(1)7.13 Imaging of the Pulmonary Veins in Patients with Atrial Fibrillation M

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7.13

Imaging of the Pulmonary Veins in Patients with Atrial Fibrillation

M. Poon, C. Learra

prevalence of Afib in patients over the age of 80 is greater than 6% (Fuster 2001). As the population of developed countries ages in the next 50 years, it is expected that Afib will become a major health- related issue and a contributor to rising health-care costs (Wolf 1991, Flegel 1987). The increased rate of death due to Afib is mainly attributed to cardiac- related rather than due to thromboembolism (Dries 1998). In patients examined by nuclear myocardial perfusion studies, the presence of Afib is a poor prognosticator. Furthermore, Abidov et al. recently reported that, in these patients, the finding of Afib independently increases the risk of adverse cardiac events to an extent greater than perfusion and function variables (Abidoy 2004).

The treatment of Afib has evolved greatly in the last decade. Nonetheless, the pharmacological approach has not been optimal due to a myriad of drug-related side effects, and surgical treatment is effective but not practical. As catheter ablation of Afib continues to gain popularity and wider accep- tance in the medical community, advanced tomo- graphic imaging of the heart, particularly using multi-slice CT, begins to take on a more important role in the planning and follow-up of patients undergoing this procedure.

7.13.1.1 Nomenclatures

Afib can be classified as either acute or chronic. Sys- temic conditions, such as excessive alcohol intake, pulmonary disease, pulmonary embolism, or hyper- thyroidism, are known contributing causes of acute or new-onset Afib. Chronic Afib can be permanent, persistent, or paroxysmal. In permanent Afib, the heart is unable to convert to sinus rhythm. Persistent Afib usually lasts longer than 30 days and will not revert back to sinus rhythm without interventions, such as with chemical agents or electrical cardiover- sion. Paroxysmal Afib is relatively common, occurs unpredictably, and is usually short-lived and self- terminating. In about 45% of patients, paroxysmal Afib occurs without associated underlying disease and as such it is known as “lone Afib” (Levy 1999).

However, all types of Afib are associated with an increased risk of stroke.

C o n t e n t s

7.13.1 Introduction 296 7.13.1.1 Nomenclatures 296 7.13.1.2 Clinical Presentation 297

7.13.2 Pharmacological Treatment Options 297 7.13.2.1 Thromboembolic Complications 297 7.13.2.2 Treatment of Atrial Fibrillation:

Rate vs. Rhythm Control 297 7.13.2.3 Clinical Outcomes of Pharmacological

Treatments 297

7.13.3 Non-pharmacological Treatment of Atrial Fibrillation: Catheter Ablation 298 7.13.3.1 Anatomy and Physiology of the Pulmonary

Veins 298

7.13.3.2 Anatomic Variants of the Pulmonary

Veins 298

7.13.3.3 Radiofrequency Ablation 299

7.13.4 The Role of Imaging in the Era of Catheter Ablation of the Pulmonary Veins 299 7.13.5 Multi-slice CT Imaging of the Pulmonary

Veins and Left Atrium 299 7.13.5.1 Scan Protocol 299 7.13.5.2 Image Post-processing 300

7.13.6 The Role of Multi-slice CT in Catheter Ablation of Aﬁ b 302

7.13.6.1 Pre-ablation 302 7.13.6.2 Ablation 302 7.13.6.3 Post-ablation 302 7.13.7 Conclusions 303

References 305

7.13.1 Introduction

Atrial fibrillation (Afib) is the most common cardiac dysrhythmia requiring treatment and it accounts for approximately one-third of hospitalizations for rhythm disturbances (Fuster 2001). Over 2.2 mil- lion Americans have paroxysmal or persistent Afib (Go 2001, Page 2004). Afib is much more common in the elderly, as evidenced by the fact that the

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7.13.1.2

Clinical Presentation

Symptoms of Afib usually relate to the rapid heart rate and the irregularity of the rhythm. Afib is not well-tolerated in elderly individuals with left ventricular hypertrophy and diastolic dysfunction or in patients with significant mitral valve disease or restrictive cardiomyopathy. The majority of patients with Afib complain of palpitation, dyspnea, fatigue, light-headedness, and syncope. Hemodynamic com- promise in Afib patients is due to the loss of atrioventricular synchrony and atrial contribution to diastolic filling, stroke volume, and cardiac output.

