Smartwatch-Detected Sinus Tachycardia Unmasking AL Cardiac Amyloidosis in a Young Adult

Abstract

Background

The clinical presentation of immunoglobulin light-chain (AL) can be very heterogenous resulting in delayed diagnosis and treatment. The use of wearable health technology is rapidly expanding. This case explores the important role this technology can play in the diagnosis of cardiac amyloidosis particularly in younger adults.

Case Summary

A 36-year-old woman presented with frequent high heart rate alerts on her smartwatch with mild nonspecific symptoms. Further investigations led to cardiac magnetic resonance imaging that raised suspicion for amyloidosis with Mayo Clinic stage III immunoglobulin A lambda AL cardiac amyloidosis confirmed on laboratory and histological testing. The sinus tachycardia was attributed to atrial amyloid infiltration. Plasma cell therapy resulted in an excellent cardiac and hematological response with normalization of resting sinus heart rates.

Discussion

This case highlights an atypical presentation of cardiac AL amyloidosis. Smartwatch monitoring and alerts were central to early diagnosis and treatment.

Take-Home Messages

This case demonstrates the potential role that wearable-technology has in early detection of AL cardiac amyloidosis. To achieve a timely diagnosis of AL cardiac amyloidosis, physicians should remain inquisitive; subtle abnormalities in cardiac biomarkers or electrocardiograms should prompt further investigation.

Visual Summary

Visual Summary.

Sinus Tachycardia Unmasking Al Cardiac Amyloidosis

Created with BioRender.

History of Presentation

A 36-year-old woman was receiving frequent high resting heart rate alerts from her smartwatch over a 3-month period that prompted her to consult her primary care physician with subsequent cardiology referral. This alert is triggered when the optical sensor of the smartwatch detects a resting heart rate exceeding a default threshold of 120 beats/min for 10 minutes while inactive.¹ Rhythm strips recorded with the watch showed sinus tachycardia. She had experienced some palpitations and fatigue in the preceding months that she attributed to working in a stressful environment. Review of her longitudinal smartwatch heart rate trends demonstrated a progressive rise in median resting heart rate over the preceding 2 years (Figure 1). Clinical examination was normal. Resting 12-lead electrocardiogram showed sinus tachycardia at 108 beats/min with low limb-lead voltage, Q waves in the anterior precordial leads, and inferolateral T wave inversion (Figure 2). Cardiac biomarkers were abnormal with a moderately elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) of 1,193 ng/L (normal <300) and a minimally elevated high-sensitivity troponin I of 19 ng/L (normal <16). Additional laboratory investigations, including thyroid function tests and hemoglobin, were within normal range. A limited echocardiogram showed preserved biventricular function with normal wall thickness; interventricular septal wall 1.06 cm and left ventricular posterior wall 1.14 cm in diastole. Cardiac magnetic resonance imaging (MRI) was arranged.

Figure 1.

Scatter Plot of Smartwatch Recorded Resting Heart Rates Before Presentation

Continuous red line indicates 7-day rolling hourly median daytime trend.

Figure 2.

Electrocardiogram at Presentation Showing a Resting Sinus Tachycardia of 109/minute, Anterior Q Waves, Inferolateral T Wave Inversion and Low Limb-Lead Voltage

Past Medical History

The patient had attended a cardiologist 2 years previously for evaluation of chronic palpitations prompted by occasional resting high heart rate alerts from her smartwatch. Electrocardiogram was normal and a 24-hour Holter monitor showed intermittent sinus tachycardia with average heart rate of 88 beats/min and <1% premature ventricular complex burden. An echocardiogram demonstrated normal systolic function with normal wall thickness.

Differential Diagnosis

The differential diagnosis at this juncture includes an emerging cardiomyopathy. The persistent sinus tachycardia has many potential etiologies including endocrinopathy, autonomic dysfunction, an atrial myopathy, or a benign inappropriate sinus tachycardia. Given the broad differential, cardiac imaging is essential to further evaluate.

