Farbod Raiszadeh, MD, PhD, Luigi Di Biase, MD, PhD, FACC, FHRS, Pasquale Santangeli, MD, Rodney Horton, MD, Conor Barrett, MD, Stephan Danik, MD, Alessandro Paoletti Perini, MD, Francesco Santoro, MD, Sanghamitra Mohanty, MD, Rong Bai, MD, Javier E. Sanchez, MD, J. Joseph Gallinghouse, MD, J. David Burkhardt, MD, Andrea Natale, MD, FACC, FHRS, FESC
A 66-year-old man with hypertension and a history of bilateral hernia surgery was referred to our institution with persistent shortness of breath after two pulmonary vein isolations (PVIs) performed at another institution. At admission, he denied any chest discomfort, palpitations, syncope, or dizziness. The patient’s arrhythmia history started in 2003 when he first developed symptomatic episodes of atrial fibrillation (AF). After determination of normal left ventricular function on echocardiogram, the arrhythmia was initially treated both with propafenone and flecainide at the appropriate doses, but this was ineffective. The patient’s AF became more persistent, and he underwent several cardioversions. In 2006, he underwent his first PVI procedure with no complications. A CT scan performed 3 months after PVI showed no evidence of pulmonary vein (PV) stenosis. Five months after ablation, the patient developed atrial flutter, which required cardioversion. In 2008, the patient underwent a redo PVI procedure.
One month after the redo procedure, the patient started to experience progressively worsening dyspnea on exertion with daily activities such as walking on a flat surface. At admission, the results of blood screening tests and physical examination were normal. To establish the diagnosis, the patient had a CT scan and an echocardiogram 11 months after the redo procedure. The echocardiogram confirmed a normal LV EF but showed an enlarged pulmonary artery with increased pulmonic valve velocities consistent with pulmonary hypertension. There was also evidence of mild right ventricular hypertrophy and mild tricuspid regurgitation.
A transesophageal echocardiogram was performed to better assess the cardiac structures, but this was technically difficult and had suboptimal echocardiographic images. No thrombus was seen in the left atrium or the left atrial appendage. EF was estimated at 60%, and other cardiac structures were poorly visualized. Only the left superior PV was properly visualized and showed increased velocities on its distal portion on Doppler echocardiogram consistent with a significant stenosis. A CT scan was performed showing complete occlusion of the left inferior pulmonary veins (LIPVs) and severe stenosis of both left and RSPV. An enlarged pulmonary artery was also noted (Figures 42-1and 42-2). Due to the presence of significant dyspnea and pulmonary hypertension related to PV stenosis of three PVs, the decision was made to recommend balloon angioplasty and possible stenting of the stenotic PVs. On angiography, the left superior, left inferior, and RSPVs were found severely stenosed (>90%) and were dilated with balloon angioplasty. There was no significant gradient across the stenotic segments following the dilation.
FIGURE 42-1 A 2-D CT scan image showing complete occlusion of the left inferior pulmonary veins (LIPVs) and severe stenosis of both left and right superior pulmonary veins (RSPVs).
FIGURE 42-2 A 3-D CT scan image of the same patient (Figure 42-1) showing an enlarged pulmonary artery due to severe stenosis in three out of the four pulmonary veins.
Pulmonary vein stenosis/occlusion is defined as >70% narrowing of a PV and affects 3.4% of patients following catheter ablation of atrial fibrillation. The incidence of PV stenosis is partly explained by the method of ablation and partly by the experience of the operator and the volume of cases performed.1-3 The incidence rate of PV stenosis is decreasing due to advances in intraprocedural imaging modalities and in improved ablation methods that limit the burning in the antrum of the PV,2 but given the increasing and widespread use of catheter ablation as a treatment modality for atrial fibrillation, the overall incidence of this complication may rise.
