**4. Clinical "red flags"**

When approaching a patient with CP, jugular venous pressure (JVP) increases, with specifically an abnormal increase during inspiration explicated by the incompliance of pericardium that impedes the venous blood, that usually increases because of suction inspiratory forces, to enter into the RV. This phenomenon (*Kussmaul's sign*) is opposite to normal condition when, during inspiration, usually JVP falls because more blood enters into RV. Moreover, JVP increase is associated to peculiar invasive pressure patterns (sharp descending *"y"* wave associated to rapid ventricle diastolic inflow and, if sinus rhythm is present, sharp descending *"x"* wave associated with late systolic inflow produced by atrial contraction) [7]. Consequently, the presence of peripheral edema, hepatomegaly, and, eventually, ascites are the cornerstone of clinical assessment. Finally, although the presence of restricted RV diastolic filling, most of all during inspiration when the higher venous return is not followed by an increase of ventricular filling, tricuspid flow increases with respect to mitral flow, explaining the presence, frequently, of a peripheral pulse markedly diminished, or even abolished, during ordinary or quiet inspiration (*paradoxical pulse*) secondary to the decrease of LV filling and, consequently, the drop of systolic pressure (>10 mmHg) during inspiration.

Finally, an essential clinical feature of CP is a *pericardial knock*, a high-pitched sound that occurs in early diastole and is best heard at the left sternal border and/or the cardiac apex [8].

### **5. Non-invasive imaging "red flags"**

The essential technique for non-invasive assessment of CP is echocardiography that, moreover, is widely available and cost-saving. Therefore, it should be considered a firstline exam in patients with suspicion of CP. This is because, beside echocardiography,

**Figure 3.**

*Multimodality imaging of pericardial thickening and calcifications. Chest X Ray (A), Cardiac CT (B) and Cardiac MRI (C) revealing extensive pericardial calcifications (red arrows) suggesting pericardial constriction physiology. This is confirmed at Cardiac MRI by the presence of septal bounce phenomenon (\*).*

diagnosis of CP can be challenging with other techniques given the fact that there are no specific findings pathognomonic of pericardial constriction. As a matter of fact, atrial fibrillation at EKG can be a frequent finding in this subset of patients but, given its high prevalence in general population, lacks adequate specificity. On chest X-rays, pericardial calcification is not always seen and, when encountered, is not necessarily an expression of constrictive physiology [9]. Moreover, another useful but not specific marker of CP is pulmonary vascular congestion and redistribution on chest X-rays, secondary to the increase of LV filling pressures. Similarly, a CT scan permits to detect even small spots of pericardial calcification and minor increases of pericardial thickness (>2 mm) [10]. This applies also to MRI, without the need for iodinated contrast or ionizing radiations but with reduced accuracy than CT in detecting small calcifications and measuring thickness (**Figure 3**). Nonetheless, although pericardial morphology can be described precisely, physiologic repercussions of CP on ventricular diastole cannot be estimated directly and can be only presumed by hepatic venous congestion, ascites, and pleural effusions. A step-forward is obtained by Cine acquisition in which ventricular-wall-motion abnormalities and ventricular-contour distortion secondary to localized adhesions to pericardium (corresponding to areas of major pericardial calcifications) can be visualized, and moreover, ventricular inter-dependence can be derived by leftward interventricular septal shift during early diastole (*septal bounce*) [11].

Consequently, given the limitations of the aforementioned non-invasive techniques, echocardiography, when feasible (optimal ultra-sonographic window is not always available), is the exam of choice in this subset of patients. Importantly, a respirometer is mandatory in order to detect respirophasic changes of ventricular diastolic filling and septal movements [12].

Similar to Cine CT or MRI, first step of assessment of CP by echocardiography is the observation of thickened pericardium [13], with or without areas of tethering on myocardium, usually at the level of the right free wall, appreciated on sub-costal and apical 4-chambers views. In addition, septal bounce phenomenon during inspiration, a constant finding of CP, can be highlighted as a septal notch in an M-mode long-axis parasternal view [14].

