01Approach to the Critical Patient/attcp54

Immediate priorities

›Hemodynamic threat recognition

›Low cardiac output state

›Cool extremities

›Altered mental status

›Hypotension SBP < 90 mmHg

›Acute decompensated heart failure

›Severe dyspnea at rest

›SpO2 < 90% on room air

›If cardiogenic shock, urgent advanced heart failure or cardiac surgery consult

›Bridge to transplantation planning

›Mechanical circulatory support consideration

›Arrhythmia and conduction threat

›Atrial fibrillation with rapid ventricular response

›Hemodynamic instability threshold for cardioversion

›Rate control preferred when stable

›High-degree AV block

›Suggests infiltrative process (amyloidosis, sarcoidosis)

›Transcutaneous pacing readiness

›Ventricular arrhythmia

›Defibrillator availability

›Antiarrhythmic selection based on underlying etiology

›Thromboembolic threat

›Stroke or peripheral embolism at presentation

›CT head without contrast for acute stroke

›Anticoagulation status review

›Massive pulmonary embolism

›Differentiate from primary RCM hemodynamics

02History/hx90

Presentation pattern

›Cardinal symptoms

›Dyspnea on exertion

›Most common presenting symptom

›Impaired ventricular filling at higher heart rates

›Fatigue and exercise intolerance

›Fixed or reduced stroke volume

›Inability to augment cardiac output with demand

›Lower extremity edema

›Bilateral, progressive

›May reach thigh level in severe cases

›Abdominal distension

›Ascites from elevated right heart pressures

›Early satiety from hepatomegaly and bowel edema

›Additional symptoms

›Orthopnea and paroxysmal nocturnal dyspnea

›Pulmonary venous congestion

›Increased venous return in recumbent position

›Palpitations

›Atrial fibrillation very common

›Ventricular arrhythmia in infiltrative disease

›Syncope or presyncope

›Arrhythmia or severely impaired cardiac output

›High-risk alarm feature

Risk factors

›Infiltrative causes

›Amyloidosis risk factors

›Age > 60 years for ATTR

›African American descent (Val122Ile TTR variant)

›Monoclonal gammopathy (AL amyloidosis)

›Sarcoidosis risk factors

›Young to middle-aged adults

›African American predilection

›Known pulmonary or systemic sarcoidosis

›Storage and metabolic causes

›Hemochromatosis

›Hereditary (HFE gene mutations)

›Transfusion-related iron overload

›Fabry disease

›X-linked lysosomal storage disorder

›Young men with renal and neurologic features

›Iatrogenic and environmental causes

›Chest radiation therapy

›Hodgkin lymphoma history

›Breast cancer radiotherapy

›Anthracycline chemotherapy

›Cumulative dose-dependent injury

›Doxorubicin most common offender

›Endomyocardial fibrosis

›Tropical regions (sub-Saharan Africa, South America)

›Eosinophilic infiltration mechanism

Clues to etiology

›Amyloidosis-specific clues

›Bilateral carpal tunnel syndrome

›Especially bilateral or recurrent carpal tunnel

›ATTR amyloid deposits in tenosynovium

›Lumbar spinal stenosis

›Multiple orthopedic surgeries without resolution

›ATTR soft-tissue amyloid

›Biceps tendon rupture

›Spontaneous or minimal-trauma rupture

›Amyloid-laden tendon

›Peripheral neuropathy or autonomic dysfunction

›Variant ATTR or AL amyloidosis

›Postural hypotension and diarrhea

›Periorbital purpura

›Pathognomonic for AL amyloidosis

›Vascular fragility from amyloid deposition

›Macroglossia

›AL amyloidosis pattern

›Impaired speech and swallowing

›Sarcoidosis clues

›Skin rash (erythema nodosum, lupus pernio)

›Bilateral hilar lymphadenopathy on prior imaging

›Uveitis or anterior chamber inflammation

›Family history

›Cardiomyopathy, sudden cardiac death, heart failure

›Genetic RCM shares mutations with HCM (MYH7, TNNI3, TNNT2, ACTC1)

