Amyloid Case Series: Hemodynamic Patterns, Echocardiographic Findings, and Diagnostic Lessons
A Case Series with Practice-Changing Conclusions for Cardiac Amyloidosis Recognition
Medical Associates Department of Nephrology | University of Illinois College of Medicine at Peoria | University of Dubuque Physician Assistant Program | Butler College of Osteopathic Medicine
Author: Andrew Bland, MD, FACP, FAAP
For confidential patient identifiers, see [[RHC_Case_Collection_Further_Information]].
Executive Summary
This document presents a series of cardiac amyloidosis cases encountered in clinical practice at Medical Associates, Dubuque, Iowa, between February and March 2026. Each case underwent right heart catheterization and echocardiography, providing paired invasive and noninvasive hemodynamic assessment. The series includes two biopsy-confirmed amyloidosis cases and one strongly suspected case, all sharing a unifying hemodynamic signature: preserved or near-preserved ejection fraction with critically reduced cardiac output (the EF-CO dissociation), Forrester Profile C hemodynamics, and Group 2 pulmonary hypertension.
Key Findings - All three cases had EF ≥45% on echocardiography with CI ≤1.75 L/min/m² on right heart catheterization — the EF-CO dissociation that defines infiltrative cardiomyopathy - Case B (Lyons) proves that a 19 mmHg RA-to-PCWP gradient does NOT exclude amyloidosis — biopsy-confirmed despite non-restrictive hemodynamics - Case C (Hoenigmann) demonstrates that echo RVSP (44 mmHg) underestimates true PA pressures (historically 60–70 mmHg) in low-output states - In Case B, the proteinuria pattern (43% non-albumin gap) and suppressed uninvolved light chain redirected the diagnosis when hemodynamics were misleading - These cases have changed clinical practice: RHC is now ordered earlier and more frequently for HFpEF/HFmrEF patients with disproportionate clinical severity
1. Introduction: Why This Case Series Matters
Cardiac amyloidosis remains underdiagnosed. Literature documents a median 13-month diagnostic delay (Ladefoged 2020, PMID: 32586582), a 44% misdiagnosis rate (Quarta 2012, PMID: 22362904), and detection in only 10% of screened patients (Shchendrygina 2024, PMID: 38324394). The preserved ejection fraction is consistently implicated as the primary cognitive trap.
This case series, accumulated over approximately 8 weeks at a single nephrology practice, demonstrates that the problem is not rare. Three patients with suspected or confirmed amyloidosis presented with cardiogenic shock-range hemodynamics masked by “normal” echocardiographic ejection fractions. Each case adds a specific diagnostic lesson that, taken together, redefine how infiltrative cardiomyopathy should be screened for in the heart failure population.
The for full hemodynamic data, derived parameters, and teaching points for each case, see the companion document: [[RHC_Case_Collection_Hemodynamic_Atlas]].
2. Case Summaries
Case A: Dennis Felton — Lambda AL Amyloidosis, Cardiac Ascites Masquerading as Cirrhosis
Demographics: 75-year-old male Presentation: Massive diuretic-refractory ascites, nodular liver on imaging, initially diagnosed as “cirrhosis” by hepatology Diagnosis: Lambda AL amyloidosis (IgA lambda clone, <0.010 g/dL; lambda FLC 285 mg/L, dFLC 232 mg/L) Outcome: Deceased
| Domain | Key Finding |
|---|---|
| Echo | EF 55% — “normal systolic function” |
| RHC | CI 1.15 L/min/m², CO 2.66, PCWP 28, RA 23, SV ~33 mL |
| PH | Group 2 CpcPH, PVR 4.8 WU, mPAP 40.7 |
| Forrester | Profile C (cold and wet) |
| EF-CO dissociation | EF 55% → CI 1.15 (cardiogenic shock with “normal” EF) |
| Hemodynamic equalization | PCWP 28, RVEDP 25, RA 23 — near-equalized (3 mmHg PCWP-RVEDP gradient) |
| Light chains | Lambda 285 mg/L, kappa 53.1 mg/L, ratio 0.19, dFLC 232 mg/L |
