p.(V142I)-Associated Variant Transthyretin Amyloid Cardiomyopathy Complicating Complex Congenital Heart Disease

Abstract

Background

p.(V142I)-associated variant transthyretin amyloid cardiomyopathy (ATTRv-CM) is biologically aggressive and predominantly affects individuals of African ancestry.

Case Summary

A 51-year-old Nigerian man was diagnosed with double outlet right ventricle by the adult congenital heart disease service, although challenging social circumstances hindered adherence to clinic appointments. He re-established regular contact after 3 years and underwent workup for corrective surgery. Cardiac amyloidosis was suspected on repeat echocardiogram and confirmed on cardiac magnetic resonance and bone scintigraphy. Genetic sequencing later identified homozygosity for the p.(V142I) transthyretin variant. He was referred for emergency transplant assessment after developing cardiogenic shock. Unfortunately, he died despite receiving supportive therapies.

Discussion

Homozygous p.(V142I)-ATTRv-CM presents earlier and advances more aggressively than its heterozygous counterpart. This unusual case highlights the diagnostic pitfalls when genetics, adult congenital heart disease, and advanced heart failure intersect.

Take-Home Message

In patients of African ancestry, a high index of suspicion for p.(V142I)-ATTRv-CM is needed to prompt early diagnosis and initiation of disease-modifying therapies.

Visual Summary

History of Presentation

A 51-year-old man of Nigerian descent presented to his local emergency department with NYHA functional class IV symptoms characterized by progressive dyspnea, orthopnea, and peripheral edema. He was hypotensive (89/64 mm Hg) on arrival and a chest X-ray confirmed the presence of pulmonary edema (Figure 1). Twelve-lead electrocardiogram revealed sinus rhythm with a left posterior fascicular block and right bundle branch block and low-voltage QRS complexes in the limb leads (Figure 2). Despite initial intravenous diuretic therapy, he developed cardiogenic shock and type 1 respiratory failure complicated by supraventricular tachycardia, atrial fibrillation, and nonsustained ventricular tachycardia. Following stabilization with direct current cardioversion, continuous positive airway pressure ventilation and central venous dopamine infusion in the intensive care unit, he was transferred to the regional advanced heart failure center for assessment of cardiac transplantation.

Figure 1.

Anteroposterior Projection Chest X-Ray on Admission Demonstrating Pulmonary Edema and Cardiomegaly

Figure 2.

12-Lead Electrocardiogram on Admission Demonstrating Sinus Rhythm With Heart Rate of 92 beats/min, Right Bundle Branch Block, and Left Posterior Fascicular Block

Past Medical History

This patient was given a provisional diagnosis of “hole in the heart” in Nigeria but declined corrective surgery as he was asymptomatic. After relocating to the United Kingdom in 2022, he received a formal diagnosis of Tetralogy of Fallot-type double outlet right ventricle (TOF-type DORV) through his local adult congenital heart disease service by way of transthoracic echocardiogram (TTE) and noncontrast cardiac magnetic resonance (CMR) imaging following repeated hospitalizations with decompensated cardiac failure.

Challenging social circumstances hindered adherence to outpatient clinic appointments. He had relocated with limited specialist follow-up until 2025 where he re-established contact with his local adult congenital heart disease team and agreed to undergo workup for corrective surgery. TTE was repeated and raised suspicion for cardiac amyloidosis. Contrast-enhanced CMR later confirmed characteristic imaging findings of cardiac amyloidosis. Serum immunofixation and electrophoresis were performed and detected oligoclonal bands, raised kappa free light chains, and a mildly elevated kappa/lambda ratio; this necessitated a bone marrow biopsy, which excluded a plasma cell dyscrasia with negative Congo Red staining for amyloid. A referral to the regional amyloidosis service for further management was made, at which time he had no associated symptoms of peripheral neuropathy, lumbar spinal stenosis, or carpal tunnel syndrome. His regular medications included daily doses of dapagliflozin (10 mg), bumetanide (5 mg), spironolactone (50 mg), and weekly metolazone (2.5 mg).

