Continuing Education Activity

Heart failure is a condition in which the heart loses its ability to pump blood efficiently to the rest of the body. Right heart failure is most commonly a result of left ventricular failure via volume and pressure overload. Clinically, patients will present with signs and symptoms of chest discomfort, breathlessness, palpitations, and body swelling. This condition is evaluated using non-invasive techniques such as echocardiography, nuclear angiography, MRI, 64-slice CT, as well as invasive hemodynamic measurements. Management is aimed at increasing right ventricular contractility, reducing right ventricular afterload and optimizing volume status. This activity reviews the evaluation and management of right heart failure and highlights the role of the interprofessional team in improving care for affected patients.

Objectives:

• Review the presentation of a patient with right heart failure.
• Describe the workup of a patient with right heart failure.
• Identify the treatment options for right heart failure.
• Outline the importance of collaboration and communication among the interprofessional team members to recognize the clinical signs of heart failure and evaluate it using non-invasive and invasive measures which will enhance the delivery of care for the affected patients.

Introduction

When addressing heart failure, most commonly, the left ventricle (LV) is the topic of discussion, and the right heart overlooked. However, the right ventricle (RV) is unique in structure and function and is affected by a set of disease processes that rival that of the LV. This article will review the normal structure and function of the RV, describe the pathophysiology of RV failure (RVF), and detail the medical and surgical management of the various disease processes during which RVF occurs.[1][2]

Etiology

Right ventricular failure (RVF) is most commonly a result of left ventricular failure (LVF), via pressure and volume overload.[3]

In addition to LVF, there are other conditions of pressure overload that lead to RVF. These include transient processes such as:

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

Furthermore, chronic conditions of pressure overload may lead to RVF. These include:

• Primary pulmonary arterial hypertension (PAH) and secondary pulmonary hypertension (PH) as seen in chronic-obstructive pulmonary disease (COPD) or pulmonary fibrosis)
• Congenital heart disease (pulmonic stenosis, right ventricular outflow tract obstruction, or a systemic RV).

The following conditions result in volume overload causing RVF:

• Valvular insufficiency (tricuspid or pulmonic) 
• Congenital heart disease with a shunt (atrial septal defect (ASD) or anomalous pulmonary venous return (APVR)).

Another important mechanism that leads to RVF is intrinsic RV myocardial disease. This includes:

• RV ischemia or infarct
• Infiltrative diseases such as amyloidosis or sarcoidosis
• Arrhythmogenic right ventricular dysplasia (ARVD)
• Cardiomyopathy
• Microvascular disease.

Lastly, RVF may be caused by impaired 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 a result of LVF, and patients with biventricular failure have a 2-year survival of 23% versus 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 one-fifth of cases. In the Egyptian Heart Failure-LT registry, 4.5% of patients presenting with acutely decompensated heart failure had RVF versus 3% in other regions of the European Society of Cardiology. It has been proposed that this difference is due to the increased prevalence of rheumatic heart disease in this region.

Pathophysiology

During fetal development, the RV accounts for approximately 66% of the cardiac output, and via the ductus arteriosus and foramen ovale, shunts blood to the lower body and placenta. At birth, exposure to oxygen and nitric oxide, as well as lung expansion, leads to 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 RV becomes thinner.[6]

Anatomically the structures and resulting function of the RV and the LV are vastly different. For example:

• The LV is elliptical and made of thick muscle fibers wrapped in two anti-parallel layers separated by a circumferential band. This results in a complex contraction that involves torsion, thickening, and shortening.
• The RV, in contrast, takes a triangular and crescentic shape and is made up of both a superficial layer that runs circumferentially and parallels to the atrioventricular groove and a deeper layer that runs longitudinally from the base to the apex. Because of its structure, the contraction of the RV is limited to longitudinal shortening of the tricuspid annulus towards the apex. The RV free wall is displaced inward toward the septum and traction is created by the septum as it moves toward the LV in systole. 
• The RV is more heavily trabeculated and contains a circumferential moderator band at the apex. 
• The tricuspid valve (TV) is unique in that it has a large annulus and is tethered by greater than three papillary muscles which make it vulnerable to structural deformation under sustained increased pressure or volume loading.
• Because the RV is substantially thinner than the LV with lower elastance, the RV is much more susceptible to increases in afterload. A modest change in PVR may result in a marked decrease in RV stroke volume. This is evident in patients with pulmonary arterial hypertension (PAH), pulmonary embolism (PE), mitral valve disease with secondary pulmonary hypertension (PH), and the adult respiratory distress syndrome (ARDS). The thinner RV is also more sensitive to the pericardial constraint.

