A Retrospective study on constrictive pericarditis and suggestions on diagnostic criteria

doi:10.21203/rs.3.rs-1567684/v1

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A Retrospective study on constrictive pericarditis and suggestions on diagnostic criteria

https://doi.org/10.21203/rs.3.rs-1567684/v1

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Background: The diagnosis of constrictive pericarditis (CP) is a challenge. There is no standard echocardiographic diagnosis criteria of CP yet. This study analyzed and summarized the features of 25 patients with CP, and then proposed suggestions of diagnostic criteria. It is hoped that the suggestions may help professionals make decisions in their daily practice, and patients get timely diagnosis and effective treatment.

Methods: Twenty-five patients with CP were selected for the retrospective study. The clinical and echocardiographic imaging data were analyzed and summarized. At end of the article, suggestions on diagnostic criteria of CP were put forward.

Results: The main clinical manifestations were fatigue, breathlessness and exertional dyspnea (88%) and signs of edema of lower limbs (84%), hepatomegaly and jugular vein filling (84%). Echocardigraphic features included pericardial thickening (88%) and calcification (60%), pulmonary hypertension (52%), IVC dilation (80%) , left and/or right atrial enlargment (100%), diastolic flattening of the LV posterior wall (72%), septal shudder and bounce (64%), restrictive LV and RV diastolic filling pattern (100%), early filling changes of mitral and tricuspid flow (80% and 60% respectively), mitral annulus reversus (73%).

Conclusions: Echocardiography is a simple and valuable examination for CP. The echocardiographic diagnostic criteria are valid and might be further promoted.

contractive pericarditis

echocardiography

diagnostic criteria

Contractive pericarditis is characterized by restricted diastolic filling of ventricles, caused by thickening, fibrosis and calcification of pericardium, with or without myocardial fibrosis or atrophy. It is found that the incidence rate of pericarditis was 27.7 per 100,000 people, while about 1.8% of acute pericarditis patients will progress to CP.

The most common cause of CP is idiopathic or viral, accounting for 42 ~ 49% of CP. Other causes include post-cardiac surgery (11 ~ 37%), post radiation therapy (9 ~ 31%), connective tissue disorder (3 ~ 7%), post-infectious causes (TB or purulent pericarditis, 3 ~ 6%) and miscellaneous causes(malignancy, trauma, drug-induced, asbestosis, sarcoidosis, uraemic pericarditis,<10%) in developed countries[1].

The diagnosis of CP is a challenge. Patients often suffer from fatigue, breathlessness, exertional dyspnea, abdominal swelling, peripheral oedema, pleural effusion or ascites. But these presentations lack specificity. Multimodality cardiovascular imaging, including echocardiography, computed tomography (CT), and cardiac magnetic resonance (CMR), is recommended in patients suspected for CP[2]. Echocardiography is recognized one simple and valuable examination for accurate evaluation of cardiac function. However, there is no diagnostic standard yet. This is probably the reason why the diagnostic accuracy of CP is relatively low, about 51–73%[3].

This study is based on a retrospective analysis of 25 CP patients confirmed by surgery and multimodality imaging in our hospital. Suggestions on CP diagnostic criteria are put forward in order to optimize the diagnostic system, and enable patients to be diagnosed early and treated effectively.

25 patients diagnosed as chronic constrictive pericarditis who came to our hospital from August 2010 to December 2021 were selected, including 15 males and 10 females, aged 25–78 years. Twenty-three were diagnosed by multimodality imaging. Among those, 21 cases were performed pericardiectomy and confirmed by pathology, and 2 cases were treated conservatively. Two other cases were missed diagnosis but confirmed by pathology during cardiac surgery. Patients’ clinical and paraclinical data during in-hospital period and follow-up were noted. Information in the study included medical records, physical examination, epidemiological data, echocardiographic data and additional tests (radiography thoracic and cardiac imaging data). The equipment including Phillip Epic7C, Siemens SC2000, Vivid7 were used for echocardiographic examination. Routine two-dimensional, M-mode, pulse Doppler and tissue Doppler were performed. Continuous variables are expressed as mean ± SD and the categorical variables as percentages.

Fatigue, breathlessness and exertional dyspnea were the most frequent symptoms, found in 22 patients (88%), among which 10 patients (40%) were troubled by recurrent attacks. Oedema of lower limbs were found in 16 patient (84%), and hepatomegaly and jugular vein filling were found in 16 patients (84%). Four patients (16%) had pleural effusion and ascites. In five patients(20%), a history of confirmed other symptoms, such as cough or palpitation was found.

