BMS 200 - Cardiology 6 PDF

BMS 200 – Cardiology 6 Heart Failure, Cardiomyopathies, and Valvular Heart Disease Outcomes Describe the general pathological findings and pathophysiologic consequences of: Valvular stenosis, valvular regurgitation, valvular prolapse Relate the pathophysiology of common valvular diseases to fin...

BMS 200 – Cardiology 6 Heart Failure, Cardiomyopathies, and Valvular Heart Disease Outcomes Describe the general pathological findings and pathophysiologic consequences of: Valvular stenosis, valvular regurgitation, valvular prolapse Relate the pathophysiology of common valvular diseases to findings on the physical exam Describe the basic epidemiology, pathogenesis, clinical features, and prognosis of the following valvular heart disorders: Aortic regurgitation, Calcific aortic stenosis, Bicuspid aortic valves Mitral valve prolapse, Mitral regurgitation, Rheumatic heart disease Describe the basic epidemiology, pathogenesis, clinical features, and prognosis of the following cardiomyopathies: Hypertrophic cardiomyopathy, Dilated cardiomyopathy (hereditary) Restrictive cardiomyopathy CAD-related ventricular failure, Hypertensive heart disease Outcomes Relate the cellular and gross pathophysiologic adaptations in heart failure to underlying etiologic and risk factors Compare the pathogenesis, clinical features, diagnostic findings, and complications of left-sided and right-sided congestive heart failure Compare the pathogenesis, clinical features, diagnostic findings, and complications of HFpEF and HFrEF Briefly describe the pharmacologic mechanism of action and related adverse effects of common medications used to treat heart failure Heart Failure – an Introduction A normal ventricle should be: ▪ Compliant – diastolic filling occurs at low atrial pressures, and the atria do not have to undergo hypertrophy to fill the ventricle at the end of diastole The ventricle should be able to relax quickly and most filling should take place in early diastole ▪ “Strong” – a ventricle should generate enough force at rest with low diastolic pressures/preload to meet the needs of the body Calcium should be quickly released and re- sequestered each cycle There should be a significant reserve of function for when activity increases Heart Failure – an Introduction Heart failure can occur for many reasons: ▪ Increased afterload (overload) of the ventricles over long periods of time Ventricles become hypertrophic, increasing wall thickness and eventually chamber size Molecular changes → decreased contractility ▪ Impaired oxygen supply in a setting of chronic ischemic heart disease May or may not involve sites of infarcted tissue ▪ Impaired ability to relax (reduced compliance) due to fibrosis or poorly-characterized molecular changes ▪ Disorders that damage the myocardium and impair compliance or contractility Known as cardiomyopathies Heart Failure – an Introduction Prevalence of heart failure U.S. adults ≥20 years of age by sex and age from the National Health and Nutrition Examination Survey (NHANES), 2013– 2016 Biggest underlying etiologies/risk factors for heart failure Note – kind of weird stats here, don’t quite add up to 100% Atherosclerosis alone (not shown here) is responsible for about 2/3  Heart Failure – P-V loops The pathogenesis of heart failure is still being clarified, though it’s clear that there are two major phenotypes: ▪ Systolic dysfunction (A) – impaired force of contraction/contractility → reliance on elevated preload for adequate cardiac output ▪ Diastolic dysfunction (B) – elevated diastolic pressures are evident, but force of contraction/contractility is maintained Despite elevated diastolic pressures, there may be impaired EDV  Heart Failure – P-V loops The pathogenesis of heart failure is still being clarified, though it’s clear that there are two major phenotypes: ▪ Systolic dysfunction (A) is mostly referred to in the literature as heart failure with reduced ejection fraction (HFrEF) ▪ Diastolic dysfunction (B) – is mostly referred to in the literature as heart failure with preserved ejection fraction (HFpEF) although in the diagram below the EF is reduced slightly from normal  Pathophysiologic Pathways in CHF As heart failure progresses, two major problems arise: “Forward flow” problems – impaired cardiac output to a range of tissues impairs function ▪ Major tissues that experience decreased perfusion include the brain, the heart, the kidneys, and the extremities Sometimes reduced flow to the viscera can lead to abdominal pain, but uncommon ▪ Impaired venous return from the pulmonary veins → LV Pathophysiologic Pathways in CHF “Backwards” problems – congestion ▪ As LV CO declines, blood congests in the pulmonary