›Up to 75% of idiopathic RCM has identifiable genetic cause

›Hereditary ATTR

›Neuropathy and cardiac disease in first-degree relatives

›Vitreous opacities in some hereditary variants

Past medical history

›Key comorbidities

›Known amyloidosis, sarcoidosis, hemochromatosis, Fabry disease

›Malignancy with chest radiation or anthracycline exposure

›Chronic inflammatory conditions (rheumatoid arthritis, IBD)

›AA amyloidosis risk from sustained inflammation

›Prior thromboembolic events

›Chronic kidney disease complicating management

›Pericardial history

›Prior pericarditis or cardiac surgery

›Raises constrictive pericarditis as mimic

›Critical differential before proceeding to RCM diagnosis

03Physical Exam/exam67

Vitals and general

›Stability assessment

›Heart rate

›Tachycardia common from low output state

›Rate dependence on heart rate for cardiac output

›Blood pressure

›Low-normal or hypotensive

›Narrow pulse pressure suggests reduced stroke volume

›Respiratory rate

›Elevated with pulmonary congestion

›>= 24 per minute as severity marker

›Oxygen saturation

›Room air SpO2 below 92% as admission trigger

›General appearance

›Cachexia and muscle wasting

›Chronic low-output state and poor nutrition

›Cardiac cachexia adverse prognostic marker

›Respiratory distress at rest

›Orthopnea position preference

›Accessory muscle use with decompensation

Cardiovascular exam

›Jugular venous pressure

›Elevated JVP

›Prominent x and y descents

›Y descent rapid in restrictive physiology

›Kussmaul's sign

›JVP rises with inspiration

›More classic for constriction but may occur in RCM

04Differential Diagnosis/ddx44

Critical mimics

›Constrictive pericarditis

›ICD-10 I31.1

›Potentially curable with pericardiectomy

›Distinguishing features favoring constriction

›Tissue Doppler e' > 8 cm/s (reduced in RCM < 8 cm/s)

›Respirophasic septal shift (septal bounce) present

›Discordant ventricular pressure changes on catheterization

›Pericardial thickening > 4 mm on CT or MRI

›Features favoring RCM

›Concordant ventricular pressure changes

›Markedly reduced e' velocity

›Tissue characterization on CMR (fibrosis, infiltration)

›Cardiac tamponade

›ICD-10 I31.4

›Pericardial effusion with hemodynamic compromise

›Equalization of pressures and pulsus paradoxus

›Hypertrophic cardiomyopathy with restrictive physiology

›ICD-10 I42.2

›Genetic overlap (MYH7, TNNI3 shared mutations)

›LV wall thickness predominant in HCM

Cardiac causes of similar presentation

›Hypertensive heart disease with HFpEF

›ICD-10 I11.0

›Chronic hypertension history

›LV hypertrophy without infiltrative pattern

›Valvular inlet obstruction

›Mitral stenosis (ICD-10 I05.0)

05Laboratory Tests/lt61

Core workup

›Cardiac biomarkers

›BNP or NT-proBNP

›Significantly elevated in RCM

›BNP > 600 pg/mL typical (median ~124 pg/mL in constrictive pericarditis)

›Helps differentiate RCM from constriction though overlap exists

›Troponin

›May be chronically elevated in infiltrative disease

›Amyloidosis and sarcoidosis myocardial injury

›Complete blood count

›Anemia as heart failure exacerbant

›Eosinophilia suggests hypereosinophilic syndrome

›Comprehensive metabolic panel

›Renal function for diuretic management

›Liver function from hepatic congestion

›Electrolytes (sodium, potassium, magnesium)

Etiology-specific labs

›Amyloidosis workup

›Serum protein electrophoresis (SPEP) with immunofixation

›Monoclonal protein detection for AL amyloidosis

›Sensitivity for M-protein increased with immunofixation

›Urine protein electrophoresis (UPEP) with immunofixation

›Bence-Jones protein detection

›Complements SPEP for complete AL screening

›Free light chains (serum)

