Restrictive Cardiomyopathy (M/A)

Restrictive CM (MA59)

= restrictive filling and reduced diastolic volume of one/both ventricles, with Nl/near Nl systolic fx and wall thickness

Epi

-least common of the 4 WHO CM's (DCM, HCM, RCM, arrhythmogenic RV CM)

-peds pts: 2.5-5% of all peds CMs

-avg Dx age 5yo, median 5yrs

-boys>girls if >1yo in one study, no diff in another study

Genetics

-Desmin, troponin I, RSK2 mutations assoc w it in kids; lamanin A/C and transthyretin in adults

-Desmin- main intermediate filament of skel and cardiac muscle--> maint structure and fx'l integrity of myofibrils, fx as cytoskeletal prtn, linking Z bands to the plasma membrane.

-xx can --> RCM +/- skeletal myopathy; +/- conductive system dz

-Auto Dominant mainly

-Troponin I- xx seen w RCM and HCM; and both phenotypes seen in same family

-Coffin-Lowry Syndrome- x-linked mutation in RSK2 gene--> dev delay, short, dysmorphic face, progressive skeletal deformity, with 14% w cardiac anomalies, rarely CM

-Emery-Dreifuss muscular dystrophy- x-linked and autosomal, bc xx to lamin A and C--> DCM, atrial & ventric arrhythmias, conduction xx, sudden death, and reports of RCM

Etiology

-infiltrative vs noninfiltrative

-storage dz, endomyocardial dz, myocarditis, & s/p OHT

-#1 in adults is endomyocardial fibrosis if in tropics, and amyloidosis outside tropics

Endomyocardial Disease - Endomyocardial Fibrosis

-most common in tropics/subtropical Africa (Uganda, Nigeria espec)

-usually biventricular

-signif AV vlv regurg if MV or TV involved

-only palliative Tx available

-Histology- fibrosis at endocardium, mainly at LV apex, MV aparratus, and RV apex

-not much cellular infiltrate

-? etiology, though occurs in areas w parasites, though not much eosinophilia

HyperEosinophilic Syndrom - Loffler Endocarditis

-similar to EMF, but HES occurs in temperate climates, and there's persistent high eosino's, and HES also involves other organs- brain, lungs, bn marrow

-? maybe bc of parasite or allergic, granulomatous, hyperSn rxn, or neoplastic ??

-Histology- eosino myocarditis (DDx EMF), inflmy rxn in small intramural cor vessels w thrombi and fibrinoid change, and endocardial mural thrombi and fibrotic thickening

-Sx- wt loss, f, cough, rash, HF

-systemic embolism common

-die fr cardiac xx

-Tx for hypereosinophilia- strds, hydroxyurea, vincristine

-Cardiac Tx- digox, diuretics, AL reduction, antigcoag

-surgery- repair MV or TV PRN, excision of fibrotic endocardium; often need reinterventions

Infiltrative & Storage Diseases

-lysosomal d/o- Hurler, Gaucher, Fabry, glyc storage dz

-Hemochromatosis fr Fe OD (but usually causes DCM)

-Nephropathic Cystinosis (auto rec)--> intracellular accum cystine, along w renal failure, htn

-Sarcoidosis- noncaseating granulomas (more in adults)--> systolic dysfx, pericarditis, conduction xx, sudden death.

Drugs & Tx Agents

-Anthracyclines, Seratonin, Methysergide, Ergotamine, Hg agents, Busulfan, mediastinal radiation

Idiopathic RCM

-#1 in kids outside of tropics; only 30% have +FHx and determining a genetic cause is unlikely

Pathology

-big LA compared to LV

-Nl LV size, no LVH

-usually otherwise structurally Nl heart

-Histology- varied amt of fibrosis and myocyte hypertrophy

Pathophysiology

-Diastolic Dysfx bc stiff/poorly compliant ventricle that's not able to relax well

-Rapid/Early filling phase Nly occurs as the LV P drops below that of the LA, just after MV opens, which accounts for most of the LV filling. Then during diastasis the amt of filling d/o HR, and permits only <5% of the filling. Then, in the last phase of diastole, atrial systole accts for about 15% of filling.

