relate to  congenital  or acquired  cardiovascular disease , an exception is  commotio cordis , in which the heart is structurally normal but a potentially fatal loss of  rhythm  occurs because of the accident of timing of a blow to the chest. Its fatality rate is about 65% even with prompt  CPR  and  defibrillation , and more than 80% without. [ 4 ] [ 5 ]


Age 35 serves as an approximate borderline for the likely cause of sudden cardiac death. Before age 35, congenital abnormalities of the heart and blood vessels predominate. These are usually asymptomatic prior to the fatal event, although not invariably so. [ 6 ]  Congenital cardiovascular deaths are reported to occur disproportionately in African-American athletes. [ 7 ]


After age 35, acquired  coronary artery disease  predominates (80%), [ 6 ]  and this is true regardless of the athlete's former level of fitness. [ citation needed ]


Various  performance-enhancing drugs  can increase cardiac risk, though evidence has been inconclusive about their involvement in sudden cardiac deaths. [ 8 ]


Cardiomyopathies are generally inherited as  autosomal dominants , although recessive forms have been described, and dilated cardiomyopathy can also be inherited in an  X-linked  pattern. Consequently, in addition to tragedy involving an athlete who succumbs, there are medical implications for close relatives. Among family members of  index cases , more than 300 causative  mutations  have been identified. However, not all mutations have the same potential for severe outcomes, and there is not yet a clear understanding of how these mutations (which affect the same  myosin  protein molecule) can lead to the dramatically different  clinical characteristics  and outcomes associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). [ 9 ]


Since HCM, as an example, is typically an autosomal dominant trait, each child of an HCM parent has a 50% chance of inheriting the mutation. In individuals without a family history, the most common cause of the disease is a "de novo" mutation of the gene that produces the β-myosin heavy chain. [ citation needed ]


Sudden cardiac death can usually be attributed to cardiovascular disease or commotio cordis, but about 20% of cases show no obvious cause and remain undiagnosed after autopsy. Interest in these "autopsy-negative" deaths has centered around the " ion channelopathies ". These electrolyte channels are pores regulating the movement of sodium, potassium and calcium  ions  into cardiac cells, collectively responsible for creating and controlling the electrical signals that govern the heart's rhythm. Abnormalities in this system occur in relatively rare genetic diseases such as  Long QT syndrome ,  Brugada syndrome , and  Catecholaminergic polymorphic ventricular tachycardia , all associated with sudden death.  Consequently, autopsy-negative sudden cardiac deaths (no physical abnormalities identified) may comprise a larger part of the channelopathies than previously anticipated. [ 10 ] [ 11 ]


Heritable connective tissue diseases are rare, each disorder estimated at one to ten per 100,000, of which  Marfan syndrome  is the most common. It is carried by the FBN1 gene on chromosome 15, which encodes the connective protein fibrillin-1, [ 12 ] [ 13 ]  inherited as a dominant trait. This protein is essential for synthesis and maintenance of elastic fibers. Since these fibers are particularly abundant in the  aorta , ligaments, and the  ciliary zonules  of the eye, these areas are among the worst affected. Everyone has a pair of FBN1 genes and, because transmission is dominant, those who have inherited one affected FBN1 gene from either parent will have Marfan syndrome. Although it is most frequently inherited as an autosomal dominant, there is no family history in 25% of cases. [ 14 ]


Recruiting practices aimed at attracting athletes who are unusually tall or who have an unusually wide arm span (characteristics of Marfan syndrome) can increase the prevalence of the syndrome within sports such as basketball and volleyball. [ 15 ]


After a disease-causing mutation has been identified in an index case (which is not always accomplished conclusively), the main task is genetic identification of carriers within a pedigree, a sequential process known as "cascade testing". Family members with the same mutation may show different severities of disease, a phenomenon known as "variable  penetrance ". As a result, some may remain asymptomatic, with little lifelong evidence of disease. Nevertheless, their children remain at risk of inheriting the disorder and potentially being more severely affected. [ 16 ]