Chronic persistent tachycardia may result in a potentially reversible form of cardiomyopathy (Lemery 1987, Packer 1986). Up to 21% of cases of newly diagnosed Afib are asymptomatic (Kerr 1996).

Unfortunately, the first presentation of asymptomatic Afib could be a devastating neurological event, such as stroke or transient ischemic attack.

7.13.2

Pharmacological Treatment Options

7.13.2.1

Thromboembolic Complications

All patients over the age of 60 and with chronic Afib should be placed on either antiplatelet therapy or oral anticoagulants. The latter is recommended in those patients with mitral stenosis or a history of thromboembolism, diabetes mellitus, coronary artery disease, hypertension, prosthetic heart valves, documented atrial thrombus on trans-esophageal echocardiogram, congestive heart failure, or thyro- toxicosis (Fuster 2001, Page 2004, Albers 2001).

7.13.2.2

Treatment of Atrial Fibrillation: Rate vs. Rhythm Control

The primary goal in the treatment of acute or chronic Afib is to achieve either rhythm or rate control. How- ever, it is a well-recognized clinical fact that the current pharmacological treatment options for either form of

Afib are neither effective nor safe. It is clinically easier to achieve rate control than rhythm control. Rate control agents include β-blockers, calcium-channel blockers, and digoxin. These can be used alone or in combination, depending on the clinical limitations of the underlying comorbid disorders of the patient and the initial response to the selected treatment.

β-Blockers are usually more effective than calcium channel blockers for rate control, while digoxin is mainly used as adjunctive therapy and rarely as a first-line treatment option. The goal is to achieve a resting heart rate of 60–80 bpm or an exercise heart rate of 90–115 bpm (Fuster 2001). Rate control can be problematic in patients with tachy-brady syndrome or sick-sinus syndrome, in which a pacemaker is often needed to avoid profound bradycardia resulting from any one of the three rate control agents.

With the exception of β-blockers, most rhythm control agents are associated with significant adverse effects and usually are not recommended in patients with structural heart disease, either hypertrophic or dilated cardiomypathy. Most recently, the use of class IC anti-arrhythmic agents, such as propafe- none and flecainide, was shown to be effective for out-patient treatment of recurrent Afib in patients with a normal heart or mild heart disease (Alboni 2004). Class III and IA agents are not recommended in patients with QT-interval prolongation. The most effective and the least pro-arrhythmic antifibril- latory agent, amiodarone, is associated with significant side effects, especially with long-term and high-dose usage (Hohnloser 1995).

7.13.2.3

Clinical Outcomes of Pharmacological Treatments

Mortality and morbidity were comparable using long- term rate or rhythm control treatment in patients with persistent Afib (van Gelder 2002, Wyse 2002, Carlsson 2003, Hohnloser 2000). Similar favorable results with rate control treatment in patients with lone Afib have been reported (Rienstra 2004).

Thus, rate control is an accepted and safe treatment option for Afib in patients with minimal symptoms or in patients with great difficulty in maintaining sinus rhythm. Anticoagulation is needed regardless of which control method is used.

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7.13.3

Non-pharmacological Treatment of Atrial Fibrillation: Catheter Ablation

The discovery that the pulmonary veins harbor the spontaneous wavelets that lead to the onset of paroxysmal Afib has ushered in a new non-pharmacological treatment option for paroxysmal Afib using radiofrequency catheter ablation (Haissa- guerre 1998). The ablation technique has evolved over the past few years, from the use of focal vein ablation to circumferential ablation near the ostia of the pulmonary veins with or without additional left atrial linear lesions (Oral 2003, Hsu 2004). While catheter ablation was initially used to treat patients with mostly normal left ventricular function, more recently this approach has been found to also be useful in restoring and maintaining sinus rhythm in patients with Afib and congestive heart failure (Hsu 2004, Chen 2004).

