Constrictive pericarditis (CP) is a potentially curable cause of diastolic heart failure. The scarred, and non-compliant pericardium causes restraint to early diastolic ventricular filling, resulting in the equalisation of intracardiac diastolic filling pressures, producing the so-called “single diastolic chamber”. Ventricular filling pressures become markedly elevated and predominantly right heart failure (RHF) ensues.
Differentiating between restrictive cardiomyopathy and CP
CP is an often challenging clinical diagnosis that demands a high index of suspicion in patients who present with heart failure with preserved ejection fraction (HFpEF). At particular risk are patients who have undergone prior cardiac surgery, those who have previously been diagnosed with pericarditis of any aetiology, and those who have been exposed to chest radiotherapy .
- Depressed left ventricular systolic function does not rule out the diagnosis; it can occur secondary to advanced CP once myocardial atrophy develops and in combined constrictive pericardial and restrictive myocardial disease after prior radiotherapy [1,2].
- Impaired systolic function can also occur secondary to a tachyarrhythmia-induced cardiomyopathy in patients who develop atrial arrhythmias that are poorly rate controlled.
- Restrictive cardiomyopathy (RCM) remains the most important differential diagnosis.
Differentiating between RCM and CP is reliant on demonstrating the two hallmark physiological features of CP, dissociation of intrathoracic and intracardiac pressures and enhanced ventricular interdependence [1,3]. Modern transthoracic echocardiography (TTE) techniques allow a diagnosis to be established in the majority of cases, and invasive haemodynamics and advanced imaging techniques, including cardiac computed tomography and cardiac magnetic resonance imaging, are reserved for challenging cases and/or surgical planning .
The importance of establishing the diagnosis early on in the course of the disease cannot be overemphasised as timely surgical pericardiectomy, before the onset of New York Heart Association Class III or IV symptoms, is associated with a significantly lower risk of 30-day surgical mortality [1,4].
Whilst fibrous, adherent CP with or without calcification necessitates surgical pericardial resection, transient CP, a reversible inflammatory pericardial syndrome, can recover with appropriate anti-inflammatory therapy . The use of 18F-labelled fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG PET/CT) for prospective identification of patients with persistent pericardial inflammation, who may benefit from a trial of anti-inflammatory therapy, has yielded promising results in a small cohort of patients [N=16] and requires further study .
Recent TTE data have, however, revealed that it can be more accurately diagnosed by TTE, particularly in a population with a high prevalence of tuberculous pericarditis . To what degree effusive-constrictive pericarditis is associated with an increased risk of progressing to fibrous CP remains to be accurately defined.
Effusive-constrictive pericarditis, in which elevated diastolic filling pressures persist despite the relief of a pericardial effusion, appears most commonly to complicate tuberculous pericarditis . It occurs as a consequence of epicardial inflammation that continues to restrict diastolic ventricular filling after the pericardial space has been evacuated of fluid. It is traditionally defined by the invasive demonstration of persistently elevated right heart filling pressures after the drainage of a pericardial effusion causing pericardial tamponade .
Prevalence and aetiology of CP
The true prevalence of CP remains to be defined . It is known to occur in 0.2-0.4% of patients who have undergone cardiac surgery and has been assessed to occur in less than 1% of cases after idiopathic pericarditis [10,11,12]. In the developed world it most commonly occurs after idiopathic pericarditis, followed by prior cardiac surgery and exposure to prior chest radiotherapy [1,4]. More uncommon aetiologies include rheumatological diseases, malignancy and trauma . The incidence of post-tuberculous CP has always been comparatively low in the developed world as compared to the developing world.
In two large series from the Mayo Clinic, one from 1936 to 1982, and the other from 1985 to 1995, tuberculous pericarditis (TBP) was identified as the aetiology for CP in just 4% and 3% of cases, respectively [13,14]. In sub-Saharan Africa and Asia, TB continues to be the most common cause of CP. The true incidence of tuberculous CP in the developing world is, in all likelihood, underestimated owing to the challenge in establishing a definite diagnosis of TBP during the effusive stage of the disease. It is currently estimated to be 31.65 cases per 1,000 person years, and is second only to purulent disease as a cause of constriction at 52.74 cases per 1,000 person years .
A recent series that evaluated outcomes after pericardiectomy for CP, within a region with a high prevalence of TB, identified only 29.8% of cases as being secondary to confirmed TBP . In Asian series, TB pericarditis is reported to be the underlying aetiology in 20-80% of cases [16,17]. Resurgence in tuberculous CP in developed nations is very likely given the increase in refugees to these areas from the developing world.
Iatrogenic CP may also become more common with the increased uptake of invasive electrophysiology procedures within the pericardial space . Descriptions of iatrogenic CP are currently limited to individual case reports and the true impact thereof remains to be seen.
Early on in the course of the disease, patients may present with symptoms secondary to a reduction in cardiac output rather than those due to elevated filling pressures. These include fatigue and exertional dyspnoea, commonly referred to as “out of puff”. Once the filling pressures become significantly elevated, and systemic venous pressure rises, signs of overt RHF develop . Despite signs of RHF, and given the varying spectrum of clinical presentation and symptoms, patients often undergo extensive workup for the evaluation of ascites or pleural effusions before referral for cardiac evaluation. These commonly include invasive gastrointestinal and thoracic procedures . It is therefore important that clinicians maintain a high index of suspicion for CP as the underlying cause for heart failure symptoms in individuals who have undergone prior cardiac surgery, chest radiotherapy (particularly for breast carcinoma and lymphoma) and who have suffered from pericarditis in the past .
Direct questioning, particularly for a prior history of pericarditis, is relevant in any patient presenting with HFpEF. However, it is not unusual for patients with CP to have suffered from a remote or even undiagnosed episode of pericarditis in the past. This makes the assessment for a possible aetiology that much more challenging.