Screening athletes for cardiac disease can be problematic because of low prevalence and inconclusive performance of various tests that have been used. Nevertheless, sudden death among seemingly healthy individuals attracts much public and legislator attention because of its visible and tragic nature. [ 17 ]


As an example, the  Texas Legislature  appropriated US$1 million for a pilot study of statewide athlete screening in 2007. The study employed a combination of questionnaire, examination and  electrocardiography  for 2,506 student athletes, followed by  echocardiography  for 2,051 of them, including any students with abnormal findings from the first three steps. The questionnaire alone flagged 35% of the students as potentially at risk, but there were many  false positive  results, with actual disease being confirmed in less than 2%. Further, a substantial number of screen-positive students declined repeated recommendations for follow-up evaluation. (Individuals who are conclusively diagnosed with cardiac disease are usually told to avoid competitive sports.) It should be stressed that this was a single pilot program, but it was indicative of the problems associated with large-scale screening, and consistent with experience in other locations with low prevalence of sudden death in athletes. [ 18 ]


Sudden cardiac death occurs in approximately one per 200,000 young athletes per year, usually triggered during competition or practice. [ 6 ]  The victim is usually male and associated with  association football ,  basketball ,  ice hockey , or  American football , reflecting the large number of athletes participating in these sustained and strenuous sports. [ 3 ]  For a normally healthy age group, the risk appears to be particularly magnified in competitive basketball, with sudden cardiac death rates as high as one per 3,000 annually for male basketball players in  NCAA  Division I. [ 19 ]  This is still far below the rate for the general population, estimated as one per 1,300–1,600 and dominated by the elderly. [ 20 ]  However, a population as large as the United States will experience the sudden cardiac death of a competitive athlete at the average rate of one every three days, often with significant local media coverage heightening public attention. [ 17 ]


In the United States approximately 8 to 10 deaths per year can be attributed to sudden cardiac death in  NCAA  with overall rate of 1 per 43,000. [ 21 ] [ 22 ]


These athletes, with notable careers, experienced sudden cardiac death by age 40.


Takotsubo cardiomyopathy  or  takotsubo syndrome  ( TTS ), also known as  stress cardiomyopathy , is a type of non- ischemic   cardiomyopathy  in which there is a sudden temporary weakening of the  muscular portion of the heart . [ 4 ]  It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called  broken heart syndrome . [ 5 ]


Examples of physical stressors that can cause TTS are  sepsis ,  shock ,  subarachnoid hemorrhage , and  pheochromocytoma . Emotional stressors include bereavement, divorce, or the loss of a job. [ 6 ]  Reviews suggest that of patients diagnosed with the condition, about 70–80% recently experienced a major stressor, including 41–50% with a physical stressor and 26–30% with an emotional stressor. [ 7 ] [ 8 ]  TTS can also appear in patients who have not experienced major stressors. [ 8 ] [ 9 ]


The pathophysiology is not well understood, but a sudden massive surge of  catecholamines  such as  adrenaline  and  noradrenaline  from extreme stress or a tumor secreting these chemicals is thought to play a central role. [ 10 ]   Excess catecholamines, when released directly by nerves that stimulate cardiac muscle cells, have a toxic effect and can lead to decreased cardiac muscular function or " stunning ". [ 11 ] [ 12 ]  Further, this adrenaline surge triggers the arteries to  tighten , thereby raising blood pressure and placing more stress on the heart, and may lead to  spasm of the coronary arteries  that supply blood to the heart muscle. [ 10 ]  This impairs the arteries from delivering  adequate blood flow and oxygen  to the heart muscle. [ 10 ]  Together, these events can lead to  congestive heart failure  and decrease the  heart's output  of blood with each squeeze. [ 10 ]


