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Cardiac amyloid heart disease , state of the art power point lecture 2025

Abdul-Razek Maaty
Abdul-Razek Maaty

Infiltrative heart disease

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State-of-the-Art Cardiac Amyloidosis Abdul Razek A Maaty, MD Professor of Medicine Mansoura Faculty of Medicine Mansoura Egypt
Cardiac Amyloidosis
History /Amyloid Rudolph Virchow in 1854 adopted the term amyloid to refer to tissue deposits of material that stained in a similar manner to cellulose when exposed to iodine Amyloid: blue staining with iodine . Cellulose (amylum) has the same staining.
Amyloidoses are a diverse group of disorders whose effects are felt in every part of the body and every corner of the globe. The hallmark of these diseases is the aggregation and deposition of misfolded protein as insoluble amyloid fibrils.
Amyloidosis
What is Confusing About this Disease?
Cardiac Amyloidosis
Main Types of Cardiac Amyloidosis
Main Types of Cardiac Amyloidosis ~95%
Amyloidosis Subtypes that Affect Heart ~5% Type Protein % of CA Extracardiac signs AFib Fibrinogen 留 Rare Renal, proteinuria AApoAI Apolipoprotein A-I Rare Renal, proteinuria AApoAII Apolipoprotein A-II Rare Renal, proteinuria AApoAIV Apolipoprotein A-IV Unknown Renal, proteinuria A硫2M A硫2-microglobulin 80% Dialysis, CTS, AGel Gelsolin 5% Cutis laxa
Incidence and Prevalence AL 3 12 cases per million persons per year ATTR Uncertain A common rare disease ATTR Autopsy 25% of patients aged > 80 years ATTR Non-invasive 15 of HFpEF 15% of TAVR for LF-LG AS 5% of suspected HCM 1% of 99m Tc scan for noncardiac causes
Pathophysiology of Cardiac Amyloidosis
Mechanisms of Myocardial Dysfunction in CA Infiltrative/Toxic
Suspicion of Cardiac Amyloidosis European Heart Journal (2021) 42, 15541568
Red Flags for Suspicion of CA MGUS = (Monoclonal Gammopathy of Undetermined Significance)
Clinical Picture of CA
Unique Red Flags of CA
Popeye Sign
Diagnostic Approaches Invasive * Tissue biopsy (Gold-standard)/ Histopathology Non-invasive ECG Echocardiography Cardiac Magnetic Resonance Imaging (CMR) Nuclear Scintigraphy* ATTR-CA Monoclonal protein screen* AL-CA TTR gene sequencing and counseling* ATTRm Cardiac Biomarkers * Diagnostic and subtyping (AL versus ATTR)
Diagnostic Approaches
ECG in CA Low voltage complexes (QRS amplitude 5mm in limb leads or 10mm in all precordial leads). Atrial fibrillation and flutter (20%). Pseudo-infarct pattern. Intraventricular conduction delay. High-degree atrioventricular (AV) block. Low-voltage ECG + LVH on cardiac imaging = infiltrative cardiomyopathy.
ECG in CA
Echocardiography in CA
Echocardiography in CA
CMR in Cardiac Amyloidosis Abnormal gadolinium kinetics with LGE in LV/RV/Atrial wall -AL subendocardial -ATTR transmural Elevated native T1 values (not require contrast) Increased extracellular volume DDx: other causes of LVH ( HCM, sarcoid or hypertension) Normal CMR, cardiac amyloid is extremely unlikely
CMR in Cardiac Amyloidosis
Classic Hallmark of CA
Nuclear Scintigraphy Bone-avid (seeking) Radiotracers 99mTc-PYP: 99mtechnetium-labeled pyrophosphate 99m Tc-DPD: 99m technetium-labeled 3,3-diphosphono-1,2 propanodicarboxylic acid 99m Tc-MDP (HMDP): 99m technetium-labeled hydroxyMthylene DiphosPhonate Planar imaging initially plus SPECT to confirm Grade Cardiac / rib uptake (Perugini Score) Grade 0 No myocardial uptake with rib uptake No Grade 1 Myocardial uptake less than rib uptake Mild Grade 2 Myocardial uptake equal to rib uptake Moderate Grade 3 Myocardial uptake higher than rib uptake Severe
Nuclear Scintigraphy Cornerstone of ATTR-CA diagnosis -Non-biopsy, non-invasive -Affordable -Highly sensitive Heart to Contralateral Lung ratio (H/CL) of 1.5, giving a sensitivity of 97% and specificity and PPV of 100% for ATTR-CM
Biomarkers and Genetics Troponin T or I (TnT or TnI) Small-vessel ischemia BNP/ NT-proBNP More in AL-CA FLC/SPIE/UPIE AL-CA Urine for proteinuria TTR protein Genetic testing (TTR gene sequencing and counseling) Point mutations of the TTR gene ( most common is Val122Ile) So far, 130 known TTR variants
Serum/Urine Tests for AL *MGUS = Monoclonal Gammopathy of Undetermined Significance MGUS may convert to multiple myeloma
Histologic Findings
Pathology of Amyloidosis Stain Congo red Amorphous pink deposit Light microscopy Congo red Pathognomonic apple-green birefringence Cross polarized light microscope Subtyping can be performed by Immunohistochemistry Mass spectroscopy (precursor protein)
Diagnosis of Cardiac Amyloidosis European Heart Journal (2021) 42, 15541568
Algorithm for Non-invasive Diagnosis of CA
Medication/ Summary
Available and Future Disease-modifying Therapies in ATTR European Heart Journal (2021) 42, 15541568
Proposed Therapeutics in ATTR European Heart Journal (2021) 42, 1554 1568
Novel/ FDA Approved Drugs
Graphic Take Home Message

