**1. Introduction**

76 Echocardiography – In Specific Diseases

Zeymer, U.; Margenet, A.; Haude, M.; et al. (2010). Randomized compaeison of eptifibatide

Zijlstra, F.; Beukema, W.P.; van't, H.A.; Liem, A.; Reiffers, S.; Hoorntje, J.C.; Suryapranata,

Zijlstra, F.; de Boer, M.J.; Hoorntje, J.C; Reiffers, S.; Reiber, J. & Suryapranata, H. (1993). A

myocardial infarction. *N Eng J Med*, Vol.38, pp. 680-684.

*Am Coll Cardiol*, Vol. 3; 56(6), pp. 463-469.

*Am Coll Cardiol*. Vol.29, pp. 908–912.

versus abciximab in primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: results of the EVA-AMI trail. *J* 

H. & de Boer MJ.(1997). Randomized comparison of primary coronary angioplasty with thrombolytic therapy in low risk patients with acute myocardial infarction. *J* 

comparison of immediate angioplasty with intravenous streptokinase in acute

The role of echocardiography in patients with atrial fibrillation (AF) has been changing gradually according with recent advance in echocardiographic instruments and better understanding for AF. Historically, M-mode echocardiography applied to AF patients has focused on the diagnosis of underlying organic heart diseases and on the detection of left atrial (LA) thrombi. These are not surprising because AF had been the highest risk of ischemic stroke in the era of incomplete anticoagulation therapy. Thereafter, LA size, volume and functions have been foci assessed by echocardiography. These echocardiographic procedures have been conducted for prediction and prevention of recurrence of AF paroxysms (Barbier et al, 1994; Verdecchia et al, 2003; Vasan et al, 2003). Spontaneous echo contrast has also been an established B-mode echocardiographic finding with highly predictive value of ischemic stroke. After the development of Doppler echocardiography, pulmonary venous flow (PVF) evaluation is a routine laboratory investigation for patients with and without AF. The usefulness of PVF evaluation is not limited to assess LA or left ventricular (LV) functions, but has expanded to investigation of various aspects of AF (Tabata et al., 2003). PVF recording increases its usefulness when it is combined with recordings of Doppler LV inflow pattern. This article reviews the established usefulness of PVF estimation in patients with permanent AF, and then focuses on the potential usefulness of PVF assessment in AF progression, i.e., during sinus rhythm (i.e., interval of paroxysms of AF), during ongoing paroxysmal AF, and further during the longterm AF management.

#### **2. Clinical Perspectives of AF**

AF is one of the most common sustained arrhythmias in daily clinical practice. There has been a great advance in the exploration of the etiologies of AF. These are the subject of several overlapping schemes of individual pathogenesis, i.e., atrial overload and stretch, myocardial ischemia and inflammation, degeneration and subsequent fibrosis of atrial myocardium, neurohumoral or metabolic factors, and other unknown factors. Therefore, clinical presentations of AF are very broad. This arrhythmia occurs in a variety of clinical

Pulmonary Venous Flow Pattern and Atrial Fibrillation: Fact and Controversy 79

characteristic f-waves become gradually small in amplitude and high in frequency. On the other hand, contractile remodeling provides poor LA contraction and structural remodeling causes LA dilatation. Histologically, LA myocardium in patients with AF shows infiltration of inflammatory cells, interstitial fibrosis and loss of contractile myocytes, leading to slow,

> Pathogenesis of atrial fibrillation

Atrial degeneration and progressive remodeling

PVF recording is feasible not only by transesophageal echocardiography (TEE) but also by transthoracic echocardiography (TTE). According with the prevalence of PVF estimation by TTE, there have been investigations comparing the PVF recorded by TTE with that recorded by TEE. To date, TTE estimation of PVF is reported to provide reliable quantitation of PVF recorded by TEE in patients with and without organic heart diseases (Masuyama et al., 1995). **Fig. 2** is an actual Doppler PVF pattern during an entire cardiac cycle recorded by TTE. When ultrasound probe is positioned at the apex of chest wall, a four-chamber apical view is obtained. Then color jet is visualized in the upper LA of real-time, B-mode image. This color image is forward blood flow signals in right superior PV (**Fig. 2**, upper). After overall color Doppler interrogation, Doppler velocimetry is obtained by positioning the

The PVF profile is characterized as forward flows during LV systolic (**S**) and early diastolic (**D**) phases, and as reversed flow during late diastole when LA contracts (**Ar**). There are strictly two components within the **S** wave of PVF, i.e., **S1** is caused by active LA relaxation

sampling gate 2-3 cm distal from the orifice of right superior PV (**Fig. 2**, lower).