Takotsubo cardiomyopathy occurs worldwide. [ 11 ]  The condition is thought to be responsible for 2% of all  acute coronary syndrome  cases presenting to hospitals. [ 11 ]  Although TTS has generally been considered a  self-limiting disease , spontaneously resolving over the course of days to weeks, contemporary observations show that "a subset of TTS patients may present with symptoms arising from its complications, e.g. heart failure,  pulmonary edema ,  stroke ,  cardiogenic shock , or  cardiac arrest ". This does not imply that rates of shock/death of TTS are comparable to those of acute coronary syndrome, but that patients with acute complications may co-occur with TTS. [ 6 ]   These cases of shock and death have been associated with the occurrence of TTS secondary to an inciting physical stressor such as  hemorrhage , brain injury sepsis,  pulmonary embolism  or severe  chronic obstructive pulmonary disease  (COPD). [ 11 ]


It occurs more commonly in postmenopausal women. [ 11 ]  The name "takotsubo" comes from the Japanese word  takotsubo  "octopus trap", because the left ventricle of the heart takes on a shape resembling an  octopus trap  when affected by this condition. [ 13 ]


A study published in the  Journal of the American Heart Association  in October 2021 found a steady annual increase in takotsubo cardiomyopathy among both women and men from 2006 to 2017, with the sharpest increases among women 50 and older. [ 14 ]


The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated  electrocardiogram  (ECG) changes mimicking a  myocardial infarction  of the  anterior wall . During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome the name  takotsubo  ("octopus trap")  in  Japan , where it was first described. [ 15 ]


Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms. [ 16 ]  Examples of emotional stressors include grief from the death of a loved one, fear of public speaking, arguing with a spouse, relationship disagreements, betrayal, and financial problems. [ 16 ]  Acute  asthma , surgery,  subarachnoid hemorrhage ,  chemotherapy , and  stroke  are examples of physical stressors. [ 16 ]  In a few cases, the stress may be a happy event, such as a wedding, winning a jackpot, a sporting triumph, or a birthday. [ 17 ] [ 18 ]


Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful or emotional event. [ 12 ]   Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after experiencing emotional stress. Some patients have a preceding clinical stressor (such as a brain injury,  asthma  attack or exacerbation of a chronic illness) and research has indicated that this type of stress may even occur more often than emotionally stressful triggers. [ 9 ]  Roughly one-third of patients have no preceding stressful event. [ 19 ]  A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections – such as  Parvovirus B19  – which occur more frequently during the winter. [ 1 ]


Women, specifically postmenopausal women, are at greatest risk of developing TTS. [ 12 ]  This has led some researchers to theorize about the possible protective effects of estrogen in preventing TTS. [ 20 ] [ 6 ]


It is currently being investigated if certain genetic traits associated with catecholamine receptors found on cardiac muscle cells play a role in the development of TTS. [ 20 ]   There is limited evidence tying TTS directly to a specific genetic expression or mutation, however there is currently a widely held hypothesis supporting the idea of the interaction between environmental factors and the interplay of genetic predisposition leading to the susceptibility to microvascular alterations that contribute to the TTS disease process. [ 6 ]


Certain  endocrine  diseases including  pheochromocytoma  and  thyrotoxicosis  have been identified as potential risk factors for TTS. [ 21 ] [ 22 ]  The relationship between  thyroid  function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary  hyperthyroidism  and a high set point of  thyroid homeostasis  (encoding type 2  allostatic load ) are common phenomena. [ 23 ]  A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS. [ 23 ]  Especially hyperthyroidism is highly prevalent in takotsubo cardiomyopathy, and it seems to predict a poor prognosis in terms of complications and mortality. [ 24 ]  This observation was confirmed by results of the international GEIST registry, which demonstrated that thyrotoxicosis is associated with significantly increased fatality, whereas hypothyroidism indicates a better survival. [ 25 ]


