Exploring the causes of stiff left atrial a case series

Authors: Sukriti Banthiya, Medhat Chowdhury, Dhruva Govil, Harsh Thacker, Souheil Saba

Abstract

Background

Stiff left atrial syndrome (SLAS) is a complication that occurs due to left atrial scarring following procedures such as radiofrequency catheter ablation for atrial fibrillation.

Case summary

We present a series of four patients with pre-existing conditions that ultimately were diagnosed as SLAS. In each case, clinical manifestations of SLAS may overlapped with other conditions and required a high index of clinical suspicion and diligent hemodynamic assessment to differentiate it from other concomitant cardiac conditions.

Discussion

We aim to highlight key differentiating diagnostic features from overlapping cardiac conditions and to summarize current treatment options for patients with SLAS.

Introduction

Heart failure with preserved ejection fraction may occur in conditions unrelated to ventricular diastolic function, rather may be due to impairment of left atrial structure and function. This is referred to colloquially as stiff left atrial syndrome (SLAS).^1^ First documented in 1988, the diagnosis of SLAS presents challenges due to its non-specific symptoms and overlap with other cardiac conditions.^2^ Furthermore, the limited awareness among healthcare professionals about this condition may result in under-recognition, misdiagnosis, and mistreatment. Our case series aims at highlighting the possible etiologies, keys to diagnosis, and management strategies for this complex condition.

Summary figure

Patient 1

A 75-year-old male with permanent atrial fibrillation presented with dyspnea and orthopnea. He had previously undergone a bioprosthetic mitral valve replacement (MVR) for severe mitral regurgitation (MR), maze procedure and left atrial appendage closure 6 years ago. Transthoracic echocardiogram (TTE) revealed an enlarged left atrium, preserved left ventricular function, and mitral valve bioprosthesis without dehiscence, stenosis, or regurgitation. NT-ProBNP level was 500 pg/mL (Reference 0–852). Electrocardiogram (ECG) demonstrated atrial fibrillation. The pulmonary artery pressure was elevated at 65 mmHg along with moderately dilated right atrium and ventricle. Diagnostic right heart catheterization (RHC) revealed pulmonary artery (PA) hypertension (44 mmHg), pulmonary capillary wedge pressure (PCWP) (32 mmHg) with large V waves (54 mmHg). A diagnosis of SLAS was made and the patient was treated with bumetanide and spironolactone. Despite medical intervention with diuretics, he developed gradually progressive heart failure with cardiac cirrhosis, portal hypertension and hepatic encephalopathy. He died 4 years later.

Patient 2

A 77-year-old female with severe pulmonary hypertension in the setting of severe mitral valve stenosis presented with dyspnea on exertion. ECG demonstrated Mobitz type 1 AV block. RHC showed PA pressure 45 mmHg, PCWP 25 mmHg, and left ventricular end diastolic pressure 11 mmHg. She underwent an MVR but had persistent pulmonary hypertension after the procedure. RHC after MVR showed PA pressure (55 mmHg), PCWP (25 mmHg), and large V waves in the absence of MR or ventricular septal defect suspicious for SLAS. TTE showed biventricular heart failure with reduced ejection fraction (20%–25%). Left Heart Catheterization (LHC) demonstrated severe left main and triple vessel disease. She was treated with Furosemide, Carvedilol, Lisinopril and spironolactone, and Diltiazem was discontinued. The patient died of a cardiac arrest due to a presumed myocardial infarction 1 year later.

Patient 3

A 68-year-old female with permanent atrial fibrillation and history of radiotherapy for right breast cancer presented with worsening isolated dyspnea on exertion. NT-ProBNP was 605 pg/mL (reference 0–353 pg/mL). ECG demonstrated atrial fibrillation. TTE showed severe right and left atrial dilation with no mitral regurgitation. An RHC was performed which demonstrated moderate PA hypertension (29 mmHg), PCWP (52 mmHg) with giant V waves apparent on the tracing (Supplementary material online, Figure 5C). A transesophageal echocardiogram (TEE) showed no significant mitral regurgitation and the presence of systolic blunting of the pulmonary vein flow (Supplementary material online, Figure 6A and 6B) consistent with SLAS. There was no history of atrial ablation, prior atriotomy, or open heart surgery; hence radiotherapy was suspected as the unique predisposing factor. The patient symptoms were medically managed with Bumetanide and Spironolactone.

