Right heart failure: Clinical manifestations and diagnosis

INTRODUCTION — Right heart failure (RHF) is a clinical syndrome in which symptoms and signs are caused by dysfunction of the right heart structures (predominantly the right ventricle [RV] but also the tricuspid valve apparatus and right atrium) or pericardium, resulting in impaired ability of the right heart to perfuse the lungs at normal central venous pressures [1-3]. The terms RHF and RV dysfunction are not synonymous, as some patients have asymptomatic RV dysfunction, and not all RHF is caused by RV dysfunction. Many specific cardiovascular disorders lead to the clinical syndrome of RHF through a variety of mechanisms.

This topic will address unique aspects of pathophysiology, clinical manifestation, and diagnosis of RHF. Evaluation of the cause and management of RHF are discussed separately. (See "Right heart failure: Causes and management".)

Other aspects of HF are discussed separately, including the diagnosis and evaluation of HF, management of HF with reduced ejection fraction (HFrEF), and management of HF with preserved ejection fraction (HFpEF). (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Determining the etiology and severity of heart failure or cardiomyopathy" and "Overview of the management of heart failure with reduced ejection fraction in adults" and "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis" and "Treatment and prognosis of heart failure with preserved ejection fraction".)

ETIOLOGY — RHF may develop acutely or chronically and may be caused by acquired or congenital forms of cardiovascular disease [1,2]. The most common causes of RHF are acquired forms of left-sided HF, particularly HFpEF and various causes of HFrEF. Evaluation of patients with RHF to identify the cause is discussed separately. (See "Right heart failure: Causes and management", section on 'Evaluating the cause of right heart failure'.)

PREVALENCE AND DEMOGRAPHICS — The broad array of causes of the clinical syndrome of RHF and the lack of standardized definitions [3] make it difficult to reach precise estimates on the prevalence of RHF, but it is highly prevalent in patients with HFrEF or HFpEF. A meta-analysis estimated the prevalence of RV dysfunction in patients with HFrEF at 48 percent [4]. In HFpEF, the prevalence of RV dysfunction is estimated to be somewhat lower at 20 to 40 percent, depending upon the method used to assess RV function [5-7]. However, RV function may deteriorate during exercise as compared with rest [8,9], so even among patients with left-sided HF and normal RV function at rest, there may be significant impairments in RV functional reserve during exercise [10].

Among patients with HF, patient characteristics associated with RHF and RV dysfunction include higher pulmonary artery pressures, higher left atrial pressure, lower left ventricular (LV) ejection fraction, coronary artery disease, male sex, obesity, pulmonary disease, sleep-disordered breathing, and diabetes mellitus [5,6,11,12]. Among patients with HFpEF, additional clinical features associated with RHF include atrial fibrillation and evidence of left atrial remodeling [5,11,13,14]. In a study of 271 patients with HFpEF, development of atrial fibrillation was the strongest risk factor predicting incident development of RV dysfunction [11]. Opening of the pericardium in patients undergoing cardiac surgery has been found to cause a reduction in longitudinal RV function and a gain in transverse shortening [15]. Chronic kidney disease is commonly associated with RHF, and this relationship is believed to be in part related to renal venous hypertension caused by elevated central venous pressures [16-18]. (See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology", section on 'Increased renal venous pressure'.)

PATHOPHYSIOLOGY — The pulmonary circulation is a high compliance, low resistance vascular bed that accommodates a large volume of blood flow with minimal increase in pressures under normal conditions [19]. As such, the RV normally ejects blood at very low pressure, as compared with the much thicker-walled LV. Thus, the RV is generally far more afterload sensitive than the LV [19,20]. For this reason, acute increases in pulmonary artery (PA) pressure, such as that caused by acute pulmonary embolism, may precipitate cardiogenic shock because the RV cannot generate sufficient pressure to maintain pulmonary perfusion [21]. (See "Epidemiology and pathogenesis of acute pulmonary embolism in adults", section on 'Pathophysiologic response to PE'.)