| M-protein | IgA lambda, essentially undetectable on SPEP (<0.010 g/dL) |
| Key teaching | An M-protein of <0.010 g/dL with CI 1.15 represents end-stage disease, not a benign finding. M-protein level should NEVER be used to gauge severity in AL amyloidosis. |
Full case report: [[Cardiac_Amyloidosis_Diagnostic_Challenges_Case_Report]], [[Felton_AIMCC_Final]]
Case B: Geralynn Lyons — Confirmed Amyloidosis Despite Non-Restrictive Hemodynamics
Demographics: 84-year-old female Presentation: Decompensated heart failure, failed diuresis (Cr 2.0 → 4.5), ICU with levophed + furosemide drip Diagnosis: Systemic amyloidosis — fat pad Congo red positive (subtype pending at death; clinically kappa AL) Outcome: Deceased
| Domain | Key Finding |
|---|---|
| Echo | EF 45%, IVSd 1.3 cm, LVPWd 1.2 cm, RWT 0.47, LV Mass Index 153 g/m² |
| Echo Diastology | Septal e’ 4 cm/s, E/e’ 37, Grade III+ restrictive filling |
| RHC | CI 1.75 L/min/m², CO 2.97, PCWP 30, RA 11, SV 31 mL |
| PH | Group 2 IpcPH, TPG ~0, PVR ~0 |
| Forrester | Profile C |
| EF-CO dissociation | EF 45% → CI 1.75 (borderline dissociation — EF mildly reduced but CI severely reduced) |
| Hemodynamic equalization | NOT PRESENT — RA 11, RVEDP 13, PCWP 30 = 19 mmHg RA-to-PCWP gradient |
| Light chains | Kappa ~17 mg/L, ratio ~5, lambda suppressed at ~3.4 mg/L (floor of normal) |
| Proteinuria | Protein/Cr 7.9, Albumin/Cr 4.5 → 43% non-albumin gap |
| Cardiac biomarkers | BNP >4,500, Troponin I 60 |
| Key teaching | Absence of diastolic equalization does NOT exclude amyloid. Asymmetric (left-dominant) infiltration produces elevated PCWP with relatively normal RA. The proteinuria pattern and suppressed uninvolved light chain redirected the diagnosis when hemodynamics were misleading. |
Full case reports: [[Lyons-Geralynn-Amyloidosis-Case-2026-03]], [[Severe_HF_Edema_Nephrotic_Proteinuria_Teaching_Review]]
Case C: Carol Hoenigmann — Suspected Infiltrative Cardiomyopathy, Workup Pending
Demographics: 79-year-old female Presentation: Anasarca, pulmonary hypertension, right-sided heart failure, cor pulmonale Diagnosis: Suspected infiltrative cardiomyopathy (ATTR vs. hypertensive); workup pending Outcome: Alive — structural heart team consulted
| Domain | Key Finding |
|---|---|
| Echo | EF 60–65%, IVSd 1.2 cm, LVPWd 1.1 cm, RWT 0.56, LVDD 3.9 cm (small cavity) |
| Echo RV | Markedly dilated RV and RA, TAPSE 17 mm (at failure threshold), mod-severe TR, RA area 22 cm² |
| Echo Diastology | E/A 2.8, DT 140 ms (Grade III restrictive), e’ 9–10, E/e’ 11 (indeterminate) |
| Echo RVSP | 44 mmHg — underestimates (historically 60–70 mmHg when compensated) |
| RHC | CI 1.22 L/min/m², CO 2.27, PCWP 22, SV 29.1 mL |
| Forrester | Profile C |
| EF-CO dissociation | EF 60–65% → CI 1.22 (the most dramatic dissociation in the series) |
| Key teaching | The highest EF in the series produces the lowest SV (29.1 mL). Echo RVSP underestimates PH in shock. Grade III restrictive filling with E/e’ in indeterminate range — trust E/A and DT over E/e’ when they disagree. TAPSE at exactly 17 mm = right ventricle at precipice. |
Recommended workup: Tc-99m PYP scan, serum free light chains, SPEP/UIEP, cardiac MRI if tolerated
3. Comparative Analysis
3.1 The EF-CO Dissociation Spectrum
| Case | EF | CI (L/min/m²) | SV (mL) | CO (L/min) | Amyloid Status |
|---|---|---|---|---|---|
| A (Felton) | 55% | 1.15 | ~33 | 2.66 | Confirmed lambda AL |
| B (Lyons) | 45% | 1.75 | 31 | 2.97 | Confirmed (fat pad +) |
| C (Hoenigmann) | 60–65% | 1.22 | 29.1 | 2.27 | Suspected |
The two highest EFs (Cases A and C) produce the two lowest cardiac outputs. Case C is the most dramatic: EF 60–65% — the “best” EF in the series — paired with the worst SV (29.1 mL) and the second-worst CI (1.22). The EF is a ratio (SV/EDV); when the ventricle is small and stiff (LVDD 3.9 cm in Case C), it ejects a normal percentage of a tiny volume.
