109. Nuclear and Multimodality Imaging: Cardiac Amyloidosis

CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of multimodality imaging evaluation for cardiac amyloidosis. Show notes were created by Dr. Hussain Khalid (University of Florida general cardiology fellow and CardioNerds Academy fellow in House Thomas). To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora! Collect free CME/MOC credit just for enjoying this episode! CardioNerds Multimodality Cardiovascular Imaging PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll Subscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show Notes & Take Home Pearls - Nuclear and Multimodality Imaging: Cardiac Amyloidosis Episode Abstract: Previously thought to be a rare, terminal, and incurable condition in which only palliative therapies were available, multimodality imaging has improved our ability to diagnose cardiac amyloidosis earlier in its disease course. Coupled with advances in medical therapies this has greatly improved the prognosis and therapeutic options available to patients with cardiac amyloidosis. Multimodality imaging involving echocardiography with strain imaging, 99mTc-PYP Scan, and cardiac MRI can help diagnose cardiac amyloidosis earlier, monitor disease progression, and even potentially differentiate ATTR from AL cardiac amyloidosis. Five Take Home Pearls Cardiac amyloidosis results from the deposit of amyloid fibrils into the myocardial extracellular space. The precursor protein can either be from immunoglobulin light chain produced by clonal plasma cells (in the setting of plasma cell dyscrasias) or transthyretin (TTR) produced by the liver (which can be “wild type” ATTR caused by the deposition of normal TTR or a mutant ATTR which is hereditary). These represent AL Cardiac Amyloidosis and ATTR Cardiac Amyloidosis respectively.Remember that amyloidosis can affect all aspects of the heart:the coronaries, myocardium, valves, electrical system, and pericardium! Be suspicious in a patient with history of HTN who has unexpected decrease in the need for antihypertensive agents with age or presents with a lower-than-expected blood pressure.Multimodality imaging can assist with the diagnosis of cardiac amyloidosis in patients with a high clinical suspicion, monitor disease progression, and even potentially differentiate ATTR from AL cardiac amyloidosis.Strain imaging assessment of global longitudinal strain (GLS) in patients with amyloid may demonstrate relatively better longitudinal function in the apex compared to the base, termed “apical sparing” or “cherry on top” (though in advanced stages the base to apex strain difference tends to become smaller). This has a 93% sensitivity and 82% specificity in identifying patients with cardiac amyloidosis and is particularly helpful with differentiating true cardiac amyloidosis from “mimics” such as hypertrophic cardiomyopathy, aortic stenosis, or hypertensive heart disease.When the clinical suspicion for cardiac amyloidosis is high, a semiquantitative grade ≥ 2 (myocardial uptake ≥ bone) on 99mTc-PYP Scan combined with negative free light chain and immunofixation assays (to rule out AL cardiac amyloidosis) can diagnose ATTR cardiac amyloidosis and exclude AL cardiac amyloidosis w/ 100% PPV! Furthermore, this can circumvent the need for endomyocardial biopsy. Echocardiography and cardiac MRI (CMR) are helpful for building the clinical suspicion for cardiac amyloidosis.When there is suspicion for AL cardiac amyloidosis, tissue biopsy is mandatory. Quotable: - Nuclear and Multimodality Imaging: Cardiac Amyloidosis “Even if you’re starting fresh, you should not do this test (technetium pyrophosphate scan) without a SPECT CT; you could be sending patients to therapy that costs anywhere between $25,000 to $250,000 per year for a disease that they don’t have.” --13:22 Detailed Show Notes 1. What is amyloidosis? What are the main precursor proteins in cardiac amyloidosis? Amyloidoses are protein-folding disorders in which proteinaceous deposits known as amyloid can infiltrate multiple organs. Cardiac amyloidosis is typically secondary to two main subtypes: 1) immunoglobulin light chain produced by clonal plasma cells (AL cardiac amyloidosis), and 2) transthyretin produced by the liver (ATTR cardiac amyloidosis). AL and ATTR account for >95% of cardiac amyloidosis. Rare precursors include serum amyloid A (AA) and apolipoprotein A-1 (ApoA-1).AL cardiac amyloidosisOverall incidence of AL amyloidosis is estimated to be 8.0-14.4 million persons per year in the USA with cardiac involvement in ~50% of patients. Median survival of patients with cardiac AL amyloidosis is 6 months from the onset of heart failure. Survival has improved with earlier detection and advancements