Right Heart Failure

Etiology

RVF most commonly arises from LVF, which causes congestion, increased pressure, and volume overload in the right ventricle.[3] Besides LVF, acute pulmonary conditions that create pressure overload in the right heart can lead to RVF, including the following:

• Pneumonia
• Acute pulmonary embolism
• Mechanical ventilation
• Acute respiratory distress syndrome (ARDS)

Meanwhile, chronic pressure overload conditions contributing to RVF include the following:

• Primary pulmonary arterial hypertension (PAH)
• Secondary pulmonary hypertension
• Congenital heart disease, including pulmonic stenosis, right ventricular outflow tract obstruction, the Ebstein anomaly, tetralogy of Fallot, transposition of great arteries, and hypoplastic left heart

The following conditions result in volume overload causing RVF:

• Right-sided (tricuspid or pulmonic) valvular insufficiency
• Congenital defects with shunts, such as atrial septal defect and anomalous pulmonary venous return

Another important mechanism that leads to RVF is intrinsic right ventricular myocardial disease. The spectrum of disorders with this pathology includes the following:

• Right ventricular ischemia or infarction
• Infiltrative diseases such as amyloidosis or sarcoidosis
• Arrhythmogenic right ventricular dysplasia
• Genetic cardiomyopathies
• Microvascular disease.

RVF may also arise from impaired right ventricular filling, which is seen in the following conditions:

• Constrictive pericarditis
• Tricuspid stenosis
• Systemic vasodilatory shock
• Cardiac tamponade
• Superior vena cava syndrome
• Hypovolemia

Epidemiology

RVF is most often due to LVF, and patients with biventricular failure have a 2-year survival of 23%, compared to 71% in patients with LVF alone.[4][5] In the CHARITEM registry, RVF accounted for 2.2% of heart failure admissions and was secondary to LVF in more than 1/5 of cases. The Egyptian Heart Failure-LT registry reported that 4.5% of patients with acutely decompensated heart failure had RVF, compared to 3% in other regions under the European Society of Cardiology. This difference may be attributed to the higher prevalence of rheumatic heart disease in the region.

Pathophysiology

During fetal development, the right ventricle produces approximately 66% of the cardiac output and, through the ductus arteriosus and foramen ovale, directs blood to the lower body and placenta. At birth, oxygen exposure, nitric oxide, and lung expansion cause a rapid decrease in pulmonary vascular resistance (PVR). The lungs, which were bypassed in utero, become a low-pressure, highly distensible circuit. The thick-walled fetal right ventricle becomes thinner.[6]

The anatomy and resulting function of the right ventricle differ significantly from the left ventricle. For example:

• The right ventricle has a triangular and crescentic shape, consisting of a superficial layer that runs circumferentially parallel to the atrioventricular groove and a deeper layer that extends longitudinally from the base to the apex. This structure limits right ventricular contraction to longitudinal shortening of the tricuspid annulus toward the apex. The free wall of the right ventricle moves inward toward the septum, while the septum contributes to traction by shifting toward the left ventricle during systole.
• The right ventricle is more heavily trabeculated and contains a circumferential moderator band at the apex.
• The tricuspid valve has a large annulus and is tethered by more than 3 papillary muscles, making it vulnerable to structural deformation under sustained pressure or volume overload.
• The thinner wall and lower elastance of the right ventricle render it highly susceptible to afterload increases. Even a modest rise in PVR can significantly reduce right ventricular stroke volume, as seen in conditions such as PAH, pulmonary embolism, mitral valve disease with secondary pulmonary hypertension, and ARDS. The thinner right ventricle is also more sensitive to pericardial constraint.

Like the left ventricle, contraction of the right ventricle depends on preload under normal physiologic filling pressures. Excessive filling of the right ventricle can cause the septum to shift toward the left ventricle, leading to ventricular interdependence and impaired left ventricular function.

Due to lower right-sided pressures and wall stress, the oxygen requirement of the right ventricle is lower than that of the left ventricle. Coronary blood flow and oxygen extraction are also lower in the right ventricle. Consequently, the right ventricle is less vulnerable to ischemic damage. Increases in oxygen demand in the right ventricle are compensated by increased coronary flow or higher oxygen extraction, as seen in PAH cases or during exercise.