Patient 4

A 73-year-old male with persistent atrial fibrillation, history of aortic, and MR with mechanical mitral and aortic valve replacement presented with dyspnea. TTE revealed enlarged left atrium, preserved left ventricle function and mechanical mitral valve prosthesis without dehiscence, stenosis, or regurgitation. He underwent an RHC which showed PA pressure (34 mmHg), PCWP (30 mmHg) with large V waves suggestive of SLAS. The patients’ symptoms improved with initiation of Spironolactone and he has not been hospitalized for heart failure exacerbation.

Discussion

We aim to highlight with our case series, potential mechanisms that could lead to the development of SLAS. SLAS has been recognized as a complication following procedures such as MVR, MAZE procedure, and radiofrequency catheter ablation (RFCA), as seen with Patient 1 in our case series.^2,3^ In a study by Gibson et al.^3^, 1.4% of patients who underwent RFCA developed SLAS. It is hypothesized that the formation of an iatrogenic scar in the left atrium (LA) following ablative procedures leads to loss of contraction, development of prominent V waves on LA pressure tracings, reduced response to LA baroreceptors, and decreased compliance with elevated pulmonary venous pressures.^1^ The added insult in case one may be due to surgical appendage closure, as has been reported previously.^4^ This may be explained by the loss of the capacitance function of the left atrial appendage and impaired hemodynamic response to pressure–volume overload in patients who undergo left atrial appendage occlusion. A recent study by Kim et al.^5^ supported this hypothesis, however, the association of left atrial appendage occlusion with clinical heart failure remains controversial.

In patients with mitral stenosis and severe mitral regurgitation (Patients 2 and 4), SLAS may develop due to chronic remodeling as a result of chronic overstretching and ultimately scar formation.^3,6,7^ Observations from recent papers suggest atrial fibrillation and MR may create a self-sustaining cycle by inducing atrial myopathy.^8^ While there is literature to support the presence of this phenomenon, there is a paucity of data with regard to the proportion and outcomes of patients who undergo surgery with pre-existing LA scarring. The ALIVE trial aims to investigate the impact of pre-existing atrial fibrosis on post-surgical outcomes.^9^

The third case highlights an unusual suspect, radiotherapy induced SLAS. In current literature, there is only a single reported case of SLAS after radiotherapy for breast cancer that was found to have occurred in close temporal association with radiotherapy.^10^ Our case suggests that patients may remain at increased risk even if free of the disease early after radiation. Furthermore, In a pilot study of seven patients by Huang et al.^11^, a significant dose–dependent relationship was found between LA scar appearance in Late Gadolinium Enhancement-Magnetic Resonance Imaging (LGE-MRI) and patients with history of external beam radiation therapy (EBRT) regardless of time between EBRT and LGE-MRI assessment. Although speculative, the late effects of EBRT associated with the development of SLAS may be due to chronic remodelling following the initial injury, further propagating fibrosis.

