Acute Rh Fever - due to interaction bn GAS, host, and environment
-AbNl immune response to GAS--> acute inflmy illness @ jts, brain, heart, skin
-Carditis can --> signif M&M - degree of which is very variable
-can resolve or persists and form ch rh valvar dz
Epi:
-#1 acquired heart dz in dvping countries
-much decline in developed countries over 20th century
-first before abx- bc better SES, then bc of PCN against strep --> decr acute Rh carditis mortality fr 8-30% to about 0%; and about disappeared by 1980s, but then by 1988 there were outbreaks in US:
-mainly in suburbs/rural white middle class pts w no clear cut crowding, and usually without a preceding sore throat that prompted medical attention. ?why, maybe bc of certain GAS strains
-15-20million ppl have RHD worldwide, w 2.4million kids bn 5-14yo
-In dvping countries, the RF is often unnoticed, and the ch RHD occurs faster and w worse xx
-233000-492000 deaths/yr fr RHD, 95% are in dvping countries
-also have incr risk for endocarditis and stroke
Environment:
-GAS pharyngitis incidence hasn't changed much, and no change in host resistance to GAS, so the diff in #s bn dvp'd and nondvp'd countries likely isn't related to the GAS itself- environment & SES factors
-overcrowding, poor nutrition, poor hygiene, lack of healthcare, incr GAS virulence
-less healthcare--> less primary prevention of RF, and less 2y ppx
-Seasonal RF variation paralleling that of GAS pharyngitis - both more common in winter/spring (but no seasonality in tropics)
Host:
-Kids 5yo-15yo most commonly affected
-RF uncommon at <5yo, rare at <2yo, and uncommon at >35yo
-RF at <5yo usually p/w arthritis (chorea rare)
-in older kids, cardiac xx is more severe and persistent RHD is common
-Adults w RF more likely to have jt xx than heart xx
-Recurrence is usually as teen/young adult
-Chorea more common in girls
-some genetic factors probability (based on FHx and twin-twin studies)
Strep Infection:
-most kids have at least 1 sore throat a year, w 10-30% fr GAS (#1 bacterial cause)
-Strep most common in kids 5-15yo; uncommon at <2yo
-GAS can be + in both true infection and in carriers, but only true infections--> Ab response & RF risk
-Some GAS strains are more likely to cause RF than others,
- "M protein" is the major virulence factor- cross reacts antigenically with human heart & brain tissue
-Encapsulated/mucoid strains are worse
Pathogenesis:
-likely due to a delayed immune rxn to Rh strain of GAS --> molecular mimicry--> attack host tissues
-recent evidence shows that GAS infection at skin (not throat) is the most often one assoc w RF
-RF Sx usually occur 10 days to 5wks (avg 18 days) after GAS pharyngitis
NHx:
-Px of RHD d/o severity of initial carditis and on RF recurrence
-mild carditis w/o recurrence--> resolution more likely
-most get better within 6 months after acute illness if just MR alone
-more sev carditis (e.g. heart failure/CM) --> more likely to have persistent RHD w AR less likely to disappear than MR
-pre abx, 60-90% of RF pts got chronic RHD, w decrease to 35-60% w PCN
-boys>girls
-if <5yo or male--> more severe cardiac xx and commonly have persistent ch RHD
Path:
-inflmn of CT in heart, jts, subQ tissue
-carditis - 2 phases:
-Exudative phase x2-3 weeks after dz onset- interstitial edema, cellular infiltration, collagen fragmentation, scattered fibrinoid deposition.