Differential Diagnosis

Differential diagnoses for his acute presentation included decompensated cardiac failure related to the unrepaired TOF-type DORV or cardiac amyloidosis. Transthyretin amyloid cardiomyopathy (ATTR-CM) can be classified by the sequence of transthyretin (TTR) gene into either “wild-type” (ATTRwt-CM) or variant (ATTRv-CM) forms. In this case, ATTRv-CM was strongly suspected because of the patient's age and ethnicity but light-chain amyloid cardiomyopathy (AL-CM) needed exclusion.

Investigations

TOF-type DORV was described on initial TTE and CMR through the presence of a nonrestrictive ventricular septal defect, infundibular stenosis, and >50% override of aorta from the morphologic hypertrophied right ventricle. On repeat TTE, features of cardiac amyloidosis were identified alongside the preexisting congenital heart disease. These include significant biventricular hypertrophy and impairment, impaired diastology, low cardiac output, and severe tricuspid regurgitation (Figure 3, Video 1, Video 2, Video 3, Video 4, Video 5, Video 6). This was supported by contrast-enhanced CMR with the addition of late gadolinium enhancement pattern, native T1 relaxation time, and myocardial extracellular volume when compared with imaging from 3 years earlier (Figures 4 and 5).

Figure 3.

Echocardiogram of a 51-Year-Old Man With an Unrepaired Double Outlet Right Ventricle With Tetralogy of Fallot-type Physiology and Echocardiographic Features Suggestive for Cardiac Amyloidosis

(A and B) Parasternal long-axis views demonstrating septal hypertrophy with interventricular septal wall thickness in end-diastole (IVSd) of 17 mm (seen in light blue), a large ventricular septal defect (VSD) and an aorta that overrides the right ventricle by more than 50%; bidirectional flow is seen across the VSD using color Doppler. (C to E) Modified short-axis view demonstrating an overriding aorta, dilated right atrium, and severe infundibular stenosis (pulmonary valve maximum velocity = 3.9 m/s). (F) Apical 4-chamber view demonstrating hypertrophy of both left and right ventricular walls (right ventricular wall diameter = 18 mm on diastole) with an impaired left ventricular ejection fraction of 49% and reduced global longitudinal strain of −9.3%. Both atria are dilated (indexed right atria area = 15.4 cm/m², indexed left atria volume = 34 mL/m²). Of note, pulsed-wave Doppler across the mitral valve inflow demonstrated a mitral valve peak E velocity of 1.4 m/s and mitral valve E deceleration time of 140 ms. Average E/e’ of the left ventricle on tissue Doppler imaging was 19.6. Coupled with a severe tricuspid regurgitation (as illustrated in H), this patient fulfills the British Society of Echocardiography criteria for impaired diastolic function with elevated filling pressures. (G) Modified apical 4-chamber view of the right ventricle illustrates a hypertrophied right ventricular (RVH) free wall with impaired right ventricular systolic function (tricuspid annular plane systolic excursion = 14 mm, S′ velocity 7.4 cm/s and right ventricular fractional area change of 20%. (H) Severe tricuspid regurgitation measured in the parasternal short-axis view with tricuspid regurgitation maximal velocity of 4.9 m/s, which is in keeping with pulmonary hypertension.

Figure 4.