The maze procedure consists of surgically iso- lating the Afib-initiating wavelets by creating long, superficial surgical incisions in the left atrium. The resulting scars block electrical conduction of the wavelets that lead to paroxysmal Afib. This surgical treatment is effective and is usually done at the time of open-heart surgery, particularly during repair or replacement of the mitral valve (Cox 1993).

7.13.3.1

Anatomy and Physiology of the Pulmonary Veins

The pulmonary veins are formed by the confluence of small venules originating from the lung periph- ery. These venules merge into larger veins, converge toward the lung root, and eventually enter the left atrium. Typically there are four pulmonary veins, designated as right superior (RS), right inferior (RI), left superior (LS), and left inferior (LI); however, four discrete pulmonary venous orifices in the left atrium are present in only 75–80% of individuals (Ho 2003).

The principal function of the pulmonary veins is to return oxygenated blood from the lungs to the left atrium. The vascular structure of the pulmonary veins, which is similar to that of other veins in the body, consists of three layers: a thin endothelium, an irregular medial layer of smooth muscle and

fibrous tissue, and a thick fibrous adventitia. The inner lining of the left atrium is continuous with the pulmonary veins in that the left atrial myocardium is embedded in the media of the proximal portion of all four pulmonary veins, forming sleeve-like extensions. The amount of myocardial penetration into the pulmonary veins varies from species to species and it also varies between the upper and lower veins.

The presence of myocardial cells in the pulmonary veins is thought to play an important role in deter- mining the electrophysiological properties of these veins. Unlike the smooth muscle of the pulmonary veins, striated muscle within the left atrium and the sleeve-like extensions are electrically active. It has been implicated that the veno-atrial junction and the myocardium in the veins help initiate and maintain Afib (Shah 2001). The RS vein drains the right upper and middle lobes of the lung. The LS vein drains the left upper and the lingular lobes. The inferior veins drain the lower lobes of their respective sides. The RS pulmonary vein is usually the largest, and the ostial size of the superior pulmonary veins is usually larger than that of the inferior veins. In their report of 42 patients with Afib, Scharf et al. reported the following average sizes of the pulmonary veins: RS:

19.8 mm, LS: 19.2 mm, RI: 16.0 mm, and LI: 17.3 mm (Scharf 2003).

7.13.3.2

Anatomic Variants of the Pulmonary Veins

The anatomy of the pulmonary veins is more vari- able than that of the pulmonary artery. Embryo- logically, the entire network of pulmonary veins originates from a single common pulmonary vein.

Anatomical variations in the number, branch- ing patterns, and length of the pulmonary trunk (defined as the distance from the ostium to the first ordered branch) occur as a result of the under- or over-incorporation of the common pulmonary vein into the left dorsal atrium (Bliss 1995). An extreme and rare form of under-incorporation involves the persistence of the common pulmonary vein such that it forms a narrowing in the left atrium (gen- erally known as cor triatriatum). Other common anomalies include: joint pulmonary vein, either common left or common right pulmonary vein (in

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2.4–25% of individuals); separate right middle lobe pulmonary vein (19–23%); and anomalous pulmonary venous return (<1%) (Scharf 2003, Cronin 2003, Lacomis 2003).

7.13.3.3

Radiofrequency Ablation

Access to the pulmonary veins and left atrium is obtained via a trans-septal approach through a patent foramen ovale or a trans-septal puncture under fluoroscopic guidance. Typically, one mapping (Lasso) catheter and one ablation catheter are needed to perform standard radiofrequency (RF) ablation, which employs a tissue temperature of up to 52°C with a maximum power output of 30–40 W (Hsu 2004, Ho 2001). Anticoagulation with intrave- nous heparin is administered following insertion of the catheters to maintain the prothrombin time at greater than twice the patient's control value. Abla- tion is performed at or within 5 mm of the pulmonary vein ostia to reduce the risk of pulmonary vein injury and subsequent development of pulmonary vein stenosis (Cronin 2004).

