BMS200 wk10 peri_myo_endocarditis POTS.pdf

BMS 200 – Cardiology 9 Pericarditis, Myocarditis, Endocarditis Orthostatic and vasovagal syndromes Outcomes Briefly describe the pathogenesis, major clinical features, and prognosis of the following clinical classifications of pericarditis: acute pericarditis, subacute pericarditis, constricti...

BMS 200 – Cardiology 9 Pericarditis, Myocarditis, Endocarditis Orthostatic and vasovagal syndromes Outcomes Briefly describe the pathogenesis, major clinical features, and prognosis of the following clinical classifications of pericarditis: acute pericarditis, subacute pericarditis, constrictive pericarditis Briefly describe the pathogenesis, major clinical features, and prognosis of infectious and non-infectious forms of myocarditis Briefly describe the pathogenesis, major clinical features, and prognosis of acute and subacute bacterial endocarditis Describe the biology, life cycle, major virulence factors, diagnosis, and clinical manifestations of infection for the following: Borrelia burgdorferi, trypanosoma cruzi, ehrlichia chaffeensis Outcomes Briefly describe the biology, major virulence factors, diagnosis, and clinical manifestations of coxsackie virus and echovirus Briefly describe the cardiac complications of COVID19 coronavirus Briefly describe the biology, major virulence factors, diagnosis, and clinical manifestations of HACEK group of bacteria Staph epidermidis and viridans streptococci Describe the pathophysiology of postural-tachycardia syndrome (POTS) and relate it to clinical features Inflammation of the structures of the heart Pericarditis ▪ Acute, subacute, and constrictive Myocarditis ▪ Infectious causes ▪ Overview of inflammatory causes Endocarditis ▪ Acute and subacute bacterial endocarditis Pericardium - Recall How much Double-walled sac that contains the heart and the roots of the great vessels pericardial fluid is ▪ Fibrous layer - Tough, inelastic dense normal? irregular CT 15 – 50 mL ▪ Serous layer - Thinner, more delicate double layer composed of mesothelium Visceral layer of pericardium ▪ aka epicardium Parietal layer of pericardium Epicardium - visceral layer of the pericardium Functions: ▪ Anchors and protects the heart ▪ Prevents overfilling of heart with blood ▪ Allows heart to work in friction-free environment Note – epicardium also contains coronary vessels, nerves, and fat Acute pericarditis Most common pathologic process impacting the pericardium ▪ Between 1% and 5% of cases of acute chest pain more likely in younger patients Major causes are: ▪ Viral causes – coxsackie virus A and B, echovirus, other less * common organisms ▪ Bacterial, fungal causes – as extensions from pneumonia Many – streptococcal, staphylococcal, TB, opportunistic fungal infections ▪ Rheumatic fever & autoimmune disorders (RA, SLE, AS) ▪ Cancer (invasion of the pericardium) and CKD (increased filtration → excess pericardial fluid) Kidney disease ▪ After cardiac injury – traumatic or post-infarction (both fairly rare) Ga ▪ Idiopathic – often a cause can’t be identified (likely viral) Acute pericarditis – general pathogenesis If extracellular fluid volume increases over long periods of time (CHF, CKD) then fluid can accumulate and there may be limited inflammation ▪ Pericardial effusion instead of pericarditis – very little protein, very few leukocytes Inflammatory damage/responses can be caused by all of the etiologies in the last slide ▪ Particular type of inflammation known as fibrinous inflammation – the normally smooth surface of the heart is covered by a shaggy-looking inflammatory exudate with deposition of fibrin Leukocytes (mostly macrophages), protein present in the pericardial fluid  Acute pericarditis – clinical features Chest pain – especially in infectious, idiopathic or autoimmune causes ▪ Tends to be severe and sharp – sometimes is pleuritic in nature (often accompanied by pleural inflammation) Pleuritic pain? ▪ Located retrosternally/precordially, can have similar radiation to ischemic chest pain – often confused with angina Tends to be better sitting up + leaning forward than lying down Troponin and ECG can be confusing – troponin can be elevated with epicardial