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Dilated CM (MA57)
Dilated CM (MA57)
Pathogenesis:
=cardiac dilation & decr syst fx
-? bc of infection, metab, ischemic, toxic, genetic factors --> c/s it as a conclusion to a broad array of xx
-Epi- 36/100,000 ppl prevalence
-Idiopathic DCM- usually ASx as child, w Sx starting in 40s. --> likely a subtle xx initially, then progression over decades
-FHx can be a clue to check echo, for hereditary forms only.
-limited guidelines for Dx and Tx, and current Tx has limited impact on Px in at least 1/3 of kids, will eventually die or get OHT
Cardiac Dilation
-Fx d/o preload, afterload, contractility, and HR
-Nly, dilation is a response to physiologic demands (just like hypertrophy)
-Frank-Starling Law--> incr PL--> incr CO
-incr LVEDV can be an adaptation to poor DO2 (e.g. ch anemia), decr ventric filling time (ch atrial tachycardia), or contractile dysfx (acute ischemic insult)
-but with idiopathic DCM, the dilation is (eventually) maladaptive
-Cardiothoracic Ratio on CXR does predict Mortality in DCM pts (!)
-In familial DCM, LV dilation seen in 10-20% of ASx relatives, and does predict later progression to DCM
-? if initial dilation is adaptive response to myocellular dysfx or if it is the primary, pathologic xx of ventric remodeling.
-Either well, unless wall thickness increases, the dilation will lead to incr wall stress (Law of Laplace...), and so a mismatch of DO2 and VO2 (bc DO2 unchanged, but VO2 increased).
-Law of Laplace: Wall Stress = (Pressure)(radius)/2
-decr post wall thickness in DCM --> worse Px
Myocellular Hypertrophy & Death
-Acquired HF bc of ischemia or incr AL--> hypertrophy to adapt and maintain myocardial performance
-In DCM, the myocardial mass is incr, but only bc of incr interstitial collagen content. The LV post wall is usually Nl/decr thickness.
-The compensatory hypertrophy in DCM does show hypertrophy of viable myocytes, but there is a loss of myofibrils and cardiac myocytes, w/o ability to regenerate, (so over time you lose myocytes as they die). This coupled w chamber enlargement --> inability to compensate with increased wall thickness.
-Myocyte loss in ch DCM occurs via:
-apoptosis
-subclinical necrosis (see elevated cardiac enzymes in blood)
-more cell death--> worse Px
Extracellular Matrix Remodeling
-myocytes are only 1/3 the total myocardial cells in the heart
-fibroblasts, vasc sm muscle, endothelial cells make up the rest. These continue to be able to proliferate, unlike myocytes.
-ECM is made of CT prtns- collagen, fibronectin, laminin --> scaffold to maint architecture and myocyte alignment, and transmit mechanical force generated by the myocytes
-Ventric remodeling is a pathology of heart failure due to:
-fibroblasts proliferate
-mechanically stable cross-linked collagen degrades
-excess of poorly cross-linked collagen is deposited into the interstitium
-DCM: --> incr myocardial mass bc of intestitial fibrosis, and ventric dilation and wall thinning bc of slippage of the myocytes which were previously aligned
-ACEI and ARBs help reverse/limit the remodeling
Familial DCM
-20-25% of cases are familial
-avg age of Dx was in 30-40s, but there were kids <10yo also Dx w Sx/ASx DCM
-of kids who present w idiopathic DCM, 8-19% are familial DCM
-usually Auto Dom, less commonly x-linked in males w inherited mutation fr moms who have only mild to no Sx
Penetrance & Expression
-some pts also have skeletal myopathies, cardiac conduction syst dz, and atrial arrhythmias
-some don't have much DCM Sx, w penetrance as low as 5-20%
-and if pt presents w DCM, you might not think it was familial bc parent had low penetrance...
-So, screen all 1st degr relatives bc early dx/tx can prevent xx
DCM Genes
-LMNA (encodes lamin, a nuclear membrane prtn)
-SCN5A (encodes cardiac Na Ch)
-many other prtns too..
Clinical Heterogeneity
-many w familial also have xx of other systems - subclinical skeletal xx, etc
-may have same gene --> DCM or HCM d/o what type of mutation made...