7.13.4

The Role of Imaging in the Era of Catheter Ablation of the Pulmonary Veins

Of the imaging modalities currently available for visualizing the pulmonary veins, MRI and CT are the most noninvasive, reproducible, and free of technical problems related to the operator or acous- tic window. Today, multi-slice CT with advanced cardiac gating has distinct advantages over MRI in that multi-slice CT is significantly faster in image data acquisition and less problematic in scanning patients who are claustrophobic or have implanted devices. Multi-slice CT allows a 3D view of the heart and thus unlimited viewing angles. Furthermore, it is able to provide important additional image information on coronary artery anatomy and function without the need for additional contrast administra- tion or radiation exposure (Achenbach 2001, Juer- gens 2002). Multi-slice CT with 16 or more detector slices offers a significant improvement in temporal

and spatial resolution compared to earlier single- or 4-slice CT. As such, 16 or more detector slices allow a more precise determination of the ostial diameter and an accurate assessment of anatomical anomalies and pathology that might affect the success of the procedure or contribute to procedural complications.

A recent report by Wood et al. evaluated the accuracy of assessment of pulmonary vein anatomy in patients with Afib (Wood 2004). Four imaging modalities were compared: multi-slice CT, trans- esophageal echocardiogram, intracardiac echocardiography (ICE), and venography. Multi-slice CT identified the greatest number of pulmonary ostia followed by ICE. Compared with multi-slice CT or ICE, venography overestimated and TEE underes- timated ostial diameters (Wood 2004). Yuan et al.

recently reported the intra- and inter-observer variability of pulmonary vein measurements from multi- slice CTA (Yuan 2004). The study found that pulmonary vein ostial measurements have fewer variables when made by a single observer and mean diameter measurements are more precise than a single, maximum diameter measurement (Yuan 2004).

7.13.5

Multi-slice CT Imaging of the Pulmonary Veins and Left Atrium

7.13.5.1 Scan Protocol

In order to evaluate the pulmonary veins and left atrium, we use a similar protocol to the one that we routinely use for coronary CTA. This protocol is optimized for non-invasive coronary angiography.

All ECG-gated images shown in this section were obtained with a 16-slice CT scanner. For contrast- enhanced multi-slice CT of the heart, the following parameters were employed: 16 × 0.75-mm collimation, 0.42-s rotation time, temporal resolution of 105–210 ms, 120 kV, and 500 mAs, resulting in a total scan time of about 28 s to cover the entire thorax, from the apices to the lung bases. The entire scan was acquired during a breath-hold following deep inspiration, using retrospective electrocardio- graphic gating. One hundred ml of iodinated con-

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trast agent were infused at 4 ml/s using a dual injec- tor. This was followed by a chaser bolus of 50 ml of saline at the same flow rate. Arrival of the contrast agent in the ascending aorta was monitored using an automatic bolus-tracking system. Data acquisition was started 4–6 s after the attenuation coefficient in the ascending aorta reached a pre-set threshold of 100 HU. Alternatively, we found that the use of a timing bolus instead of the automatic bolus-tracking system was equally efficacious but the timing protocol required an additional small amount of contrast infusion. For the timing bolus, 20 ml of iodinated contrast agent were infused at 4 ml/s followed by a similar bolus of 50 ml of saline at the same flow rate. For coverage of the entire thorax, a time delay duration was used that was equal to the time it took for the bolus contrast plus saline chaser to reach the peak of the timing bolus curve. The data sets were reconstructed at mid- to end-diastole for optimal image quality, with a 1.0-mm slice thick- ness, in 0.6-mm increments. Spatial resolution of the reconstructed images was 0.6 × 0.6 × 1.0 mm.