The cause of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed. [ 26 ]  It is well documented that elevated catecholamine levels have been implicated in the vast majority of TTS cases. Theories suggest a link between brain activation of stress-related biochemicals (including  neuropeptides ) and the effects these chemicals have on areas of the heart, especially  neuropeptide Y . [ 27 ]  More specifically, adrenal stimulation by the sympathetic nervous system has been noted in cases ranging from physical events such as ischemic stroke, to emotional events such as depression or loss of a loved-one. [ 28 ]  How these increased levels of catecholamines act in the body to produce the changes seen with TTS is not clearly understood. [ 6 ] [ 11 ] [ 12 ] [ 20 ]   Research supports the widely-held understanding that microvascular dysfunction and coronary vasospasm caused by a rapid influx of catecholamines to cardiac myocytes results in apical stunning and transient cardiomyopathy. [ 6 ] [ 11 ] [ 12 ]


It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality. [ 12 ]  For instance, estrogen, which confers protection to women by improving blood flow to heart muscle, is one biochemical pathway implicated in the TTS disease process. Once this protective mechanism is reduced through the decreased production of estrogen after menopause, there is thought to be an increase in endothelial dysfunction predisposing an individual to vasoconstriction and cardiac ischemia. [ 11 ]  An inciting stressful event elicits the release of catecholamines into the blood stream to create increased heart muscle activity and metabolism. This leads to further cardiac microvascular endothelial dysfunction through oxidative stress, alteration of ion-mediated channels, and electrolyte disturbances which ultimately alter myocardial cell membrane permeability and dysfunction. [ 6 ] [ 12 ]  Coupled with direct heart muscle toxicity, this crescendo of factors are implicated in the ballooning and heart failure characteristically seen in TTS. [ 6 ] [ 11 ] [ 12 ] [ 20 ]


A 2019 case involved a 60-year-old woman presenting with TTS due to over-consumption of  wasabi , mistaking it for  avocado . [ 35 ]


Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the  Mayo Clinic . Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group,  Gothenburg University ,  Johns Hopkins University , the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the  European Society of Cardiology . [ 36 ]  All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac  troponin . [ 36 ]


Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7–2.2% of patients presenting with  acute coronary syndrome . [ 1 ]  While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome previously went undiagnosed before it was described in detail in the Japanese literature. Evaluation of individuals with takotsubo cardiomyopathy typically includes a  coronary angiogram  to rule out occlusion of the  left anterior descending  artery, which will not reveal any significant blockages that would cause the  left ventricular  dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within two months. [ citation needed ]


The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The  ECG  findings often are confused with those found during an acute anterior wall  myocardial infarction . [ 37 ] [ 38 ]  It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by  chest pain ,  shortness of breath , ST-segment elevation, T-wave inversion or QT-interval prolongation on  ECG . Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant  coronary artery disease . [ 1 ]


The diagnosis is made by the  pathognomonic  wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or  dyskinetic . This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been described classically as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and, rarely, local ballooning of other segments. [ 1 ] [ 39 ] [ 40 ] [ 41 ] [ 42 ]


The ballooning patterns were classified by Shimizu et al. as  takotsubo type  for apical akinesia and basal hyperkinesia,  reverse takotsubo  for basal akinesia and apical hyperkinesia,  mid-ventricular type  for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and  localised type  for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction. [ 40 ]


In short, the main criteria for the diagnosis of takotsubo cardiomyopathy are: the patient must have experienced a stressor before the symptoms began to arise; the patient's ECG reading must show abnormalities from a normal heart; the patient must not show signs of coronary blockage or other common causes of heart troubles; the levels of cardiac enzymes in the heart must be elevated or irregular; and the patient must recover complete contraction and be functioning normally in a short amount of time. [ 43 ]


The treatment of takotsubo cardiomyopathy is generally supportive in nature, for it is considered a transient disorder. [ 45 ]  Treatment is dependent on whether patients experience heart failure or acute hypotension and shock. In many individuals, left ventricular function normalizes within two months. [ 46 ] [ 47 ]   Aspirin  and other heart drugs also appear to help in the treatment of this disease, even in extreme cases. [ 48 ] [ 49 ]  After the patient has been diagnosed, and myocardial infarction (heart attack) ruled out, the aspirin regimen may be discontinued, and treatment becomes that of supporting the patient. [ 50 ]  There is currently no internationally agreed protocol for treatment of this condition. [ citation needed ]