3.2 Wall Thickness and Remodeling Pattern
| Case | IVSd (cm) | LVPWd (cm) | LVDD (cm) | RWT | Pattern |
|---|---|---|---|---|---|
| A (Felton) | Not available from initial echo | — | — | — | — |
| B (Lyons) | 1.3 | 1.2 | 5.1 | 0.47 | Concentric hypertrophy |
| C (Hoenigmann) | 1.2 | 1.1 | 3.9 | 0.56 | Concentric hypertrophy |
Both cases with wall thickness data show concentric hypertrophy (RWT > 0.42). Case C has the higher RWT (0.56) with a smaller cavity (3.9 cm), the more classically infiltrative pattern. In neither case did the echocardiographic impression raise amyloid as a differential — the walls were described as “hypertrophied” without consideration of infiltrative etiology.
3.3 Diastolic Function Comparison
| Parameter | B (Lyons) | C (Hoenigmann) | Teaching Point |
|---|---|---|---|
| E/A | Not reported | 2.8 | Grade III restrictive |
| DT | Not reported | 140 ms | Short — restrictive |
| Septal e’ | 4 cm/s | 9 cm/s | Lyons has floor-level e’ (classic amyloid); Hoenigmann preserved |
| E/e’ | 37 | 11 | Lyons severely elevated; Hoenigmann indeterminate |
| PCWP (RHC) | 30 | 22 | Both elevated — e’ and E/e’ don’t always correlate |
Case B has the classic amyloid diastolic signature: e’ of 4 cm/s with E/e’ of 37. Case C has preserved e’ velocities (9–10 cm/s) — suggesting either the infiltrative process has not yet fully replaced the myocardium, or a different etiology (hypertensive). However, the E/A of 2.8 and DT of 140 ms are Grade III restrictive regardless, and the RHC confirms PCWP 22.
Clinical Pearl: When E/e’ says “indeterminate” but E/A says “restrictive” and the RHC confirms elevated PCWP, trust the E/A and the RHC. The e’ velocity in Case C has not yet reached the floor seen in advanced amyloidosis — this may represent earlier disease or a different etiology, but it does not exclude infiltrative cardiomyopathy.
3.4 Right Heart Involvement
| Parameter | A (Felton) | B (Lyons) | C (Hoenigmann) |
|---|---|---|---|
| RA (mmHg) | 23 | 11 | Est. 15 |
| RVEDP (mmHg) | 25 | 13 | — |
| RV dilation | — | — | Marked |
| TR severity | — | — | Mod-severe |
| TAPSE | — | — | 17 mm (threshold) |
| RVSP (echo) | — | — | 44 (underestimate) |
| Historical PA | — | — | 60–70 mmHg |
Case A shows the most advanced biventricular disease (near-equalization: RA 23, RVEDP 25, PCWP 28). Case C shows the most structurally abnormal right heart (marked dilation, mod-severe TR, TAPSE at failure threshold). Case B had the most left-dominant pattern (RA 11 with PCWP 30).