-Proliferative/Granulomatous phase x months-years - Aschoff nodules form (pathognomoic for RF) seen at endocardium, subendocard, and myocardium = perivascular aggregation w central fibrinoid changes in collagen surrounded by/infiltrated by large Owl Eye multinucleated cells
-Pericarditis- white, fibrinous, stringy/shaggy exudate
-lymphocytic and mono cell infiltration, +/- Aschoff nodules
-rarely causes adhesions, so no constrictive carditits
-Myocarditis- enlarged ventricles/atria
-edematous myocardium, inflmn, but no cell damage seen on histo
-inflmy foci w lymphos, macros, etc, and Aschoff bodies
-often see 1st degr AV B, but histologically Nl conduction system
-Endocarditis- see valvulitis (so the most important part!)
-1-2mm firable, fibrinous, verrucous vegetations at atrial surface of MV or on ventric surface of Ao valve, at site of valve closure.
-MV leaflets are swollen/vascularized, and then granulation tissue w thickening and fibrosis of the valve, along w chordal fibrosis/fusion eventually; --> MS or MR w ch RHD
-chordal elongation, +/- rupture, w prolapse of ant leaflet of MV, annular dilation, poor leaflet coaptation, MR --> often see post-lat directed MR jet--> fibrotic thickening of post LA (MacCallum patch). Ao vlv prolapse might be what causes acute rh AR
-Immunopathogenesis
-cross reactivity of GAS breakdown products = molecular mimicry..., Ab injur valvar endothelium--> vasc adhesion molecules w T and B cell infiltration/macros etc.
-Vasculitis
-cor arteries and Ao may be involved
Sx/Si:
Dx:
-Jones criteria used because there's no pathognomonic test
-latest version has higher Sp, less Sn, which is ok in US but consider broader criteria outside...
Dx = h/o strep infection && 2 major OR 1 major + 2 minor
-Major = polyarthritis, carditis, chorea, erythema marginatum rash, subQ nodules
-Minor = fever, arthralgia, incr acute phase reactants, long PR
-GAS Infection =
-Can Dx RF if pt doesn't have above criteria, but does have chorea alone, or indolent carditis detected months after the acute illness, or a past h/o RF/RHD
-Can be hard to Dx recurrent RF it pt has ch RHD... can't ddx acute carditis fr the ch..., but it is important because steroids won't help if the pt has ch Rh valve dz, and might delay better Tx
-so WHO guidelines--> Dx recurrence if +recurrent RF attack in pt w/o RHD that meets Jones criteria, and +recurrent RF in pt w h/o RHD needs to meet 2 minor and GAS infection
Arthritis
-1-5 week latency after GAS
-migratory polyarthritis is #1 major criteria met (40-70%) (but least Specific!)
-migrates fr large to large jt, knee, ankle, elbow, wrist
-note that Sx might not be classic bc of NSAID use...
-some only have monoarthritis
-red, swollen, tender, pain out of proportion to exam
-resolves in 3-4 weeks without Tx
-Inverse severity to carditis (!!) ?why, maybe it leads to earlier Tx...
-Sx respond to ASA in 2-3 days. If no change after this time c/s a new Dx
-some relapse after 6 weeks
-Some pts get a diff kind of arthritis:
-Post-strep Reactive Arthritis- after 7-10 day latent period, nonmigratory, persistent, w/o good NSAID response.