Moreover, dilation of supra-hepatic and inferior vena cava is observed in a subcostal view in almost all patients with CP.

Central role in echocardiographic assessment of CP is played by Doppler hemodynamic evaluation. Most of the times, Doppler findings can confirm constrictive physiology without the need for invasive confirmation. Mitral and tricuspid inflows are characterized by high early diastolic velocities (E wave) with short deceleration time and significant respiratory variations in 2/3rd of patients [15]. Mitral E wave variation

>25% (minimum at the end of inspiration) and tricuspid E wave variation>40% (maximum at the end on inspiration) are considered pathognomonic of CP, although absence of respiratory variation does not exclude the diagnosis (**Figure 3**). As a matter of fact, the presence of respiratory variations of mitral- and tricuspid-inflow-Doppler patterns alone can be present also without CP, like in patients with severe COPD due to higher respiratory variations of intra-thoracic pressures. Nonetheless, patients with COPD present a marked increase of inferior vena cava and supra-hepatic vein systolic forward flow velocity, whereas in patients with CP, this increase is blunted [16]. It is important to remember that in patients with CP, during inspiration, tricuspid flow is relatively increased with respect to mitral flow, but absolute flow is limited by pericardial constriction and, therefore, cannot increase significantly. A higher positive predictive value (96%) is offered by supra-hepatic-vein-Doppler pattern characterized by a decrease of expiratory diastolic forward velocities with large expiratory diastolic reversals.

Another useful parameter to detect CP is obtained by mitral annular tissue Doppler assessment of early diastolic velocity (e'wave), with evidence of *"annulus reversus"*, consistent with similar or slower lateral-wall relaxation with respect to septal wall (e'septal/e'lateral ratio > 0.91) when in normal conditions the opposite occurs, that has 95% of positive predictive value of CP [17]. Interestingly, absolute values of medial e'waves could be normal (septal e'wave > 9 cm/seg) or even increased (*annulus paradoxus*) despite the evidence of increased LV diastolic pressures (ratio E/e' > 13) [18]. This phenomenon is explicated by the predominance of longitudinal cardiac relaxation of septum during LV diastolic filling because lateral wall is frequently entrapped and tethered by thick and calcified pericardium. This marker, also, has 95% of positive predictive value for CP diagnosis (**Figure 4**). Unfortunately, both *annulus reversus* and *annulus paradoxus* are affected by a significant proportion of false negative results (50% and 57% of negative predictive values, respectively). Consequently,

#### **Figure 4.**

*Tissue Doppler characteristics of constrictive pericarditis. Contrary to normal physiology, in constrictive pericarditis lateral wall relaxation velocity (white arrow) during early diastole (e'wave) is usually is frequently reduced in comparison with septal e'wave (annulus reversus). This occurs because lateral wall is frequently entrapped and tethered by thick and calcified pericardium (white line). Moreover, although diastolic filling restriction is present, septal e'wave can be normal (> 8 cm/second) and can be used as a reliable marker of constriction in order to differentiate the latter with myocardial restriction (annulus paradoxus).*

### *Constrictive Pericarditis DOI: http://dx.doi.org/10.5772/intechopen.109793*

a multi-parametric approach is warranted to assess a patient with suspected CP, and in doubtful cases or when quality of echocardiography is sub-optimal (challenging acoustic window, respirometer not available), a multi-modal assessment with CT and/or MRI can be helpful in identifying calcifications, ventricular wall distortions, *septal bounce* during inspiration, and systemic vein congestion [19]. Finally, if doubts still persist, right- and left-heart catheterization is essential for invasive pressure measurement and, therefore, demonstration of equalization of RV and LV-end-diastolic pressures secondary to the non-compliance of pericardium, a common constraint for both ventricles.