While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes. [ 51 ]  It is important that the individual stay physically healthy while learning and maintaining methods to manage stress, and to cope with future difficult situations. [ citation needed ]


Although the symptoms of takotsubo cardiomyopathy usually go away on their own and the condition completely resolves itself within a few weeks, some serious short and long-term complications can happen that must be treated. [ 52 ]  These most commonly include  congestive heart failure  and very  low blood pressure , and less commonly include  blood clotting  in the apex of the left ventricle,  irregular heart beat , and  tearing of the heart wall . [ 52 ]


For patients in acute heart failure,  ACE inhibitors ,  angiotensin receptor blockers , and  beta blockers , are considered mainstays of heart failure treatment. But use of beta blockers specifically for takotsubo cardiomyopathy is controversial, because they may confer no benefit. [ 45 ]


For people with cardiogenic shock, medical treatment is based on whether a  left ventricular outflow tract  (LVOT) obstruction is present. [ 53 ]  Therefore, early  echocardiography  is necessary to determine proper management. For those with obstructed LVOTs  inotropic  agents should not be used, but instead should be managed like patients with  hypertrophic cardiomyopathy , (e.g.  phenylephrine  and  fluid resuscitation ). [ 45 ]  For cases in which the LVOT is not obstructed, inotropic therapy (e.g.  dobutamine  and  dopamine ) may be used, but with the consideration that takotsubo is caused by excess catecholamines. [ 53 ]


Furthermore, mechanical circulatory support [ 54 ]  (MCS) with an  intra-aortic balloon pump  (IABP) is well-established as supportive treatment. [ 53 ] [ 55 ]


Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most. [ 1 ] [ 15 ] [ 39 ]  Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months. [ 1 ] [ 30 ] [ 31 ] [ 32 ]  Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger. [ 1 ] [ 19 ]  While men experience TTS at much lower rates than women, they also experience much higher rates of complication, reoccurrence, and mortality; the cause of this sex difference is still unknown, but it is hypothesized that the social aspect of the doctor-patient interaction affects the way that physicians recognize and generate individual treatment plans for men compared to women. [ 56 ]  Stress cardiomyopathy is now a well-recognized cause of acute  congestive heart failure , lethal  abnormal heart rhythms , and  rupture of the heart wall . [ 13 ]


Takotsubo syndrome represents about 2% of all patients (and 5–6% of all female patients) who are initially diagnosed with acute coronary syndrome (ACS). [ 6 ] [ 57 ]  It accounts for 0.02% of all hospitalizations in the US. [ 6 ]  About 90% of TTS patients are women, [ 6 ] [ 57 ]  whose mean age is about 68 years, and 80% of whom are older than 50 years. [ 6 ]  About 2.2% of TTS cases had the reversed (basal) variant. [ 57 ]  Recurrence rate of TTS is about 1.8% per-patient year. [ 6 ]


Rees, et al. wrote in 1967 that the death of a close relative increases the risk of dying within one year by a factor of seven. [ 58 ]


Engel wrote about sudden and rapid death during psychological stress in 1971 and itemized 8 causation categories: (1) on the impact of the collapse or death of a close person; (2) during acute grief; (3) on threat of loss of a close person; (4) during mourning or on an anniversary; (5) on loss of status or self-esteem; (6) personal danger or threat of injury; (7) after the danger is over; (8) reunion, triumph, or happy ending. He proposed these events provoke neurovegetative responses, involving both the flight-fight and conservation-withdrawal systems, conducive to lethal cardiac events, particularly in individuals with preexisting cardiovascular disease. [ 59 ]


Although the first scientific description of takotsubo cardiomyopathy was not until the 1990s, Cebelin and Hirsch wrote about human stress cardiomyopathy in 1980. The two looked at homicidal assaults that had happened in  Cuyahoga County, Ohio , the past 30 years, specifically those with autopsies who had no internal injury, but had died of physical assault. They found that 11 of 15 had  myofibrillar  degeneration similar to animal stress studies. In the end, they concluded their data supported "the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart". [ 60 ]