venous circulation → elevated pressures in pulmonary capillaries → development of pulmonary edema and thickening of arterioles/arteries in the lung ▪ As RV CO declines, blood congests in the systemic venous circulation → elevated pressures in systemic capillaries → edema Hepatic congestion & splenomegaly Dependent edema  Pathophysiologic Pathways in CHF Since the left ventricle experiences the greatest afterload, it is usually the “first to fail” ▪ As pulmonary congestion increases, the afterload of the RV also increases → development of RV failure There are situations where the right ventricle is the “first to fail” ▪ Lung disease → areas that are Cor pulmonale. hypoxic/poorly ventilated → heart from a patient with pulmonary vasoconstriction pulmonary hypertension markedly hypertrophied right ▪ Known as cor pulmonale – ventricle common causes include COPD RV free wall thickness nearly and obstructive sleep apnea equals the left  Comparison of Microcirculation - Review Pulmonary Microcirculation Controlled by O2 concentrations ▪ constriction in response to decreased oxygen levels ▪ how does this compare to other vascular beds? Why does this make sense? Pathophysiologic Pathways in CHF In the end, both ventricles suffer dysfunction in heart failure and there is some reduction in both compliance (diastolic dysfunction) and force of contraction (systolic dysfunction) ▪ However, most cases of heart failure can be clearly dichotomized into HFrEF and HFpEF The heart is typically hypertrophied in two common patterns that differ from physiologic, or “healthy” hypertrophy that is common in athletes ▪ Concentric hypertrophy ▪ Eccentric hypertropy Pathophysiologic Pathways in CHF Concentric hypertrophy ▪ Thought to be earlier in the development of HF ▪ Thickened ventricular wall, no increase in chamber size ▪ Increased thickness is thought to minimize wall stress Eccentric hypertrophy ▪ Ongoing remodeling → eccentric hypertrophy as myocytes increase in length ▪ Usually associated with a decrease in ejection fraction and increased symptoms Pathophysiologic Pathways in CHF Molecular adaptations in the failing heart: The structure of myocytes and surrounding tissue is altered over time – known as ventricular remodelling ▪ Increased expression of fetal forms of myosin that use ATP more effectively but generate less force ▪ Increased expression of TGF-beta leads to deposition of extracellular matrix in the extracellular spaces ▪ Myocytes themselves enlarge, but the capillary network in the hypertrophic heart tends to be less extensive than in physiologic hypertrophy Pathophysiologic Pathways in CHF Signaling pathways implicated in HF: Angiotensin II – as cardiac output to the kidneys decreases → increased AT II ▪ AT II can also be released by “stressed” cardiac cells AT II can directly bind to myocyte and myofibroblast receptors → hypertrophy, proliferation of myofibroblasts, and increased deposition of connective tissue Increased AT II also increases volume and vasoconstriction → worsened edema and afterload Pathophysiologic Pathways in CHF Signaling pathways implicated in HF: Beta-adrenergic signaling is increased in early heart failure → receptor downregulation Long-term beta-adrenergic signaling also results in hypertrophy and fibrosis, and even eventually apoptosis of myocytes ▪ long-term activation of the SNS in the heart is maladaptive, even though short-term activation improves cardiac function ▪ Exact signaling mechanisms are currently being studied Pathophysiologic Pathways in CHF Signaling pathways implicated in HF: Other detrimental pathways: ▪ Endothelin-1: potent vasoconstrictor that is also a growth factor for cardiomyocytes ▪ Inflammatory cytokines: activate JNK and MAPK pathways that seem to be linked to maladaptive remodeling and apoptosis Pathophysiologic Pathways in CHF Signaling pathways implicated in HF: Calcium homeostasis in the failing heart ▪ Ryanodine receptors release less calcium per AP ▪ SERCA calcium uptake is inhibited ▪ The net effect seems to be elevated diastolic calcium levels and impaired calcium spikes during contraction Beneficial pathways: ▪ Activation of IGF-1 and PI3K pathways seem to be the major routes that drive physiologic (healthy) hypertrophy  CHF Pathophysiology & Neurohormonal Activation Activation of the SNS and RAAS initially leads to: ▪ Increased HR, BP, contractility ▪ Retention of sodium and water Increases preload and cardiac output Over time, things get out of hand ▪ Excessive vasoconstriction and volume retention Baroreceptor dysfunction that permits elevated pressures and decreases PNS tone ▪ Increased ADH release → increased volume ▪ Excessive SNS activation → decreased renal perfusion… which leads to