inflammation/damage and the ECG will often exhibit non-specific ST-elevation in a non-vascular distribution - T Pericardial friction rub – a raspy, “scratchy” sound that can be * present during systole and diastole ▪ However, this finding can be transient as more fluid accumulates – thought to be caused by inflamed pericardial surfaces “rubbing” ▪ With more fluid, becomes difficult to hear heart sounds (or the rub) Acute pericarditis – ECG & auscultatory findings (FYI) Note the “everywhere” ST elevation – that’s weird for an MI ▪ No one coronary artery would cause ST elevation in that many leads Acute pericarditis – diagnosis, treatment, prognosis Echocardiography is the main method of diagnosis → ▪ CT or MRI can also contribute and provide detail about pericardial thickening Most cases of idiopathic or viral pericarditis are self-resolving, and anti-inflammatory medications are helpful for symptom resolution * 3 ▪ High-dose aspirin, NSAIDs, colchicine, steroids * ▪ Depending on the cause, a significant minority will have recurrences Complications – constrictive pericarditis, recurrences, cardiac tamponade Acute pericarditis – additional info Most cases of acute pericarditis are presumed to be viral – usually an organism can’t be found ▪ Typically occurs 10 – 12 days of a presumed viral infection ▪ Fever and near-simultaneous development of sharp chest pain is the typical presentation Acute pericarditis can transition to subacute and constrictive pericarditis ▪ Aren’t really clear definitions for subacute pericarditis - usually means symptoms/effusions for > 4-6 weeks ▪ With long-term inflammation, can progress to constrictive pericarditis ▪ Longer-term, slower development of effusions are better tolerated by a patient – slow accumulation of up to 2 L of fluid can occur before tamponade emerges – metastases to the pericardium are a common cause In those that experience recurrence, a hole (pericardiotomy) may need to be left in the pericardium for fluid to drain Constrictive pericarditis Chronic Sometimes after acute pericarditis the pericardium “scars” ▪ Often obliteration of the pericardial cavity with chronic inflammation of the visceral pericardium – can even calcify ▪ Can greatly restrict cardiac filling – therefore known as constrictive pericarditis ▪ Causes include TB pericarditis, post-traumatic/surgical/radiation pericarditis, neoplastic disease, CKD, or idiopathic Kind of looks like a restrictive cardiomyopathy: ▪ congestion in the venous system with relatively preserved stroke volume (still reduced though) and reduced EDV Because the heart cannot fill as much - ▪ fatigue, neck vein distention, hepatosplenomegaly Uncommon complication of acute pericarditis ▪ Can be diagnosed by US or MRI ▪ Pericardial resection is the treatment Pericardial tamponade Accumulation of fluid in the pericardial space that is severe enough that it acutely obstructs flow into the ventricles – usually acute accumulation ▪ Cause of obstructive shock, and can be rapidly fatal ▪ Thankfully uncommon ▪ Causes include ruptured ventricular aneurysm, severe acute pericarditis, cardiac trauma, aortic dissection ▪ As little as 250 mL in the pericardium, if it develops acutely, can cause death Clinical features: ▪ Hypotension, muffled heart sounds, distended neck veins → shock Emergent removal of fluid from the pericardial space (pericardiocentesis) is necessary ▪ More later in Emerg Med * Myocarditis Inflammation of the heart which can lead to: ▪ Dilated cardiomyopathy → heart failure ▪ Conduction blocks (or sometimes a predisposition to ventricular tachycardia) ▪ Rarely sudden cardiac death (likely due to dysrhythmia) We’ll focus on infectious causes of myocarditis today – typical etiologic agents include: ▪ Viral causes – echovirus and coxsackie virus (common in this part of the world) ▪ Lyme disease – Lyme myocarditis is usually fairly benign, but rarely it can cause serious myocarditis ▪ Trypanosomiasis cruzi – a parasite common in South America that causes serious myocarditis ▪ Ricketsia ricketsii, ehrlichia chaffeensis – uncommon causes of myocarditis, but can be deadly Myocarditis – Pathogenesis How can infection damage the myocardium? ▪ Invasion of the