Cardiovascular Magnetic Resonance Imaging Characteristic for Cardiac Amyloidosis in a 51-Year-Old Man With Unrepaired Double Outlet Right Ventricle With Tetralogy of Fallot-type Physiology

(A) Horizontal long-axis 4-chamber and (B) 3-chamber steady-state free-precession cine views, respectively. Biventricular hypertrophy is present and systolic dysfunction is impaired in both ventricles (left ventricular ejection fraction = 30%, right ventricular ejection fraction = 40%). Both atria are dilated and there is bowing of the interatrial septum toward the right atria in keeping with elevated left atrial pressure. The interatrial septum is thickened (5 mm). The aortic root is seen overriding the ventricular septal defect. There is aortomitral discontinuity with left-to-right shunt (Qp:Qs = 3.5). (C) Midventricular short-axis view demonstrates increase in maximal wall thickness (left ventricle: 19 mm at mid-inferoseptal wall; right ventricle: 13 mm mid-inferior wall). (D to F) Late gadolinium imaging (phase-sensitive inversion recovery) demonstrating a characteristic pattern of myocardial uptake for cardiac amyloidosis. There is extensive circumferential and transmural uptake in both ventricles, interatrial septum, left atria, and subvalvular apparatus of both mitral and tricuspid valves. Myocardial nulling kinetics are reversed. (G) Modified look-locker imaging sequence demonstrating a mildly elevated native T1 of 1,079 ms. (H) Myocardial extracellular volume (ECV) mapping demonstrating an elevated overall ECV of 56% using a hematocrit of 0.41 suggesting high amyloid burden.

Figure 5.

Serial CMR Imaging Between 2022 and 2025 Demonstrating an Increase in End-Diastolic Maximal Wall Thickness From 13 mm to 19 mm

Pattern of late gadolinium enhancement uptake is consistent with cardiac amyloidosis. This case highlights the importance of performing contrast-enhanced cardiac magnetic resonance (CMR) in patients with unexplained increase in left ventricular wall thickness, as it permitted tissue characterization leading to an eventual diagnosis of cardiac amyloidosis. eGFR = estimated glomerular filtration rate; Hs-Troponin I = high-sensitivity Troponin I; LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction; LVESV = left ventricular end systolic volume; LVSV = left ventricular stroke volume; NT-proBNP = N-terminal pro–B-type natriuretic peptide; RVEF = right ventricular ejection fraction.

The interpretation of serum free light-chain ratio, a key biochemical component of excluding a monoclonal gammopathy, was challenging in the context of renal impairment. Because free light chains are primarily cleared by the kidneys, estimated glomerular filtration rate is a major determinant of the serum concentration. In the presence of previous oligoclonal bands on serum immunofixation, and an elevation in the kappa/lambda free light-chain ratio above the estimated glomerular filtration rate–adjusted cutoff to exclude a monoclonal gammopathy (Table 1), a diagnosis of ATTR-CM could not be secured using the validated nonbiopsy diagnostic criteria. However, the subsequent findings of Perugini grade 3 99m technetium-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy (Figure 6) and genotyping demonstrating homozygosity for the p.(V142I) TTR variant were collectively much more in keeping with ATTR-CM than AL-CM. Moreover, the inability to detect a paraprotein using serum mass spectrometry virtually excluded the possibility of a low-level clone causing AL-CM. Thus, although an endomyocardial biopsy would have been required to diagnose ATTRv-CM with absolute certainty, a high probability diagnosis of ATTRv-CM was concluded by video multidisciplinary team (MDT) consensus between the National Amyloidosis Center and Midlands Amyloidosis Service. It was also agreed that neither TTR stabilizer nor silencer therapies would positively influence his outcome in view of the advanced disease stage and it was, therefore, agreed not to further pursue a tissue diagnosis but instead refer him to the transplant MDT for consideration of urgent cardiac transplantation.

Table 1.