Like the LV, contraction of the RV is preload dependent at normal physiologic filling pressures, and excessive RV filling can result in a shift of the septum towards the LV and ventricular interdependence causing impaired LV function.  

Because of lower right-sided pressures and wall stress, the oxygen requirement of the RV is lower than that of the LV. Coronary blood flow to the RV is lower, as is oxygen extraction. For this reason, the RV is less susceptible to ischemic insults, and increases in oxygen demand are met via increases in coronary flow as is the case in PAH or increased oxygen extraction which occurs with exercise.

RV function is affected by atrial contraction, heart rate, and synchronicity. Each of these has important clinical implications, and RVF for any reason is a strong prognostic indicator.

The response of the RV to a pathologic load is complex. The nature, severity, chronicity, and timing (in utero, childhood or adulthood) each play a role in how the RV responds to an increased load. For example, in childhood, when confronted with congenital pulmonic stenosis, fetal right ventricular hypertrophy (RVH) persists and allows the RV to compensate for the increase in afterload.

In adulthood, however, the ability of RV to tolerate a chronic increase in afterload, such as that seen in PAH, is poor. In the early stages of PAH, the RV responds to elevated pulmonary arterial pressures (PAP) by increasing contractility, with little to no change in RV size. As PAP continue to rise, the RV myocardium begins to hypertrophy, and RV stroke volume (SV) is maintained. This, however, is not enough to normalize wall stress, and subsequently, dilatation occurs. This is accompanied by rising filling pressures, decreased contractility, loss of synchronicity as the RV becomes more spherical, and dilatation of the TV annulus resulting in poor coaptation of the valve leaflets and functional tricuspid regurgitation (TR). The TR worsens the RV volume overload, RV enlargement (RVE), wall stress, contractility and cardiac output.

This differs from the response of the RV to an acute increase in afterload, such as that seen with an acute PE. In this case, the RV responds with an increase in contractility and end-diastolic volume, but does not have time for the adaptations that are seen in chronic RVF to occur, and quickly fails when unable to generate enough pressure to maintain 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.

Clinically, patients present with the signs and symptoms of hypoxemia and systemic venous congestion. These include:

• Breathlessness
• Chest discomfort
• Palpitations
• Swelling.

Common findings on the exam include:

• Jugular venous distension 
• Hepatojugular reflux
• Peripheral edema
• Hepatosplenomegaly/hepatic pulsation
• Ascites
• Anasarca
• S3 gallop
• TR murmur
• RV heave
• Signs of concomitant LVF
• Paradoxical pulse.

When severe, presyncope or syncope may occur when the RV is unable to maintain cardiac output. This is accompanied on the exam by the following:

• Hypotension
• Tachycardia
• Cool extremities
• Delayed capillary refill
• Central nervous system depression
• Oliguria. 

Evaluation

After the history and physical, the evaluation continues with an electrocardiogram, arterial blood gas, blood lactate, and chest x-ray.  Blood work should include markers of end-organ function (renal and hepatic panel) to assess severity. A D-Dimer is useful in the diagnostic workup of suspected PE. There are no biomarkers specific for RVF, however B-type natriuretic peptide and cardiac troponin are highly sensitive for early detection of RVF and myocardial injury. When elevated, these are associated with poor prognosis in RVF due to PAH. [7][8]

Noninvasive Measures

Echocardiography

The assessment of RV function can be challenging because of its location, shape and afterload dependence. Two-dimensional echocardiography (2DE) is the first-line and most commonly used non-invasive imaging modality to assess RV size, hemodynamics, and function.  Images are acquired in multiple cross-sectional planes, and and the following measurements obtained:

• Quantification of RV enlargement (RVE) and right atrial enlargement (RAE): Because of its shape, quantitative assessment of RV function is difficult and is often described qualitatively in comparison with LV function. A normal RV should not be more than two-thirds the size of the LV. RVE is a strong prognostic indicator.
• TAPSE: Used to quantify the movement of tricuspid annulus toward the apex and estimates RV function. This has been a good predictor in patients with PAH and LVF, however, in patients with congenital heart disease or after cardiac surgery, it is less reliable.
• Right ventricular strain: Another useful tool to assess RV function. The strain is a composite measurement of RV loading and dysfunction- abnormal strain patterns have been associated with disease progression, higher diuretic doses, and mortality in PAH.   The strain has also been shown to predict RVF after implantation with a left ventricular assist device (LVAD) and predicts clinical outcomes in those referred for heart transplantation.
• Fractional area of change (FAC): An important quantitative measurement of RV systolic function derived either by 2DE or magnetic resonance imaging (MRI). It has been shown to be an independent predictor of HF, sudden death, stroke and mortality in PE and in myocardial infarction.
• Myocardial performance index (MPI): Estimates global ventricular function and is calculated by adding the isovolumic contraction and relaxation times divided 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 prognostic indicator in PAH. 
• Eccentricity index: A useful measurement of RVE. Acquired in the short-axis view, at end-systole and end-diastole, the eccentricity index is a ratio of the length of two perpendicular minor-axis diameters, one of which bisects and is perpendicular to the interventricular septum. This allows for a quantitative measurement 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 RA filling pressure. A normal IVC collapses more than 50% with inspiration and is associated with a RA pressure less than 10 mmHg. By measuring the maximum TR velocity and using a modified Bernoulli equation, the systolic PAP may be estimated. The diastolic PAP may be estimated by using the  same equation on the pulmonic regurgitant jet or by transposing the pulmonary opening time on the tricuspid regurgitant velocity curve and calculating the pressure gradient between the RA and the RV.

Three-dimensional echocardiography has also been used more recently to quantify RV volumes and ejection fraction using a modified Simpson’s method (summation of disks). This has been validated to correlate well with the gold standard MRI, but is time-consuming and less feasible given the proximity of the RV to the sternum and its trabeculations.

Nuclear Angiography

First-pass radionuclide ventriculography was for a long time the gold standard to measure RV ejection fraction (RVEF). A bolus of the 99m-Tc 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 RV volumes and sensitivity to cardiac arrhythmia.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI), as mentioned previously, is now the gold-standard for the measure of RV volumes and function. In addition to measuring RV mass, volumes and chamber dimensions, MRI can calculate and quantify regurgitant volumes, delayed enhancement, scar burden, strain, perfusion, and pulmonary pulsatility. Also, changes in the global function of the RV after medical therapy have been shown to have a direct correlation to the functional class and survival in patients with PAH.

MRI is limited by its temporal resolution, its contraindication in those 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 RV volumes. However, acquisition of RV parameters cannot be obtained simultaneously with LV parameters or CT angiography. This results in the need for additional radiation exposure which is not negligible, and therefore CT is not routinely used for this purpose.

Invasive Hemodynamic Measurement

Right heart catheterization (RHC) or pulmonary artery catheterization (PAC) is often very useful in making the diagnosis and tailoring management in RVF. 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 for unexplained diagnostic or treatment-resistant cases, for the continuous and accurate measurement of right and left-sided filling pressures, cardiac output, and PVR.

The hemodynamic variables obtained in a RHC have important prognostic significance. A high RA pressure and low cardiac output have repeatedly been shown to be associated with poor outcomes in PAH. In addition, a PVR greater than three Woods units and pulmonary vascular compliance (SV/pulmonary pulse pressure) have both been associated with poor outcomes in LVF as well as PAH.

Treatment / Management

Management of Acute Right Ventricular Failure

Medical Management

Management of acute RVF starts with an assessment the severity of the patient’s condition and the decision to admit the patient to the intensive care unit (ICU) or intermediate care unit when appropriate. Rapid identification and management of triggering factors (i.e., sepsis, arrhythmias, drug withdrawal) are necessary. In the case of an RV infarct, rapid revascularization is essential, as is reperfusion therapy in a patient with a high-risk PE. As infection portends a very poor prognosis in acute RVF, preventative measures and prompt detection and treatment of infection are important.[9][10]

The mainstay of treatment focuses on three tenants: optimizing volume status, increasing RV contractility, and reducing RV afterload.

Volume loading may be appropriate if the patient is hypotensive and has low or normal filling pressures. Placement of a PAC or central venous pressure monitoring is often helpful as while the RV is preload dependent. Volume loading may over distend the RV and result in a further decline in cardiac output. If volume overload is present, IV diuresis is indicated, or renal replacement therapy if volume removal cannot be accomplished with medication. In addition to improving symptoms, diuresis has the additional benefits of reducing TR, restoring synchronous RV contraction, and reducing ventricular interdependence. Sodium restriction, daily weights, and strict monitoring of fluid intake and urine output is advised to aid in maintaining euvolemia.

Efforts should also be made to restore sinus rhythm in patients with atrial arrhythmias given the contribution of atrial contraction to cardiac output in RVF. In addition, hemodynamically significant tachy- and bradyarrhythmias should be treated. Digoxin has been shown to be of some benefit in patients with severe PAH. However, care must be taken in the critically ill patient given its narrow therapeutic window and possible side effects.