ETIOLOGY AND PATHOPHYSIOLOGY
Pulmonary vein stenosis is a clinical condition caused by delivery of radiofrequency energy within or at the orifice of the PVs. The exact etiology and pathophysiology of PV stenosis after catheter ablation of atrial fibrillation is not completely understood. Application of radiofrequency lesions within the PVs or close to the ostium of PVs is the culprit. Animal models of PV stenosis suggest periadventitial inflammation and collagen deposition as the likely mechanisms leading to stenosis formation.4 This is supported by imaging findings of fibrosis in perihilar PV tissues and presence of inflammatory protein precursors in involved PV areas.5-7 Extensive ablation of PVs in dogs was shown to result in necrotic atrial myocardium interspersed with macrophages and red cells after 2 weeks and replacement of necrotic myocardium by collagen and appearance of organized thrombus by 4 weeks. Occlusion of PVs accompanied by cartilaginous metaplasia happens around 6 to 8 weeks, followed by replacement of necrotic atrial muscle with collagenous matrix and neovascularization in about 10 to 14 weeks after ablation.6 The series of steps that lead from the application of radiofrequency energy around or inside the PV ostia to the stenosis of PVs can be summarized as:
• Proliferation of the elastic lamina/intima
• Fibrosis and endovascular contraction
Clinical presentation of PV stenosis is widely variable in patients.1-4 Severe stenosis of a single PV can be asymptomatic in a large number of cases. In symptomatic patients, the clinical presentation of PV stenosis can include any of the following symptoms:
• Chest pain
• Decreased exercise tolerance
• Recurrent lung infection
• Pulmonary hypertension (is rare and requires severe stenosis of multiple PVs)
The severity of clinical symptoms is related to the number of involved PVs, the severity and length of stenosis, and the time course of stenosis formation.4,8
The diagnosis of PV stenosis after catheter ablation of atrial fibrillation relies on a high index of suspicion and obtaining appropriate imaging studies. Misdiagnosis is very common in patients with PV stenosis (pulmonary embolism, lung cancer, pneumonia, and new onset of asthma are most commonly misdiagnosed) because symptoms may occur far from the procedural time.1-3 This is why timely imaging following catheter ablation is crucial even in asymptomatic patients. Indeed, most of the cases with PV stenosis are asymptomatic and may progress insidiously. Those who are symptomatic demonstrate a myriad of nonspecific symptoms.
Chest x-ray is usually not helpful in diagnosing PV stenosis. As demonstrated in the case history above, transesophageal echocardiogram (TEE) does not always provide clear images of the PVs in order to rule out PV stenosis. CT scan with contrast and MRI with contrast are the main imaging modalities used in diagnosis of PV stenosis9,10 (Figure 42-3). Many groups recommend assessment of PV diameter using CT scan or MRI 3 months after PVI together with comparison of preablation measurements to ensure best identification of PV stenosis after ablation because the caliber remains relatively stable beyond 3 months after an ablation11 (Figure 42-4). However, late progressions from a mild stenosis to a more severe stenosis have been described, and repeat imaging study is required in any patient who develops new symptoms suggestive of PV stenosis.2
FIGURE 42-3 A 3-D CT scan of the same patient (Figures 42-1 and 42-2) showing complete occlusion of the left inferior pulmonary veins (LIPVs) and severe stenosis of both right superior PV (RSPV) and left superior PV (LSPV).
FIGURE 42-4 Preablation (A) and postablation (B). (A) A 2-D CT scan with contrast shows normal pulmonary venous anatomy and (B) thickening and narrowing of the venoatrial junction at the left superior pulmonary vein from 16 to 5 mm (arrow) with associated occlusion of a left tributary vein of the anterior apical left upper lobe. Minimal narrowing of the right and left inferior pulmonary veins. (Reproduced with permission from Feld GK, Srivatsa U, Hoppe B. Ablation of isthmus dependent atrial flutters. In: Huang SS, Wood MA, editors. Catheter ablation of cardiac arrhythmias. Philadelphia: Elsevier; 2011)
In patients with moderate to severe stenosis, a ventilation/perfusion (V/Q) scan may be useful because it provides a reliable measure of the functional impact of the stenosis. Usually, more than 70% narrowing is required to have an abnormal (V/Q) scan.