Si/Sx
Hx
-Sx onset often gradual, unless p acute viral myocarditis
-SOB, DOE bc low CO and pulm vn congestion
-fulminant pulm edema
-younger pts- incr RR< SOB, irritable, decr PO
-recent URI, rh fever signs --kawasaki dz may coexist in pts w CM bc of these inflmy dz
-check FHx well
-check exposure to toxins, espec prev chemoTx
-check for h/o Tyrpanosomiasis and Lyme dz if recent travel...
-check for recent h/o cardiac surgery, tachyarrhythmias
PE
-HF--> anxious, diaphoresis, tachy, incr RR, grunting if pulm edma w alv collapse, incr WOB, orthopnea in older kids, wheeze not responsive to b-blockers (usually)
-fever if infection that causes pt to present bc of exacerbation of prev'ly subtle Sx
-low BP bc poor CO
-tachycardia; c/s SVT & VT
-down/lateral apical impulse
-RV lift if incr PAP
-S1 Nl, loud P2
-S3-4 gallop rhythm
-abd distention, Hepatomegaly, ascites, pretibial edema, cool/poorly perfused extrem bc vasoconstriction
ECG- sinus tachy; if SVT/VT- Tx aggressively bc poorly tolerated (may be the cause of the DCM)
-LVH w incr L precordial voltages
-NonSp ST and T wave changes
-if deep Q waves at I and aVL --> c/s ALCAPA
CXR-enlarged silhouette bc of LA and LV dilation
-LAE --> LMSB elevation
-pulm vn congestion and pulm edema
-reticular incr pulm vasc markings
-pl effusion w loss of sharp post and lat pleural angles
Doppler Echo
-see enlarged LA and LV; increased End diast and End syst volumes
-decr syst fx
-segmental dyskinesis if ischemic cause for the DCM
-In diastole, nonapposition of MV to the IVS can be measured as E pt septal sepration
-it is displaced, most notable on M mode, reflects LV enlargement
- +/- fibroelastosis
-check for cor art xx- aneurysm, ectasia
-see dilated IVC/SVC
-pericardial/pleural effusion
-check for MR w doppler
-if TR, check RV P
-check Asc Ao doppler- see decr fwd Q, and diastolic flow reversal at desc Ao
Cath
-do cath if see cor art xx
-do for endomyocardial Bx
-c/i xx is LV thrombus
-check hemodynamics...
Tx
-DCM HF--> low CO, fluid retention, incr periph constriction all bc of neurohumoral activation to maintain a good perfusion pressure.
-Tx goals- incr CO, incr DO2, sustain vital organ fx
Combined Inotropic & Vasodilator Support
-Milrinone & Amrinone (PDE inhibitors) --> incr Stroke Work and CO, decr SVR & PVR
==> lusitropic effect w better ventric relaxation and compliance
-amrinone xx--> not used anymore
-Milrinone--> incr intracellular Ca via inhib PDE III
-xx = thrombocytopenia, low BP, arrhythmias
-no longitudinal studies to show if it helps pts w CM and decompensated HF
-PRIMACORP trial- mildr didn't have same xx reported in adults
-it was often used in combo w a vasoconstrictor like dobutamine, which can incr CO too...
-t1/2 is 1-4hrs. must adjust dose for renal xx
-Levosimendan- Ca sensitizing Rx, starting to be used in adults w acute decompensated HF
-binds to troponin-C in cardiac myocytes --> improve contractility
-opens ATP sensitive K ch--> periph arterial & venous dilation
-no incr in VO2 of myocardium or arrhythmias
-limited pediatric data
Catecholamines
-Dopamine, Dobutamine, Isoproterenol, Epinephrine--> stim adrenergic R' directly or indirectly
-avg t1/2 si 2-7min, w steady state by 10-15min
-response to catechol gtt is limited by a decr in beta R' density & fx via down regulation p ch stim
-Low Dose DA- incr Q renal, incr GFR, incr Na excretion
-High Dose DA- incr C, incr PVR, cause arrhythmias
-Dobutamine- incr contractility, CO, SV, cause periph vasodilation at "reasonable" doses, thus decr LV filling P; at higher doses it can --> vasoconstriction and tachycardia
-be careful giving cathechols if also giving b-blockers, bc the a-adrenergic stim can --> adverse xx on myocardium via incr SVR, higher filling P's, tachy, and incr VO2. If there's a total b-blockade, an a-adrenergic crisis can occur--> htn and reflex bradycardia. PDEI are Tx of choice if pt is taking b-blockers.