›Kappa/lambda ratio

›Abnormal ratio suggests AL amyloidosis

›TTR gene sequencing

06Diagnostic Tests/dt123

Scoring Systems

›Heart failure staging tools

›NYHA Functional Classification

›Class I: No symptoms with ordinary activity

›Class II: Slight limitation with ordinary activity

›Class III: Marked limitation with less than ordinary activity

›Class IV: Symptoms at rest

›Important for transplant listing criteria (Class III-IV)

›ACC/AHA Heart Failure Staging

›Stage A: Risk factors without structural disease

›Stage B: Structural disease without symptoms

›Stage C: Structural disease with symptoms

›Stage D: Refractory heart failure

›Transplant risk tools

›SHFM (Seattle Heart Failure Model)

›Estimated 1, 2, 5-year survival

›Guides transplant listing urgency

›HFSS (Heart Failure Survival Score)

›Multivariate risk stratification

›LVEF, heart rate, IVCD, peak VO2, sodium, ischemia

›Differentiating RCM from constrictive pericarditis

›No validated single scoring tool

›Multi-modality assessment required

›Invasive hemodynamics as gold standard when noninvasive inconclusive

MRI

›Cardiac MRI (CMR) indications

›Tissue characterization

›First-line for identifying underlying etiology

›Late gadolinium enhancement (LGE) pattern critical

›Amyloidosis pattern on CMR

›Diffuse subendocardial or transmural LGE

›Difficulty nulling myocardium (elevated T1)

›Native T1 mapping elevated (> 1050 ms at 1.5T typical)

›Extracellular volume fraction > 40% diagnostic for amyloid

›Sarcoidosis pattern on CMR

›Patchy mid-wall or epicardial LGE

›Predilection for basal septum and lateral wall

›Active inflammation on T2 mapping

›Hemochromatosis pattern on CMR

›Reduced T2* signal from iron deposition

›T2* < 20 ms indicates significant iron loading

›T1 mapping also reduced

›Idiopathic or sarcomeric RCM

›May show patchy fibrosis or no LGE

›Biatrial enlargement prominent

›Normal LV wall thickness and volume

›CMR operational considerations

›Gadolinium contraindicated in severe renal impairment (eGFR < 30)

›Non-contrast T1/T2 mapping still informative

›Pacemaker and ICD compatibility assessment required

CT

›Cardiac CT indications

›Pericardial assessment

›Pericardial thickness > 4 mm supports constrictive pericarditis

›Pericardial calcification in chronic constriction

›Critical to differentiate from RCM before management

›Coronary anatomy

›Exclude obstructive coronary disease

›Non-invasive alternative to coronary angiography in low-to-intermediate risk

›Structural assessment

›Biventricular morphology

›Biatrial size quantification

›Bone scintigraphy (nuclear imaging)

›Tc-99m PYP/DPD/HMDP scintigraphy

›High sensitivity and specificity for ATTR cardiac amyloidosis

›Grade 2 or 3 uptake highly specific when monoclonal protein absent

›Must exclude AL amyloidosis (SPEP/UPEP/FLC) before interpreting as ATTR

›Non-invasive alternative to biopsy for ATTR diagnosis

›FDG-PET CT for sarcoidosis

›Active granulomatous inflammation detection

›Sensitivity 89%, specificity 78% for cardiac sarcoidosis

›Guides biopsy site and treatment response

›CT chest

›Normal cardiac silhouette with enlarged atria

›Pulmonary congestion, Kerley B lines, pleural effusions

›Hilar lymphadenopathy in sarcoidosis

Ultrasound

›Echocardiography (first-line imaging)

›Structural findings

›Biatrial enlargement (pathognomonic finding)

›Normal or small LV cavity volume

›Normal or mildly reduced LVEF (> 50% in most)

›LV wall thickness variable by etiology

›Granular sparkling texture in amyloidosis

›Diastolic function assessment

›Restrictive filling pattern

›E/A ratio > 2

›Deceleration time < 150 ms

›Elevated E/e' ratio (> 14) indicating elevated filling pressures

›Tissue Doppler imaging

›Mitral annular e' velocity reduced (< 8 cm/s) in RCM

›e' < 5 cm/s suggests severe myocardial disease

›Contrast with constriction where e' often > 8 cm/s (annulus paradoxus)