chronically elevated release of renin + AT2 to maintain blood flow to the kidney RAAS - Review This model applies to renal release of renin & AT2 from the kidney ▪ Does not apply to release of AT2 from cardiomyocytes Renin release can be caused by decreased perfusion AND activation of the SNS Protection against fluid overload Both atrial (ANP) and B-type natriuretic peptide (BNP) have similar functions ▪ BNP is released by “stretched” ventricles Over time the heart failure patient seems to become resistant to BNP and ANP ▪ no longer leads to sodium and water loss ▪ FYI – some medications (known as neprilysin inhibitors) help reduce this resistance Heart Failure – General Clinical Features Symptoms ▪ Fatigue is universal ▪ “Left-sided” symptoms: orthopnea, dyspnea, angina, impaired cognitive function Can cause chronic kidney disease (CKD) and exacerbate ischemic heart disease ▪ “Right-sided” symptoms: dependent edema, RUQ pain Signs ▪ Pitting edema, hepatosplenomegaly Hepatojugular reflux is a poorly-characterized sign – alternatives include blood pressure measurement during Valsalva ▪ Elevated JVP, displacement of the apical impulse, S3 or S4 ▪ Crackles, wheezing, and sometimes pleural effusions depending on the extent of pulmonary edema  New York Heart Association Classification Functional Limitation Clinical Assessment Commonly- Class used clinical Class I None Ordinary physical activity does not cause undue fatigue, dyspnea, staging tool palpitations, or angina Doesn’t always Class II Mild Comfortable at rest. Ordinary correlate well to physical activity (e.g., carrying heavy objective packages) may result in fatigue, measurements dyspnea, palpitations, or angina (i.e. EF) Class III Marked Comfortable at rest. Less than ordinary physical activity (e.g., How one judges getting dressed) leads to symptoms symptom severity/quality of Class IV Severe Symptoms of heart failure or angina life are present at rest and worsened with any activity Heart Failure - Diagnosis HF is usually diagnosed with echocardiography ▪ HFrEF – decreased ejection fraction Normal EF is > 50%, HFrEF is diagnosed when EF < 40% ▪ HFpEF – normal (>50%) EF but: Left ventricular hypertrophy Atrial enlargement, abnormal ventricular wall movement More challenging diagnosis than HFrEF BNP – a natriuretic factor that is released by the ventricle in response to increased strain ▪ Can be helpful to diagnose both chronic HF and acute exacerbations of CHF Chest X-ray can help identify cardiomegaly and pulmonary edema ▪ Not as specific or sensitive as echocardiography, though Chronic IHD → CHF Chronic IHD (coronary artery disease) is the most common cause of heart failure (60% of CHF) ▪ the majority of the rest of the cases are due to hypertension (2nd most common), valvular abnormalities, or patients with congenital heart disease Clinical Features of CHF due to IHD: ▪ Myocardial hypertrophy and fibrosis are present as with most etiologies of CHF May see “scars” caused by healed old infarcts ▪ Although there is both systolic and diastolic function, usually presents as HFrEF – the left ventricle is usually the first to be involved  Review - atherosclerosis Progression from fatty streak → deposition of oxidized LDL → migration and activation of macrophages → ▪ Calcification, accumulation of cholesterol, foam cell development ▪ Increased deposition of extracellular matrix under the intima ▪ A variably-stable fibrous cap with underlying necrotic tissue and immune cells ▪ Stenosis of the lumen and impaired blood flow Review – risk factors and the development of atherosclerosis Smoking, high blood pressure, oxidative stress increase endothelial damage Lp(a) – likely increases endothelial damage through increasing immune cell recruitment at a developing plaque ▪ May also inhibit breakdown of clots Diabetes and dyslipidemia (including metabolic syndrome): ▪ Diabetes – LDL is more likely to be incorporated into the intima in the setting of AGEs in the endothelium – likely site of oxidation of LDL ▪ AGEs can also increase general inflammation, leading to increased oxidative stress ▪ Increased LDL → increased oxidized LDL → deposition in fatty streaks → activation of macrophages (via the scavenger receptor)  Chronic hypertension → CHF As mentioned above, long-term hypertension can cause CHF (second most common cause of CHF) ▪ Typically see concentric LV hypertrophy – wall thickens, but the chamber size does not tend to increase Over time can proceed to eccentric hypertrophy ▪ Microscopy shows hypertrophied cardiomyocytes ▪ As with many causes of heart failure, often hypertrophy does not result in increased capillary density Heart failure is one of the leading causes of death due to hypertension