When hemodynamic instability is present, vasopressors are indicated. Norepinephrine is the pressor of choice to improve systemic hypotension and restore cerebral, cardiac and end-organ perfusion.   Inotropes, including dobutamine, levosimendan, and the phosphodiesterase-3 inhibitor milrinone are also helpful in that they improve contractility and cardiac output. Dobutamine is the inotrope of choice in RVF, as it leads to increased myocardial contractility via the beta receptor and vasodilatation/decreased afterload via the beta receptor. Caution should be taken however with dobutamine and milrinone as both may reduce systemic pressure. If this occurs, the addition of a vasopressor may be required.

If pressure overload is the etiology of the RVF, as is the case in PAH, afterload reduction with pulmonary vasodilators is the primary therapy. These drugs target three therapeutic pathways, nitric oxide (NO), endothelin and prostacyclin. It has been demonstrated that regardless of the class of drug used; acute responsiveness has prognostic significance in acute RVF. In addition to lowering afterload, some of these agents, such as the endothelin receptor antagonist (ERA) bosentan and the phosphodiesterase-5 (PDE5) inhibitor sildenafil, have also been shown to directly increase RV contractility. The pulmonary vasodilators used to treat acute RVF include:

• Inhaled nitric oxide (iNO) acts via the cyclic guanosine monophosphate (cGMP) pathway to cause pulmonary vasodilatation. It is rapidly inactivated by hemoglobin in the capillaries of the lung, thereby preventing systemic hypotension. The iNO acts only in ventilated areas of the lung, lowering PAP and PVR and improving oxygenation, without worsening hypoxia due to the ventilation-perfusion mismatch or shunting that can be seen with the systemic vasodilators. The iNO has been well studied in patients with acute RVF and has been shown in combination with dobutamine to improve CO, oxygenation, and PVR. Caution must be taken to avoid methemoglobinemia, and iNO must be withdrawn slowly to avoid hemodynamic decompensation from rebound PH.
• The intravenous (IV) prostacyclins epoprostenol and treprostinil act via the cyclic adenosine monophosphate pathway to result in potent pulmonary vasodilatation, systemic vasodilatation, and inhibition of platelet aggregation. Epoprostenol is the prostacyclin of choice for critically ill patients with acute RVF given its 6-minute half-life. Epoprostenol is started at 1 ng/kg/min to -2 ng/kg/min and up-titrated as tolerated, with caution in patients with comorbidities, hypoxemia or hemodynamic instability. Like iNO, the prostacyclins decrease PAP and PVR and increase cardiac output, however dose-dependent side effects (hypotension, nausea/vomiting/diarrhea, and headache) often limit titration. Prospective data demonstrating treatment benefit of IV prostacyclins in acute RVF is limited.
• Iloprost and treprostinil: inhaled prostacyclins. Both reduce PVR and improve cardiac output, with less systemic side effects. While treprostinil may also be given subcutaneously, it is inferior in critically ill, hemodynamically unstable patients due to its unpredictable absorption and longer half-life.
• ERAs and PDE5-inhibitors: oral, pulmonary vasodilators that reduce PAP, reduce PVR, and improve cardiac output in patients with RVF. ERAs block the endothelin-A and endothelin-B receptors in endothelial and vascular smooth muscle cells, reducing the vasoconstrictive, proliferative and proinflammatory effects of endothelin. The use of ERAs in the ICU is limited by their longer half-life and hepatotoxicity (bosentan). PDE5-inhibitors block degradation of cGMP. In addition to the previously mentioned hemodynamic effects, PDE5i have been shown to reduce hypoxic pulmonary vasoconstriction (HPV) and the up-regulation of pro-inflammatory cytokines induced by HPV.   The limited data for the use of PDE5-inhibitors in the ICU suggest a potential benefit in patients with RVF after mitral valve repair, coronary artery bypass grafting, or LVAD placement, and to reduce rebound PH in PAH patients weaning from iNO.

Caution must be taken with patients requiring mechanical ventilation, as excessive tidal volumes (V) and positive end-expiratory pressure (PEEP) increase PAP, RAP and RV afterload. Also, PEEP may worsen the picture by reducing venous return in the preload-dependent RV. While permissive hypercapnia leads to vasoconstriction, thereby increasing PAP and worsening RVF, hyperventilation acutely reduces PAP and acidosis-induced vasoconstriction. Care must be taken to avoid high V in this setting. The optimal ventilator setting for the patient with RVF is that which delivers adequate oxygenation and ventilation with the lowest V, plateau pressure, and PEEP.