Physician perspective

The key features of SLAS include dyspnea, right heart failure disproportionate to the degree of left heart failure, and pulmonary hypertension. It is characterized by the presence of large V waves (Supplementary material online, Figure 1A) on PCWP tracings in the absence of significant MR, left ventricular diastolic failure, or marked increase in PA pressure.^1^ The diagnostic criteria for SLAS has not been well defined and currently remains a diagnosis of exclusion. Given the limited data on sensitivity and specificity of available diagnostic tools in current literature, inferences are drawn from conditions that share similar pathophysiology that allow identification of surrogate markers of atrial dysfunction. In SLAS, decreased LA compliance due to atrial scarring leads to steepened slope of the pressure–volume curve during atrial filling with resultant increase in left atrial pressure during late systole, post-capillary pulmonary hypertension and markedly elevated V waves. Making a diagnosis of SLAS requires a combination of clinical suspicion, imaging, and hemodynamic assessment to differentiate it from other structural heart diseases that can present similarly. In patients with risk factors and symptoms suggestive of SLAS, the presence of pulmonary hypertension in the absence of severe MR on TTE should prompt consideration for hemodynamic evaluation with RHC. LA function is commonly evaluated with TTE using LA volume, E/e’ and transmitral E gradient. LA expansion index (LAEi) may be a reliable non-invasive parameter for estimation of PCWP.^12^ A recent study showed that LA strain imaging was able to differentiate between stiff LA and those with LV diastolic dysfunction during RHC, highlighting the potential to explore other non-invasive surrogates that may aid in the diagnosis of SLAS.^13^ Echocardiographic features of SLAS include systolic blunting of the pulmonary vein inflow pattern on TEE or S-wave reversal.^14^ These features may also be seen with severe MR, however, prior reports have indicated that the timing of S-wave reversal in SLAS may occur earlier than in MR.^14^ Cardiovascular magnetic resonance imaging (CMR) is the gold standard for LA volumetric quantification. Furthermore, LA late gadolinium enhancement on CMR can detect the extent of atrial fibrosis and has shown strong correlation with LA stiffness index in patients with atrial fibrillation.^15^

In cases of suspected SLAS without prominent PCWP V waves, cardiopulmonary testing with invasive hemodynamic assessment may aid in unmasking presence of V waves during exercise.^1^ The presence of large V waves alone is non-specific and may occur in other conditions such as MR and heart failure with preserved ejection fraction (HFpEF).^1^ Simultaneous measurements of left ventricular end diastolic pressure (LVEDP) via left heart catheterization may be valuable in distinguishing SLAS from HFpEF. A disproportionate elevation in LVEDP compared to PCWP is observed in HFpEF.^1^ Pulmonary vein stenosis, a well-known complication of RFCA ablation for atrial fibrillation, typically shows damping of PCWP or loss of V waves compared with LVEDP and LA pressure on RHC.^16^ In these cases, computed tomography timed for pulmonary vein enhancement or magnetic resonance imaging may be used for delineating the pulmonary vein ostia anatomy to confirm the diagnosis.^1,16^

Diuretics are considered the mainstay treatment and lead to improvement in New York Heart Association functional class.^3^ Effective management of blood pressure can help reduce the burden of left ventricular diastolic dysfunction on the LA, potentially mitigating the progression of SLAS. In patients with symptoms that are refractory to optimal diuretic therapy, the addition of phosphodiesterase inhibitor, sildenafil has shown improvement in exercise capacity and PA systolic pressures.^17^ However, phosphodiesterase inhibitors should be used cautiously as they could potentially precipitate pulmonary edema by increasing venous return to a non-compliant atrium. Surgical interventions such as atrial septostomy may provide clinical benefit for severe cases of SLAS refractory to medical therapy.^18^ It alleviates left-sided pressures by unloading of the LA via a left-right shunt, allowing for LA volume to shift down to the more compliant range in the LA pressure–volume curve. In a recent study, Aslam et al.^18^ demonstrated significant improvement in symptoms and LA hemodynamics with atrial balloon septostomy as a method to relieve LA pressure, though long-term follow up is necessary to evaluate its efficacy and impact on right sided hemodynamics. Interatrial stenting, a procedure found to be effective in patients with HFpEF, can improve the patency of atrial septostomy in SLAS to maintain therapeutic benefit.^19^ In patients with severe symptoms refractory to treatment, heart transplant has been performed with positive clinical outcomes.^20^

Future directions

Several key questions as they pertain to the diagnosis and management of SLAS remain unanswered. Future research efforts must be focused on identifying risk factors for SLAS and their impact on the progression of atrial dysfunction. Prospective studies are also necessary to evaluate the long-term outcomes of interventions targeted at offloading LA pressure in patients with SLAS, such as atrial septostomy and interatrial stents, which have shown promise in cases that are refractory to medical management. Finally, given the growing global burden of atrial fibrillation and increasing use of catheter ablation, there is a pressing need for clinical practice guidelines to address the initial evaluation and treatment algorithms of SLAS, a potential complication.

Supplementary Material