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Cardiac amyloid heart disease , state of the art power point lecture 2025

  • 1. State-of-the-Art Cardiac Amyloidosis Abdul Razek A Maaty, MD Professor of Medicine Mansoura Faculty of Medicine Mansoura Egypt
  • 3. History /Amyloid Rudolph Virchow in 1854 adopted the term amyloid to refer to tissue deposits of material that stained in a similar manner to cellulose when exposed to iodine Amyloid: blue staining with iodine . Cellulose (amylum) has the same staining.
  • 4. Amyloidoses are a diverse group of disorders whose effects are felt in every part of the body and every corner of the globe. The hallmark of these diseases is the aggregation and deposition of misfolded protein as insoluble amyloid fibrils.
  • 6. What is Confusing About this Disease?
  • 8. Main Types of Cardiac Amyloidosis
  • 9. Main Types of Cardiac Amyloidosis ~95%
  • 10. Amyloidosis Subtypes that Affect Heart ~5% Type Protein % of CA Extracardiac signs AFib Fibrinogen 留 Rare Renal, proteinuria AApoAI Apolipoprotein A-I Rare Renal, proteinuria AApoAII Apolipoprotein A-II Rare Renal, proteinuria AApoAIV Apolipoprotein A-IV Unknown Renal, proteinuria A硫2M A硫2-microglobulin 80% Dialysis, CTS, AGel Gelsolin 5% Cutis laxa
  • 11. Incidence and Prevalence AL 3 12 cases per million persons per year ATTR Uncertain A common rare disease ATTR Autopsy 25% of patients aged > 80 years ATTR Non-invasive 15 of HFpEF 15% of TAVR for LF-LG AS 5% of suspected HCM 1% of 99m Tc scan for noncardiac causes
  • 13. Mechanisms of Myocardial Dysfunction in CA Infiltrative/Toxic
  • 14. Suspicion of Cardiac Amyloidosis European Heart Journal (2021) 42, 15541568
  • 15. Red Flags for Suspicion of CA MGUS = (Monoclonal Gammopathy of Undetermined Significance)
  • 19. Diagnostic Approaches Invasive * Tissue biopsy (Gold-standard)/ Histopathology Non-invasive ECG Echocardiography Cardiac Magnetic Resonance Imaging (CMR) Nuclear Scintigraphy* ATTR-CA Monoclonal protein screen* AL-CA TTR gene sequencing and counseling* ATTRm Cardiac Biomarkers * Diagnostic and subtyping (AL versus ATTR)
  • 21. ECG in CA Low voltage complexes (QRS amplitude 5mm in limb leads or 10mm in all precordial leads). Atrial fibrillation and flutter (20%). Pseudo-infarct pattern. Intraventricular conduction delay. High-degree atrioventricular (AV) block. Low-voltage ECG + LVH on cardiac imaging = infiltrative cardiomyopathy.
  • 25. CMR in Cardiac Amyloidosis Abnormal gadolinium kinetics with LGE in LV/RV/Atrial wall -AL subendocardial -ATTR transmural Elevated native T1 values (not require contrast) Increased extracellular volume DDx: other causes of LVH ( HCM, sarcoid or hypertension) Normal CMR, cardiac amyloid is extremely unlikely
  • 26. CMR in Cardiac Amyloidosis
  • 28. Nuclear Scintigraphy Bone-avid (seeking) Radiotracers 99mTc-PYP: 99mtechnetium-labeled pyrophosphate 99m Tc-DPD: 99m technetium-labeled 3,3-diphosphono-1,2 propanodicarboxylic acid 99m Tc-MDP (HMDP): 99m technetium-labeled hydroxyMthylene DiphosPhonate Planar imaging initially plus SPECT to confirm Grade Cardiac / rib uptake (Perugini Score) Grade 0 No myocardial uptake with rib uptake No Grade 1 Myocardial uptake less than rib uptake Mild Grade 2 Myocardial uptake equal to rib uptake Moderate Grade 3 Myocardial uptake higher than rib uptake Severe
  • 29. Nuclear Scintigraphy Cornerstone of ATTR-CA diagnosis -Non-biopsy, non-invasive -Affordable -Highly sensitive Heart to Contralateral Lung ratio (H/CL) of 1.5, giving a sensitivity of 97% and specificity and PPV of 100% for ATTR-CM
  • 30. Biomarkers and Genetics Troponin T or I (TnT or TnI) Small-vessel ischemia BNP/ NT-proBNP More in AL-CA FLC/SPIE/UPIE AL-CA Urine for proteinuria TTR protein Genetic testing (TTR gene sequencing and counseling) Point mutations of the TTR gene ( most common is Val122Ile) So far, 130 known TTR variants
  • 31. Serum/Urine Tests for AL *MGUS = Monoclonal Gammopathy of Undetermined Significance MGUS may convert to multiple myeloma
  • 33. Pathology of Amyloidosis Stain Congo red Amorphous pink deposit Light microscopy Congo red Pathognomonic apple-green birefringence Cross polarized light microscope Subtyping can be performed by Immunohistochemistry Mass spectroscopy (precursor protein)
  • 34. Diagnosis of Cardiac Amyloidosis European Heart Journal (2021) 42, 15541568
  • 35. Algorithm for Non-invasive Diagnosis of CA
  • 37. Available and Future Disease-modifying Therapies in ATTR European Heart Journal (2021) 42, 15541568
  • 38. Proposed Therapeutics in ATTR European Heart Journal (2021) 42, 1554 1568
  • 40. Graphic Take Home Message