›Valvular assessment

›Mitral regurgitation grade

›Tricuspid regurgitation for RVSP estimation

›Exclude mitral stenosis and tricuspid stenosis

›Right ventricular assessment

›RV diastolic dysfunction

›TAPSE for RV systolic function

›Biatrial enlargement pattern

›Advanced echocardiographic techniques

›Speckle tracking strain imaging

›Global longitudinal strain (GLS) reduced in amyloidosis

›Relative apical sparing pattern (apical GLS > basal GLS) in amyloid

›Apical sparing ratio > 1 strongly suggests cardiac amyloidosis

›Respirophasic septal motion

›Absent or minimal in RCM

›Exaggerated septal bounce in constrictive pericarditis

›Hemodynamic ultrasound

›IVC diameter and collapsibility

›Dilated non-collapsing IVC indicates elevated RAP

›RAP estimate 15 to 20 mmHg

›Pleural effusion assessment

›Bilateral pleural effusions common

›Thoracentesis guidance if symptomatic

›Cardiac catheterization

›Hemodynamic pattern

›Elevated and equalized diastolic pressures

›LVEDP and RVEDP within 5 mmHg

›Dip-and-plateau (square root sign) on ventricular pressure tracing

›Concordant respirophasic ventricular changes

›Both LV and RV peak pressures rise together with inspiration

›Contrasts with discordant changes in constriction

›Pulmonary artery hypertension

›Elevated mPAP from chronic left-sided filling pressures

›Severe pulmonary hypertension may preclude transplantation

07Disposition/dispo50

Admission criteria

›Indications for hospitalization

›Decompensated heart failure

›New or worsening dyspnea at rest or minimal exertion

›SpO2 < 92% on room air

›Significant peripheral edema or ascites with clinical impact

›Hemodynamic instability

›SBP < 90 mmHg

›Low-output signs (cool extremities, altered mentation)

›Arrhythmia

›New atrial fibrillation requiring rate control or cardioversion

›High-degree AV block

›Ventricular arrhythmia

›New diagnosis requiring etiology workup

›Urgent echocardiogram, BNP, amyloid screening

›Bone scintigraphy or CMR scheduling

›Syncope

›Arrhythmic or low-output etiology evaluation

›ICU indications

›Cardiogenic shock

›Vasopressor or inotrope requirement

›Mechanical circulatory support

›Respiratory failure

›Non-invasive ventilation or intubation

›Refractory arrhythmia

›Hemodynamically unstable ventricular arrhythmia

Transfer criteria

›Indications for transfer to advanced center

08Treatment/t116

Diuretic therapy

›Loop diuretics (mainstay of symptomatic treatment)

›Furosemide IV for acute decompensation

›40 to 80 mg IV initial dose

›Double prior oral dose if tolerating

›Continuous infusion 5 to 20 mg/hour for refractory congestion

›Furosemide PO for maintenance

›20 to 160 mg daily or twice daily

›Titrate to achieve and maintain dry weight

›Torsemide PO alternative

›Superior oral bioavailability vs furosemide

›10 to 80 mg daily

›Caution with overdiuresis

›Noncompliant ventricle critically dependent on preload

›Overdiuresis causes hypotension, prerenal azotemia, low output

›Target daily weight loss 0.5 to 1 kg maximum

›Thiazide or aldosterone antagonist addition

›Metolazone 2.5 to 5 mg PO

›Combination with loop diuretic for diuretic resistance

›Hyperkalemia and electrolyte monitoring required

›Spironolactone 25 to 50 mg daily

›Mild diuretic effect

›Avoid if eGFR < 30 or hyperkalemia

›No proven mortality benefit in RCM specifically

Rate and rhythm management

›Atrial fibrillation management

›Rhythm control preferred over rate control

›Preserve atrial contractility for diastolic filling

›Loss of atrial kick is particularly deleterious in RCM

›Rate control when rhythm control not feasible

›Avoid excessive rate reduction

›Heart rate dependence for cardiac output in RCM

›Target heart rate 60 to 80 bpm at rest

›Anticoagulation for atrial fibrillation

›All patients unless absolute contraindication

›High thromboembolic risk in RCM with AF

›Direct oral anticoagulants preferred (apixaban, rivaroxaban)