Chorea
-Sydenham chorea- neuropathologic changes and inflmn at basal ganglia, cerebral cortex, cerebellum
-10-30% of RF have it in kids >10yo its mainly F
-involuntary, purposeless movements, incoordination, weakness, emotional lability
-see abrupt irratic movements of limbs/face, w fidghetiness, facial grimaces, tongue movements like back of worms, halting explosive speech, pronation of hands when arems extended above the head (pronator sign), irregular hand contractions when asked to squeeze an object (milkmaid's grip), hyperextension of fingers when hands extended fwd w eyes closed (spooning), and clumsiness
-often also see irritability, decr attn, lack of cooperation, OCD dx
-usually bilat, can be unilateral
-Sx decr w rest, incr w effort/excitement
-Resolve by 15wks to 6mo in 3/4 of pts
-latency bn GAS and chorea is 1-6months, longer than arthritis and carditis
-APR are usually Nl and ASO might be as well
-many pts have Nl neuroimaging (MRI/CT), so only do it if atypical Sx..., same w EEG
-must ddx PANDAS- pediatric a/i neuropsych d/o assoc w strep infections) - ?bc of poststrep rxn, a/i rxn that cross react w basal ganglia, like Sydenham's..., PANDAS pt also have impulsivity, motor hyperactivity, separation anxiety, oppositional behavior. DDx bc diff Px- PANDAS respond to plastmapheresis or IVIG
Carditis
-this is the xx that -->s the long term M&M
-30-70% pts w RF get carditis
- = #1 acquired heart dz in kids/teens in dvping countries
-Pancarditis, but really the important xx is the valvulitis- MV or AoV--> MR/AR
-Varied Sx: ASx w murmur through critical illness w heart failure
-13-64% of RF pts have severe heart failure (= 15-50% of the pts w carditis)
-Sx vary likely bc some present after 2nd or more episode of RHD, so more likely to be sick
-80% of carditis pts present within 2 weeks of the RF (so if u don't see CV xx by 2wks of RF illness, then there's a low chance of getting it within the acute phase)
-Sx will decrease as the inflmn decreases
-if mild Sx--> likely completely resolve; if mod-sev--> likely persistent/evolving RHD
MR:
-95% of acute rh carditis has MR as the major xx
-annular dilation + chordal elongation--> AbNl coaptation, +/- ant MV leaf prolapse
-if (rare) mitral vlv cord rupture--> flail mitral leaflet--> sev MR
-Mild acute MR--> ASx usually
-Mod-Sev acute MR--> LV myocardium can't handle the vol OD to LV--> incr LH filling P--> pulm vn congestion--> pulm edema--> L CHF Sx: DOE, orthopnea, paroxysmal nocturnal dyspnea, cough, hemoptysis; if 2y phtn, then --> R CHF Sx, TR, RV dysfx
-if <5yo--> insidious onset of fever, decr appetite, lethargy, fatigue, vague pains, thus--> delay Dx
-PE: incr precordial activity, tachypnea, incr WOB, high pitched, regurgitant, holosys MR murmur @apex that radiates to L axilla- best heard at end-expiration w pt in left lateral decub.
-Pt may have severe MR and only a soft murmur
-check for relative MS that can dvp- low pitched middiastolic apical M bc of incr Q thru MV bc of MR
AR:
-20-25% acute Rh carditis pts get AR, most w MR too
-?bc of leaflet prolapse
-Mild acute AR--> ASx usually
-Mod-Sev acute AR--> CHF Sx- LV doesn't have time to deal w the vol OD fr the large AR--> decr fwd stroke volume + incr LV EDP--> combo that causes low CO (decr fwd SV bc of AR) & pulm edema (less filling bc of high EDP).
--> tachycardia/tachypnea
-unlike pt w ch AR, the PP is narrow often (bc low fwd CO) and pulses not bounding
-increased precordial activity, +/- displaced apical impulse
-descresc distolic murmur- softer, lower pitched and shorter than ch AR
-+/- LVOTO murmur fr incr flow--> short systolic ejection murmur
-+/- low pitched, mid to late diastolic rumble murmur w presystolic accentuation at apex
= Austin-Flint murmur - softer/shorter w acute vs ch sev AR
-Acute AR less likely than MR to resolve as the rh inflmn stops... (!)
-Note that the heart failure doesn't occur if there's no AR or MR!
Pericarditis:
-4-11% of pts w acute RF
-assoc w L side valve disease always! if not the case, c/s DDx
-positional chest/shoulder pain fr pericarditis..