Digoxin
-Cardiac glycoside- blocks Na-K ATPase pump --> incr intracellular Ca
-the main long-term Rx used to incr ventric contraction
-?if a good inotrope, but still used a lot
-may also have CNS effects to decr sympathetic tone--> decr HR, so better filling
-Use w caution if acutely ill kid
-may have decr renal fx, so can --> drug toxicity
-if inflamed myocardium, can --> ventric arrhythmias
-must ensure electrolytes (espec K) are Nl
-often controversial to use in kids
Diuretics
-Lasix- blocks electrolyte reabs at Henle loop
--> low K; give spiro to limit this...
-Spiro improves adult survival by blocking aldosterone action--> better NHYA class
Vasodilator Agents
-Nitroprusside & Hydralazine- dilate periph vessels--> decr afterload, incr CO, decr filling P, by relaxing the sm muscle cells in the arterioles.
-Prolonged nitroprusside--> cyanide accum after its metabolism
-hydralazine prolonged can --> lupus like reactin
-ACE- Captopril & Enlapril most often used in kids
-fx by inhib Angiotensin II synth which causes vasoconstriction and bradykinin breakdown (bradykinins cause vasodilation)
-K sparing by inhib aldosterone secretion
-widely accepted for DCM HF Tx in kids, after large multicenter adult studies showing improved survival in ch CHF; no pediatric data
Beta-Blockers
-Carvedilol- blocks beta R' and also vasodilates--> improved LV fx and clinical status in adults w HF
-Metoprolol & Carvedilol have been used in kids
Nesiritide
-Recombinant B-type Natriuretic Peptide--> balanced dilation of arteries and vns
--> incr GFR, and incr diuresis & natriuresis, and neurohumoral suppression of sympathetic RAA sys
-some studies show good tolerance to it w improved diuresis, but others show worsening renal fx
Other Tx Options
-Antiplatelet & Antithrombotic Rx used bc of incr risk of thrombi in pts w large chambered heart w blood stasis
-Warfarin; Heparin then Warfarin
-Salt/Water restriction
-follow daily weights to assess diuresis
-If Carnitine defic--> CM, so supplement w carnitine soon
-can confirm the etiology by testing urine/bld
-Antiarrhythmia Rx and RF ablation for tachycardia induced DCM
-Procrainamide is effective but has negative inotropic effects
Cardiac Resynchronization Tx
-in adults w LBBB and decr fx has shown to improve sx an decr hospital adm in adults, but few data in kids...
Cardiac Transplantation
-c/s transplant if short term survival unlikely, or pt has sev Sx unresponsive to Tx
-age at presentation, arrhythmias, heart size can determine timing for transplant
-LVEDP >25mHg predicts poor outcome and thus is an indication for OHT
-greatest risk of death or OHT is assoc w age <1yo or >12yo and female gender
-Transplant survival 1 yr 90%, 5yr 83% (ref 83)
NHx of Congestive CM
-difficult to predict bc it is so heterogeneous
-high survival if an identifiable and treatable cause like carnitine defic
-idiopathic CM-
-1yr survival 63-90%
-20-80% at 5yr
-die fr ventric arrhythmias and progressive intractable ventric failure, or OHT xx (less common)
-1/2 of survivors have improved cardiac fx
-h/o viral URI w/in 3mo prior to presentation is assoc w better survival
-arrhythmia doesn't always predict poor outcome
-many have treatable arrhythmias like SVT; survival can be better than nonarrhythmia pt if well ctrld
-Echo estimates of ventric dysfx to predict Px-
-SF 21% among survivors, 12% among nonsurvivors on avg
-after 6mo f/u SF 34% in survivors, and 11% in nonsurvivors
-Intracardiac thrombi seen in 16-23% of pts on echo
-not a predictor of survival
-CT ratio on CXR, ECG showing ST-T wave changes, LVH, LAE, RAE, and RVH all don't reliably predict Px
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Dilated Cardiomyopathy Lecture Notes- Dr. WJ Dreyer 01/2013
Dilated Cardiomyopathy Lecture Notes- Dr. WJ Dreyer 01/2013
CM = structural or fxl abNLy, intrinsito the myocardiom, w/o congen hrt dz.../pulm vasc dz/htn...