Nomal pericardial thickness (2mm) were measured in 3 cases. Pericardial thickening was found in 22 cases (88%), and the thickness of pericardium ranged from 0.3cm to 1.2cm (0.61 ± 0.58cm). The most common thickening sites were the posterior and inferior wall of left ventricle (n = 15, 60%). Diffuse thickening were found in 2 cases (8%). Pericardial calcification was found in 15 cases (60%) in different parts and varying degrees. (Fig. 1)

Severe abnormal cardiac morphology (Fig. 1) was found in 2 cases (8%) due to severe thickening and calcification of pericardium. Almost all cases had left atrium and/or right atrium enlargement, and 5 cases (20%) had small ventricle. Severe mitral regurgitation was found in only one patient (4%) duo to abnormal cardiac morphology caused by severe pericardial calcification. Other patients had mild-moderate mitral and tricuspid regurgitation. Pulmonary artery systolic pressure (PASP) ranged from 22mmHg to 55mmHg (37.4 ± 17.84mmHg), and pulmonary hypertension was found in 13 cases (52%). IVC dilated in different degrees (2.5 ± 1.35cm) in 20 cases (80%). (Fig. 2)

Diastolic flattening of the LV posterior wall endocardium was found in 18 patients (72%). Abrupt posterior motion of the ventricular septum in early diastole (septal shudder and bounce) were showed in 16 patients (64%). Among these 17 patients, 13 (52%) showed obvious “V-shaped cut” (Fig. 2). The ventricular septal respiratory drift, that is ventricular septum moving toward the left ventricle with inspiration and toward the right ventricle with expiration, was found in only 9 patients (36%) from the obtained data.

All patients showed restrictive LV and RV diastolic filling pattern. 15 patients (60%) showed high early (E) velocity and E/A > 2, 18 patients (72%) showed DT < 160ms (Fig. 3), 4 patients (16%) showed E/A < 1, and 6 patients (24%) showed E/A > 1. The respiratory variability of mitral and tricuspid inflow velocity couldn’t be measured in patients with atrial fibrillation. Mitral inflow velocity changing more than 25% were found in 16 patients (80%). According to the data of tricuspid inflow velocity pulse waves, the variation rate more than 40% in expiration and inspiration were found in 12 cases (60%). (Fig. 4)

Early diastolic velocity (e’) from the medial and lateral mitral annulus by tissue Doppler were obtained from 15 patients. Normal or increased mitral media annulus velocity (e'≥8cm/s) were matured in 12 patients (80%). Mitral annulus reversus, that is lateral mitral annulus e′ is usually lower than e′ from the medial annulus, were found in 11 patients (73%). (Fig. 5)

Constrictive pericarditis (CP) is a condition in which pericardial thickening, adhesion and often calcification, which limits diastolic filling of the ventricles[4]. Pericarditis may impact the epicardial myocardium. Long-term pathological condition may lead to myocardial atrophy, fibrosis, fat infiltration and calcification[5]. Meanwhile, thickening and calcification of pericardium compress the coronary artery, resulting in the decrease of blood flow, which leads to myocardial ischemia[6]. Chronic pericardium constraint, myocardial degeneration and ischemia may lead to irreversible cardiac dysfunction. Therefore, it is very important for CP to make an early diagnosis and perform pericardiectomy.

The normal pericardium is less than 2mm. In patients with constrictive pericarditis, the pericardium loses elasticity and is replaced by dense fibrous tissue with calcification. This rigid shell limits the filling of ventricles. Echocardiography is usually the initial diagnostic procedure in patients with suspected CP. Pericardial thickening and calcification and abnormal ventricular filling pattern can be measured. The characteristic changes on M-mode echocardiography include moving straightly of the LV posterior wall in middle-late diastole, abrupt posterior motion of the ventricular septum in early diastole with inspiration (septal shudder and bounce)[7]. In the study, most patients showed diastolic moving straightly of the LV posterior wall, especially pericardium was damaged in this position.

In CP, ventricular relaxation is limited, which dues to obstruction of venous reflux, resulting in jugular venous distension as well as inferior vena cava. Blood flows into the ventricles from atria very quickly in early diastole due to the increased pressure in atria. However, ventricular relaxation is suddenly restricted by the inelastic pericardium in middle-late diastole, and the pressure in the ventricles rises rapidly. Thereby, the pressure gradient between atrium and ventricle reaches a balance quickly. The characteristic changes on pulse wave are high early (E) velocity, a shortened deceleration time, and a reduced atrial (A) wave[8]. All patients in the study showed different degrees of restrictive ventricular filling disorder.