-friction rub might obscure other murmurs or may be intermittent
-tamponade and constrictive pericarditis is rare
Erythema Marginatum
-uncommon (<5% of pts w RF)
-bright pink macule/papule (usually macular) spreading w serpiginous borders, then central clearing
-painless, not itch
-+blanch w pressure
-@ trunk/proximal limbs. Evanescent- can change quickly so easily missed
-accentuated w hot bath/shower
-seen early on, but can recur later (months/yrs later)
-usually assoc w carditis
SubQ Nodules
-uncommon (<10% RF pts)
-can also occur w SLE or RA
-0.5-2cm diameter, round, firm, freely movable, nontender, w/o inflmn
-in crops at extensor surfaces of jts/bony prominences- elbow, wrist, knee, ankle, scalp, spine
-last days/weeks
-always assoc w carditis
Minor Jones Criteria
-fever --at onset of RF w temps 101-104F (pts that p/w chorea may be afebrile...)
-arthralgia -- jt pn w/o objective findings of inflmn - @ large jts (not used if +arthritis)
-incr APRs -- CRP, ESR, -helps ddx indolent RHD w vs an acute carditis
-note ESR may be low w heart failure, then incr as HF improves
-1st degr AV block (long PR) -- but 1/3 pts w GAS and no RF have long PR
-no assoc bc 1st AVB and RHD risk
other sx- anorexia, malaise, anemia, FHx
GAS+
-rapid/Ag strep test (but low Sn&Sp)
-ASO titer- pks 3-4wks p infection 85-90% Sn in RF pts
Echo:
-check valves, fx, chamber size, effusion
MV:
-MV usually Nl if mild acute rh MR,
-nodular leaflet thickening that later disappear
-long cords/annular dilation if pt has heart failure
-ant mitral leaf prolapse
-DDx Barlow syndrome which has redundant, myxomatous MV and prolapse
-with RHD, only the coapting part of the ant leaflet prolapses, so no billowing of medial part
-MR jet usually post-laterally directed
-check for cord rupture/flail valve
AoV:
-check for prolapse
DDx pathologic vs physiologic AR and MR- WHO guidelines
-color jet >1cm long
-color jet seen in at least 2 planes
-color jet mosaic w pk velocity >2.5m/s
-& Doppler signal holosystolic for MR and holodiastolic for AR
Cath:
-rarely needed, Bx doesn't help Dx
Chronic Rheumatic Heart Disease:
MR-ch MR #1 RHD in kid/teen, while MS is #1 for adults >30s
-Unlike acute RHD, ch MR is bc of leaflet shortening, rigid, deformed, and retraction, w chordal fusion and shortening--> abNl coaptation--> MR
--> LV dilation--> change pap muscle orientation--> impair coaptation more--> more MR
-ch MR--> compensatory LV dilation--> more stroke volume to maint fwd flow
-bc LV and LA dilate, the LV filling P (EDP) doesn't rise much initially so pt ASx for yrs at first
-sev ch MR may --> LV dysfx w decr EF, incr end systolic volume, incr LV filling P and LAP
--> Sx- DOE, etc
-incr precordial activity w displaced apical impulse bc LV dilation
-soft S1, widely split S2 bc LV ejection time is shorter bc of early Ao vlv closure
-pulm htn--> loud P2
-MR murmur will radiate to L axilla if the regurg jet is directed to post-lat LA wall; if medially directed then hear it at base of heart.