Jugular venous pressure
The most important diagnostic clue is often found in the careful inspection of the jugular venous pressure (JVP), elevated in 93% of patients with CP, and its waveforms . Quite often the right heart filling pressures are so markedly elevated that the level of the JVP resides within the cranium when the patient is examined in the 45° recumbent position. The level of the JVP may only become visible with the patient in an upright position, and it is therefore imperative to evaluate for it with the patient standing when the diagnosis is suspected .
Markedly elevated right atrial (RA) pressure results in rapid early diastolic filling of the right ventricle (RV). RV filling is in turn brought to an abrupt halt as the inelastic pericardium leads to an abrupt rise in intracavitary pressure during early filling, limiting ventricular volume. The resultant rapid x- and y-descents in RA pressure are respectively due to apical displacement of the tricuspid annulus, followed by rapid early diastolic filling of the RV. They are appreciated in the JVP waveform as rapid, double inward, or collapsing, deflections (Video 1) . These are easily discernible from the prominent single outward deflection produced by CV-waves in the setting of severe tricuspid regurgitation, an important differential diagnosis to exclude as a cause for RHF . Early on in the course of CP, the JVP may be mildly elevated, and careful attention to the waveform will alert the astute clinician to the possible diagnosis. Kussmaul’s sign, observed as either a failure of the JVP to drop, or more commonly a paradoxical inspiratory rise in the JVP, occurs in only 21% of CP cases and is therefore not a sensitive sign . Similarly, pulsus paradoxus, an exaggerated inspiratory drop in systemic blood pressure >10 mmHg, also occurs in a minority (20%) of patients .
Rapid x- and y-descents seen in the JVP of a patient with constrictive pericarditis. These are appreciated as rapid inward “flicking”/collapsing deflections in the presence of an elevated JVP. (Courtesy of Dr. Annari van Rensburg)
Once the disease process is advanced, ascites develops, commonly out of proportion to the degree of pedal oedema. In the absence of careful examination of the JVP, the diagnosis may therefore be overlooked and hepatic pathology may become the focus of investigation. A further consequence of elevated systemic venous pressure is the development of transudative pleural effusions. Dyspnoea can therefore not only be due to the reduced cardiac output state, but also occur as a result of limited diaphragmatic excursion in those with ascites, and be further compounded by large pleural effusions.
Palpation of the precordium
Palpation of the precordium for the finding of a diastolic apex beat or diastolic precordial impulse is just as important as meticulous inspection of the JVP. The abrupt termination to early diastolic ventricular filling that occurs in CP results in the apical impulse being palpable in diastole, rather than in systole [21,22]. To confirm this finding, the apical impulse should be timed against the carotid pulse. Apart from evaluating for the apex, a careful search for diastolic pulsations across the precordium and epigastrium should be undertaken. In our experience, a diastolic impulse is best appreciated either left parasternal or in the epigastrium, and is a useful clinical sign, particularly when the apex beat is impalpable .
Auscultatory findings include a high-pitched early diastolic pericardial knock, audible shortly after the second heart sound and best heard over the left sternal border (Audiofile 1) . It occurs earlier in diastole than an S3 does, and increases in intensity during inspiration . The pericardial knock corresponds to the sudden and abrupt cessation in early ventricular filling caused by the loss of pericardial elasticity that limits ventricular compliance, and has been demonstrated to occur 90-120 ms after aortic valve closure . Sudden instantaneous splitting of the second heart sound on inspiration, whilst described, is perhaps not as useful a clinical sign as the finding of a pericardial knock .
Audiofile 1 (headphones are required).
Typical early diastolic pericardial knock recorded from a patient with constrictive pericarditis. Notice how the intensity of the diastolic pericardial knock increases on inspiration.
It has been our experience, particularly in the setting of post-tuberculous CP, that careful inspection of the JVP, assessing for a diastolic apex beat or precordial impulse and the finding of a pericardial knock, are the most useful clinical signs in a suspected case of CP. This triad of clinical findings was considered to be of particular value before the advent of TTE and remains relevant in the current era of advanced cardiac imaging .
Despite the significant elevation in atrial filling pressures, atrial fibrillation tends to occur in a minority of cases and is also a marker of advanced disease, as is cardiac cachexia [15,20]. Functional tricuspid regurgitation (TR) occurs in a significant number of patients with CP and the classic pansystolic murmur of TR may also be audible .
Constrictive pericarditis, a disease with particularly high morbidity and mortality, remains a challenging clinical diagnosis, and one that is frequently overlooked. It is a potentially curable cause of diastolic heart failure, anti-inflammatory therapy being potentially effective in those with transient CP and pericardiectomy being the treatment in those with chronic disease. The commonest aetiologies are idiopathic pericarditis, prior cardiac surgery and chest radiotherapy in the developed world and TB pericarditis in the developing world. A high index of suspicion for CP is required in those with a predisposing factor and diastolic heart failure. Careful attention to the JVP and its waveforms is of the utmost importance in the clinical evaluation of a suspected case, as is the search for a diastolic apex beat, or precordial impulse, and the auscultatory finding of a pericardial knock.
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Notes to editor
Charles Kyriakakis, MD; Philip Herbst, MD; Anton Doubell, MD, PhD
Division of Cardiology, Stellenbosch University and Tygerberg Hospital, Cape Town,
Author for correspondence:
Dr. Charles Kyriakakis, Division of Cardiology, 8th floor, Green Avenue, Tygerberg Hospital, Parow Valley, Cape Town, 7505, South Africa
Tel: +27 21 938 44 00
None of the authors has declared any potential conflicts of interest with respect to the research, authorship and/or publication of this article.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.