›Warfarin for amyloidosis with mechanical valve or renal impairment

›Conduction system disease

›Permanent pacemaker for high-degree AV block

›Sinus node dysfunction or complete heart block

›Particular risk in cardiac sarcoidosis

›ICD consideration

›Sustained ventricular arrhythmia history

›Cardiac sarcoidosis with reduced LVEF or arrhythmia

›Not routinely indicated for idiopathic RCM with preserved EF

Anticoagulation

›Thromboembolic prophylaxis

›Atrial fibrillation anticoagulation

›Apixaban 5 mg PO twice daily (2.5 mg if >= 2 of: age >= 80, weight <= 60 kg, creatinine >= 133 micromol/L)

›Rivaroxaban 20 mg PO daily with evening meal

›Warfarin target INR 2 to 3

›Anticoagulation for pediatric RCM

›Recommended at diagnosis regardless of AF status

›High baseline thromboembolic incidence

›Weight-based anticoagulation per pediatric hematology guidance

Disease-specific therapies

›ATTR cardiac amyloidosis

›Tafamidis (Vyndaqel/Vyndamax)

›Tafamidis meglumine 80 mg PO daily

›Tafamidis free acid 61 mg PO daily (Vyndamax)

›ATTR-ACT trial: 30% relative risk reduction in mortality and CV hospitalization

›Indicated for ATTR-CM with NYHA Class I-III

›Class I recommendation in 2023 ACC/AHA guidelines

›CRISPR/RNA silencing agents (for hereditary ATTR)

›Patisiran 0.3 mg/kg IV every 3 weeks

›Vutrisiran 25 mg SC every 3 months

›Primarily for hereditary ATTR with polyneuropathy

›Avoid digoxin in amyloidosis

›Increased sensitivity to toxicity from amyloid binding

›Risk of severe bradyarrhythmia

›Avoid ACE inhibitors and ARBs if hypotension risk

›Poor tolerance due to autonomic dysfunction and low output

›AL cardiac amyloidosis

›Hematology-directed chemotherapy

›Bortezomib-based regimens (VCD: bortezomib, cyclophosphamide, dexamethasone)

›Daratumumab-based regimens for eligible patients

›Goal: rapid suppression of clonal plasma cells

›Autologous stem cell transplant

›Selected patients with cardiac function adequate for transplant

›Cardiac transplantation alone without hematologic therapy not recommended

›Amyloid continues to infiltrate new heart

›Hemochromatosis

›Therapeutic phlebotomy

›450 to 500 mL weekly until ferritin < 50 mcg/L

›Maintenance every 2 to 4 months thereafter

›Reversal of early iron cardiomyopathy possible

›Iron chelation (transfusion-related overload)

›Deferasirox 10 to 40 mg/kg PO daily

›Deferoxamine IV or SC for severe overload or intolerance

›Sarcoidosis

›Corticosteroids

›Prednisone 40 to 60 mg PO daily initial dose

›Taper over months guided by imaging and biomarkers

›Evidence strongest for conduction disease and ventricular arrhythmia

›Steroid-sparing agents for maintenance

›Methotrexate or azathioprine

›Fabry disease

›Agalsidase beta enzyme replacement therapy

›1 mg/kg IV every 2 weeks

›Slows progression when started before severe fibrosis

›Migalastat for amenable GLA variants

›123 mg PO every other day oral chaperone therapy

Cardiac transplantation

›Transplant evaluation

›All patients with NYHA Class III-IV despite optimal medical therapy

›Contraindications

›Severe irreversible pulmonary hypertension (PVR > 6 Wood units fixed)

›Active malignancy

›Significant non-cardiac comorbidities

›AL amyloidosis

›Sequential cardiac then autologous stem cell transplant approach in selected patients

›Cardiac transplant alone without plasma cell treatment leads to amyloid recurrence

›ATTR amyloidosis

›Combined heart and liver transplant for hereditary ATTR (liver produces TTR protein)

