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.
Right ventricular failure (RVF) is most commonly a result of left ventricular failure (LVF), via pressure and volume overload.
In addition to LVF, there are other conditions of pressure overload that lead to RVF. These include transient processes such as:
Furthermore, chronic conditions of pressure overload may lead to RVF. These include:
The following conditions result in volume overload causing RVF:
Another important mechanism that leads to RVF is intrinsic RV myocardial disease. This includes:
Lastly, RVF may be caused by impaired filling which is seen in the following conditions:
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.
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.
Anatomically the structures and resulting function of the RV and the LV are vastly different. For example:
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.
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:
Common findings on the exam include:
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:
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. 
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:
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.
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.
Management of Acute Right Ventricular Failure
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.
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:
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.
Right heart failure is a systemic disorder that can affect many organs and hence is best managed by a multidisciplinary 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. (Level V)
|||Malamba-Lez D,Ngoy-Nkulu D,Steels P,Tshala-Katumbay D,Mullens W, HEART FAILURE ETIOLOGIES AND CHALLENGES TO CARE IN THE DEVELOPING WORLD: AN OBSERVATIONAL STUDY IN THE DEMOCRATIC REPUBLIC OF CONGO. Journal of cardiac failure. 2018 Oct 22 [PubMed PMID: 30359689]|
|||Zhuravleva MV,Prokofiev AB,Shih EV,Serebrova SY,Gorodetskaya GI, [Novel Possibilities in Pharmacotherapy of Patients With Chronic Heart Failure]. Kardiologiia. 2018 Oct [PubMed PMID: 30359220]|
|||Westphal JG,Bekfani T,Schulze PC, What's new in heart failure therapy 2018? Interactive cardiovascular and thoracic surgery. 2018 Oct 9 [PubMed PMID: 30304450]|
|||Uduman J, Epidemiology of Cardiorenal Syndrome. Advances in chronic kidney disease. 2018 Sep [PubMed PMID: 30309456]|
|||Nochioka K,Querejeta Roca G,Claggett B,Biering-Sørensen T,Matsushita K,Hung CL,Solomon SD,Kitzman D,Shah AM, Right Ventricular Function, Right Ventricular-Pulmonary Artery Coupling, and Heart Failure Risk in 4 US Communities: The Atherosclerosis Risk in Communities (ARIC) Study. JAMA cardiology. 2018 Oct 1 [PubMed PMID: 30140848]|
|||Cannavo A,Bencivenga L,Liccardo D,Elia A,Marzano F,Gambino G,D'Amico ML,Perna C,Ferrara N,Rengo G,Paolocci N, Aldosterone and Mineralocorticoid Receptor System in Cardiovascular Physiology and Pathophysiology. Oxidative medicine and cellular longevity. 2018 [PubMed PMID: 30327709]|
|||Hamada-Harimura Y,Seo Y,Ishizu T,Nishi I,Machino-Ohtsuka T,Yamamoto M,Sugano A,Sato K,Sai S,Obara K,Yoshida I,Aonuma K, Incremental Prognostic Value of Right Ventricular Strain in Patients With Acute Decompensated Heart Failure. Circulation. Cardiovascular imaging. 2018 Oct [PubMed PMID: 30354477]|
|||Sano H,Tanaka H,Motoji Y,Mukai J,Suto M,Takada H,Soga F,Hatani Y,Matsuzoe H,Hatazawa K,Shimoura H,Ooka J,Nakayama K,Matsumoto K,Yamada H,Emoto N,Hirata KI, Echocardiography during preload stress for evaluation of right ventricular contractile reserve and exercise capacity in pulmonary hypertension. Echocardiography (Mount Kisco, N.Y.). 2018 Oct 16 [PubMed PMID: 30328154]|
|||Ibrahim NE,Januzzi JL Jr, Established and Emerging Roles of Biomarkers in Heart Failure. Circulation research. 2018 Aug 17 [PubMed PMID: 30355136]|
|||Rohit S,Rahul M, Efficacy of heart failure reversal treatment followed by 90 days follow up in chronic heart failure patients with low ejection fraction. Journal of Ayurveda and integrative medicine. 2018 Oct 1 [PubMed PMID: 30287144]|
|||Peterson PN,Allen LA,Heidenreich PA,Albert NM,Piña IL, The American Heart Association Heart Failure Summit, Bethesda, April 12, 2017. Circulation. Heart failure. 2018 Oct [PubMed PMID: 30354400]|