With chronic, sustained increases in PA pressure (as in most acquired forms of RHF), there are hypertrophic adaptations in the RV that allow for maintenance of forward flow despite the increase in RV afterload [1,20]. Overtime, this adaptive hypertrophy progresses and becomes maladaptive, leading to RV dilation and progressive myocardial dysfunction [11]. With increasing RV volumes, there is dilation of the tricuspid valve apparatus, causing functional tricuspid regurgitation. This further increases the volume load in the right atrium and RV, promoting further dilation and increasing severity of tricuspid regurgitation as part of a vicious cycle [11]. Atrial fibrillation often develops in the setting of progressive atrial enlargement, but the relationship is bidirectional, as atrial fibrillation also leads to worsening RV dysfunction. (See "Etiology, clinical features, and evaluation of tricuspid regurgitation", section on 'Pathophysiology' and "The management of atrial fibrillation in patients with heart failure", section on 'mechanisms of cardiac dysfunction'.)

Right-sided chamber dilation increases total heart volume, but total heart size is constrained by the pericardium, which cannot acutely enlarge as much as the heart. Pericardial constraint can cause near equalization of diastolic pressures in the left and right sides of the heart [20,22,23]. The RV and LV share common muscle fibers in the interventricular septum, and RV dysfunction may compromise LV diastolic filling by shifting the septum from right to left in a process termed "diastolic ventricular interaction" [22]. In this setting, left-sided cardiac pressures are elevated, but the LV may still be relatively underfilled due to excessive RV congestion, particularly during exercise as RV volumes further increase due to enhanced venous return [9]. Similarly, LV systolic function may be impaired in the setting of RHF through systolic ventricular interaction [5,24]. (See "Approach to evaluation of the right ventricle in adults", section on 'Pathophysiology'.)

Impaired RV systolic function, increasing tricuspid valve regurgitation, and impaired LV filling reduce forward stroke volume and cardiac output [9]. This leads to neurohormonal activation that promotes renal sodium and water retention [25]. The consequent volume overload and myocardial dysfunction cause marked elevation in central venous pressure. This increases hydrostatic pressures in the tissues and reduces lymph flow. This reduces fluid removal from the interstitial and alveolar spaces of the lungs, promoting development of pulmonary edema [26]. Systemic venous hypertension elsewhere in the body leads to gut and lower extremity edema, ascites, and liver dysfunction from congestive hepatopathy that may progress to cirrhosis [27]. Increases in central venous pressure also increase renal vein pressure and play a key role in promoting cardiorenal syndrome [16-18,28]. (See "Congestive hepatopathy" and "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology", section on 'Pathophysiology'.)

CLINICAL MANIFESTATIONS

Common clinical settings — Patients with RHF typically have an antecedent history of known left-sided HF, valve disease, pulmonary hypertension, or congenital heart disease. However, some patients will present with de novo symptoms and signs of RHF (such as unexplained ascites or dyspnea) to primary care physicians and non-cardiology specialty clinics, such as gastroenterology or pulmonary medicine.

Symptoms and signs — Symptoms are often nonspecific and similar to those in patients with left-sided HF, but often more severe [1,2]. Dyspnea on activity and increased fatigability with activity are common. Orthopnea and paroxysmal nocturnal dyspnea may be reported in patients with biventricular HF. Patients may also complain of chest discomfort, which often resembles angina, caused by elevation in intracardiac pressures that reduces coronary perfusion pressure and may cause subendocardial ischemia. Patients describe abdominal distention, anorexia, and early satiety due to hepatosplanchnic congestion and gut edema. Exercise capacity is characteristically depressed in patients with RHF due to left HF or other causes [8,9].