ECG gating significantly improves overall image quality. The entire data set can be used to assess the anatomy and pathology of the coronary arteries and veins. This additional information may be useful when assessing the presence of coronary artery anomalies, arterial patency, and coronary venous anatomy prior to the placement of a bi-ventricular pacemaker.

7.13.5.2

Image Post-processing

Image post-processing is routinely done on a dedi- cated work-station that generates 3D models of the left atrium and pulmonary veins. The 3D model of the left atrium and its associated pulmonary veins and appendage is reconstructed to eliminate sur- rounding structures, such as the aorta, vertebral column, ribs, lung parenchyma, and peripheral pulmonary arteries (Fig. 7.93). The optimal view of the pulmonary veins and left atrium without overlap from adjacent structures, such as the proximal seg- ments of the pulmonary arteries, is a dorsal-cranial view with right or left posterior oblique angulations (Fig. 7.94). To measure the diameter and area of a pulmonary vein, the central axis of each pulmonary vein is first identified in 3D images (Fig. 7.95). A slice oblique to the central axis of the chosen image is obtained by rotating the image perpendicular to the center line. The oblique plane is then adjusted until the plane is just distal to the junction of the pulmonary vein and the left atrium. The area of the pulmonary vein ostium is measured by manually tracing out the lumen in the oblique MPR view and the minimum and maximum ostial diameters are measured with digital calipers along perpendicular lines drawn by the operator through the center line of the ostium. The same procedure is repeated for all the ostia of the pulmonary veins.

Fig. 7.93. 3D image of the left atrium and its as- sociated pulmonary veins and appendage obtained using 16-slice CT and 16 × 0.75-mm collimation

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Fig. 7.94. Dorsal cranial view of the left atrium and pulmonary veins reconstructed from a data set obtained with 16-slice CT using 16 × 0.75-mm collimation. L/RS Left/right superior, L/RI left/right inferior, LL left lingula, RML right middle lobe, L/RSL left/right superior lobe, SSLIL/SSRIL supe- rior segment of left/right inferior lobe, BSL/BSRIL basilar segment of left/right inferior lobe

LI LSL

LS RS

RI LL

BSLIL BSRIL

SSRIL SSLIL

RSL RML

Fig. 7.95. a 3D view of the LA and pulmonary veins. b Oblique clip-plane perpendicular to the center line of the left inferior pulmonary vein. c Measurements of pulmonary vein maximum and minimum diameters in oblique MPR view. Data were obtained with 16-slice CT using 16 × 0.75-mm collimation and 0.37-s rotation speed

a b

c

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7.13.6

The Role of Multi-slice CT in Catheter Ablation of Aﬁ b

Today, multi-slice CT has become a versatile tool in the field of cardiac imaging. It provides important 3D anatomical information of the entire thorax, has an unlimited field-of-view, and is completely non-invasive. In addition, multi-slice CT greatly decreases the potential complications often associated with this highly technical and laborious procedure. It provides valuable 3D information of the atria and their associated venous connections from both epicardial and endocardial perspectives. The role of multi-slice CT in the clinical assessment of patients for catheter ablation of Afib can be divided into three phases:

7.13.6.1 Pre-ablation

Multi-slice CT can be a valuable imaging tool for the pre-ablation assessment of the anatomy and anatomical variants, e.g., an anomalous pulmonary vein. It allows accurate sizing of the pulmonary vein ostia in order to avoid catheter-vein mismatch. Moreover, it

aids in the evaluation of potentially disastrous procedure-related thromboembolic complications from atrial septal aneurysm with thrombus, right atrial thrombus (Fig. 7.96), left atrial tumor (Fig. 7.97), or left atrial appendage thrombus (Fig. 7.98).