List of Relevant Laboratory Findings

Laboratory Tests	Values	Reference Range
Baseline values in 2022
Urea and electrolytes
Sodium	140 mmol/L	133-146 mmol/L
Potassium	4.2 mmol/L	3.5-5.3 mmol/L
Urea	8.0 mmol/L	2.5-7.8 mmol/L
Creatinine	118 mmol/L	64-104 mmol/L
Estimated glomerular filtration rate	63 mL/min/1.73 m2
N-terminal pro–B-type natriuretic peptide (NT-proBNP)	2,030 ng/L	0-400 ng/L
High-sensitivity Troponin I (HS-Troponin I)	103 ng/L	< 34 ng/L
Hospital admission in April 2025
Serum protein electrophoresis
Immunoglobulin A	2.5 g/L	0.8-4.0 g/L
Immunoglobulin G	40.2 g/L	6.0-16.0 g/L
Immunoglobulin M	0.85 g/L	0.5-2.0 g/L
Serum immunofixation	Oligoclonal bands detected
Kappa light chain	121.47 mg/L	6.3-39.0 mg/L
Lambda light chain	38.04 mg/L	5.9-36.7 mg/L
Kappa/lambda ratio	3.19	0.46-2.62a
Urine Bence-Jones protein	Negative
Hospital admission in September 2025
Urea and electrolytes
Sodium	131 mmol/L	133-146 mmol/L
Potassium	4.3 mmol/L	3.5-5.3 mmol/L
Urea	27.5 mmol/L	2.5-7.8 mmol/L
Creatinine	130 mmol/L	64-104 mmol/L
Estimated glomerular filtration rate	54 mL/min/1.73 m2
NT-proBNP	4,113 ng/L	0-400 ng/L
HS-Troponin I	214 ng/L	< 34 ng/L
Hemoglobin	143 g/L	130-171 g/L
White cell count	6.95 x 109/L	3.26-11.20 x 109/L
Platelets	142 x 109/L	150-400 x 109/L
C-reactive protein	34 mg/L	0-5 mg/L
Liver function tests
Albumin	28 g/L	35-50 g/L
Total protein	82 g/L	60-80 g/L
Bilirubin	127 μmol/L	< 21 μmol/L
Alanine aminotransferase	663 U/L	0-55 U/L
Alkaline phosphatase	151 U/L	30-130 U/L
International normalized ratio	1.6	0.8-1.2
Urine albumin-Creatinine ratio	0.3 mg/g	< 30 mg/g
Serum protein electrophoresis
Immunoglobulin A	2.99 g/L	0.8-4.0 g/L
Immunoglobulin G	44.7 g/L	6.0-16.0 g/L
Immunoglobulin M	0.98 g/L	0.5-2.0 g/L
Serum immunofixation	Polyclonal immunoglobulins
Kappa light chain	106.17 mg/L	6.3-39.0 mg/L
Lambda light chain	43.46 mg/L	5.9-36.7 mg/L
Kappa/lambda ratio	2.44	0.46-2.62a
Urine Bence-Jones protein	Negative

NT-proBNP demonstrated an upward trend peaking at 11,204 ng/L on the final days of his life when he developed Society for Cardiovascular Angiography and Interventions stage D cardiogenic shock triggered by sepsis.

^aAdjusted for estimated glomerular filtration rate 45-59 mL/min/1.73 m².

Figure 6.

^99mTechnetium Labeled 3,3-Diphosphono-1,2-Propanodicarboxylic Acid Scintigraphy Illustrating Perugini Grade 3 Myocardial Uptake on Whole-Body Planar Imaging Using a Single-Photon Emission Computed Tomography-Computed Tomography Scanner

During his inpatient admission for transplant assessment, he underwent hemodynamic assessment by right heart catheterization supported by intravenous dopamine. This confirmed a left-to-right shunt (Qp:Qs 2.2:1) with combined pre- and postcapillary pulmonary hypertension (mean pulmonary artery pressure 48 mm Hg; mean pulmonary capillary wedge pressure 26 mm Hg; pulmonary vascular resistance 2.75 Wu). This hemodynamic profile reflected his dual pathology. Classically, an infundibular stenosis protects the pulmonary vasculature from pulmonary overcirculation; however, the development of p.(V142I)-ATTRv-CM in our patient resulted in elevated left ventricular filling pressures, thus increasing the left-to-right shunt through the unrestricted ventricular septal defect and flow to the pulmonary circulation.