The syndrome reached international audiences through the media in 2005 when the  New England Journal of Medicine  wrote about the syndrome. [ 61 ]


Traumatic cardiac arrest  ( TCA ) is a condition in which the  heart  has  ceased  to beat due to  blunt  or  penetrating trauma , such as a  stab wound  to the  thoracic  area. [ 1 ]  It is a  medical emergency  which will always result in death without prompt advanced medical care.  Even with prompt medical intervention, survival without  neurological  complications is rare. [ 2 ]  In recent years, protocols have been proposed to improve survival rate in patients with traumatic cardiac arrest, though the variable causes of this condition as well as many coexisting injuries can make these protocols difficult to standardize. [ 3 ]  Traumatic cardiac arrest is a complex form of  cardiac arrest  often derailing from  advanced cardiac life support  in the sense that the emergency team must first establish the cause of the traumatic arrest and reverse these effects, for example hypovolemia and haemorrhagic shock due to a penetrating injury. [ citation needed ]


Traumatic cardiac arrest can occur in patients following any severe blunt or penetrating  injury to the chest . Following the traumatic event, the heart ceases to pump blood through the body. Unlike medical cardiac arrest, there are several potentially reversible causes that may result in cardiac arrest in the setting of trauma. Clinicians will rapidly assess for these causes, and interventions will be directed to the specific cause. [ 4 ]


In both blunt and penetrating trauma, massive  internal  or  external bleeding  may decrease the volume of blood is available to be pumped by the heart to the body. This is considered  preload  dependent arrest. [ 4 ]


Tension pneumothorax  is caused when air is able to enter the space between the  lung  and the  chest wall , but is not able to escape. The increasing pressure within the chest cavity prevents blood from returning from the body to fill the heart.


Hemothorax  occurs when injury to the chest results in bleeding into the thoracic cavity. Similar to tension pneumothorax, increasing pressure prevents the return of blood from circulation to the heart.


In the setting of trauma,  cardiac tamponade  results from an acute  pericardial effusion , the accumulation of blood within the sac that surrounds the heart. As this sac is filled with fluid, the pressure on the heart is increased, and the chambers of the heart are unable to fill with blood.


Inability to maintain  oxygenation  in trauma patients may be a result of  airway  compromise due to mechanical injury or obstruction or due to loss of the  respiratory drive  from  cervical spine  or  peripheral nerve injury . [ 4 ]  These conditions result in the  hypoxia  that may lead to cardiac arrest.


Patients will present following a traumatic event most often with  pulseless electrical activity  (PEA). Patients will exhibit low blood pressure with pulses that cannot be palpated. Patients will progress into  asystole  if the underlying condition is not reversed. Other non-specific signs and symptoms associated with impending traumatic cardiac arrest may include sweating,  altered mental status ,  rapid  or  slow breathing , and signs of trauma (bruising,  laceration , fractures, etc.). [ 4 ]


Diagnosis of traumatic cardiac arrest is initially made with  electrocardiogram  with EMS or in the emergency department. Clinicians will also order diagnostic testing that may include  chest x-ray , bedside ultrasound and  echocardiogram , and blood gas levels. A  type and cross  will be ordered to match the patient to receive blood transfusion if necessary.


Other work-up involved in diagnosis of a trauma patient may include  e-FAST ,  RUSH exam ,  CBC , pelvic X-ray, and  CT  of the head, neck, chest, abdomen, and pelvis.


Treatment of traumatic cardiac arrest is guided by  advanced trauma life support guidelines . Standard advanced cardiac life support guidelines are inappropriate for use in traumatic cardiac arrest, as they are directed primarily at treating pathology originating within the heart itself. [ 5 ]  As clinicians begin to intervene, they will simultaneously seek reversible causes of the arrest. Management begins by establishing multiple points of IV access and evaluating the patient's airway and breathing. Other interventions may include  thoracostomy  and  thoracotomy , as well as treatment of the underlying cause of arrest.