Physical examination is notable for jugular venous distention, often with a prominent V wave and positive Kussmaul sign. Lower extremity edema (generally bilateral and pitting) is usually present. Patients may appear cachectic, with loss of muscle mass despite stable or increased body weight, due to worsening fluid retention. Abdominal distention with a positive fluid wave (consistent with ascites) and hepatomegaly may be seen. Common findings on cardiac examination include an RV heave on palpation in the precordial region, a loud P2 sound (caused by pulmonary hypertension), and a murmur of tricuspid regurgitation (generally a holosystolic murmur over the left lower sternal border). (See "Examination of the jugular venous pulse" and "Examination of the precordial pulsation", section on 'Right ventricular impulse' and "Auscultation of heart sounds", section on 'Factors determining the intensity of S2' and "Auscultation of cardiac murmurs in adults", section on 'Tricuspid regurgitation'.)

Initial tests — Initial tests include serum electrolytes, complete blood count (which often reveals anemia), tests of kidney function (blood urea nitrogen and serum creatinine), liver biochemical tests, an electrocardiogram, and a chest radiograph. Measurement of the level of plasma natriuretic peptide (B-type natriuretic peptide or N-terminal proBNP) is suggested if a diagnosis of HF is uncertain. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Natriuretic peptide'.)

In patients with chronic RHF, kidney function tests typically reveal evidence of chronic kidney disease, often with marked elevation in blood urea nitrogen relative to serum creatinine. (See "Assessment of kidney function" and "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology", section on 'Diagnosis'.)

Congestive hepatopathy caused by RHF commonly causes elevation in serum bilirubin, which is generally mild but can be severe with acute severe RHF. Serum alkaline phosphatase levels are usually normal or minimally elevated with acute RHF, but greater elevations may be seen with chronic severe RHF. Serum aminotransferase levels are elevated in about one-third of patients with congestive hepatopathy. Hypoalbuminemia is observed in some patients but does not correlate with the degree of histologic liver damage and may be caused by malnutrition and protein-losing gastroenteropathy caused by elevated lymphatic pressure. Mild elevation in the prothrombin time is commonly seen and may be caused by impaired hepatic synthetic function as well as other factors. (See "Congestive hepatopathy", section on 'Laboratory testing'.)

Electrocardiography may reveal atrial fibrillation and/or evidence of RV strain, with T-wave inversions in the anterior precordial leads. (See "ECG tutorial: Chamber enlargement and hypertrophy", section on 'Right ventricular hypertrophy'.)

Levels of plasma natriuretic peptides are generally elevated in patients with RHF, but these markers do not distinguish between RHF and left-sided HF. (See "Natriuretic peptide measurement in heart failure".)

Chest radiography typically shows an enlarged right heart border, often accompanied by findings of left-sided HF. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Chest radiograph'.)

DIAGNOSIS

When to suspect right heart failure — RHF should be suspected in patients with symptoms and signs of RHF, particularly in the presence of an acute or chronic condition that may cause or precipitate RHF. (See 'Common clinical settings' above.)

Evaluation of patients with left-sided HF (LHF) should include evaluation for RHF as, LHF is the most common cause of RHF [1]. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults".)

Diagnostic criteria — A clinical diagnosis of RHF is made when central venous pressure is elevated (>10 mmHg) and there is evidence of right heart dysfunction or pericardial disease. We identify decompensated RHF if there is elevated central venous pressure together with reduced cardiac index (<2.2 L/min/m²) and/or reduced stroke volume index (<38 mL/m²). These hemodynamic findings are associated with adverse outcomes for RHF associated with a number of different causes, including various forms of pulmonary hypertension (PH) and congenital heart disease [29-31].

A definitive diagnosis of RHF requires invasive assessment, which is indicated when treatment decisions will be altered by the information. Since RHF is defined as a clinical syndrome caused by inability of the right heart to perfuse the lungs at normal filling pressures, the gold standard for diagnosis of RHF is direct demonstration of elevated RV filling pressure (central venous pressure), with or without a reduction in cardiac output [3]. (See 'Cardiac catheterization' below.)

