Left Ventricular Hypertrophy

Left Ventricular Hypertrophy as a Marker of Cardiac Involvement in AL Amyloidosis

Introduction

AL (primary) amyloidosis is a systemic illness with deposition of misfolded immunoglobulin light chain amyloid fibrils in multiple organs, including the heart, kidneys, liver, and gastrointestinal tract. Cardiac involvement is a key predictor of morbidity and mortality.

Left ventricular hypertrophy (LVH) on echocardiography is a characteristic finding of cardiac amyloidosis, representing infiltrative myocardial deposition of amyloid fibrils. Awareness of LVH in the setting of systemic AL amyloidosis is important for:

Early recognition of cardiac involvement
Prognosis
Selection of therapy
Monitoring of therapy response
This complete guide addresses:
Pathophysiology of cardiac involvement in AL amyloidosis
Diagnostic strategies to LVH in amyloidosis
Clinical presentation and complications
Prognostic significance
Management approaches and therapeutic implications
Directions for future research on cardiac amyloidosis

Epidemiology of Cardiac Involvement

Cardiac involvement is present in ~50% of AL amyloidosis patients.
LVH is among the most frequent echocardiographic findings.
With increasing older age and greater systemic amyloid burden, there is increased prevalence.
Male predominance reported in some reports.

Risk Factors for Cardiac Amyloidosis

Increased circulating free light chains
Prolonged delay in diagnosis of AL amyloidosis
Multi-organ involvement, especially renal and hepatic
Genetic variants that affect amyloidogenic potential

Pathophysiology of Left Ventricular Hypertrophy in AL Amyloidosis

Mechanisms of LVH

Amyloid infiltration:

Extracellular deposition of light chain fibrils in myocardial interstitium
Results in augmented ventricular wall thickness with no actual myocyte hypertrophy

Myocardial stiffening:

Impacts diastolic relaxation, leading to diastolic heart failure
Residual ejection fraction in early phases

Microvascular involvement:

Amyloid deposits in coronary arterioles decrease perfusion
Also leads to ischemia and fibrosis

Neurohormonal activation:

Long-term myocardial stress initiates fibrosis and LV remodeling

Pathologic Features

Symmetric LV hypertrophy
Interstitial amyloid deposits
Inflammatory infiltration is minimal
Sparing of epicardial coronary arteries early on

Clinical Manifestations

Early Cardiac Symptoms

Fatigue and intolerance to exercise
Mild dyspnea with exertion
Palpitations or asymptomatic LVH

Advanced Cardiac Symptoms

Congestive heart failure (diastolic, preserved EF)
Peripheral edema and ascites
Pulmonary congestion
Arrhythmias (atrial fibrillation, conduction blocks)
Syncope or presyncope

Red Flags for Cardiac Amyloidosis

LVH on echocardiogram with low-voltage ECG
Discrepancy between wall thickness and QRS amplitude
Rapidly progressive heart failure in older adults

Diagnostic Evaluation

Echocardiography

Imaging modality of first choice for the detection of LVH
Suggestive findings of cardiac amyloidosis:
Symmetric wall thickening of the LV
Biatrial enlargement
Diastolic dysfunction (restrictive filling pattern)
Speckled or granular appearance of the myocardium

Electrocardiography (ECG)

Low-voltage QRS complexes in the presence of LVH
Pseudoinfarction patterns (Q waves in the absence of CAD)
Conduction disturbances (bundle branch blocks, AV block)

Cardiac Biomarkers

NT-proBNP: Raised due to myocardial stress
Troponin T/I: Suggests chronic myocardial injury
Light chain ratio: Establishes systemic amyloidosis

Cardiac MRI

Late gadolinium enhancement demonstrates diffuse subendocardial or transmural deposition
Measures myocardial involvement
T1 mapping and extracellular volume fraction measure amyloid burden

Endomyocardial Biopsy

Definitive gold standard diagnosis
Establishes amyloid deposition in myocardial tissue
Congo red staining and mass spectroscopy employed for amyloid typing

Prognostic Implications

Cardiac involvement is the greatest predictor of mortality for AL amyloidosis
Median survival:
In the absence of cardiac involvement: ~4 years
With cardiac involvement: 6–12 months
LVH is associated with:
Greater risk of heart failure
Higher NT-proBNP and troponin levels
Reduced response to chemotherapy

Mayo Clinic Staging

Includes NT-proBNP, troponin, and free light chain difference
Higher stage predicts poorer prognosis
LVH frequently parallels advanced stages

Treatment Strategies

General Principles

Early identification of LVH enables timely initiation of treatment
Multi-disciplinary management involving hematology, cardiology, nephrology

Disease-Modifying Therapy

Bortezomib-based regimens: First-line treatment of choice
Cyclophosphamide + dexamethasone in patients with hepatic or renal impairment
Autologous stem cell transplant in selected individuals
Choice of treatment based on degree of cardiac involvement

Heart Failure Management

Diuretics: Manage congestion, mindful of avoiding hypotension
Beta-blockers and ACE inhibitors: With caution, usually ill-tolerated
Pacemakers or ICDs: In arrhythmias or conduction abnormalities

Advanced Interventions

Heart transplantation in solitary cardiac amyloidosis (exceptional)
Combined organ transplant (heart and kidney) for multi-organ failure

Case Studies

Patient X:

61-year-old man with LVH, dyspnea, and nephrotic-range proteinuria
Echocardiogram: Symmetric LV thickening
Outcome: Poor, died within 6 months despite treatment

Patient Y:

Incidental finding of early LVH on echocardiogram
Aggressive chemotherapy given
Outcome: Stabilization and better cardiac biomarkers

Patient Z:

Advanced LVH with low-voltage ECG and arrhythmias
Multidisciplinary treatment and palliative management
Outcome: Symptom control, median survival ~3 months

Clinical Pearls

AL amyloidosis LVH is infiltrative cardiomyopathy, rather than usual hypertrophy
Echocardiographic thickening of the LV wall with low-voltage ECG is extremely suggestive
Early diagnosis profoundly affects choice of therapy and prognosis
Multi-organ evaluation is essential for wholesome management
Palliative treatment should be considered in advanced disease with extreme LVH

Future Directions

New treatments: Monoclonal antibodies that specifically target amyloid fibrils (e.g., CAEL-101)
Imaging advances: T1 mapping, strain imaging for early detection
Biomarkers: NT-proBNP and troponin kinetics for monitoring response to therapy
Genetic studies: Elucidating light chain amyloidogenic variants
Personalized medicine: Therapy according to severity of LVH and amyloid burden

Conclusion

Left ventricular hypertrophy is a critical indicator of cardiac involvement in AL amyloidosis. Diagnosing LVH in systemic amyloidosis:

Allows earlier diagnosis
Informs risk stratification and choice of therapy
Allows prediction of prognosis and survival
Facilitates planning for multidisciplinary care
Early identification of LVH can significantly impact patient outcomes by allowing timely intervention and careful monitoring of cardiac function in AL amyloidosis.

Left Ventricular Hypertrophy