myocardium – for example, when a virus invades a myocyte and causes lysis ▪ Early cytokine release in response to infection can depress myocardial function, but does not in itself cause damage ▪ Adaptive immune response → Granuloma formation Prolonged release of cytokines → fibrosis and damage to the ECM → dilation ▪ May develop into long-term attack of the heart via antibodies or continued T-cell responses Fibrosis can cause conduction blocks or dysrhythmia development Myocarditis - Pathogenesis  Clinical Features, Diagnosis Acute viral myocarditis can present with symptoms and signs of acutely-developing heart failure ▪ Can also present with chest pain and ECG changes suggestive of pericarditis or acute myocardial infarction ▪ May present with atrial or ventricular tachyarrhythmia Typical patient picture: young to middle-aged adult with progressive dyspnea and weakness ▪ few days or weeks after a viral syndrome that was accompanied by fever and myalgias ECG, echocardiogram, and troponin are the initial * * diagnostic options ▪ MRI can often visualize soft tissues like the heart quite well – may provide info re: inflammation and scarring within the heart Bacterial endocarditis – a quick overview Typical pathologic sequence: ▪ Damaged endocardium or abnormal surface within the heart (i.e. a device or prosthetic valve) forms a thrombus ▪ Bacteria that have virulence factors that allow thrombus invasion colonize the thrombus ▪ The resulting inflammatory mass can: Damage the endocardium, in particular heart valves Break off and cause strokes or other thromboembolic arterial obstructions that can result in inflammation at the site of obstruction Cause unique “weird” hemorrhagic/ischemic findings (i.e. retinal hemorrhages) Whatever the sequence, acute bacterial endocarditis is an * extremely dangerous condition and must be dealt with urgently Acute bacterial endocarditis Vegetation = mass of platelets, fibrin, microorganisms, and some inflammatory cells ▪ Usually involves a valve, but can - - occur on a device or area of & endocardium - near turbulent flow or that has suffered damage ▪ Vegetations are weak and friable, and can break off and spread Most common etiologies: ▪ Large bacterial loads – dental/gingival disease, people who inject drugs (often right-sided valves involved) ▪ Valvular damage or recent valvular surgery ▪ Congenital heart disease (in particular VSD) Acute bacterial endocarditis The type of infectious agent causing the problem tends to determine whether the presentation is acute and immediately life-threatening/valve-destroying or whether it follows a less stormy, subacute course * ▪ Nasty acute bugs – staphylococcus aureus, streptococcal species, rarely pneumococcus ▪ More slow-growing, “less damaging” bugs – HACEK group, enterococcus Terminology: ▪ NBTE – non-bacterial thrombotic endocarditis – often the first step to an infected vegetation ▪ NBTE most commonly develops in those with mitral regurgitation, aortic stenosis, aortic regurgitation, VSDs and other congenital heart disease Turbulent blood flow Signs and symptoms of infective endocarditis Clinical Feature Frequency Fever, chills, sweats: 80 – 90% Acute – high fevers Subacute – lower fevers that spike intermittently Anorexia, weight loss, malaise (subacute most 40 – 75% noticeable) Myalgias, arthralgias, back pain 15 – 30% Heart murmur (may not present until some time > 80% after onset) Arterial emboli 20 – 50% Splenomegaly 15 – 50% Nail clubbing 10 – 20% Neurologic manifestations (CVAs) 20 – 40% Peripheral manifestations 2 – 15% Infective endocarditis Assorted endocarditis info: S ▪ Peripheral manifestations include Osler nodes (painful raised papules – nodules on digits), Janeway lesions (painless hemorrhagic pustular lesions on soles or palms) and Roth spots (retinal hemorrhages with a pale centre ▪ FYI – Duke criteria (see next slide) used to diagnose infective endocarditis Subacute bacterial endocarditis ▪ Present for weeks – months with a gradual progression, usually slow and limited valvular damage Exception → valve rupture/serious damage or a major embolic event Duke criteria - FYI Microbes that impact the heart Borrelia burgdorferi (Lyme