Because the two ventricles are in one "fixed" space, the interaction between the ventricles is strengthened. Septal shudder and bounce in early diastole, even “V-shaped cut”, and ventricular septal respiratory drift can be found in CP[9].

Restricted by thickened calcified pericardium, the radial and rotational movements of ventricles decreased. Therefore, the movement of ventricular long axis is compensatory enhanced. A normal range or increased mitral media annulus velocity (e'≥8cm/s) on tissue Doppler imaging can be detected[10]. This might be a clue that early constriction is present especially for elderly patients, and a opposite in other causes of heart failure[11]. Meanwhile, the adhesion and pathological changes of LV lateral pericardium reduced its movement. Mitral annulus reversus can be measured on tissue Doppler imaging. This is consistent with strain analysis[12].In the traceable tissue Doppler data in this study, the incidence of annulus reversus is lower, which is related to the location of pericardial adhesion and the degree of damage of epicardial myocardium.

Usually, the pressure in pericardial cavity changes with the pressure in thoracic cavity when breathing. In patients with CP, the hard pericardium prevents the pressure change in the thoracic cavity from being transmitted to the pericardial cavity, which leads to the pressure separation between the thoracic cavity and the cardiac cavity. At the end of inspiration, the pressure of pulmonary vein decreases, and the gradient from pulmonary vein to LA also decreases. Afterwards, the filling volume of LA and LV decreases. On the contrary, at the end of expiration, the RV filling pressure increases, the pressure gradient between RA and RV decreased, and then the RV filling volume decreased. Mitral inflow velocity may fall by as much as 25–40%, and tricuspid velocity greatly increase (> 40%) in the first beat after inspiration[13]. Mitral and tricuspid inflow velocity changing were found in most patients (80% and 60% respectively) in the study.

Pathological changes and ultrasonic manifestations were summarized in the study. Basic pathological changes of CP include pericardial lesions (thickening, adhesion, fibrosis or calcification), heart shape and structural variation, pathophysiological triad (ventricular dependence, thoracic-intracardiac pressure separation, compensatory enhancement of long axis motion in early diastole), and restrictive pattern of ventricular diastolic filling, which is the final result caused by pathological factors. Different pathological changes manifested as different ultrasonic characteristics (Table 1).

Table 1

Basic pathological changes and echocardiographic findings of CP
Basic pathological changes		Ultrasonic signs
Pericardial thickening, adhesion, fibrosis or calcification		1. Pericardial thickening or calcification
Heart shape and structural variation		2. Heart shape variation, ventricular septal bending, ventricular cavity deformation, atrial enlargement
Pathophysiological triad	Ventricular dependence	3.abnormal interventricular septal motion
		3.1 septal early diastole "V-shaped cut"
		3.2 septal shudder and bounce in early diastole
		3.3 septal respiratory drift
	Thoracic-intracardiac pressure separation	4.1 >25% fall in mitral inflow velocity in the first beat after inspiration
	Thoracic-intracardiac pressure separation	4.2 > 40% increase in tricuspid inflow velocity in the first beat after inspiration
	Compcompensatory enhancement of long axis motion in early diastole	5.1 e’from the medial mitral annulu s > 8cm/s
		5.2 mitral annulus reversus
Restrictive pattern of LV and RV diastolic filling		6.1 mitral inflow vave E/A > 1.5, DT < 160ms
		6.2 tricuspid inflow vave E/A > 2.1, DT < 120ms
		6.3 marked dilation (> 2.0cm) and absent or diminished (< 50%) collapse of the IVC

The study showed that even patients with confirmed diagnosis of CP may not accord with all typical ultrasonic manifestations, including 2D, M-mode, tissue Doppler and pulse Doppler. Furthermore, how to make a correct diagnosis for patients with atypical clinical and echocardiographic features and those in early stage of CP is a great challenge. Unfortunately, the ultrasonic diagnostic criteria of CP are not clearly defined yet in the current guidelines and studies.

On the basis of the result of this study, we put forward the following suggestions on diagnostic criteria for CP, that is, evidence of restrictive pattern of ventricular diastolic filling combined with one ultrasonic manifestation is suspicious CP, combined with three is confirmed with CP, and combined with two is highly suspicious CP (Table 2). All patients in the study met this diagnostic criteria well, including 15 confirmed cases, 8 highly suspicious cases, and 2 suspicious cases (misdiagnosed cases).