Surgical Management and Interventional Therapies

For patients with reversible RVF refractory to medical therapy, surgical options are indicated either as a bridge to recovery or transplantation. Surgery may also be indicated for patients with RVF in the setting of valvular heart disease, congenital heart disease, and chronic thromboembolic pulmonary hypertension (CTEPH). Adequate preoperative diuresis is imperative, and the use of pulmonary vasodilators and inotropes peri-operatively may be needed. In addition, the irreversible end-organ damage is a contraindication for surgical management.

Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) may be indicated as salvage therapy in patients with massive PE and refractory cardiogenic shock following systemic thrombolysis.   ECMO may also be used as a bridge to lung or heart-lung transplantation in patients with severe RVF due to end-staged PAH.

Mechanical support with a right ventricular-assist device (RVAD) may be an option for the patient with isolated RVF awaiting transplant. However, ECMO may be a better treatment option for unloading the RV in the setting of severely increased PVR as pumping blood into the PA may worsen PH and cause lung injury.

Patients with RVF due to LVF may benefit from LVAD implantation, with improved PAP before heart transplantation and possibly improved post-transplant survival. However, LVADs may worsen or lead to new RVF due to alterations in RV geometry and flow/pressure dynamics and biventricular support may be required.

Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with CTEPH and is often curative. PTE has been shown to improve functional status, exercise tolerance, quality of life, gas exchange, hemodynamics, RV 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 1000 dyn/cm to 1200 dyn/cm). Outcomes with PTE have been shown to directly correlate with the surgeon and center experience, concordance between the anatomic disease and PVR, preoperative PVR, the absence of comorbidities (particularly splenectomy and ventricular-atrial shunt) and post-operative PVR. Operative mortality in an experienced center is between 4% to 7%, and PTE should not be delayed in operative candidates in favor of treatment with pulmonary vasodilator therapy.

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

Balloon atrial septostomy (BAS) is indicated for PAH patients with syncope or refractory RVF to decompress the RA and RV and improve CO via the creation of a right-to-left shunt. BAS may be used as a bridge to transplantation or as palliative therapy in advanced RVF/PAH and has a role in third world countries in which pulmonary vasodilators are not available. Mortality associated with BAS is low (approximately 5%), particularly in experienced centers, however spontaneous closure of the defect often necessitates repeating the procedure.   Contraindications of BAS include high RAP (greater than 20 mmHg), oxygen saturation less than 90% on room air, severe RVF requiring cardiorespiratory support, PVRI greater than 55 U/m and LV end-diastolic pressure greater than 18 mmHg.

Cardiac resynchronization therapy (CRT) restores mechanical synchrony in the failing LV, leading to improved hemodynamics and reverse remodeling and improved morbidity and mortality in LVF.  Animal studies and small case series suggest that RV pacing results in acute hemodynamic improvement in patients with RVF in the setting of PAH, however, no data show long-term clinical benefit in this population.

Ultimately, heart, lung, or combined heart-lung transplantation (HLT) is the treatment of last-resort for end-staged RVF. In patients with RVF due to PAH, RAP greater than 15 and CI less than 2.0 are poor prognostic indicators and referral for transplantation is indicated. It remains unclear at which point the RV is beyond recovery, however, in general, the RV is resilient, and most often lung transplant alone is sufficient with estimated 1-year-survival of 65% to 75% and 10-year survival of 45% to 66%.

Congenital patients with RVF in the setting of Eisenmenger syndrome may undergo lung transplantation with repair of simple shunts (ASDs) at the time of surgery or combined HLT, which has demonstrated a survival benefit in this population.

Differential Diagnosis

• Cirrhosis

• Community-Acquired pneumonia (CAP)

• Emphysema

• Goodpasture syndrome

• Idiopathic pulmonary fibrosis (IPF)

• Interstitial (Nonidiopathic) Pulmonary fibrosis

• Myocardial infarction

• Nephrotic syndrome

• Neurogenic pulmonary edema

• Pneumothorax imaging

• Pulmonary embolism (PE)

• Respiratory failure

• Venous insufficiency

• Viral pneumonia

Enhancing Healthcare Team Outcomes

Right heart failure is a systemic disorder that can affect many organs and hence is best managed by an interprofessional team. The outcomes of patients with RVF is worse than those with LVF, but it does depend on the cause and other comorbidities. Patients with persistently elevated pulmonary artery pressures have the worst outcomes. Many of these patients require repeat admissions and also have prolonged stays. Despite the various therapies for RVF, the outcomes have not greatly improved over the past two decades. While heart transplant is the ideal treatment for patients with no lung pathology, the shortage of donors is a limiting factor.[11] (Level V)