Management

On admission to the regional center (Table 2), the patient was in stage C cardiogenic shock according to the Society for Cardiovascular Angiography and Interventions SHOCK staging system.¹ He was promptly optimized on dopamine and intravenous diuretic therapy resulting in transient improvement in organ perfusion. He subsequently underwent a comprehensive pretransplant evaluation including invasive hemodynamic assessment and psychosocial evaluation. Social assessment revealed that the patient lived alone in temporary accommodation with limited social and logistical support—factors deemed likely to complicate post-transplant care and adherence to medication.

Table 2.

Timeline of Significant Events

Time	Event
2022-2025	Emigrated from Nigeria to the United Kingdom. Diagnosed with TOF-type DORV by local ACHD team. Multiple hospital admissions with decompensated cardiac failure. Lost to follow-up due to challenging social circumstances.
April 2025	Relocation and re-established contact with local ACHD team. Abnormal monoclonal gammopathy screen. CMR: extensive LGE pattern characteristic of amyloidosis; ECV 56%.
May 2025	Bone marrow trephine: No evidence of plasma cell dyscrasia, Congo Red stain negative.
July 2025	99m technetium-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade 3 suggesting ATTR-CM. Referral to regional amyloid service.
Hospital admission
September 10, 2025	Admitted with SCAI class C cardiogenic shock.
September 26, 2025	Right heart catheterization confirmed left-to-right shunt and combined pre- and postcapillary pulmonary hypertension.
October 6, 2025	Homozygosity for TTR mutation encoding Val142Ile (p.V142I) confirmed.
October 15, 2025	Progression of cardiogenic shock to SCAI class D.
October 17, 2025	Palliative approach to care and patient's death.

ACHD = adult congenital heart disease; ATTR-CM = transthyretin amyloid cardiomyopathy; CMR = cardiac magnetic resonance imaging; DORV = double outlet right ventricle; ECV = extracellular volume; LGE = late gadolinium enhancement; SCAI = Society for Cardiovascular Angiography and Interventions; TOF = Tetralogy of Fallot; TTR = transthyretin.

Meanwhile, the patient developed sepsis secondary to hospital-acquired pneumonia and progressive hemodynamic deterioration to Society for Cardiovascular Angiography and Interventions stage D cardiogenic shock. Temporary mechanical circulatory support was not technically feasible either centrally or peripherally because of cardiac (bidirectional unrepaired shunt) and peripheral vascular anatomy (small-caliber femoral arteries), respectively. Given the combination of hemodynamic instability, prohibitive anatomic constraints, and inadequate social support, the cardiac transplant MDT concluded that he was not a candidate for advanced heart failure therapies including durable mechanical circulatory support or transplantation.

Outcome and Follow-Up

Despite optimal supportive measures, the patient's condition progressively worsened. Focus of care was redirected toward palliation and symptom relief; he died shortly thereafter. Three months later his surviving first-degree relatives were invited to undergo presymptomatic cascade genetic screening.

Discussion

ATTRv-CM, caused by p.(V142I) mutation, is a rare autosomal dominant hereditary form of cardiac amyloidosis. Unlike the sporadic ATTRwt-CM, it presents earlier and progresses more aggressively. To our knowledge the coexistence of ATTRv-CM with TOF-type DORV has not been previously described. Our case highlights the fulminant course of p.(V142I)-ATTRv-CM in a homozygous carrier with coexisting complex congenital heart disease and therapeutic challenges in end-stage heart failure.