Table 2

Echocardiographic diagnostic criteria for constrictive pericarditis
Diagnostic catalog	1. Pericardial thickening or calcification (Echo or CT )
	2. (typical) Heart shape variation, ventricular septal bending, ventricular cavity deformation
	3. Abnormal interventricular septal motion: ① "V-shaped cut"; or ②septal shudder and bounce; or ③ septal respiratory drift
	4. Respiratory variation increase in mitral and tricuspid inflow velocity: ① >25% changing in mitral inflow velocity or ② >40% changing in tricuspid inflow velocity
	5. Compcompensatory enhancement of long axis motion in early diastole: ① e' from the medial mitral annulus > 8cm/s; or ② mitral annulus reversus
	6. Restrictive filling pattern of LV and RV diastolic filling: ① mitral inflow vave E/A > 1.5, DT < 160ms; or ② tricuspid inflow vave E/A > 2.1, DT < 120ms; or ③ marked dilation(> 2.0cm) and absent or diminished (< 50%) collapse of the IVC
Conform	Any 3 items in diagnostic catalog 1 ~ 5 and 6
Highly suspicious	Any 2 items in diagnostic catalog 1 ~ 5 and 6
suspicious	Any 1 item in diagnostic catalog 1 ~ 5 and 6

It should be emphasized that we only discussed the echocardiographic diagnostic criteria for CP in the study. The clinical diagnosis of CP should not ignore the importance of other imaging techniques such as CT or CMR. Comprehensive evaluation of multimodality imaging is more conducive to making a correct diagnosis.

Constrictive pericarditis is a serious clinical syndrome which is not easy to diagnose. Based on this retrospective study, effective diagnostic criteria were presented. We hope that the criteria will be extended to facilitate the standardized diagnosis of CP. Thereby, patients can be diagnosed correctly and treated effectively.

Data Availability Statement

All data supporting the conclusions of this article are available from the corresponding author by request.

Acknowledgements

None.

Funding

None.

Contributions

JL and CL conceptualized the study and reviewed the manuscript.RL and GC acquired and analyzed the data and critically reviewed the manuscript.DS, WL and XL acquired and analyzed the data. ZW reviewed and finalized the manuscript. All authors have had full access and take full responsibility for the data. All authors read and approved the final manuscript.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Qingdao University Affiliated Hospital committee. All patients signed an informed consent in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflicts of interest, financial or otherwise.

Adler Y, Charron P, Imazio M, et al. 2015 ESC guidelines for thediagnosis and management of pericardial diseases: the task force for the diagnosis and management of pericardial diseases of the European Society of Cardiology ( ESC ). Endorsed by: the European Association for Cardio-Thoracic Surgery( EACTS)[J]. Eur Heart.2015, 36 ( 42) : 2921-2964.
Chetrit M, Parent M, Klein AL. Multimodality imaging in pericardial diseases. Panminerva Med. 2021;63(3):301-313.
Sung-A Chang, Jae K. Oh. Constrictive Pericarditis: A Medical or Surgical Disease? J Cardiovasc Imaging. 2019, 27(3): 178-186.
Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y. Controversial issues in the management of pericardial diseases. Circulation. 2010;121:916-928.
Chang SA. Tuber culous and infectious pericarditis. Cardiol Clin. 2017;35:615-22.
Chetrit M, Natalie Szpakowski N, Desai MY. Multimodality imaging for the diagnosis and treatment of constrictive pericarditis. Expert Rev Cardiovasc Ther. 2019;17(9):663-672.
Alajaji W, Xu B, Sripariwuth A, et al. Noninvasive Multimodality Imaging for the Diagnosis of Constrictive Pericarditis. Circ Cardiovasc Imaging. 2018;11(11):e007878..
Klein AL, Abbara S, Agler DA, et al. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial disease: endorsed by the Society for cardiovascular magnetic resonance and society of cardiovascular computed tomography. J Am Soc Echocardiogr.2013,04;26:965–1012.e15.
Welch TD, Ling LH, Espinosa RE, et al. Echocardiographic diagnosis of constrictive pericarditis: Mayo clinic criteria. Circ Cardiovasc Imaging. 2014. 19;7:526–534.
Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: An update from the American society of echocardiography and the European association of cardiovascular imaging. J Am SocEchocardiogr.2016;29:277–314.
Miranda WR, Oh JK. Constrictive Pericarditis: A Practical Clinical Approach. Prog Cardiovasc Dis. 2017;59(4):369-379.
Yared K, Baggish AL, Picard MH, et al. Multimodality imaging of pericardial diseases. JACC Cardiovasc Imaging. 2010;3:650-660.
Kumar M, Padhy A, Munjal R, Gupta A. Short term clinical and echocardiography outcomes of pericardiectomy in constrictive pericarditis. J Cardiovasc Thorac Res. 2021;13(2):169-173.

No competing interests reported.

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A Retrospective study on constrictive pericarditis and suggestions on diagnostic criteria

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