›Heart transplant alone with tafamidis for wild-type ATTR selected cases

›Bridge to transplant

›Mechanical circulatory support

›LVAD limited by RV failure risk in biventricular diastolic restriction

›BIVAD or total artificial heart in selected cases

›Inotrope infusion as bridge (dobutamine 2 to 10 mcg/kg/min)

09Special Populations/sp83

Pregnancy

›Pregnancy considerations in RCM

›Pregnancy generally contraindicated in advanced RCM

›Fixed cardiac output cannot accommodate increased circulatory demands

›Maternal mortality risk is high in NYHA Class III-IV

›Preconception counseling essential

›Hemodynamic changes of pregnancy

›40 to 50% increase in blood volume

›Increased heart rate and cardiac demand

›Noncompliant ventricle unable to increase stroke volume

›If pregnancy occurs in mild RCM

›High-risk obstetric and cardiology co-management

›Frequent monitoring throughout gestation and postpartum

›Postpartum period highest risk for decompensation

›Medication safety in pregnancy

›Diuretics

›Use cautiously; avoid overdiuresis

›Furosemide category C; use only if benefit outweighs risk

›Anticoagulation

›Low molecular weight heparin preferred in first trimester and near delivery

›Warfarin teratogenic especially 6 to 12 weeks gestation

›Direct oral anticoagulants contraindicated in pregnancy

›Tafamidis

›Insufficient safety data; generally avoid in pregnancy

›ACE inhibitors and ARBs

›Absolutely contraindicated in pregnancy (fetal renal toxicity)

›Beta-blockers

›Labetalol or metoprolol generally safer in pregnancy

›Monitor for fetal bradycardia and growth restriction

Geriatric

›Epidemiologic burden in older adults

›Wild-type (senile) ATTR amyloidosis

›Almost exclusively affects men > 60 to 70 years

›Significant underdiagnosis historically

›Prevalence rising with aging population and better diagnostics

›RCM with HFpEF overlap

›Difficult to distinguish from hypertensive HFpEF

›Bone scintigraphy clarifies ATTR contribution

›Management modifications in older adults

›Diuresis

›Higher risk of orthostatic hypotension and falls

›Cognitive effects from electrolyte disturbances

›Slower diuresis with close renal monitoring

›Anticoagulation

›Bleeding risk assessment (HAS-BLED score)

›Renal function and drug interactions with DOACs

›Apixaban has favorable bleeding profile in older adults

›Tafamidis in older adults

›Well tolerated in ATTR-ACT trial population (mean age 74 years)

›Benefit in NYHA Class I-II greater than Class III

›Frailty and transplant candidacy

›Chronological age less important than functional and physiologic age

›Transplant centers increasingly considering older recipients

›Frailty indices used alongside standard criteria

Pediatrics

›Epidemiology in children

›RCM is rare in children

›Less than 5% of pediatric cardiomyopathies

›More common in girls

›Genetic cause predominates

›Sarcomeric mutations (TNNI3 most common)