The p.(V142I) variant is the commonest TTR variant in the United States with a prevalence of 3% to 4% in individuals of African descent; approximately 1 in 5,000 individuals are homozygous carriers of p.(V142I)-ATTRv.^2,3 Homozygous carriers exhibit higher disease penetrance and a more aggressive phenotype, typically presenting with advanced cardiomyopathy and a 10-year reduction in median survival compared with heterozygous carriers.^3,4 In our homozygous patient with p.(V142I)-ATTRv-CM, cardiac infiltration and associated dysfunction was the primary driver of his rapid clinical decline, consistent with a more aggressive phenotype compared with that of wild-type ATTR-CM.⁴ His congenital heart disease contributed cumulatively to mortality over time through progressive heart failure. Advancing age and the failure to achieve repair before the onset of pulmonary hypertension served as negative prognostic indicators based on observations derived from a retrospective review of 254 adult survivors of DORV.⁵

This case is atypical as this patient had coexisting complex congenital heart disease, which led to diagnostic pitfalls. The DORV with bidirectional shunt provided an alternative explanation for symptoms of decompensated cardiac failure and some of the structural changes observed on TTE. However, the increase in left ventricular wall thickness could not be attributed to abnormal loading conditions alone and was discrepant with the low-voltage QRS complexes detected on electrocardiogram. CMR provided additive information through tissue characterization, phenotypic differentiation, and exclusion of phenocopies such as sarcoidosis. Overall, this patient exhibited imaging features consistent with an advanced amyloid cardiomyopathy, as is often associated with the p.(V142I) TTR variant by the time of diagnosis resulting in poor functional status and high mortality.⁴

Cardiogenic shock is a rare presentation in ATTRv-CM but signals advanced disease that heralds a poor prognosis. Case series have reported that patients with ATTR-CM requiring vasoactive support for cardiogenic shock experience in-hospital mortality rates approaching 40%.⁶ Impaired left ventricular ejection fraction was predictive of mortality, and in our patient, the coexisting unrepaired DORV conferred additional prognostic burden. Although TTR-directed therapies have an established benefit, outcomes are still poor when started in patients diagnosed late with advanced disease when heart transplantation should be considered.^7,8 In a multicenter study spanning 3 decades, Razvi et al⁹ demonstrated cardiac transplantation for ATTR-CM improves survival (100% 1-year, 90% 5-year) with negligible risk of cardiac allograft amyloid recurrence in the short and medium term. In our case, the patient experienced rapid clinical deterioration and significant social constraints precluded cardiac transplantation.

Social determinants of health significantly influenced this patient's adverse outcome alongside the aggressive disease biology. Data from the UK National Health Service, with free at the point of use health care, demonstrated that patients with p.(V142I) with ATTRv-CM attended health care providers as frequently as ATTRwt-CM patients before diagnosis, supporting the concept that disease phenotype drives disparities in outcome.⁴ Meanwhile, data from the United States highlighted the influence of low socioeconomic status, measured by area deprivation index, in determining adverse outcomes, which were observed predominantly in Black patients.¹⁰ We can therefore postulate that our patient's challenging social circumstances likely contributed to delays in diagnosis and initiation of disease-modifying therapies. Given the higher prevalence of the p.(V142I) variant in individuals of African ancestry, these observations highlight the potential impact of social determinants of health on disease trajectory and signal an unmet need to improve outcomes among this cohort.

Conclusions

Homozygous p.(V142I)-ATTRv-CM manifests earlier and progresses more rapidly compared with other forms of ATTR-CM. The presence of coexisting congenital heart disease can hinder early recognition of infiltrative cardiomyopathy. However, timely diagnosis provides opportunities to intercede in disease progression through disease-modifying therapies and to plan advanced heart failure strategies.

Visual Summary.

Flow Diagram Illustrating the Journey to Diagnosing Cardiac Amyloidosis in a Homozygous Carrier of the p.(V142I) TTR Variant With Concomitant Double Outlet Right Ventricle With Tetralogy of Fallot-type (TOF-type DORV) Physiology

^99mTc-DPD = ^99mTechnetium labeled 3,3-diphosphono-1,2-propanodicarboxylic acid; ATTRv-CM: variant transthyretin amyloid cardiomyopathy; CMR = cardiac magnetic resonance; ECV = extracellular volume; MDT = multidisciplinary team meeting; NR = normal reference range; RV = right ventricle; TTR = Transthyretin.