7.13.6.2 Ablation

A high-resolution 3D image of the left atrium facil- itates mapping of the pulmonary vein ostia and placement of the electrophysiology and ablation catheters. Software is currently being developed to incorporate 3D images generated from multi-slice CT into the work-station used for carrying out RF catheter ablation of the pulmonary veins (Fig. 7.99)

7.13.6.3 Post-ablation

The potential for post-procedural complications related to RF ablation cannot be understated. Rou- tine follow-up CT is not only indicated, but a good clinical practice after RF ablation. The reported complications include pulmonary vein stenosis or

Fig. 7.96. MPR image and dimensions of a right atrial throm- bus. Data were obtained using 16-slice CT with 16 × 0.75-mm collimation and 0.42-s rotation time

Length 17.18 mm

Length 18 mm

Fig. 7.97. Left atrial osteosarcoma (white arrows) invading the right inferior pulmonary vein Data were obtained using 16-slice CT with 16 × 0.75-mm collimation and 0.42-s rotation time

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Fig. 7.98a,b. Left atrial appendage thrombus (white arrow) and a large left atrium in a patient with chronic atrial ﬁ brillation on oral anticoagulant. a Axial view, b two-chamber view. Data were obtained using 16-slice CT with 16 × 0.75-mm collimation and 0.42-s rotation time

a b

infarction (Ravenel 2002, Yang 2001, Robbins 1998), pulmonary vein or left atrial perforation and hematoma (Wu 2001), and pericardial effusion/tam- ponade, pulmonary fibrosis, pulmonary hypertension (Ravenel 2002). Focal stenosis of the pulmonary vein is observed frequently after RF catheter ablation applied within the vein, but usually is without clinical significance. However, ablation within multiple pulmonary veins may cause pulmonary hypertension. Atrio-esophageal fistula is a known complica- tion of RF ablation for Afib. Treatment of pulmonary vein stenosis using trans-catheter angioplasty alone yielded favorable results in up to one year of follow- up (Qureshi 2003). Purerfellner et al. also reported favorable clinical outcome during up to 9 months of follow-up in a group of highly symptomatic patients with ablation-related pulmonary vein stenosis who were treated with dilatation alone or dilatation plus stenting (Purerfellner 2004).

7.13.7 Conclusions

Afib is a common medical problem with potentially catastrophic consequences. Anticoagulation is indicated in patients over the age of 60, and in patients

with significant structural heart disease. Pharmaco- logical options for the two common treatment meth- ods, rate and rhythm control, are less than ideal due to the numerous and potentially harmful effects of the drugs. The discovery that the pulmonary veins are the potential source of the wavelets that initiate the paroxysm of Afib has opened up a new treatment option for this common ailment. RF catheter ablation has been demonstrated to be efficacious in the treatment of paroxysmal Afib and selected cases of persistent Afib. RF ablation is equally effective in patients with normal or compromised cardiac function. Pre- ablation planning and post-procedural follow up evaluation are best done non-invasively with tomo- graphic imaging. Multi-slice CT has emerged as the non-invasive image modality of choice in the pre- and post-ablation assessment of patients undergoing Afib ablation. For this application, 16-slice CT scanners have been shown to provide appropriate anatomical information. The newer 64-slice CT scanners, with improved temporal and spatial resolution, will fur- ther improve visualization of the pulmonary system in patients with irregular heart rate during the scan.

The increased volume coverage of 64-slice CT allows evaluation of the entire arterial and pulmonary system within one examination and with one injec- tion of contrast agent (Fig. 7.100).

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Fig. 7.99. Screen shot of a planning work-station for performing RF ablation of the pulmonary veins. An AP view of the vol- ume-rendered image (upper left) of the pulmonary veins and the left atrium generated from a 16-slice CT examination with 16 × 0.75-mm collimation and 0.37-s rotation time. The same view can be generated on the mapping system, with red circles showing the ablation sites, as a basis for electrophysiological mapping of the ablation procedure

Fig. 7.100. ECG-gated 64-slice CT examination of the arterial and pulmonary system. A large scan range of 28 cm can be examined with temporal and high spatial resolution in a breath-hold time of less than 20 s, thus covering the entire thoracic vasculature, includ- ing the pulmonary vein. (Case courtesy of Mayo Clinic Rochester)

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