Diagnostic testing — Diagnostic testing for RHF includes the above described clinical evaluation (history, physical examination, and initial laboratory testing to identify symptoms and signs of RHF) and tests to assess the right (and left) heart, starting with echocardiography with additional imaging as needed. (See 'Clinical manifestations' above and "Approach to evaluation of the right ventricle in adults", section on 'Approach to evaluation of the RV'.)

Echocardiography — Echocardiography with Doppler plays an essential role in the evaluation of a patient with suspected RHF [1,2]. The RV has a complex geometry, shaped like a triangle in the long axis and a crescent situated over the LV in the short axis. Therefore, RV volume is difficult to measure by echocardiography, but clinically relevant measures of RV dimension provide information on remodeling. RV systolic function is measured by a number of indices based upon 2D imaging, tissue Doppler, and strain imaging [2,20,32]. Right atrial size, the size and collapsibility of the inferior vena cava, tricuspid regurgitation severity, and estimated pulmonary artery (PA) pressure all provide important information as to the severity of RV dysfunction, the degree of right heart congestion present, and the magnitude of coexisting PH. (See "Approach to evaluation of the right ventricle in adults" and "Echocardiographic assessment of the right heart".)

In patients with RHF following left ventricular assist device (LVAD) placement, LVAD device settings are adjusted to minimize interventricular septal bowing on echocardiography. (See "Management of long-term mechanical circulatory support devices", section on 'Right heart failure'.)

Additional imaging — If the results of echocardiography are non-diagnostic (technically suboptimal or otherwise limited), additional cardiac imaging is indicated. Cardiovascular magnetic resonance imaging (CMR) is generally the preferred advanced imaging approach to assess RV structure and function. (See "Approach to evaluation of the right ventricle in adults", section on 'Additional evaluation'.)

Cardiovascular magnetic resonance imaging — CMR is the most accurate method to quantify RV volumes, RV ejection fraction, and RV mass; it also enables assessment of regional RV and LV wall motion and myocardial scar and inflammation (via contrast enhancement) [20]. (See "Approach to evaluation of the right ventricle in adults", section on 'Cardiovascular magnetic resonance'.)

Inflammation and tissue fibrosis may be evaluated using gadolinium-enhanced contrast imaging, but the role of such assessment is not established for general assessment of RHF. Use of gadolinium-enhanced contrast imaging to assess myocardial disease is discussed separately. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Gadolinium contrast techniques'.)

Computed tomography — If CMR is unavailable or contraindicated, or there is a concurrent indication for computed tomography (CT; such as suspected acute pulmonary embolism), cardiac CT may be used to assess RV size and function [1]. However, CT entails exposure to ionizing radiation exposure.

Radionuclide imaging — Radionuclide imaging is less commonly used in the current era given poorer spatial resolution as compared with CMR and CT but may provide useful information when performed for other indications (eg, stress testing to evaluate ischemic heart disease).

Right upper quadrant ultrasonography — The role of ultrasonography and other testing in confirming a diagnosis of congestive hepatopathy is discussed separately. (See "Congestive hepatopathy", section on 'Diagnosis'.)

Cardiac catheterization — Cardiac catheterization is the definitive test to diagnose RHF and is indicated when this information cannot be determined using noninvasive tests and is required for treatment decisions [33,34]. Right heart catheterization enables direct quantification of left and right heart filling pressures, PA pressures, pulmonary and systemic vascular resistances, and cardiac output. Left heart catheterization enables assessment of LV end-diastolic pressures as well as coronary angiography.

Cardiac catheterization is helpful in identifying the cause of RHF (particularly PH and its hemodynamic causes, acute or chronic ischemic heart disease, pericardial disease, and RHF following LVAD placement), as discussed further separately. (See "Right heart failure: Causes and management", section on 'Evaluating the cause of right heart failure'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for RHF includes a variety of other conditions that cause similar clinical features but can generally be distinguished by history, physical examination, cardiac imaging and other tests:

●Vena cava obstruction or stenosis presents with clinical manifestations like those with RHF, with subacute or acute symptoms and signs of venous obstruction or insufficiency in the absence of associated cardiac and pericardial disease. Vena cava obstruction is confirmed by imaging, as discussed separately. (See "Malignancy-related superior vena cava syndrome" and "Overview of iliocaval venous obstruction" and "Overview of thoracic central venous obstruction".)