WHO Classification of CM (divide it by phenotype)
-DCM, HCM, RCM, LVNC/other, ARVD (arrhythmogenic rv dysplasia, mainly --> rhythm xx so followed by EP mainly)
DCM
= #1 CM type
aka congestive CM
= ventric chamber enlargement w reduced syst fx, Sx of CHF
Incidence
-1/2 of peds CM
-2-8/100,000 population per year in US/Eu
Prevalence 36/100,000 ppl
Etiology- varied
-1y = intrinsic to the myocardium (genetic)
-2y = hypoxic/ischemuc (common in adults...)
-infection - p viral myocarditis
-toxic - p chemo...
-auto-imm
-arrhythmogenic
-nutritional...
Genetics- 30% w FHx - auto dom most common, varied penetrence
-mutations of structural & regulatory prtns- sarcomeric (myosin, actin), cytoskel (dystrophen), conduction (Lamin A/C), energy regulation (oxidative phosphorln), metabolic (FA oxidation xx)
Path
-biventric diln, atr enlargement w globular hrt, +/- mural thrombi, pale myocardium, w Nl cor art anatomy
-Histo- myocyte hypertrophy & degeneration, interstitial fibrosis, small clusters of lymphocytes
-decr fx, incr EDV & then over time inc EDP, w then incr wall hypertophy, so incr VO2, decr O2 efficiebcy
-decr CO--> decr renal Q--> fluid retntion, decr atr/vent compliance, LV then RV failure Sx...
-neuro-endocrine activation0 up-reg RAA sysr & symp sys 2 incr BNP & TNF alpha
Sx
-DOE, palpn, fewer w syncope; CHF sx in infancy... FTT...
PE
pale, some low BP, cool extrem, incr RR, decr BS at L side fr compression atalectasis, tachy, displaced apical impulse, muffled hrt sounds, s3 gallopm MR murmur after LV diln..., neck vn distention
CXR- CN (LA/LV), pulm venous congestion/pulm edema, LLL atalect...
ECG sinus tach w LVH, nonSp ST changes, LAE/RAE
Echo...
Dx
-FHx
-echo 1st degree relatives
-Urine organic acids, plasma aa check, lactate, pyruvate
-chem 10, selenium, CBC, CPK, troponin, LFT, carnitine, TFTs, lipids, ESR, vira; serologies/PCRm maybe gene testing
-used to do skeletal muscle biopsy- histo, EM, mitochond resp chain analysis, AcylCoA DH analysis
Cath
-defer till stable (usually not done unless poss OHT)
-r/o ALCAPA (now can do CT)
-Bx to r/o myocarditis
-eval hemodynamics, esp if ?OHT- check PVR
Tx
-Tx underlying cause if kbown
-Anticongestice Tx - diuretics
-Neuroendoc reg- ACEI
-control arrhyth- b-blocker if able
-minimize risk of thromboembolic xx (ASA ppx)
Acutely ill pt
-IV diuresis
-IV inotrope - Milrinone preferred over beta-agonists, occasionally add low dose dopa; no indication for dobutamine (bc of b1R' effects on the hrt--> down reg the R' on the hrt, then as you remove it the hrt is unprepared...); WJD doesn't like epi much either bc while BP incr, CO doesn't incr much, better off AL reducing pt
-Renal dosed Dopamine
-Mech Vent - decr VO2...
Oral Tx
-ACEI
-diuresis
-b-blockers
Anti-arrhythmic Tx
-may improve CO
-many of the Rx might decr myocard fx or be proarrhythmic
-pacing for Sx brady
-AICD PRN
b-blocker
-no peds trial demonstrating their utility
-? CHF--> invcr adrenergic tone --> incr NE/E --> ng for hrt... so use bblobkers
-adults- appear to improve survival
Anticoag
-84% pts w DCM aged 7-20yrs had cardiac thrombi on autopsy (so many are missed, >clinical signif if small...)
-if thrombi on echo--> heparin, then coumadin
-if no thrombi seen, c/s ASA or dipyridamole, c/s coumadin if very poor fx
Surgery
-VAD
-IABP (not done often, hard in small pts/inr HR pts)
-ECMO as bridge only (not good bridge to OHT...)
-OHT
Outcomes
-Survival - 1yr 63-70% ()WJD really 80-90%; 5yr out 34-66%, 10yr 50%
-highest mortality in first 2 yrs
-hard to predict Px
-if >2yo initially, LVEDP >25mmHg at cath, EFE on Bx --> worse Px
-if improve in 1sr 6mo, --> best Px...
-"1/3 complete improve, 1/3 resid Sx/decr fx, 1/3 die/OHT" - WJD: likely 40/40/20...
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