Right ventricular function is influenced by atrial contraction, heart rate, and synchronicity. Each factor significantly impacts right ventricular function and has important clinical implications.

The right ventricle’s response to a pathological load is complex and depends on factors such as the nature, severity, chronicity, and timing of the load. For example, in childhood, congenital pulmonic stenosis leads to persistent fetal right ventricular hypertrophy (RVH), allowing the right ventricle to adapt to increased afterload.

In adults, however, the right ventricle’s ability to tolerate a chronic increase in afterload, such as in PAH, is limited. In the early stages of PAH, the right ventricle responds to elevated pulmonary arterial pressures (PAPs) by increasing contractility, with little to no change in right ventricular size. As PAP continues to rise, the right ventricular myocardium begins to hypertrophy, and stroke volume is maintained.

However, the hypertrophy and maintenance of stroke volume are insufficient to normalize wall stress, leading to right ventricular dilation. This dilation is accompanied by rising filling pressures, decreased contractility, loss of synchronicity as the right ventricle becomes more spherical, and dilation of the tricuspid valve annulus. As a result, the valve leaflets fail to coapt properly, causing functional tricuspid regurgitation, which worsens right ventricular volume overload, right ventricular enlargement (RVE), wall stress, and problems with contractility and cardiac output.

Meanwhile, the response of the right ventricle to an acute increase in afterload, such as in acute pulmonary embolism, differs. The right ventricle increases contractility and end-diastolic volume (EDV) but does not have time for the adaptive changes seen in chronic RVF. Rapid failure ensues when the right ventricle cannot generate enough pressure to maintain blood flow.

History and Physical

As with all disease states, the initial assessment of RVF begins with a thorough history and physical examination. The acuity, severity, and etiology should be determined so that an appropriate treatment plan may be put in place.[7]

Clinically, patients present with the signs and symptoms of hypoxemia and systemic venous congestion. These manifestations include breathlessness, chest discomfort, palpitations, and swelling. Meanwhile, common physical examination findings include the following:

• Jugular venous distension 
• Hepatojugular reflux
• Peripheral edema
• Hepatosplenomegaly, often with hepatic pulsation
• Ascites
• Anasarca
• S3 gallop
• Tricuspid regurgitation murmur
• Right ventricular heave
• Signs of concomitant LVF
• Paradoxical pulse

In severe right heart failure, presyncope or syncope may occur when the right ventricle cannot maintain cardiac output. The physical examination findings that may accompany such symptoms include hypotension, tachycardia, cool extremities, delayed capillary refill, central nervous system depression, and oliguria.

Evaluation

Beyond the history and physical examination, the evaluation for RVF may include an electrocardiogram (ECG), arterial blood gas analysis, blood lactate levels, and chest x-ray. Blood work should include markers of end-organ function, such as renal and hepatic panels, to assess severity. A D-dimer is useful in the diagnostic workup of suspected pulmonary embolism. No biomarkers are used specifically to identify RVF. However, B-type natriuretic peptide and cardiac troponin are highly sensitive for early detection of myocardial injury in the setting of RVF. When elevated, these markers are associated with poor prognosis in RVF due to PAH.[8][9]

Noninvasive Diagnostic Modalities

Noninvasive diagnostic examinations that can help evaluate RVF include electrophysiological tools, particularly ECG, and noninvasive imaging tests, including echocardiography and magnetic resonance imaging (MRI). These diagnostic tests serve different purposes but may complement each other in certain cases, offering a more comprehensive assessment.

Electrocardiography

The electrocardiogram in RVF can show 1 or more of the following findings:

• Right axis deviation
• RS ratio of 1 or less in lead V5 or V6, with an S wave amplitude of 7 mm or more in V5 or V6
• Tall P wave in lead II or V1, known as P-pulmonale
• Rhythm abnormalities such as atrial fibrillation or flutter

These findings reflect the electrical disturbances caused by increased pressure and volume overload in the right ventricle.[10]

Echocardiography

Assessing right ventricular function can be challenging due to its location, shape, and afterload dependence. Two-dimensional echocardiography is the 1st-line and most commonly used noninvasive imaging modality to assess right ventricular size, hemodynamics, and function.[11] Images are acquired in multiple cross-sectional planes. The following measurements can be obtained:

• Quantification of right ventricular (RVE) and atrial (RAE) enlargement: Quantitative assessment of right ventricular function is difficult because of its shape. Therefore, the determination of RVE and RAE is accomplished by qualitatively comparing right and left ventricular functions. A normal right ventricle should not be more than 2/3 the size of the left ventricle. RVE is a strong prognostic indicator.