●Other causes of bilateral pitting lower extremity edema include nephrotic syndrome, bilateral deep venous thrombosis, and medications (such as dihydropyridine calcium channel blockers). These other causes of peripheral edema are distinguished from RHF by absence of evidence of elevated central venous pressure and right heart dysfunction, as well as evidence of other causes (such as proteinuria in nephrotic syndrome, history and signs consistent with DVT, and medication history). (See "Clinical manifestations and evaluation of edema in adults", section on 'Patients with bilateral leg edema'.)

●Other causes of ascites include cirrhosis, cancer, and tuberculosis (table 1). Patients with ascites should undergo a diagnostic paracentesis. In patients with congestive hepatopathy, there is typically a high ascitic protein content (generally >2.5 g/dL). (See "Evaluation of adults with ascites" and "Congestive hepatopathy", section on 'Diagnosis'.)

●The differential diagnosis of congestive hepatopathy includes other causes of liver disease, including viral hepatitis and hemochromatosis; evaluation of these alternate causes is discussed separately. (See "Congestive hepatopathy", section on 'Diagnosis'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults".)

SUMMARY AND RECOMMENDATIONS

●Definition and etiologies – Right heart failure (RHF) is a clinical syndrome in which symptoms and signs are caused by dysfunction of the right heart structures (predominantly the right ventricle [RV], but also the tricuspid valve apparatus and right atrium) or pericardial disease resulting in impaired ability of the right heart to perfuse the lungs at normal central venous pressures. RHF may develop acutely or chronically and may be caused by acquired or congenital forms of cardiovascular disease. (See 'Introduction' above and 'Etiology' above.)

●Prevalence and demographics – Although the overall prevalence of RHF has not been fully defined, RHF is highly prevalent in patients with HF with reduced ejection fraction or HF with preserved ejection fraction. (See 'Prevalence and demographics' above.)

●Pathophysiology – Acute increases in pulmonary artery pressure cause acute RHF and may result in cardiogenic shock, since the RV is far more afterload sensitive than the left ventricle (LV). (See 'Pathophysiology' above.)

Chronic RHF is most commonly caused by chronic RV pressure and/or volume overload, which causes progressive RV remodeling, leading to RV dilation and myocardial dysfunction, commonly associated with progressive functional tricuspid regurgitation. RV dilation and pericardial constraint may in turn compromise LV diastolic and systolic function. (See 'Pathophysiology' above.)

●Common clinical settings – Patients with RHF typically have an antecedent history of known left-sided HF, valve disease, pulmonary hypertension, or congenital heart disease, although some patients will present with de novo symptoms and signs of RHF (such as unexplained ascites or dyspnea) to primary care physicians and non-cardiology specialty clinics. (See 'Common clinical settings' above.)

●Clinical manifestations – Clinical manifestations of RHF include dyspnea, fatigue chest discomfort, abdominal distention with a positive fluid wave, jugular venous distention, a right ventricular heave, a loud P2, and murmur of tricuspid regurgitation (a holosystolic murmur over the left lower sternal border). Marked elevation in blood urea nitrogen relative to serum creatinine is commonly seen in patients with chronic RHF. Congestive hepatopathy caused by RHF commonly causes elevation in serum bilirubin. (See 'Clinical manifestations' above.)

●Diagnostic criteria – A clinical diagnosis of RHF is made when the central venous pressure is elevated (>10 mmHg) and there is evidence of right heart dysfunction or pericardial disease. An invasive evaluation is indicated when treatment decisions will be altered by the information. A definitive diagnosis of RHF is made by direct invasive demonstration of elevated RV filling pressure (central venous pressure). (See 'Diagnostic criteria' above.)