3.5 Pulmonary Hypertension Classification
| Case | PH Group | Subtype | PVR (WU) | Implication |
|---|---|---|---|---|
| A (Felton) | Group 2 | CpcPH | 4.8 | Fixed vascular remodeling — partially irreversible |
| B (Lyons) | Group 2 | IpcPH | ~0 | Pure passive — reversible with decongestion |
| C (Hoenigmann) | Group 2 | Presumed CpcPH | — | Historical PA 60–70 suggests remodeling |
Case A’s CpcPH (PVR 4.8 WU) represents the most advanced pulmonary vascular disease — chronic left-sided congestion has produced structural remodeling that will not fully reverse. Case B’s PVR of essentially 0 means the PH is entirely passive and reversible. Case C almost certainly has CpcPH given historical PA pressures of 60–70 mmHg.
3.6 Light Chain Patterns
| Parameter | A (Felton) | B (Lyons) | C (Hoenigmann) |
|---|---|---|---|
| Light chain type | Lambda | Kappa | Pending |
| Involved FLC | Lambda 285 mg/L | Kappa ~17 mg/L | — |
| Uninvolved FLC | Kappa 53.1 mg/L | Lambda ~3.4 mg/L | — |
| Ratio | 0.19 (low) | ~5 (high) | — |
| dFLC | 232 mg/L | ~14 mg/L | — |
| M-protein | IgA lambda <0.010 g/dL | Negative SPEP/UIEP | — |
| AL subtype likelihood | Lambda AL (70–75% of AL) | Kappa AL (25–30%) or LCDD | — |
Case A is classic lambda AL — the predominant subtype. Case B is kappa-dominant, which raised LCDD above AL in the initial differential, but fat pad biopsy confirmed amyloid (Congo red positive), establishing this as kappa AL amyloidosis rather than LCDD (which is Congo red negative).
4. Practice-Changing Conclusions
Conclusion 1: Order the Right Heart Catheterization
Every case in this series had EF ≥45% on echocardiography. Every case had CI in cardiogenic shock range on RHC. Without the RHC, the severity of hemodynamic compromise would have been invisible, and the EF-CO dissociation — the hallmark of infiltrative cardiomyopathy — would have been missed.
The threshold for RHC in HFpEF/HFmrEF should be lower than current practice. Any patient with preserved or near-preserved EF who has disproportionate symptoms, diuretic resistance, unexplained AKI with diuresis, or clinical severity that seems “too sick for this EF” should be catheterized.
Conclusion 2: Do Not Rely on Diastolic Equalization
Case B had a 19 mmHg RA-to-PCWP gradient and biopsy-confirmed amyloid. The textbook teaching that cardiac amyloidosis produces diastolic pressure equalization is true in advanced biventricular disease but fails in left-dominant or asymmetric infiltration. Using equalization as a rule-out criterion causes diagnostic delay.
Conclusion 3: The Proteinuria Pattern Redirects When Hemodynamics Mislead
In Case B, the hemodynamics said “not amyloid.” The proteinuria said “maybe amyloid.” The fat pad biopsy said “amyloid.” The albumin/creatinine vs. protein/creatinine gap (43% non-albumin protein) was the finding that redirected the workup. For nephrologists, this is the most actionable lesson: always dissect the proteinuria.
Conclusion 4: Echo Underestimates PH in Shock — Catheterize
Case C had echo RVSP 44 vs. historical PA pressures 60–70. In low-output states, the TR jet velocity drops because the RV cannot generate full systolic pressure. Echo-estimated RVSP is spuriously low. Only RHC provides accurate PA pressures in this population.
Conclusion 5: A Small M-Protein With Organ Damage Is Not Benign
Case A had an IgA lambda M-protein <0.010 g/dL — essentially undetectable by SPEP. Case B had completely negative immunofixation. In both confirmed amyloidosis cases, standard protein electrophoresis was non-diagnostic. The free light chain assay was the sensitive screening test. FLC should be ordered in every patient with unexplained HFpEF and increased wall thickness.