The CSI (cumulative stenosis index = sum of percent stenosis of the unilateral veins divided by the total number ipsilateral veins) has been proposed with a cutoff value of 75% to identify patients at greatest risk of severe symptoms and lung disease.2,11 Other diagnostic modalities include TTE, nuclear perfusion scans, and intracardiac echocardiograms (ICEs) employed during repeat catheter ablation procedures. Each of these modalities has its advantages and disadvantages (Table 42-1).
TABLE 42-1 Diagnostic Modalities Used in Diagnosis of PV Stenosis After Catheter Ablation of Atrial Fibrillation
• Interstitial lung disease
• Lung infection
• Pulmonary embolism
• Heart failure, diastolic
• Lung consolidation (cancer)
The best approach to the management of PV stenosis is prevention. Antral and segmental ablation approaches are preferred over focal and linear approaches as the risk of PV stenosis is lower with the latter. The cornerstone of prevention of PV stenosis for patients undergoing catheter ablation of atrial fibrillation is ensuring that radiofrequency lesions are not placed too distally into the PV veins.13 Use of 3-D imaging and ICE can be useful in visualizing the location of the ablation catheter during ablation.2,4 Multiple methods have been proposed to reduce the risk of PV stenosis during ablation (Table 42-2).
TABLE 42-2 Procedural Methods to Prevent Development of Future PV Stenosis after Catheter Ablation of Atrial Fibrillation
Avoiding energy delivery inside the PV
Minimizing delivered power/energy
Avoiding high temperature readings
Use of intracardiac echo
Use of cryo as power source
Use of 3-D mapping systems
Increased operator experience
In patients who develop PV stenosis and who have abnormal CSI values, early and, when required, repeated PV intervention should be considered for restoration of pulmonary blood flow and prevention of associated lung disease.2Late opening of a stenotic vein, though feasible, may not provide the same benefit in reducing a patient’s symptoms and restoring lung functionality. There is no consensus on the best approach to asymptomatic patients with PV stenosis. In these cases, CSI can be used to identify patients at higher risk for lung dysfunction and progressive disease.
For symptomatic patients with PV stenosis, angioplasty and stenting of the stenotic vein should be considered depending on the patients’ symptoms and severity of the stenotic vein. Timely intervention after diagnosis of symptomatic PV stenosis is important because later intervention, even when venous patency is restored, is not associated with significant improvement in lung perfusion and therefore does not result in symptom relief.11
Balloon angioplasty with or without stenting has been shown to achieve satisfactory results, although restenosis requiring repeat interventions is necessary in about 45% to 50% of patients2,12 (Figure 42-5). Stent size of above 10 mm is associated with higher long-term patency rate; therefore, early intervention and using larger stents (if possible) is recommended.4,14
FIGURE 42-5 Pulmonary vein angiography demonstrating significant stenosis of RSPV (left) and acute resolution of stenosis after dilatation with balloon angioplasty and placement of a stent (right).
Patients undergoing catheter ablation of atrial fibrillation should be alerted to the possibility of PV stenosis and be educated about its symptoms so they can seek medical care in case any of the nonspecific symptoms of PV stenosis develop within weeks or months after their ablation procedure.
Patients who undergo treatment procedures for PV stenosis should be regularly followed up and undergo noninvasive diagnostic imaging to determine the response to therapy and recurrence of stenosis as a significant number of patients will develop restenosis after angioplasty and stenting procedures and could potentially benefit from a repeat procedure.
In the previously described case, the patient did not undergo an imaging study after the second ablation. As we explained, imaging is very important in the timely detection of PV stenosis even in asymptomatic patients. The dyspnea reported by the patients was underestimated and not investigated for nearly a year. This resulted in severe pulmonary hypertension and pulmonary artery dilatation (as seen on CT scan). In such a case, late dilation of the occluded PVs is angiographically possible but very likely will not solve the patient’s symptoms. Indeed, this patient, despite a successful dilatation and stenting, died of severe pulmonary hypertension 2 years after the diagnosis.
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