Medications for CHF and/or angina Beta-blockers – used for angina and CHF ▪ Most beta-blockers used in IHD or CHF are relatively selective for the beta-1 epi/norepinephrine receptor ▪ IHD: Reduce cardiac oxygen demand – thus effective prophylactic for angina, other complications of IHD ▪ CHF: reduces and even reverses cardiac remodeling (less fibrosis, hypertrophy, cell death) Cardiac glycosides (digoxin) – used in CHF ▪ Cardiac glycosides inhibit the sodium-potassium pump You would think that would be a bad idea – but see next slide ▪ Increase contractility by increasing intracellular calcium, but also increase vagal tone (resulting in a slower heart rate) Increasing vagal tone helps decrease oxygen demand  Mechanism of Action - digoxin Calcium extrusion from the cytosol is partially determined by the sodium gradient Sodium-calcium exchanger As the sodium gradient is decreased with digoxin, so is the activity of the sodium-calcium exchanger Results in a somewhat increased cytosolic calcium concentration during systole Medications for CHF Diuretics – used for CHF ▪ In general, diuretics reduce blood volume, usually by increasing water and sodium loss at the kidney tubule Loop and thiazide diuretics – inhibit sodium reabsorption by inhibiting particular sodium transporters earlier in the nephron Spironolactone – blocks the aldosterone receptor → loss of sodium and water in the distal nephron ACE inhibitors (ACE-i) block angiotensin-converting enzyme that converts AT1 to AT2 ▪ They likely also have beneficial impacts on heart remodeling, just like beta-blockers  FYI – CHF strategies CHF doesn’t occur in isolation ▪ IHD, hypertension are the major causes and both are linked to diabetes Prevention of these causes ▪ Early adoption of medications that positively impact remodelling Later adoption of medications that increase CO Medications for angina Calcium channel blockers Can cause vasodilation with limited impact cardiac conduction or contractility ▪ Drugs in this class are known as dihydropyridine (DHP) calcium channel blockers (FYI example – amlodipine and nifedipine) Can cause slowing of AV conduction (slows heart rate) and decreased contractility, but with variable effects on vasodilation ▪ These medications are known as nondihydropyridine calcium channel blockers FYI – verapamil is the prototype medication here - diltiazem decreases heart rate and causes vasodilation Nitrates – converted to nitric oxide → Decreased preload (through vasodilation of veins, decreased venous return) → decreased oxygen demand Decreased afterload (through vasodilation of arterioles) → decreased oxygen demand Coronary vasodilation → increased blood supply Dyslipidemia medications – basic MOAs HMG CoA-reductase inhibitors (statins) – reduce the hepatocyte’s ability to produce cholesterol → depletion of the hepatocyte’s “intracellular supply” of cholesterol → upregulation of the LDL receptor on the hepatocyte cell membrane ▪ This increases clearance of LDL from the circulation ▪ These medications also: Decrease circulating triglyceride levels Improve endothelial function Seem to also reduce oxidative stress and inflammation at the plaque PCSK9 inhibitors block a protease known as PCSK9 on the hepatocyte membrane ▪ This protease degrades the LDL receptor – if it is blocked, then there are more LDL receptors available to clear LDL Dyslipidemia medications – basic MOAs Ezetimibe – reduces the absorption of dietary and biliary cholesterol in the small intestine ▪ This leads to a decrease in cholesterol stores in the hepatocyte → increased LDL receptor expression Niacin (not used as often now) - inhibits lipolysis in adipose tissue ▪ Therefore less release of FFAs → less production of VLDL by the liver ▪ This in turn leads to decreased circulating LDL, but main effect is decreased in TG (VLDL) synthesis ▪ Also increases HDL… however importance of this is not known Valvular Pathology - Generalities Valves are lined by endocardium with underlying dense irregular connective tissue, connected to the fibrous rings Pathological processes that damage valves: ▪ Congenital disorders – malformation of structures (improper migration, other causes) Examples – pulmonic stenosis and bicuspid aortic valves ▪ “Wear and tear” chronic damage – often a chronic inflammatory/calcific process on top of increased physical stresses Examples - Aortic stenosis and sclerosis, mitral valve calcification ▪ Inflammatory (due to infection, autoimmunity) Examples - Bacterial endocarditis, Rheumatic heart disease, lupus, ankylosing spondylitis ▪ Acute impairments in valvular function Ischemia → impaired papillary muscle function → mitral regurgitation Aortic dissection → widening of aortic root → regurgitation ▪ Idiopathic - Mitral valve prolapse Review – stenosis, prolapse, incompetence, regurgitation Pulmonic Stenosis – the valve has a more narrow than Stenosis normal orifice, and/or it is difficult to open ▪ Either way → increased strain across the wall of the heart proximal to the stenosis→ hypertrophy and complications ▪ Can also initially result in impaired outflow to structures after the stenosis → physiologic adaptations to poor outflow Regurgitation – backflow of blood across a valve ▪ Backflow of blood to chamber proximal to the regurgitation → BOTH increased EDV/preload + impaired outflow distal to the regurgitation → eventual chamber enlargement ▪ Incompetence (insufficiency) = the valve does not close completely ▪ Prolapse = excessive (backwards) valve movement into Mitral Valve the proximal chamber Prolapse Selected Valvular Pathologies - Today Aortic regurgitation Bicuspid and calcific aortic stenosis Mitral valve prolapse and mitral regurgitation Rheumatic heart disease Selected Valvular Pathologies - Today What do you need to know about these valvular pathologies? Roughly how common are they in relation to each other? Aortic regurgitation How are they caused? What sorts of symptoms are Bicuspid and calcific most likely? aortic stenosis What will you see on the physical exam… and why? In general, how do the Mitral valve prolapse prognoses of these different pathologies compare to each and mitral other? regurgitation What don’t you need to know? Any P-V loops or Wiggers diagram changes are meant to Rheumatic heart be explanatory disease ▪ Don’t memorize them – they change from patient to patient  Aorta – Aortic stenosis/sclerosis Aortic stenosis is very common ▪ ~ 5% in those > 65 years of age (one of the most common heart diseases) Progression: aortic sclerosis → asymptomatic aortic stenosis → aortic stenosis with heart failure ▪ Congenital causes – congenital bicuspid aortic valves account for about 5% of all congenital heart disease, and is one of the most common congenital valvular defects 1% of live births have a congenital heart disorder The majority of cases of severe aortic stenosis needing surgery are due to bicuspid aortic valves Aortic stenosis/sclerosis - Pathogenesis Calcific aortic stenosis - Very similar to atherosclerosis: Damage to the valvular endothelium → oxidized LDL and migration of chronic inflammatory cells → calcification and sclerosis of tissue ▪ Some myofibroblasts actually differentiate into cells that are “bone-like” (osteoblast-like) ▪ This process is accelerated in the presence of a bicuspid aortic valve As the valve calcifies → increased afterload → concentric hypertrophy of the heart Aortic regurgitation Clinically-important AR is not as common as aortic stenosis (AS) ▪ Likely ~2% prevalence of moderate AR in older patients Many etiologies – basic pathogenesis for each: ▪ Related to aortic stenosis (most common): Valvular malformation → a valve that does not open or close fully Surgery for AS → development of AR ▪ Inflammatory disorders Ankylosing spondylitis and rheumatic heart disease are the most common causes ▪ Acute damage to the valve Usually due to thoracic aortic dissection or infective endocarditis particularly dangerous causes of aortic regurgitation, can cause shock soon after it emerges Mitral Valve Prolapse Easily the most common valvular abnormality – 2-3% of the general population Pathologic findings ▪ Enlarged valve leaflets that are redundant and often “billow” into the left atrium during systole ▪ The annulus and chordae tendinae can also be enlarged, and sometimes the chordae break ▪ Microscopy – lots of myxomatous connective tissue that massively increases the thickness leaflet – full of proteoglycans with a deficit in collagen Primary causes – not well-understood, some show a deficit in the cadherins Secondary causes – associated with disorders of connective tissue that impact other organs (Marfan’s syndrome, Ehlers-Danlos Syndrome) Mitral Valve Prolapse Mitral valve prolapse (Fig. 17-38) A. A view of the mitral valve (left) from the left atrium shows redundant and deformed leaflets, which billow into the left atrial cavity. B. A microscopic section of one of the mitral valve leaflets shows conspicuous myxomatous connective tissue in the center of the leaflet. Mitral Valve Regurgitation Most cases are due to long-term MVP ▪ 15% of those with MVP develop mitral regurgitation, at which point surgical repair or replacement is necessary The remainder of MR is usually due to: ▪ Ischemia → dysfunction or actual rupture of papillary muscles Rupture can be acutely life-threatening ▪ Infective endocarditis ▪ Rheumatic heart disease ▪ Enlargement of the left atrium or left ventricle MVP and MR