Case D: Renal AL Amyloidosis Without Cardiac Catheterization (Willmes)
Biopsy Results
| Finding | Detail |
|---|---|
| Glomeruli | 24 total (2 globally sclerotic) |
| Amyloid deposits | Moderate-to-severe amorphous deposits, Congo red positive |
| Interstitium | Focal amyloid deposits; minimal fibrosis and tubular atrophy |
| Vessels | Focal amyloid involvement |
| IF — Lambda | 2-3+ (glomeruli and focal interstitium) |
| IF — Kappa | Negative |
| IF — Other | Non-specific IgM 1-2+; all others negative |
| EM | Pending (toluidine blue sections of renal medulla) |
| LCDD | Not identified |
Pending Data (to be pulled from chart)
Teaching Points
Comparison to Series
| Feature | Case A (Felton) | Case B (Lyons) | Case C (Hoenigmann) | Case D (Willmes) |
|---|---|---|---|---|
| Age/Sex | 75M | 84F | 79F | 82M |
| Light Chain | Lambda | Kappa | Pending | Lambda |
| Tissue Confirmation | Yes | Fat pad + | No | Renal bx + |
| Congo Red | + | + | N/A | + |
| RHC | CI 1.15 | CI 1.75 | CI 1.22 | Not performed |
| EF | 55% | 45% | 60-65% | Pending echo |
| Outcome | Deceased | Deceased | Alive | Active |
See [[RHC_Case_Collection_Further_Information#Case 5]] for patient identifiers.
5. Toward Publication
This four-case amyloid series (expandable as additional cases are identified) — three with paired invasive and noninvasive hemodynamic data, one with renal biopsy confirmation without RHC — contains the substrate for publication as:
- Case series: “The EF-CO Dissociation in Cardiac Amyloidosis: Three Cases of Cardiogenic Shock with Preserved Ejection Fraction”
- Educational review: “Integrating Right Heart Catheterization, Echocardiography, and Proteinuria Phenotyping in the Diagnosis of Cardiac Amyloidosis”
- Practice-changing commentary: “When Hemodynamics Mislead: Biopsy-Confirmed Amyloidosis Without Diastolic Pressure Equalization”
Target journals: JACC Case Reports, Journal of Cardiac Failure, American Journal of Kidney Diseases (nephrologist perspective), Journal of the American Society of Echocardiography.
See [[RHC_Case_Collection_Further_Information]] for patient identifiers needed for IRB submission.
References
- Ladefoged B, Dybro A, Povlsen JA, et al. Diagnostic delay in wild type transthyretin cardiac amyloidosis — a clinical challenge. Int J Cardiol. 2020;304:138-143. https://pubmed.ncbi.nlm.nih.gov/32586582/
- Quarta CC, Buxbaum JN, Shah AM, et al. The amyloidotic heart: a clinical overview. Eur Heart J. 2012;33(9):1073-1081. https://pubmed.ncbi.nlm.nih.gov/22362904/
- Shchendrygina A, Rakisheva A, Gkouziouta A, et al. Transthyretin cardiac amyloidosis: challenges in screening and early diagnosis. Heart Fail Rev. 2024;29(2):431-445. https://pubmed.ncbi.nlm.nih.gov/38324394/
- Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618-3731. https://pubmed.ncbi.nlm.nih.gov/36017548/
- Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2016;29(4):277-314. https://pubmed.ncbi.nlm.nih.gov/27037982/
- Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults. J Am Soc Echocardiogr. 2015;28(1):1-39. https://pubmed.ncbi.nlm.nih.gov/25559473/
- Mullens W, Abrahams F, Skouri HN, et al. Elevated intra-abdominal pressure in acute decompensated heart failure. J Am Coll Cardiol. 2009;53(7):589-596. https://pubmed.ncbi.nlm.nih.gov/19215833/
- Rangaswami J, Bhalla V, Blair JEA, et al. Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies. Circulation. 2019;139(4):e52-e154. https://pubmed.ncbi.nlm.nih.gov/30571348/
- Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385(1):46-58. https://pubmed.ncbi.nlm.nih.gov/34192431/
- Merlini G, Dispenzieri A, Sanchorawala V, et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers. 2018;4(1):38. https://pubmed.ncbi.nlm.nih.gov/30361501/
Version History
| Date | Change |
|---|---|
| 2026-03-18 | Initial compilation — Cases A (Felton), B (Lyons), C (Hoenigmann) |
| 2026-03-18 | Added Case D (Willmes) — lambda AL, renal biopsy confirmed, no RHC |
© 2026 Andrew Bland, MD, FACP, FAAP. For educational use within affiliated medical education programs.