-unlike w acute MR, w ch MR the intensity of the murmur correlates w MR severity
-+/- apical diastolic rumble if significant MR amt
- CXR might show big LA/LV w straight LH border and CM, +/- elevated LMSB
=+/- pulm vn congestion w intersitial edema if severe HF
-ECG: must check for arrhythmias
-Nl if mild; remainder have LAE +/- LVH but doesn't correlate w MR severity
-RVH if 2y phtn
-a-fib in adults w ch rh MV dz
-Echo: thick MV leaflets w echogenicity increased, some decr mobility, w less excursion
-abNl coaptation--> MR; check for ant leaflet prolapse
-"pseudoprolapse" = the retracted, immobile post leaflet gives impression that ant leaflet is prlapsing when it's not as the free edge of the ant leaflet doesn't go bast the annular plane during systole. still this also --> regurg bc poor coaptation
AR- ch AR bc of leaf thickening, fibrosis, contracture --> abNl coapation
--> vol OD and P OD to LV
-initial compensatory phase- ventric dilation to maint fwd SV and CO w Nl EF
-so may be ASx for years
-Then decompensate--> decr LV fx, w DOE etc
-wide PP )incr SBP and low DPB) --> bounding pulses
-incr precordial activity, apical impulse displaced lat bc dilated LV
-high pitched, descresc diast murmur at LSB in pt leaning fwd at end expiration due to AR
-murmur duration (Not intensity) is relative to degree of AR
-short syst ej murmur at midleft or upper RSB fr incr Q across the LVOT or bc of AS
-low pitched. mid-late diastolic rumble without actual MS (Austin Flint murmur) may be audible if mod-sev AR
-CXR- Nl if mild, then CM dilated Asc Ao
-ECG- w mod-sev AR--> LVH
-Echo- thick, retracte vlv, w variable commissural fusion...
MS- #1 cause is Rh fever that causes ch RHD
-usually 15-40yrs after RF onset (so pt 20-40s)
-pure MS in 25% of adults w RHD, and another 40% is combined MS/MR
-women > men
-leaflet thickening, fused commissures, cusps, cords and cordal shortening --> stenotic funnel MV
--> LV inflow obst and diastolic gradient bn LA and LV
-as LA and pulm vn P incr--> phtn
-pts often accomodate lifelstyle to gradual sx onset so are unaware of fx'l limitations...
-fatigue, exercise intolerance, then DOE, cough, wheeze, SOB, orthopnea, PND
-afib w atrial thrombi/systemic embolization uncommon in kids
-if severe MS--> sev inflow obst, hemoptysis, R heart HF fr phtn w edema and abd distention
-palpable S1 but no apical impulse displacement unless +AR/MR,
-prominent a-waves on jugualr venous pulsations
-incr S1, early diastolic opening snap, and low pitched rumbling diastolic murmur best heard at apex w pt in L lat decub. Murmur duration(not intensity) correlates w MS severity
-the interval bn S1 and the opening snap decreases w incr MS (bc incr LAP--> earlier opening snap)
-late diastolic or presystolic accentuation of the murmur might be heard bc of the incr gradient w atrial contraction.
-S1 and the snap might be inaudible if sev stenosis w a rigdi, Ca MV
-loud P2 fr 2y phtn
-TR bc of rh TV and phtn--> holosys M at LLSB, pulsatile liver, abNl jugular vn pulsations
-CXR: LAE if signif MS; may have big PA and RV
-ECG: check for a-fib, LAE if signif MS, RAD and RVH if phtn
-Echo: thick, echo dense leaflets, w commiss/cordal fusion, and abNl diastolic leaflet excursion
-hockeystick/bent knee appearance of ant MV leaflet bc limited excursion fr commiss fusion
-Post leaflet may have limited excursion/look frozen
-Valve calcifies w time, less pliable
-check MS severity- Doppler pk and mean gradients, planimetry of vlv opening, P half time, proximal doppler flow convergence
AS- occurs in ch RHD, no acute RHD, 20-40yrs after acute illness
-vlv leaflet thickening, fibrosis, commissural fusion, Ca nodules
-decr leaflet mobility, decr Ao orifice size, obstruction to flow
-Rh AS and AR occur together often
-AS onset is gradual, so ventric compensation--> no Sx, then compensation fails and pt gets angina, syncope, DOE, HF usually in 40-50s
-sev AS--> narrow PP, slow rate of rise, unless +AR
-thrill at RUSB, or suprasternal notch, +SEM at RUSB but unlike congen AS no ej click, descresc diastolic murmur if +AR too
-Echo: thick leaflets, commissural fusion, leaflet retraction, leaflet doming, incr echogenicity fr calcification, restricted motion...