Note: What would the impact be of acute MR on left atrial pressures? Pulmonary pressures? MR can be caused by chordae tendinae rupture, impaired papillary function, or papillary rupture Note as the ventricle enlarges, it could “pull” the leaflets apart Rheumatic Fever & Rheumatic Heart Disease Rheumatic fever – auto-immune reaction to infection with Group A streptococcus ▪ Can occur with strep throat OR with strep skin infection (i.e. impetigo) ▪ The “M-protein” of streptococcal antigens stimulates an immune response → antibodies & Tc also recognize epitopes on cardiac cells (particularly valves) – see next slide Mainly occurs in children and teens, recurrence can occur in young adulthood Susceptibility is genetic – 3 – 6% of the population is susceptible ▪ RHD (heart disease caused by RF) usually becomes symptomatic later (often decades for valvular disease) Can affect every layer of the heart wall – endocarditis (valves), myocarditis, pericarditis RHD – General Pathogenesis FIGURE 17-28 Biologic factors in rheumatic heart disease. GAS introduces streptococcal antigens into the body → antibodies and activated cytotoxic T cells Immune responses can cross-react with cardiac antigens, including those from myocyte sarcolemma and valvular glycoproteins. inflammation of the heart in acute rheumatic fever may involve all cardiac layers (endocarditis, myocarditis, pericarditis). Occurs 2-3 weeks after infection Active inflammation of the valves may lead to chronic valvular stenosis or insufficiency ▪ These lesions involve mitral, aortic, and tricuspid valves, in that order of frequency. Rheumatic Fever & Rheumatic Heart Disease Although RF is uncommon in North America, it is very common in less-industrialized countries ▪ 30 – 45 million worldwide affected, responsible for ~ 300 deaths/year Most people in North America with RHD contracted RF in their home country of origin ▪ The valvular damage has life-long consequences, even if damaged valves are replaced ▪ RHD occurs in a significant minority of those with RF Clinical features of RF (FYI for now): ▪ Carditis (more later) – main cause of morbidity and death ▪ Migratory polyarthritis and a temporary movement disorder (chorea) ▪ A characteristic rash and subcutaneous nodules Chronic RHD - Valvular Disease Mitral valve and aortic valves are most often involved Most common mitral valve lesion: mitral stenosis ▪ RHD is the most common cause of mitral stenosis ▪ Often the scarring along the valve and the shortening of the chordae tendinae cause the valve to be incompetent as well Most common aortic valve lesion: aortic stenosis ▪ Often the aortic commissures are fused, making them resemble a bicuspid aortic valve ▪ The aortic valve can also become incompetent as well as stenotic Aortic stenosis & regurgitation Valvular Symptoms Signs - Murmur Prognosis defect Aortic Chest pain if severe Systolic crescendo- Common cause of CHF Syncope if CO is severely decrescendo murmur If it causes LVH, a risk stenosis impaired loudest @ 2nd Rt IC space, factor for IHD Asymptomatic if not radiates to neck and Valve replacement helpful severe downwards if done prior to LVH LVH common S1 S2 S1 S1 S2 S1 Aortic Very dangerous if acute Diastolic decrescendo If significant, replacement and severe – flash murmur – can be Lt or Rt IC is necessary regurgitation pulmonary edema, space, radiates parasternally Volume-overload LVH (i.e. syncope, cardiogenic Bounding, water-hammer eccentric hypertrophy) and shock pulse (large pulse pressure) CHF over time in significant Asymptomatic if not defects severe  Mitral Valve Prolapse and Regurgitation Valvular Symptoms Signs - Murmur Prognosis defect MVP Many are asymptomatic Mid- or late-systolic “click” Most have a good Many have non-specific best heard at apex in most prognosis, do not urgently findings – pre-syncope, If regurgitation → click need surgery palpitations, poorly- followed by systolic If regurgitation develops + characterized chest pain crescendo (or cres-decres) LVH then surgery more murmur urgently needed S1 S2 S1 S1 S2 S1 Mitral Asymptomatic if Holosystolic murmur, hard If LVH or symptomatic (CHF regurgitation is minor to hear S1, usually best symptoms) then surgery Regurgitation Volume overload, CHF heard at apex but more urgently needed symptoms if severe sometimes can radiate to heart base  Mitral Valve Stenosis Valvular Symptoms Signs (Murmur) Prognosis defect Mitral Often asymptomatic – Opening snap then Symptomatic patients and when symptoms appear rumbling, diastolic murmur those with severely- stenosis it’s due to elevated atrial that is best heard at the reduced MV orifice usually pressures apex need surgery Cough, dyspnea that worsens with exercise/activity S1 S2 S1