disease) Endocarditis-causing microbes: ▪ Coagulase-negative staphylococci, streptococcus viridans, enterococcus faecalis, HACEK organisms Myocarditis-causing microbes: ▪ Coxsackie virus and echovirus ▪ SARS-CoV2 ▪ Ricketsia ricketsii ▪ Trypanosoma cruzi, ehrlichia chaffeensis Lyme disease – a quick overview Caused by Borrelia burgdorferi, a tick-borne spirochete that is quite common in the Northern Hemisphere ▪ 30,000 new cases in US/year Structure – inner membrane with a peptidoglycan layer in the middle, and then an outer membrane ▪ Flagella are present between the two membranes and allow the bacterium to move through host tissues Fastidious microbes that require a complex medium to culture ▪ lack the ability to synthesize amino acids, fatty acids, nucleotides and enzyme cofactors Lyme disease – life cycle and virulence factors Humans aren’t required for the life cycle of Lyme disease (see next slide) ▪ Certain mice maintain B. burgdorferi in nature ▪ Ticks can’t the bacteria to their offspring, so it travels from tick → reservoir animal → tick ▪ The “baby ticks” (nymphs) are better at transmitting the disease than adult ticks – hence most cases of Lyme disease occur in the spring - - Virulence factors ▪ Seem to be able to bind to complement regulatory proteins, which may protect it from attach via the complement system ▪ Constantly changes the sequence or type of their surface proteins – an immunologic “moving target” ▪ They like to hide and divide in avascular areas (tendons, joints, etc.) The natural cycle of Lyme disease. Ixodes ticks undergo a 2-year cycle that encompasses four stages: eggs, larvae, nymphs, and adults. In the summer, larvae hatch in an uninfected state and then acquire Lyme borreliae by feeding on infected rodents. Lyme borreliae survive in the midgut as the larvae molt into nymphs in the fall and are dormant through the winter. Infected nymphs feed on rodents in the late spring and early summer, resulting in the chronic infection of this natural reservoir of Lyme borreliae. The population of chronically infected rodents transmits Lyme borreliae to the next generation of ticks. 3 Nymphal ticks can also feed on humans, giving rise to the peak of human Lyme disease in the late spring and summer. The ticks molt into adults in the fall, and while their preferred host is deer, they can occasionally feed on humans, giving rise to a smaller peak of human Lyme disease in the fall. 2018 – cases of reported Lyme disease in the US Stages of Lyme infection in humans Stage 1 – erythema migrans skin rash ▪ Spreading rash that reflects the ability of the spirochete to spread through the skin ▪ Uncommon rash that is fairly specific for Lyme disease The rash itself if not painful or itchy, but is often accompanied by: ▪ Arthralgias and myalgias ▪ Fever, fatigue, headaches This is the optimal time for antibiotic therapy to clear the infection ** Stages of Lyme infection in humans Stage 2 – disseminated infection that is likely due to the bacterium infiltrating walls of blood vessels, occurs weeks – months after initial infection ▪ Can invade a wide range of organs including: Central nervous system – fatigue, aseptic meningitis, and cranial nerve palsies (in particular Bell’s palsy) Heart – one of the less common causes of myocarditis Skin – more erythema migrans lesions Joints – most common site of involvement – Lyme arthritis seems to- frequently affect the knee Stage 3 – most common late manifestation is arthritis of one or a few large joints which can be intermittent ▪ Meningoencephalitis is usually a rare complication Lyme disease – additional clinical details Although Lyme disease can be treated at all stages, a significant proportion of patients can have post- treatment Lyme disease syndrome 3 ▪ Chronic pain, neurocognitive disturbances, fatigue that lasts - months/years ▪ Antibiotics don’t seem to help this, and are not worth the side effects Diagnosis is complex ▪ Difficult to culture the organism, and often none are found in joint/blood samples ▪ Two-tiered serologic testing – ELISA followed by an immunoblot test… since it tests antibodies, though, doesn’t discriminate between past and current infection Endocarditis microbes – general