R Heart-
-ch RHD can --> TV/PV involvement
-can be organic- fr RHD, or fx'l- fr phtn bc LH dz
-TV- more xx than PV, but clinically signif xx isn't common
-TS/TR occurs w signif MV/AoV dz only
-TS- see jugualr a-wave pulsations, opening snap, low pitched diast rumble at LLSB or RLSB, periph edema hepatomegaly, RUQ tender, ascites...
Tx:
-supportive, to prevent recurrence/complications
-Antiinflmy treatement is "integral" but no evidence to show it changes the NHx of RHD
Rx Tx of Acute Rh Fever
-for carditis:
-bed rest, anti-inflmy Tx
-if pt ambulates--> longer duartion/greater severity of carditis and more freq reactivations
-but no longer need prolonged strict bed rest of the 1940s..., so some say bed/chair x4-6 wks
-ASA/steroid use is unproven but used bc pts w acute rh MR/AR improves as inflmn improves
-steroids work faster than ASA
-usually Tx for 4-6 weeks, or until ESR/CRP improve
-arthritis responds to ASA within 2-3 days
-NSAIDs ok too, but ? if okay for carditis
-chorea- phenobarb, haloperidol, valproate, corticosteroids, plasma exchange, IVIG
Rx Tx of Acute Rh Carditis and HF
-prev thought digoxin works, but now we no its not a myocardial dysfx that's important, but the valve xx that causes issues, so instead use diuretics AL reduction to decr Sx. If bad HF, then need to repair/replace it to improve M&M
Primary Prophylaxis
-Treating the strep pharyngitis markedly decr risk of RF if started within 9 days after Sx onset
-for up to 2/3 GAS pharyngitis may be subclinical--> preclude prevention
-single IM benzathine penicillin is most effective Tx, but oral can be used too but must take full 10 days
-erythromycin if PCN allergic
-no evidence tonsillectomy prevents RF
Secondary Prophylaxis
-prevent RF recurrences and severity
-40-60% of pts with cardiac involvement get recurrence, and --> more sev valvar dysfx and incr risk of ch RHD...
-treat all pts w ppx PCN bc some who didn't have carditis initially do get it later
-IM PCN is best tx, often q4 weeks but if endemic give it q3 weeks bc levels fall by that 4th week
-PCN Duration: d/o if there's acute or ch cardiac xx and amt of time since last RF attack
-if low risk (no carditis or RHD) and ?5yrs out fr the RF illness, then can stop ppx earlier than guideln
-some say use ppx indefinitely, and others stay stop by mid 20s
Endocarditis Prophylaxis
-an important RHD xx, so use SBE ppx
Rx Tx of Ch RHD
-serial evaluation, AL reduction w ACEI or CCB if ASx adult w ch sev AR and good LV fx though ? if benefit of AL reduction cor sev ch AR and same for ASx pt w sev ch MR and good LV fx
Heart Failure in Ch RHD
-if symptomatic ch MR or AR do surgery, not Rx Tx
Surgical Tx
Acute Carditis
-acute MR or AR improves after inflmn subsides
-valvuloplasty/replacement during acute illness can be lifesaving
Ch RHD
-hard to say when to correct the valve
-indications in adults w ch sev MR: Sx and/or LV dysfx, marked lV enalrgement, a-fib, pulm htn
-some say correct it in ASx pt w sev MR and good fx if you can repair vlv and not replace it
-c/s it if effective regurg area is >40mm2 or incr BNP
-indications for surgery for ch AR are simialr to MR- Sx, LV dysfx, big LV
-indications for ch rh MS- Sx, phtn, - may do perQ repair w balloon valvuloplasty unless signif MR or LA thrombus...
-indications for AS- don't go by P gradient, Tx for Sx...