Funding Support and Author Disclosures

There was no specific funding for this study. An existing joint working collaborative agreement exists between University Hospitals Birmingham NHS Foundation Trust and Pfizer. Dr Moody is supported by a Clinical Research Scholars Award from the National Institute for Health and Care Research and has received consulting fees from Alnylam, AstraZeneca, Bayer, Bristol Myers Squibb, Ionis Pharmaceuticals (formerly Akcea), and Pfizer. Dr Fontana receives an intermediate fellowship salary from the British Heart Foundation and has received consulting fees from and/or service on advisory boards for Alnylam Pharmaceuticals, Alexion/Caelum Biosciences, AstraZeneca, Eidos/BridgeBio Pharma, Prothena, Attralus, Intellia Therapeutics, Ionis, Cardior, Lexeo Therapeutics, Janssen Pharmaceuticals, Prothena, Pfizer, Novo Nordisk, Bayer, and MyCardium; research grants from Alnylam Pharmaceuticals, BridgeBio Pharma, AstraZeneca, and Pfizer; share options in Lexeo Therapeutics; and has shares in MyCardium outside the submitted work. Dr Gillmore has received consulting fees from Alnylam Pharmaceuticals, Attralus, BridgeBio Pharma, AstraZeneca, Pfizer, Ionis, Lycia, and Intellia Therapeutics and an investigator-led study grant from Alnylam Pharmaceuticals outside the submitted work. Dr Steeds has received consulting fees from AstraZeneca and speaker/conference fees from Alnylam, AstraZeneca, Bayer, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Take-Home Messages

• •Dual pathology can coexist in patients with complex congenital heart disease, which can mask disease progression and delay the diagnosis of cardiac amyloidosis; a high index of suspicion is required in patients presenting with disproportionate hypertrophy, persistently elevated cardiac biomarkers, and recurrent decompensation.
• •The homozygous p.V142I ATTRv-CM is an aggressive form of cardiac amyloidosis that presents in younger age groups, warranting early initiation of disease-modifying therapies, and advanced heart failure review and transplantation assessment.
• •Any patient with unexplained increase in myocardial wall thickness, even among those with preexisting complex congenital heart disease, should prompt consideration for contrast-enhanced CMR to exclude infiltrative disease.

Appendix

Video 1

Parasternal Long-Axis View Demonstrating Septal Hypertrophy With Interventricular Septal Wall Thickness in End-Diastole (IVSd) of 17 mm, a Large Ventricular Septal Defect (VSD), and an Aorta That Overrides the Right Ventricle by More than 50%

Video 2

Parasternal Long-Axis View With Color Doppler Demonstrating Bidirectional Flow Across the VSD

Video 3

Modified Short-Axis View Demonstrating an Overriding Aorta, Dilated Right Atrium, and Severe Infundibular Stenosis

Video 4

Modified Short-Axis View With Color Doppler Demonstrating Right Ventricular Outflow Tract Turbulence and Pulmonary Valve Maximum Velocity = 3.9 m/s

Video 5

Apical 4-Chamber View Demonstrating Hypertrophy of Both Left and Right Ventricles; an Impaired Left Ventricular Ejection Fraction of 49% and Reduced Global Longitudinal Strain of −9.3%

Both atria are dilated (indexed right atrial area = 15.4 cm²/m², indexed left atrial volume = 34.0 mL/m²).

Video 6

Modified Apical 4-Chamber View of the Right Ventricle (RV) Illustrates a Hypertrophied RV Free Wall With Impaired RV Systolic Function (Tricuspid Annular Plane Systolic Excursion = 14 mm, S′ Velocity 7.4 cm/s, and RV Fractional Area Change of 20%)