virulence factors Common streptococcal species that cause endocarditis have extracellular dextrans that facilitate adhesion to thrombotic vegetations or to damaged valvular endothelium ▪ Dextrans allow binding to platelet-fibrin complexes ▪ FimA, produced by streptococci allows adherence to the endocardium or valve Fibronectin is normally “hidden” by the endothelium/endocardium (part of ECM) ▪ Exposure of fibronectin allows particular microbes to adhere ▪ E. Faecalis, S. aureus, and the viridans group of streptocci bind well to fibronectin ▪ Medical devices can also become coated by fibronectin as well Many of these microbes can build mucopolysaccharide biofilms that aids colonization Endocarditis microbes – general virulence factors S. aureus – you’ve already talked about this bug ▪ In infective endocarditis, production of tissue factor helps to build clots, which aids invasion of S. aureus onto cardiac structures/vegetations HACEK? ▪ Haemophilus species, Aggregatibacter (formerly Actinobacillus) species, Cardiobacterium species, Eikenella corrodens, and Kingella kingae ▪ These are all gram-negative bugs that usually live in the oral cavity ▪ They are fastidious, are slow to grow, and require carbon dioxide ▪ Why do they cause endocarditis? No particular virulence factors seem to be identified outside of the fact that they happily colonized dental structures and frequent gain access to the bloodstream during dental work or flossing BMS 200 – Cardiology 9 Pericarditis, Myocarditis, Endocarditis Orthostatic and vasovagal syndromes Outcomes Briefly describe the pathogenesis, major clinical features, and prognosis of the following clinical classifications of pericarditis: acute pericarditis, subacute pericarditis, constrictive pericarditis Briefly describe the pathogenesis, major clinical features, and prognosis of infectious and non-infectious forms of myocarditis Briefly describe the pathogenesis, major clinical features, and prognosis of acute and subacute bacterial endocarditis Describe the biology, life cycle, major virulence factors, diagnosis, and clinical manifestations of infection for the following: Borrelia burgdorferi, trypanosoma cruzi, ehrlichia chaffeensis Outcomes Briefly describe the biology, major virulence factors, diagnosis, and clinical manifestations of coxsackie virus and echovirus Briefly describe the cardiac complications of COVID19 coronavirus Briefly describe the biology, major virulence factors, diagnosis, and clinical manifestations of HACEK group of bacteria Staph epidermidis and viridans streptococci Describe the pathophysiology of postural-tachycardia syndrome (POTS) and relate it to clinical features  POTS – Postural Orthostatic Tachycardia Syndrome What is it? The name describes it well – when people go from lying down to standing, they experience a > 30 beat/min increase in HR That increase in heart rate cannot be accompanied by a P A decrease in blood pressure… ▪ Otherwise that would be known as orthostatic hypotension ▪ It is normal for BP to drop when standing – if there is a less than 20/10 mm Hg drop, then that’s considered normal This is part of a set of syndromes known as dysautonomias ▪ Include POTS, orthostatic hypotension, vasovagal syncope as the more common syndromes POTS – key clinical features Symptomatic orthostatic intolerance without hypotension ▪ Accompanied by increase in HR > 120 beats/min or > 30 beats/min over supine HR What is meant by orthostatic intolerance? ▪ In response to standing, troublesome symptoms occur, which can include: Light-headedness, weakness, blurred vision Nausea, tremulousness (shakiness), and palpitations Although pre-syncopal symptoms are the defining feature, syncope does not tend to happen Women are affected 5X more often than men - This is likely the most, or at least one of the most common, dysautonomias to cause very bothersome symptoms POTS – a tricky subject Even though it requires tilt- table testing to diagnose, there are no clear single pathophysiologic mechanisms or diagnostic criteria beyond the ones mentioned in the last slide Most experts agree that there’s “more than one POTS” ▪ There are a multitude of different causes of this syndrome