Investigations

A gadolinium contrast-enhanced cardiac MRI was performed 1 week after her initial review (Siemens Avanto 1.5 T). This demonstrated normal biventricular volumes with preserved systolic function (left ventricular ejection fraction 68%, right ventricular ejection fraction 73%). There was mild basal septal left ventricular hypertrophy (14 mm at end-diastole) (Figure 3A). Atrial volumes were normal. Inversion time scout showed normal gadolinium kinetics. Late gadolinium enhancement imaging (LGE) was degraded by artifact with a suggestion of enhancement of the basal inferolateral wall (Figure 3B). The suspicion was of an early hypertrophic cardiomyopathy. However, given the suboptimal LGE imaging on an older MRI scanner, the patient was recalled for repeat focused LGE imaging with parametric mapping.

Figure 3.

Cardiac MRI Images

Cardiac MRI findings at baseline showing (A) basal septal hypertrophy at end-diastole (red arrow); (B) reduced quality short-axis late gadolinium enhancement (LGE) image showing basal inferolateral wall enhancement (yellow arrow); (C) repeat magnetic resonance imaging with improved quality short-axis LGE image demonstrating nonischemic enhancement of the basal left ventricle (blue arrow); and (D) 4-chamber LGE image with darkened blood pool and atrial enhancement (white arrow).

Repeat MRI was performed 2 months later on a newer MRI scanner (Siemens Sola 1.5 T) with unchanged morphological findings as before. Parametric mapping showed diffusely elevated native T1 values (1,117 ± 104 ms) in a mid-septal region of interest with an elevated extracellular volume fraction of 45% ± 4%. On high-quality LGE imaging, there was circumferential subendocardial enhancement of the basal mid-left ventricle extending transmurally in the basal-mid inferolateral and inferior segments. There was also patchy right ventricular and diffuse atrial enhancement with a darkened appearance of the blood pool (Figures 3C and 3D). The findings were suspicious for amyloid infiltration, a diagnosis that had not been considered in this patient's case up to this point.

A paraprotein screen was prompted by the MRI findings. An immunoglobulin A lambda monoclonal band was present on serum immunofixation with a paraprotein level of 2 g/L. Lambda free light chains were severely elevated at 255 mg/L (normal 5.7-26.3) compared with normal kappa free light chains of 7.3 mg/L (normal 3.3-19.4), yielding an abnormal kappa lambda ratio of 0.03 in the setting of normal renal function. NT-proBNP had risen to 2,150 ng/L.

The patient was admitted for urgent evaluation of immunoglobulin light-chain (AL) amyloidosis. Strain echocardiography showed reduced global longitudinal strain of −12.1% with the characteristic apical-sparing pattern of amyloidosis (Figure 4A). Cardiac output was normal at 6.7 L/min during right heart catheterization. Endomyocardial biopsy confirmed myocardial amyloid deposits with positive Congo red staining. Immunohistochemistry was diagnostic for lambda AL amyloidosis. A bone marrow aspirate and trephine biopsy demonstrated 70% plasma cells.

Figure 4.

TTE Global Longitudinal Strain Images

Global longitudinal strain (GLS) polar plot (A) showing reduced GLS with apical-sparing pattern before treatment initiation and (B) improved GLS after 2 years of treatment.

Management

The patient's biomarkers were in keeping with Mayo Clinic stage III disease. Inpatient antiplasma cell therapy was commenced with cyclophosphamide, bortezomib, dexamethasone, and daratumumab (Figure 5). On telemetry monitoring, the patient had a persistent resting sinus tachycardia up to 130 beats/min without other conduction system disease or other features of autonomic dysfunction. Her sinus tachycardia was attributed to atrial amyloid myopathy rather than a compensatory sinus tachycardia given her normal cardiac output. Ivabradine was added with good response. She was commenced on a sodium-glucose cotransporter 2 inhibitor and a mineralocorticoid receptor antagonist. During follow-up she had symptomatic short episodes of nonsustained ventricular tachycardia. Ivabradine was changed to bisoprolol 3 months into treatment and a transvenous implantable cardioverter-defibrillator was inserted.

Figure 5.

Longitudinal Serum Lambda Free Light Chains and NT-proBNP Levels and Response to Al Amyloidosis Treatment

NT-proBNP = N-terminal pro–B-type natriuretic peptide. Created with BioRender.

The patient achieved a hematological very good partial response and was transitioned to maintenance monthly daratumumab approximately 10 months into her treatment course. Oral lenalidomide was subsequently added.