• Tricuspid annular plane systolic excursion (TAPSE): This measurement quantifies the movement of the tricuspid annulus toward the apex and helps estimate right ventricular free wall function. TAPSE has been a good predictor in patients with PAH and LVF. However, this parameter is less reliable in patients with congenital heart disease or previous cardiac surgery. A TAPSE less than 1.6 cm is considered abnormal.

• Right ventricular free wall strain: This tool is also useful in assessing right ventricular function. Strain is a composite measurement of right ventricular loading and dysfunction. Abnormal strain patterns have been associated with disease progression, higher diuretic doses, and mortality in PAH. Right ventricular strain has also been shown to predict RVF after implantation of a left ventricular assist device (LVAD) and clinical outcomes in patients referred for heart transplantation.

• Fractional area of change: This important quantitative measurement of right ventricular systolic function is derived either by 2-dimensional echocardiography or MRI. Fractional area of change is an independent predictor of heart failure, sudden death, stroke, and mortality in pulmonary embolism and myocardial infarction.

• Myocardial performance index (MPI): This parameter estimates global ventricular function and is calculated by adding the isovolumic contraction and relaxation times and then dividing by the ejection time. In RVF, MPI increases as the isovolumic times increase and contraction times decrease. MPI has been shown to predict PAH in connective tissue disease and is an independent PAH prognostic indicator.

• Eccentricity index: This index is useful for assessing RVE. Acquired in the short-axis view, at end-systole and end-diastole, the eccentricity index is a ratio of the length of 2 perpendicular minor-axis diameters, one of which bisects and is perpendicular to the interventricular septum. This measurement allows for the quantitative assessment of septal flattening and distinguishes between pressure and volume overload.

All of the hemodynamic variables measured during invasive right heart catheterization (RHC) may be estimated using echocardiography. For example, the diameter and collapsibility of the inferior vena cava (IVC) in the subcostal view may be used to estimate right atrial filling pressure. A normal IVC collapses more than 50% with inspiration and is associated with right atrial pressure (RAP) of less than 10 mm Hg. By measuring the maximum tricuspid regurgitation velocity and using a modified Bernoulli equation, the right ventricular systolic pressure may be estimated. The diastolic PAP may be estimated by using the same equation with the pulmonic regurgitant jet or by transposing the pulmonary opening time on the tricuspid regurgitant velocity curve and calculating the pressure gradient between the right atrium and the right ventricle.

Three-dimensional echocardiography has also been used more recently to quantify right ventricular volumes and ejection fraction using the modified Simpson method (summation of disks). This method has been validated to correlate well with MRI, the gold standard diagnostic modality. However, this approach is time-consuming and less feasible, given the proximity of the right ventricle to the sternum and its trabeculations.

Nuclear angiography

First-pass radionuclide ventriculography was, for a long time, the gold standard for measuring right ventricular ejection fraction (RVEF). A bolus of the technetium-99m tracer is injected, and a sequence of cardiac cycles is acquired as the bolus passes through the heart. A normal RVEF is 52% plus or minus 6%, with 40% considered the lower limit of normal. Nuclear angiography is limited by its inability to measure right ventricular volumes and its sensitivity to cardiac arrhythmia.

Magnetic resonance imaging

As mentioned, MRI is now the gold standard for measuring right ventricle volumes and function. Besides the right ventricle mass, volumes, and chamber dimensions, MRI can quantify regurgitant volumes, delayed enhancement, scar burden, strain, perfusion, and pulmonary pulsatility. Changes in the global function of the right ventricle after medical therapy have also been shown to directly correlate with functional class and survival in patients with PAH. However, MRI is limited by its temporal resolution, susceptibility artifacts in patients with implantable cardiac devices, and the time required for data acquisition and analysis.