and each patient has a somewhat unique variant on a number of different pathophysiologic themes ▪ So, if there’s more than one POTS, some sort of standardized recognition needs to happen before you can standardize diagnosis https://www.mayoclinic.org/tests-procedures/tilt-table- test/about/pac-20395124#dialogId36740715 The baroreceptor reflex – a review POTS – why does it happen? Let’s unpack that last slide Pooling of blood, inappropriate arteriolar vasodilation, * Neuropathic causes of POTS less NE released ▪ Neuropathy where? ▪ For reasons that aren’t understood, patients with POTS have “pooling” of blood in the lower vascular beds Include the pelvic, splanchnic, and lower limb vessels ▪ Interestingly, this pooling might not be due to venous vasodilation, but instead due to inappropriate arteriolar - - vasodilation Studies in patients with POTS seem to indicate that less NE is released in the lower limbs in response to orthostatic or pharmacologic challenges Strangely enough, NE release was the same between controls and POTS patients in the upper extremities Other studies also find an exaggerated response to exogenously administered catecholamines… why might this be? typically do not have enough NE - when give exogenously, body may overreact bc not used to having enough NE in the lower body The baroreceptor reflex – a review Still unpacking… * Problems with RAAS - low aldosterone Hypovolemic POTS ▪ It’s easy to understand why reduced blood volume leads to tachycardia – see baroreceptor reflex again ▪ Some POTS patients seem to have reduced blood volume – 13 -22% lower plasma volume than health controls Why hypovolemia? ▪ Not sure - but the following experimental findings are observed: Elevated renin compared to aldosterone (a low aldosterone:renin ratio) Even when renin increases a lot, aldosterone does not as much Not enough retention of Na+ and water Elevated levels of angiotensin II… Body is trying to compensate for low aldosterone via elevated ATII What does this evidence suggest? Hypovolemic POTS Other findings in patients with “hypovolemia-predominant” POTS ▪ Patients who are deconditioned tend to reduce their blood volume. This is seen in: Subjects exposed to microgravity for extended periods of time experienced decreased blood volume and POTS-like responses to standing Decreases in blood volume can also be seen with prolonged bed rest ▪ It is thought that deconditioning may “unmask” inadequate aldosterone secretion in those predisposed to POTS Hyper-adrenergic POTS Some POTS patients secrete much more norepinephrine than patients without the disorder ▪ Experimental data suggests that in healthy controls, there is a doubling of plasma norepinephrine concentrations on standing ▪ In patients with POTS in the same study, there can be a * * tripling-to-quadrupling of NE release ▪ Epinephrine concentrations seem to be similar Why is there an oversecretion of NE in some? ▪ One study suggests missense mutations in catecholamine transporters → accumulation of NE in the ECF where it is released ▪ In these patients, standing actually leads to an increase in blood pressure in some Hyper-adrenergic POTS Other theories re: hyper-adrenergic POTS ▪ Activating auto-antibodies to beta-1 and beta-2 adrenoreceptors have been detected Can you think of another disorder that involves activating antibodies? Grave’s disease Heart - tachycardia How would inappropriate activation of beta-1 receptors manifest? How about beta-2? Blood vessels - pooling of blood widening of airways POTS – which therapies make sense for which cause? Therapies for POTS (which model?) Stimulates alpha 1 receptors to vasoconstrict - Midodrine – alpha-1 agonist: _________________Neuropathic helps increase BP and improve blood flow Avoidance of SNRIs: _________________ Hyperadrenergic High sodium diet: _____________ Hypovolemic Stockings & abdominal compression: ___________ Hypovolemic & neuropathic “Drink more water”: ________________ Hypovolemic Desmopressin (AVP agonist) ______________ Hypovolemic Synthetic form of vasopressin Lower extremity maneuvers: _________________ Neuropathic Beta-blockers: ______________ Hyperadrenergic Exercise: ___________________ Hypovolemic.