Outcome and Follow-Up

The patient remains on lenalidomide and monthly daratumumab and has achieved a hematological complete response. She has had a very good cardiac response to her plasma cell treatment with a 79% reduction in NT-proBNP and an improvement in her global longitudinal strain to –15% after 24 months of treatment (Figures 4B and 5). In tandem with this, her heart rate trend from her Apple Watch has shown a progressive normalization of her resting heart rate over the 2.5-year period since commencing treatment (Figure 6). She has not required a loop diuretic, had a heart failure hospitalization, or required treatment from her implantable cardioverter-defibrillator. She remains functionally very well and active with resolution of her palpitations.

Figure 6.

Scatter Plot of Smartwatch Recorded Resting Heart Rates Over the 2-Year Period Following Diagnosis and Initiation of Treatment

Continuous red line indicates 7-day rolling hourly median daytime trend.

Discussion

The prognosis of AL cardiac amyloidosis is heavily dependent on the stage of disease at diagnosis, and the response to therapy.² Mortality remains high, particularly among those with advanced cardiac involvement.³ Due to the nonspecific nature of presentation, diagnosis is often missed or made in late-stage disease with delayed treatment having devastating consequences.

Our case represents an unusual presentation of AL cardiac amyloid in a young adult with medical contact prompted by frequent high heart rate alerts from their smartwatch over a prolonged period. This led to early diagnosis and initiation of treatment before the typical presentation in later-stage disease.⁴

This case highlights a number of important points. First, the patient was well below the mean age of diagnosis of 63 years for this condition,⁴ reinforcing the potential for AL amyloid to occur in young adults particularly with atypical presentations such as in this case, which has the potential to delay diagnosis. Second, it highlights the beneficial role that monitoring of cardiovascular parameters with wearable technology can have in raising suspicion of cardiac disease.

Third, cardiac MRI was central to making the diagnosis of cardiac amyloidosis in this case and it demonstrates the improved diagnostic utility of high-quality MRI with parametric imaging particularly in early-stage cardiomyopathies with subtle or atypical presentations. In our case, the initial cardiac MRI demonstrated normal gadolinium kinetics; however, the study quality was impacted by artifact, prompting further evaluation. It is possible that over the following 2-month period there was progression in amyloid fibril deposition such that repeat imaging demonstrated a notable change in the extracellular volume (ECV) fraction and LGE burden. The repeat cardiac MRI showed classical changes of AL amyloid; markedly raised native T1 and ECV fraction increased to a lesser extent.⁵ Emerging research has shown that ECV mapping can prognosticate in AL amyloid, with the potential to guide treatment pathways based on predicted survival.⁶ Given the exponential mortality with a delayed diagnosis of AL amyloid, we advise early consideration for hematological testing in the setting of subtle or atypical cardiac imaging changes.

Although the most common arrhythmia associated with cardiac amyloidosis is atrial fibrillation, elevated resting heart rates have been described.⁷ Potential pathophysiology includes atrial amyloid infiltration, increased atrial pressures due to restrictive filling patterns, and dysautonomia. Our patient had a normal cardiac output at right heart catheterization and as such the tachycardia was unlikely to represent a compensatory response. Formal testing for dysautonomia was not performed. Often beta blockers are poorly tolerated in cardiac amyloidosis and given concerns for conduction system disease they are used with caution. Our patient responded well to the sodium (I_f) channel inhibitor ivabradine; a retrospective review of ivabradine in ATTR amyloid patients with sinus tachycardia highlighted good tolerance and clinical response.⁸

Conclusions

The availability and use of wearable health technology has rapidly expanded. This case demonstrates how high heart rate alerts on a wearable device prompted concern in both the patient and clinician, ultimately leading to a critical diagnosis of AL amyloidosis and early initiation of treatment with excellent clinical outcomes.

Given the aggressive nature of AL cardiac amyloidosis, it is necessary for clinicians to remain vigilant to atypical or subtle presentations, acknowledging it as the “the great imitator.”

Take-Home Messages

• •This case highlights the important role that wearable health technology can play in making an early time-sensitive critical diagnosis of AL cardiac amyloidosis.
• •The diagnosis of cardiac amyloidosis requires clinicians to remain vigilant and inquisitive; subtle abnormalities in cardiac biomarkers and electrocardiograms should prompt further investigation.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.