64-Slice computed tomography

Computed tomography (CT) may be used to measure RVEF and right ventricle volumes. However, CT cannot simultaneously measure the parameters of the right ventricle and left ventricle, nor can it perform CT angiography in the same scan. This limitation necessitates additional radiation exposure, which can be significant, making CT less preferred for routine measurement of right ventricle function.

Invasive Hemodynamic Measurement

Right heart or pulmonary artery catheterization is often highly useful in making the diagnosis of RVF and tailoring management. Though it is an invasive procedure, RHC is considered safe with a low complication rate, especially in experienced centers. Current practice guidelines recommend the use of RHC in cases involving an unclear diagnosis or treatment-resistant disease for continuous and accurate measurement of right- and left-sided filling pressures, cardiac output, and PVR.

The hemodynamic variables obtained in an RHC have important prognostic significance. A high RAP and a low cardiac output have repeatedly been shown to be associated with poor outcomes in PAH. In addition, a PVR greater than 3 Woods units and reduced pulmonary vascular compliance (calculated as stroke volume divided by pulmonary pulse pressure) have both been linked to poor outcomes in LVF and PAH.

Treatment / Management

Management of Acute Right Ventricular Failure 

RVF requires timely identification and targeted interventions to address its complex pathophysiology. Management includes both medical and surgical approaches, with the choice guided by severity, underlying causes, and the need to optimize right ventricular function and hemodynamics.

Medical Management

Management of acute RVF begins with assessing the severity of the patient’s condition and determining the need for admission to the intensive or intermediate care unit. Prompt identification and treatment of triggering factors, such as sepsis, arrhythmias, or drug withdrawal, are crucial. Rapid revascularization is critical for a right ventricular infarct, while reperfusion therapy is essential for patients with high-risk pulmonary embolism. As infection portends a very poor prognosis in acute RVF, preventative measures and prompt detection and treatment are important.[12][13]

The mainstay of treatment focuses on 3 tenets: optimizing volume status, increasing RV contractility, and reducing RV afterload. The interventions that help achieve these goals are described below.

Volume loading may be appropriate if the patient is hypotensive and has low or normal filling pressures. Pulmonary artery catheterization or central venous pressure monitoring can be helpful since the right ventricle is preload-dependent. However, volume repletion needs to be approached with caution, as overdistension of the right ventricle may further reduce cardiac output. Intravenous diuresis or renal replacement therapy may be indicated in cases of volume overload. Beyond symptom improvement, diuresis offers additional benefits, including reducing tricuspid regurgitation, restoring synchronous right ventricular contraction, and alleviating ventricular interdependence. Sodium restriction, daily weight monitoring, and strict oversight of fluid intake and urine output are recommended to maintain euvolemia.

Efforts should also focus on restoring sinus rhythm in patients with atrial arrhythmias, given the significant role of atrial contraction in supporting cardiac output in RVF. Additionally, hemodynamically significant tachyarrhythmias and bradyarrhythmias should be addressed. Digoxin may provide benefits for patients with severe PAH. However, caution is necessary when this drug is given to individuals who are critically ill or have renal dysfunction due to its narrow therapeutic window and potential side effects.

Vasopressors are indicated in cases of hemodynamic instability. Norepinephrine is the preferred agent to improve systemic hypotension and restore cerebral, cardiac, and end-organ perfusion. Inotropes such as dobutamine, levosimendan, and the phosphodiesterase-3 inhibitor milrinone are beneficial, as they improve contractility and cardiac output while also promoting pulmonary vasodilation. Dobutamine is the inotrope of choice in RVF cases due to its ability to increase myocardial contractility and decrease afterload through vasodilation, actions that are mediated by β-receptors. However, caution is necessary with both dobutamine and milrinone, as they may lower systemic pressure. A vasopressor may be required if systemic pressure decreases.