in oncologic treatments.AL may deposit in any tissue outside the CNS and so patients often have multiorgan involvement (kidneys, liver, etc).ATTR cardiac amyloidosisATTR typically results in cardiac amyloidosis, peripheral neuropathy, and MSK sequelae (i.e., bilateral carpal tunnel, lumbar spinal stenosis, biceps tendon rupture) with relative proportions dependent on the mutant variant.Transthyretin amyloidosis can occur secondary to the deposition ofnormal TTR (known as “ATTR wild type” or “ATTRwt”) or a mutant form (hereditary form known as “ATTR mutant” or “ATTRm”).ATTRwtHas a 15:1 male to female prevalence ratio and usually occurs in older patients (>65 y.o.)Almost always involves the heartMay be responsible for as many as 30% of heart failure with preserved ejection fraction (HFpEF) cases in patients >75 years old!ATTRmHas only a slight male predominance and occurs in younger patients (>40 y.o.)Inherited in an autosomal dominant fashion with multiple genotypes with variable degrees of penetrance and cardiac involvementThere are more than 100 genetic variants of ATTR that are associated with amyloidosis. However, only a few of these variants, including Val30Met, Thr60Ala, Ser77Tyr, and Val122Ile, are responsible for the majority of cases of hereditary ATTRAs stated in Podcast Episode #7, the specific mutation is closely linked with the age of onset, natural history, and phenotype of the affected individual!The Val122Ile mutation is the most common variant in the USA and a has prevalence of 3-4% in the US African American population. It is associated with cardiac amyloidosis with minimal neuropathy.Thr60Ala is the 2nd most common variant in the USA and is seen most commonly in those of Irish descent. It is associated with a mixed cardiomyopathy and neuropathy phenotype.Val30Met causes a prototypical hATTR polyneuropathy (heriditary ATTR with polyneuropathy also known as “Familial Amyloid Polyneuropathy”The specific genetic variant affects treatment decision and screening is indicated for individuals with known or suspected familial amyloidosis presenting w/ new symptomatic heart failure. 2. What are some classic cardiac and extracardiac manifestations of amyloidosis? For fantastic case presentations of cardiac amyloidosis including suggestive history and physical exam findings, diagnostic considerations, and recommended management, tune in to CardioNerds Podcast Episodes #7-10 and #54! As described in Podcast Episode #7, amyloidosis is associated with many classic extracardiac findings based on which organ it deposits in, and can also deposit in every layer of the heart—coronary, ventricular, valvular, electrical, and pericardial tissues! Below is a brief outline of some of the classic extracardiac and cardiac manifestations of amyloidosis.Extracardiac:ATTR: peripheral nerves (sensorimotor and autonomic defects) and musculoskeletal sequelae (bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture). Degree of cardiac vs nerve involvement differs by mutant variant as above. A prior Cleveland Clinic study showed Congo red staining of tenosynovial tissue detected amyloid deposits in 10.2% of patients undergoing carpal tunnel release surgeryAL: any tissue outside the CNS. For instance, typical organs involved include the kidneys (nephrotic syndrome), liver, intestines, and nervous system. On exam one may find macroglossia and periorbital bruising.Cardiovascular:Decreased antihypertensive medication requirements with increasing age or presenting with lower than expected blood pressurePostural hypotensionCoronary microvascular diseaseChronically elevated but flat troponin (infiltration into the coronary microvasculature)Almost all patients with cardiac amyloidosis have significantly reduced peak stress myocardial blood flow (<1.3 ml/g/min) which may explain symptoms of angina in these patients with absence of epicardial coronary artery diseaseMyocardialSigns and symptoms of both left and right heart failureRestrictive physiologyLVH tends to be greater in ATTR than in AL by time of symptom onset. This is because AL is also directly toxic, thereby causing a toxic-infiltrative cardiomyopathy. ATTR is more likely to deposit asymmetrically and thus may more closely mimic hypertrophic cardiomyopathyValvularThickened AV valves and interatrial septumParadoxical low-flow, low-gradient severe aortic stenosis (~15% of patients who undergo transcatheter aortic valve replacement have ATTRwt). The low flow and low gradient are because of restrictive filling and significant diastolic dysfunctionElectricalAV Block, Bundle Branch BlockAtrial fibrillation from infiltration of the atria (especially ATTR), chronically high left atrial pressure, and/or aging.Low voltage EKG[NJ1] [GU2] (in most cases,