›Comprehensive genetic testing mandatory

›Prognosis is poor without transplant

›Two-year survival less than 50% without transplantation

›Sudden cardiac death as presenting event possible

›Clinical differences in children

›Presentation

›Failure to thrive

›Fatigue and exercise intolerance

›Syncope or sudden death as first manifestation

›Pulmonary hypertension develops rapidly

›Severe irreversible pulmonary hypertension may preclude transplant

›Close PA pressure monitoring essential

›Management principles in children

›Diuretics

›Furosemide 1 to 2 mg/kg/dose IV or PO every 6 to 12 hours

›Spironolactone 1 to 3 mg/kg/day PO divided once to twice daily

›Careful electrolyte monitoring with weight-based dosing

›Anticoagulation

›Recommended at diagnosis regardless of AF status

›Warfarin target INR 2 to 3 in children with therapeutic monitoring

›Enoxaparin 0.5 to 1 mg/kg SC twice daily alternative

›Transplant listing

›Early listing given poor prognosis

›Weight-appropriate matching

›Sensitization management with IVIG if PRA elevated

10Background/b109

Epidemiology

›Prevalence and incidence

›Least common of the three major cardiomyopathy subtypes

›2 to 5% of all cardiomyopathy cases

›Estimated prevalence 1 to 2 per 100,000 in developed countries

›Idiopathic RCM incidence

›Rare; true prevalence difficult to estimate

›Likely underdiagnosed due to overlap with HFpEF

›ATTR amyloidosis incidence increasing

›Rising detection due to bone scintigraphy and improved awareness

›Wild-type ATTR affects up to 25% of men > 80 years at autopsy

›Demographics

›Age distribution

›Idiopathic RCM: any age including children

›ATTR wild-type: predominantly men > 60 to 70 years

›AL amyloidosis: median age 65 years at diagnosis

›Sex distribution

›Idiopathic RCM: female predominance in children

›ATTR wild-type: male predominance (> 90%)

›Fabry disease: predominantly males (X-linked) though females can be affected

›Racial distribution

›Val122Ile TTR variant: carrier frequency 3 to 4% in African Americans

›Cardiac sarcoidosis higher incidence in African Americans

›Mortality and prognosis

›5-year survival approximately 30 to 50% for idiopathic RCM

›Children with RCM 2-year survival < 50% without transplantation

›AL amyloidosis median survival < 6 months untreated, improving with modern chemotherapy

›ATTR amyloidosis median survival 3 to 4 years without tafamidis

Pathophysiology

›Core hemodynamic abnormality

›Impaired ventricular filling

›Myocardial stiffness with noncompliant ventricular walls

›Rapid rise in ventricular pressure with minimal increase in filling volume

›Diastolic heart failure (HFpEF physiology at extreme)

›Preserved systolic function (initially)

›LVEF normal or near normal

›Stroke volume reduced due to underfilling

›Markedly elevated filling pressures

›Elevated LVEDP and RVEDP

›Equalized diastolic pressures (LVEDP = RVEDP within 5 mmHg)

›Backward failure causing pulmonary and systemic venous congestion

›Non-dilated ventricles

›Distinguishes RCM from dilated cardiomyopathy

›Biatrial enlargement from chronic pressure load

›Rate dependence and fixed stroke volume

›Cannot increase stroke volume with exercise

›Cardiac output increase dependent on heart rate

›Tachycardia reduces diastolic filling time paradoxically

›Underlying disease mechanisms by etiology

›Amyloid infiltration

›Amyloid fibrils deposited in myocardial interstitium

›Extracellular volume expansion and myocyte compression

›TTR or AL light chain protein misfolding and aggregation

›Sarcoid granulomas

›Non-caseating granulomas replace functional myocardium

›Conduction system involvement causing AV block

›Fibrosis and scar replacing granulomas in healing phase

›Iron overload

›Iron deposition in cardiomyocytes

›Oxidative stress and cellular injury

›Fibrosis from iron-mediated damage

›Sarcomeric mutations

›Altered force generation and relaxation

›Myofibrillar disarray and interstitial fibrosis

›Phenotypic overlap with HCM

›Pulmonary hypertension development

›Chronically elevated pulmonary venous pressures

›Passive reactive pulmonary hypertension initially

›Progressive pulmonary vascular remodeling

›Fixed pre-capillary component may develop

›Severe fixed pulmonary hypertension precludes transplantation

Therapeutic Considerations

›Diuretic philosophy in RCM

›Congestion relief vs preload preservation tension

›Ventricular filling requires adequate preload

›Aggressive diuresis causes hypotension and low output

›Targeted toward symptom relief at minimum effective dose

›Diuretic resistance mechanisms

›Reduced GFR from low cardiac output

›Increased sodium reabsorption from RAAS activation

›Combination diuretic strategy addresses different nephron segments

›RAAS blockade limitations

›ACE inhibitors and ARBs

›Vasodilation causes hypotension in underfilled, fixed-output state

›No proven mortality benefit in RCM

›Use only if hypertension is present and tolerated

›ARNI (sacubitril/valsartan)