Neurohumoral or metabolic factors

Thyrotoxicosis Electrolyte imbalance Metabolic syndrome Sleep apnea syndrome Vagally mediated AF Exercise-induced AF

Etiology unknown

Familial AF Lone AF

AF in athlete heart

fragmented and fibrillatory conduction and poor dyssynchronous LA contractions.

Myocardial ischemia or inflammation

Myocarditis Pericarditis Cardiac surgery Infection Myocardial infarction

Fig. 1. Mechanisms favoring atrial fibrillation (AF).

Atrial stretch or overload

Valvular heart diseases

(pulmonary, systemic)

**3. Physiology of PVF**

Hypertension

Cardiomyopathy Congestive heart failure Congenital heart diseases

settings such as valvular heart diseases, postoperative conditions, heart failure, hypertension, metabolic syndrome, thyrotoxicosis, and so on (**Fig. 1**). Since valvular heart diseases were historically a main etiology of AF, echocardiographic attention to AF patients was mainly rheumatic valvular lesions and detection of LA thrombi or spontaneous echo contrast which is based on the local hemostatic changes due to rheologic abnormalities (Kwaan et al, 2004; Topaloglu et al, 2007). In relation to thrombus formation, LA appendage function was highlighted in that impaired appendage function leads to thrombus formation and high risk of embolic event (Donal et al, 2005). According to an increased prevalence of coronary artery diseases, AF has been encountered in acute myocardial infarction, after coronary artery bypass grafting surgery and chronic phase of ischemic heart disease and subsequent heart failure. On the other hand, AF is often observed in patients with another kind of arrhythmias (e.g., preexcitation syndrome) or noncardiac disorders (e.g., thyrotoxicosis, chronic obstructive pulmonary disease). AF is often encountered in subjects without systemic or organic heart diseases (so-called 'lone' AF). According with relative decline of rheumatic valvular diseases, terminology of 'nonvalvular' or 'nonrheumatic' AF becomes familiar. Wide spectrum in clinical features of AF sometimes makes the therapeutic decision-making difficult (Wyse & Gersh, 2004).

AF is classified by the duration in which this arrhythmia sustains (e.g., paroxysmal, persistent and permanent). Paroxysmal AF is characterized as rare or repetitive paroxysms of short-lasting AF, which often undergoes spontaneous conversion to sinus rhythm, but rhythm-control treatment is required depending on symptom and hemodynamic deterioration. Persistent AF has the possibility of termination either by antiarrhythmic drugs or by electrical defibrillation. Permanent AF does not restore to sinus rhythm spontaneously, and hence conservative therapeutic option is the rate-control strategy. AF is not only responsible for substantial morbidity and mortality, but also impairs quality of life by limited capacities of physical activity and heart rate regulation. To date, the most effective treatment for drug-refractory AF is radiofrequency catheter ablation. Pulmonary vein (PV) isolation by circumferential ablation of PV-LA junction is a promising technique to terminate AF. Despite the introduction of novel and sophisticated ablation techniques such as irrigation catheters, pericardial approach and ganglionated plexi ablation, periprocedural complications are not negligible.

AF is characterized to date as an age-dependent, progressive disease, i.e., AF prevalence increases steeply from 0.5% at age 50 to 59 years to 9.0% at age 80 to 89 years (Kannel et al., 1998). Progressive nature of this arrhythmia is evident in that AF becomes refractory to pharmacologic treatment and electrical defibrillation in proportion with the duration of sustaining AF. This is the main feature that distinguishes AF from many other kinds of clinical arrhythmia (Wijffels et al., 1995). In a few decades, the mechanisms of such progression of AF have been clarified by many basic experiments using AF animal models and clinical studies of AF patients. Remodeling of LA plays an important role in the genesis, maintenance and perpetuation of AF. LA remodeling is a concept including electrical, contractile and structural aspects. Electrical remodeling induces abbreviated and dispersed electrical refractoriness and inhomogeneous slow conduction of electrical impulse. These are considered to be an arrhythmogenic substrate, prerequisite of AF development. Electrocardiograms (ECG) in patients with AF demonstrate characteristic fibrillation (f) waves that are evident in right precordial leads. According to the progression of AF, characteristic f-waves become gradually small in amplitude and high in frequency. On the other hand, contractile remodeling provides poor LA contraction and structural remodeling causes LA dilatation. Histologically, LA myocardium in patients with AF shows infiltration of inflammatory cells, interstitial fibrosis and loss of contractile myocytes, leading to slow, fragmented and fibrillatory conduction and poor dyssynchronous LA contractions.

Fig. 1. Mechanisms favoring atrial fibrillation (AF).