When pressure overload is the cause of RVF, such as in PAH cases, reducing afterload with pulmonary vasodilators is the primary therapy. These medications target 3 therapeutic pathways: nitric oxide (NO), endothelin, and prostacyclin. Studies have shown that the acute responsiveness to these drugs has prognostic significance in acute RVF, regardless of the specific drug class used. Besides reducing afterload, certain agents, such as the endothelin receptor antagonist (ERA) bosentan and the phosphodiesterase-5 inhibitor (PDE5I) sildenafil, have been shown to improve right ventricular contractility directly. Pulmonary vasodilators commonly used to treat acute RVF include the following:

• Inhaled nitric oxide (iNO) activates the cyclic guanosine monophosphate (cGMP) pathway to induce pulmonary vasodilation. Rapid inactivation occurs due to hemoglobin in the lung capillaries, preventing systemic hypotension. The agent acts exclusively in ventilated areas of the lung, reducing PAP and PVR while improving oxygenation without exacerbating hypoxia from ventilation-perfusion mismatch or shunting associated with systemic vasodilators. Studies in individuals with acute RVF have demonstrated that iNO, combined with dobutamine, enhances cardiac output, oxygenation, and PVR. Methemoglobinemia must be avoided. Importantly, iNO requires gradual withdrawal to prevent hemodynamic decompensation from rebound pulmonary hypertension.

• Intravenous prostacyclins, including epoprostenol and treprostinil, act via the cyclic adenosine monophosphate pathway to achieve potent pulmonary and systemic vasodilation and inhibit platelet aggregation. Epoprostenol is preferred for critically ill individuals with acute RVF due to its short half-life of 6 minutes. Initial dosing begins at 1 to 2 ng/kg/min, uptitrated as tolerated, with caution in individuals with comorbid conditions, hypoxemia, or hemodynamic instability. Like iNO, prostacyclins decrease PAP and PVR while increasing cardiac output. However, dose-dependent side effects, such as hypotension, nausea, vomiting, diarrhea, and headache, often limit titration. Prospective data on the efficacy of intravenous prostacyclins in acute RVF remain limited.

• Iloprost and treprostinil are inhaled prostacyclins that decrease PVR and improve cardiac output while minimizing systemic side effects. Although treprostinil may also be administered subcutaneously, it is less effective in critically ill and hemodynamically unstable individuals due to unpredictable absorption and a longer half-life.

• ERAs and PDE5Is are oral pulmonary vasodilators that lower PAP and PVR and improve cardiac output in individuals with RVF. ERAs block the endothelin-A and -B receptors in endothelial and vascular smooth muscle cells, reducing the vasoconstrictive, proliferative, and pro-inflammatory effects of endothelin. However, their use in intensive care settings is limited by their long half-life and potential hepatotoxicity, as seen with bosentan. PDE5Is prevent the degradation of cyclic guanosine monophosphate. Besides their hemodynamic benefits, PDE5Is have been shown to reduce hypoxic pulmonary vasoconstriction and the upregulation of pro-inflammatory cytokines caused by hypoxic pulmonary vasoconstriction. Limited data suggest potential benefits for individuals with RVF following mitral valve repair, coronary artery bypass grafting, or LVAD placement. Preliminary evidence also indicates that these agents may have the ability to reduce rebound pulmonary hypertension during the weaning of individuals with PAH from inhaled nitric oxide.

Caution is necessary for patients requiring mechanical ventilation, as excessive tidal volumes and positive end-expiratory pressure (PEEP) increase PAP, RAP, and right ventricular afterload. Additionally, PEEP may worsen the condition by reducing venous return in the preload-dependent right ventricle. While permissive hypercapnia can lead to vasoconstriction, which increases PAP and worsens RVF, hyperventilation acutely reduces PAP and counters acidosis-induced vasoconstriction. Care must be taken to avoid high tidal volumes in this setting. The optimal ventilator settings for a patient with RVF ensure adequate oxygenation and ventilation while minimizing tidal volume, plateau pressure, and PEEP.

Surgical Management and Interventional Therapies

For patients with reversible RVF refractory to medical therapy, surgical options are indicated as either a bridge to recovery or transplantation. Surgery may also be indicated for patients with RVF due to valvular heart disease, congenital heart disease, or chronic thromboembolic pulmonary hypertension (CTEPH). Adequate preoperative diuresis is essential, and pulmonary vasodilators and inotropes may be required perioperatively. Irreversible end-organ damage is a contraindication for surgical management.