›Data limited in RCM specifically

›Hypotension risk

›Beta-blockade caution

›Rate dependence for cardiac output

›Heart rate reduction decreases cardiac output in RCM

›Avoid negative chronotropy unless clear arrhythmia indication

›Calcium channel blockers

›Verapamil and diltiazem similarly reduce heart rate and contractility

›Negative inotropic effect harmful in borderline EF

›Transplant as definitive therapy

›Only proven survival benefit for idiopathic and sarcomeric RCM

›Disease recurrence risk

›Amyloidosis recurs without treating underlying clonal disease (AL) or TTR source (hereditary ATTR)

›Sarcoidosis can recur in transplanted heart

›Waitlist mortality high; early referral critical

›Disease-modifying treatment evidence

›Tafamidis (ATTR-CM)

›Stabilizes TTR tetramer preventing amyloidogenesis

›Class I recommendation in 2023 ACC/AHA HF guidelines

›Iron reduction (hemochromatosis)

›Early intervention reverses cardiomyopathy

›Genetic family screening essential

›Sarcoid immunosuppression

›Corticosteroids reverse active inflammatory phase

›Fibrotic stage less responsive

11Patient Discharge Instructions/pdi32

copy discharge instructions

›Restrictive cardiomyopathy home care

›Take all heart medications exactly as prescribed

›Low sodium diet, 2 to 4 grams per day

›Fluid restriction, approximately 1.5 to 2 litres per day

›Weigh yourself every morning after using the bathroom and before eating

›Keep a daily weight log

›Elevate legs when sitting to reduce swelling

›Warning signs to return to Emergency Department immediately

›Sudden or rapidly worsening shortness of breath

›Swelling that gets rapidly worse (legs, abdomen)

›Weight gain of more than 2 kg over 2 days

›Fainting, passing out, or near-fainting

›Rapid or irregular heartbeat with dizziness or chest discomfort

›Chest pain or pressure

›Confusion or unusual drowsiness

›Very low urine output despite drinking enough fluids

›Activity and lifestyle instructions

›Avoid strenuous exercise unless specifically approved by your cardiologist

›Light daily activity such as gentle walking as tolerated

›Avoid alcohol

›No smoking

›Avoid excessive heat (hot tubs, saunas) which can cause blood vessel dilation and low blood pressure

›Medication notes

›Do not stop water pills (diuretics) without calling your doctor

›If you miss a dose of diuretic, do not double the next dose

›Blood thinners (anticoagulants) require regular blood tests or monitoring

›If on tafamidis, take daily without interruption

12References/r27

Guidelines and key sources

›Society guidelines

›2023 ACC/AHA Heart Failure Guideline (Heidenreich et al., JACC 2022)

›Class I recommendation for tafamidis in ATTR-CM NYHA I-III

›Heart failure staging, management, and transplant criteria

›2020 ESC Guidelines on Heart Failure

›Diagnosis and management of RCM

›Diuretic and anticoagulation recommendations

›HRS Expert Consensus Statement on Evaluation and Management of Arrhythmias in Cardiac Sarcoidosis (2014)

›Key clinical trials

›ATTR-ACT trial (Maurer et al., NEJM 2018)

›Tafamidis reduced all-cause mortality and cardiovascular hospitalization

›30% relative risk reduction vs placebo in ATTR-CM

›APOLLO-B trial (Adams et al., NEJM 2023)

›Patisiran reduced CV events in hereditary ATTR with polyneuropathy

›HELIOS-B trial (Solomon et al., NEJM 2024)

›Vutrisiran reduced mortality and CV events in ATTR-CM

›Diagnostic references

›Expert consensus on cardiac amyloidosis diagnosis (Dorbala et al., JACC 2019)

›Bone scintigraphy algorithm for ATTR diagnosis

›Multimodality imaging approach

›AHA Scientific Statement on RCM (Muchtar et al., Circulation 2021)

›Epidemiology, etiology, diagnosis, and management

›Coding references

›ICD-10 I42.5 Other restrictive cardiomyopathy

›ICD-10 E85.4 Organ-limited amyloidosis (cardiac amyloidosis)

›ICD-10 D86.85 Sarcoid myocarditis

›SNOMED CT 415068001 Restrictive cardiomyopathy

Evidence & Review