Basic life support  is commonly initiated by bystanders and first responders, but the role of basic life support in traumatic cardiac arrest is unclear. Basic life support is targeted to maintain oxygenation and circulation throughout the body, which can be lifesaving in cases of medical cardiac arrest, but does not address the frequent large volume blood loss encounters in many cases of traumatic cardiac arrest. [ 5 ]


Chest compressions  are considered the most important initial intervention in cases of medical cardiac arrest, however studies evaluating their efficacy have excluded patients with traumatic cardiac arrest. Chest compressions work to replace the cardiac function of pumping blood throughout the body, however cases where the heart is either unable to fill with blood or the total blood volume is depleted, this intervention may be ineffective. Additionally, as many of the interventions targeted at specific causes of arrest are centered around procedures performed around the patient's chest, head, and neck, compressions may interfere with definitive management. [ 5 ]


Current guidelines tailored to treatment of specific causes of traumatic cardiac arrest have improved outcomes for patients, however these guidelines may be difficult to apply in a standardized manner due to differences in pre-hospital care and the wide variety of causes of traumatic cardiac arrest compared to medical cardiac arrest. [ 3 ]  Evolving algorithms are directed at quickly identifying incidences of cardiac arrest with a traumatic source and rapidly intervening to address reversible causes. [ 3 ]


Historically, traumatic cardiac arrest was thought to lead invariably to death. More recently, evolutions of advanced trauma life support guidelines and improved understanding of the underlying causes of traumatic cardiac arrest have improved outcomes for patients. [ 5 ]  Recent studies suggest that the survival rate for traumatic cardiac arrest is similar to that of all-cause cardiac arrest. [ 6 ]  There is wide variability in the estimated survival rate based on factors that include initiation of pre-hospital care and nature of injury. [ 7 ]


Many patients who survive traumatic cardiac arrest may develop long-term neurological damage resulting from lack of circulation to the nervous system during the arrest. This damage may range from moderate disability to a persistent vegetative state. A 2012 review suggests that while survival rates of traumatic cardiac arrest are higher in children, so is the incidence of neurological complication. [ 8 ]


Twiddler's syndrome  is a malfunction of a  pacemaker  due to manipulation of the device and the consequent dislodging of the leads from their intended location.  As the leads move, they stop pacing the heart and can cause strange symptoms such as  phrenic nerve  stimulation resulting in abdominal pulsing or  brachial plexus  stimulation resulting in rhythmic arm twitching. [ 1 ]  Twiddler's syndrome in patients with an implanted  defibrilator  may lead to inadequate, painful defibrillation-shocks. [ 2 ]


Twiddler's syndrome presents with a range of symptoms, contingent on the extent of entanglement, the electrode's subsequent retraction, and the final location of the dislodged lead. [ 3 ]  Leads that become more dislodged up can activate the ipsilateral  phrenic nerves , which can result in  hiccups , involuntary breathing spasms, or diaphragmatic contractions. [ 1 ] [ 4 ]  The  brachial plexus  is stimulated by additional coiling and withdrawal of the lead, which causes regular arm twitches. [ 5 ]


Patient "twiddling," or manipulation, of the pulse generator within its skin pocket results in the device's painless dislodgment; lead dislodgement follows, eventually leading to  pacemaker  malfunction. [ 1 ]  There have also been reports of variations of this phenomenon resulting in the failure of implanted cardioverter- defibrillators  and  cardiac resynchronization therapy , which can be fatal. [ 6 ]


The condition's risk factors include being a woman, being  obese , belonging to an older age group, having  cognitive impairments , and having an implanted device that is smaller than its pocket. [ 7 ] [ 4 ] [ 8 ]  A related increase in subcutaneous tissue laxity, especially in older patients, makes it easier for the device to become dislodged. [ 6 ] [ 7 ]  Furthermore, the newer devices' smaller sizes make it easy for them to rotate inside the skin pocket. [ 3 ]