Venoarterial extracorporeal membrane oxygenation (ECMO) may be considered as salvage therapy in patients with massive pulmonary embolism and refractory cardiogenic shock after systemic thrombolysis. ECMO may also serve as a bridge to lung or heart-lung transplantation in patients with severe RVF due to end-stage PAH.

Mechanical support with a right ventricular assist device (RVAD) may be an option for patients with isolated RVF awaiting transplantation. However, ECMO may be a more effective treatment for unloading the right ventricle in cases of severely increased PVR, as pumping blood into the pulmonary artery may worsen pulmonary hypertension and cause lung injury.

Patients with RVF due to LVF may benefit from LVAD implantation, which can improve PAP before heart transplantation and potentially enhance posttransplant survival. However, LVADs may worsen or induce new RVF due to alterations in right ventricular geometry and flow or pressure dynamics, necessitating biventricular support.

Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension and is often curative. PTE has been shown to improve functional status, exercise tolerance, quality of life, gas exchange, hemodynamics, right ventricular function, and survival, particularly in patients with proximal lesions and minimal small vessel disease. PTE is not recommended for patients with massively elevated PVR greater than 1,000 to 1,200 dyn/cm. PTE outcomes directly correlate with surgeon and center experience, the alignment between anatomic disease and PVR, preoperative PVR, absence of comorbidities (especially splenectomy and ventricular-atrial shunt), and postoperative PVR. Operative mortality in experienced centers ranges from 4% to 7%. PTE should not be delayed in operative candidates in favor of pulmonary vasodilator therapy.

Surgical embolectomy or percutaneous embolectomy may be used for acute RVF in the setting of massive pulmonary embolism. However, data comparing embolectomy with thrombolysis are limited.

Balloon atrial septostomy (B-AS) is indicated for patients with PAH with syncope or refractory RVF to decompress the right atrium and ventricle and improve cardiac output by creating a right-to-left shunt. B-AS may serve as a bridge to transplantation or as palliative therapy in advanced RVF or PAH, particularly when pulmonary vasodilators are unavailable or poorly tolerated. Mortality associated with B-AS is low (approximately 5%), especially in experienced centers, although spontaneous closure of the defect may require repeat procedures. Contraindications for B-AS include RAP greater than 20 mm Hg, oxygen saturation less than 90% on room air, severe RVF requiring cardiorespiratory support, pulmonary vascular resistance index (PVRI) greater than 55 U/m, and left ventricular end-diastolic pressure greater than 18 mm Hg.

Cardiac resynchronization therapy (CRT) restores mechanical synchrony in the failing left ventricle, leading to improved hemodynamics, reverse remodeling, and enhanced morbidity and mortality outcomes in LVF. Animal studies and small case series suggest that right ventricular pacing results in acute hemodynamic improvement in patients with RVF associated with PAH. However, no data shows long-term clinical benefits in this population.

Ultimately, heart, lung, or combined heart-lung transplantation (HLT) is the definitive treatment for end-stage RVF. In patients with RVF due to PAH, a RAP greater than 15 and cardiac index less than 2.0 are poor prognostic indicators, warranting referral for transplantation. The exact point at which the right ventricle becomes irreversibly damaged is unclear. However, the right ventricle is generally resilient, and lung transplant alone is often sufficient, with an estimated 1-year survival rate of 65% to 75% and a 10-year survival rate of 45% to 66%.

Congenital patients with RVF in the setting of Eisenmenger syndrome may undergo lung transplantation with the repair of simple shunts, such as atrial septal defects, at the time of surgery or combined HLT, which has shown a survival benefit in this population.

Differential Diagnosis

The differential diagnosis of right heart failure includes the following conditions:

• Cirrhosis
• Community-acquired pneumonia
• Emphysema
• Goodpasture syndrome
• Idiopathic pulmonary fibrosis
• Interstitial (nonidiopathic) pulmonary fibrosis
• Myocardial infarction
• Nephrotic syndrome
• Neurogenic pulmonary edema
• Pneumothorax imaging
• Pulmonary embolism
• Respiratory failure
• Venous insufficiency
• Viral pneumonia

A thorough clinical assessment and judicious use of diagnostic examinations can differentiate RVF, determine its etiology, and inform management.