-In RCM: filling is completed in early diastole, and there is little/no more filling in late diastole. THe increased myocardial stiffness/decr compliance--> marked ventric P rise w just the small incr in volume fr the early filling.

-Alternate theory: Earliest phase of Diastole is Isovolumetric Relaxation- active (energy requiring) uptake of Ca ions into the SR to cause relaxation. Ischemia and hypertrophy can both --> abNl relaxation bc Ca uptake changes. RCM can --> delayed relaxation along with the restricted filling. This study proports that most of the problem is bc of a delay in relaxation, rather than a stiff myocardium, with early filling contributin 56%, middiastolic filling 28% and atrial filling 16% of filling, in their study of RCM pts.

Si/Sx

-may have initially resp sx- DOE, exercise intolerance, recurrent lower resp infection, asthma dx

-then refer to cards after seeing CM on CXR

-ascites, hepatomegaly, edema- often sent to GI first, then eventually to cardiology

-+/- gallop, murmur, loud P2

-10% present w syncope- related to ischemia, arrhythmia, thromboembolism

-some present with sudden cardiac death

ECG- very useful screen- Sx 98%

-R and/or L atrial enlargement

-ST and ST-T wave abNly common

- +/- R and/or left ventric hypertrophy

- +/- conduction xx

Holter- useful for rhythm and ST analysis

-Dr Rivenes reported 8/12 pts had signif ST changes on Holter

-arrhythmias seen: a-flutter #1, high grade 2nd and 3rd degr HB next common

CXR- 90% are abNl- CM, pulm vn congestion

Echo-

-see marked dilated atria, dwarfing ventricles

-Nl or near Nl LV systolic fx, usually, though 30% were reported to have low SF or EF

-no LVH/RVH or dilation

-some w low EF have had LVH, either concentric, midseptal bulge, apical hypertrophy

-may have troponin I xx causing a mixed RCM/HCM picture

-must look for thrombi- seen in 1/5 of peds pts w idiopathic RCM

-might obliterate the apex, also at AV vlv apparatus, leaflets

-DDx- look for pericardial thickening- may be a constrictive pericarditis and NOT RCM

-Diastolic Dysfx Doppler Pattern:

-incr LV EDP w high E/A ratio, short Mitral decel times, incr pulm vn atrial reversal velocity and duration, and pulm vn atrial reversal duration > mitral A duration

-if RCM is due to delayed relaxation (per one theory)- see big mitral A wave w middiastolic filling accounting for 28% of total ventric filling, the LV P curve showed a small but steady decline during middiastolic filling on cath, implying that the driving force for LV filling was ventric suction and not the incr LAP.

-TDI has helped DDx RCM fr constrictive pericarditis in adults

Cath/Bx-

-important for evaluation- DDx RCM fr constrictive pericarditis

-though have very similar hemodynamics

-early diastolic dip and then plateau = square root sign

-LVEDP, LAP, and PCWP are very high, and >4-5mmHg (preferably >10mmHg) more than the RAP and RV EDP.

-If the P's are equal, then volume loading may bring out a diff bn R and L side

-Phtn is common in addition to high LVEDP and/or RVEDP, with PVRs as high as 14Um3

-usually reactive even after years, but in one study40% of these being w/u for OHT had nonreactive pulm vasc bed; ?when you'll get a fixed vasc bed resistance

-most Bx are nondiagnostic bc degree of fibrosis/hypertrophy is so varied, but may see amyloidosis or evidence of a storage dz, etc

DDx

-must DDx constrictive pericarditis- similar presentation and test results

-usually can ddx w/o cath or bx

-absence of myopathic findings suggests constrictive pericarditis...

-CP--> may not have atrial enlargement on ECG/echo, def no LVH/RVH on ECG/Echo, but can see ST-T changes, see "septal bounce" on echo, see marked resp flow changes on doppler, more likely to have RAP=PWP and RVEDP=LVEDP on cath (w/in 4mmHg), Nl Bx (see video of it here: link (youtube)

-RCM--> don't see thick pericardium on echo,

-sometimes hard to classify the CM as RCM or HCM