Given its speed and ability to provide a clear image of the lead coiling and device rotation, the  chest X-ray  is the most straightforward and important diagnostic tool for Twiddler's syndrome. [ 3 ]


Repositioning the pulse generator, implanting a new lead, and uncoiling the lead are among the treatments for diagnosed cases. [ 4 ] [ 8 ] [ 5 ]


Ventricular aneurysms  are one of the many complications that may occur after a  heart attack . The word aneurysm refers to a bulge or 'pocketing' of the wall or lining of a vessel commonly occurring in the blood vessels at the base of the septum, or within the aorta. In the heart, they usually arise from a patch of weakened tissue in a  ventricular wall , which swells into a bubble filled with blood. [ 1 ]  This, in turn, may block the passageways leading out of the heart, leading to severely constricted blood flow to the body. Ventricular aneurysms can be fatal. They are usually non-rupturing because they are lined by scar tissue.


A left ventricular aneurysm can be associated with  ST elevation . [ 2 ]


Ventricular aneurysms usually grow at a very slow pace, but can still pose problems. Usually, this type of aneurysm grows in the  left ventricle . This bubble has the potential to block blood flow to the rest of the body, and thus limit the patient's stamina. In other cases, a similarly developed  pseudoaneurysm  ("false aneurysm") may burst, sometimes resulting in the death of the patient. Also, blood clots may form on the inside of ventricular aneurysms, and form  embolisms . If such a clot escapes from the aneurysm, it will be moved in the circulation throughout the body. If it gets stuck inside a blood vessel, it may cause  ischemia  in a  limb , a painful condition that can lead to reduced movement and tissue death in the limb. [ 1 ]  Alternatively, if a clot blocks a vessel going to the brain, it can cause a stroke. In certain cases, ventricular aneurysms cause ventricular failure or arrhythmia. At this stage, treatment is necessary. [ citation needed ]


Ventricular aneurysms are usually complications resulting from a  heart attack . When the heart muscle ( cardiac muscle ) partially dies during a heart attack, a layer of muscle may survive, and, being severely weakened, start to become an aneurysm. Blood may flow into the surrounding dead muscle and inflate the weakened flap of muscle into a bubble. It may also be congenital. [ citation needed ]


When a person visits the hospital or doctor with other symptoms, especially with a history of heart problems, they will normally be required to undergo an electrocardiogram, which monitors electrical activity within the heart and shows abnormalities when a cardiac aneurysm is present. It can also appear as a bulge on a chest x-ray, and a more accurate diagnosis will then be made using an echocardiogram, which uses ultrasound to 'photograph' the heart and how it functions while it beats. [ citation needed ]


It should also not be confused with a  pseudoaneurysm , [ 4 ] [ 5 ]   coronary artery aneurysm  or a  myocardial rupture  (which involves a hole in the wall, not just a bulge.)


Cardiac  diverticulum or ventricular diverticulum is defined as a  congenital  malformation of the fibrous or muscular part of the heart which is only visible during chest x-rays or during an  echocardiogram  reading. [ 6 ]  This should not be confused with ventricular diverticulum, as the latter is a sub type derived from the latter in congenital cases. it is usually asymptomatic and is only detected using imaging. Fibrous diverticulum is characterised by a calcification if present at the tip ( apex) or a thrombi that may detaches to form an emboli. Muscular diverticulum is characterised by appendix forming at the ether of the ventricles. [ 7 ]  it is a rare anomaly and can be diagnosed prenatal. Diagnosis is usually done by a chest X-ray and silhouette is viewed around the heart. Echocardiogram reading present a similar picture to ventricular  aneurysms  on the ST segment. Management is dependent on the situation presented and the severity of the case. Usually, surgical resection is advised but in prenatal cases, due to combination with other cardiac abnormalities, especially in latter  trimesters , but  pericardiocentesis  is useful technique to reduce pleural effusion or/ and secondary disorders. [ vague ]