Gaps and Knowledge in the Contemporary Management of Acute Right Ventricular Failure

Abstract

Acute right ventricular failure (ARVF) is commonly seen in the intensive care unit and constitutes a significant clinical challenge, with associated high in-hospital mortality. Recently, the treatment of ARVF has significantly changed, with the progressive implementation of mechanical circulatory support devices that now represent important tools for clinicians in treating this condition. However, despite recent advancements, the optimal approach for ARVF remains elusive, and precise treatment algorithms and comprehensive management protocols are still lacking. In the present review, we explore the pathophysiology of ARVF, highlighting the different mechanisms that may lead to this clinical entity and emphasizing the left and right heart’s complex interplay. We analyze the different therapeutic options that are now available for short- and long-term management of ARVF, with a particular focus on the advantages and disadvantages of the mechanical circulatory support devices actually used. Furthermore, we propose future directions in the field and a possible flowchart for the treatment of this condition.

Acute right ventricular failure (ARVF) can be defined as a rapidly progressive clinical syndrome characterized by systemic congestion and reduced cardiac output (CO) resulting from a failing right ventricular (RV), producing decompensated heart failure or cardiogenic shock (CS).^1–3 Many potential causes of ARVF are common in intensive care unit populations, generally divided into those due to pulmonary hypertension (PH) and those due to primary RV myocardial dysfunction.^4–6 The in-hospital mortality associated with ARVF remains particularly high, approaching 70% when mechanical circulatory support (MCS) is needed.⁷ The treatment of ARVF has profoundly changed recently, with the implementation of both surgical and percutaneous MCS devices that specifically target the RV, providing an important tool to stabilize patients with CS from ARVF.⁸ This review will discuss the pathophysiology of ARVF, including RV-left ventricular (LV) and heart-lung interactions, as well as currently available therapeutic options and future directions for the management of ARVF.

Pathophysiology and Causes of ARVF

The RV is a thin-walled, crescent-shaped chamber of the heart that pumps venous blood from the systemic circulation to the lungs for oxygenation. To achieve this, the RV manages fluctuating end-diastolic volumes resulting from respirophasic changes in venous return due to heart-lung interactions, efficiently propelling blood into the pulmonary circulation, which has high compliance and minimal resistance in a healthy individual.¹

Definition and Causes of ARVF

From a pathophysiological perspective, ARVF can be described as the rapid deterioration of RV performance, typically due to impaired contractility and alterations in loading conditions. These changes result in the RV’s inability to effectively manage systemic venous return (causing systemic congestion) and to provide forward flow to fill the LV (potentially causing hypoperfusion).⁹ ARVF usually develops in patients with preexisting chronic RV failure, exacerbated by an acute event (acute-on-chronic RV failure), but it can also arise de novo from direct acute injury affecting RV function. Moreover, most cases of ARVF are part of broader biventricular failure, and distinguishing isolated forms of ARVF is critical.

ARVF develops through 3 primary mechanisms, often interrelated (Figure 1)¹⁰:

Figure 1.

Pathophysiological mechanisms in acute right ventricular failure. The figure provides a schematic overview of the development and impact of acute right ventricular failure (ARVF). It compares the pathways leading to ARVF under de novo conditions, which arise from direct acute injury, and acute on chronic scenarios, which develop due to a worsening of preexisting conditions. The diagram outlines the heart’s short-term and long-term adaptive responses to increased afterload, emphasizing the potential for right ventricular dilatation and the associated negative outcomes on systemic circulation and organ function. CO indicates cardiac output; CVP, central venous pressure; PA, pulmonary artery; and RV, right ventricular.

• Reduced contractility

• Increased preload

• Increased afterload

Many myocardial diseases affecting the LV, such as myocardial ischemia/infarction, myocarditis, septic/stress cardiomyopathy, and various chronic cardiomyopathies, can directly cause decreased contractility of the RV. However, the RV is primarily affected in arrhythmogenic RV cardiomyopathy.¹¹

Elevated preload as a primary cause of ARVF can result from congenital heart diseases that increase pulmonary blood flow, predominantly those involving left-to-right shunts, or in cases of significant primary tricuspid valve regurgitation (TVR).¹² Furthermore, increased venous return to the right heart following left ventricular assist device (LVAD) implantation may lead to ARVF, particularly in those with limited RV contractile reserve or pre-LVAD right heart dysfunction.¹³

However, increased afterload, typically resulting from PH, is the most common cause of ARVF. PH has numerous potential causes and most often results from left heart disease that leads to increased pulmonary venous pressure (postcapillary PH). Alternatively, PH is due to heightened pulmonary vascular resistance (PVR, that is, Precapillary PH), most often from lung diseases (eg, acute respiratory distress syndrome [ARDS]) or from acute pulmonary embolism (PE) and chronic thromboembolic PH, or less frequently from numerous causes of pulmonary arterial hypertension (PAH; World Health Organization [WHO] Group 1 PAH).¹⁴ In many patients, both precapillary and postcapillary components of PH exist, and PVR may be dynamic tracking the LV filling pressure (reactive PH).

RV Response to Stressors and Clinical Consequences

The structure of the RV is specifically adapted to the high-flow, low-resistance pulmonary circulation, traditionally seen as ill-equipped to manage acute increases in afterload, and sudden rises in pulmonary pressure and PVR can precipitate ARVF. The timing of the onset of changes in loading conditions is a crucial determinant of the RV response. Acute stress induces an increase in end-diastolic and end-systolic volumes, leading to a temporary decrease in ejection fraction while maintaining stroke volume, a phenomenon known as heterometric adaptation under Starling law of the heart.¹⁵ Over time, the RV adapts to increased afterload through enhanced contractility (homeometric adaptation) and undergoes remodeling, encompassing mechanisms like myocyte hypertrophy and extracellular matrix expansion, leading to a thicker chamber wall. Concurrently, the RV undergoes remodeling towards a rounder shape with a reduced radius. Given Laplace law, which posits that wall stress directly relates to chamber radius and inversely to wall thickness, these adaptations primarily aim to diminish wall stress, mitigating the impact of increased afterload.¹⁰

When RV overburdening is prolonged, homeometric adaptation is no longer adequate and the heart resorts again to heterometric adaptation, ultimately resulting in RV dilatation that typically leads to increased filling pressures due to stiffening from fibrosis and hypertrophy, causing higher right atrial pressure (RAP) and systemic congestion. Functional TVR can also stem from RV and right atrium (RA) remodeling, worsening congestion, and reducing CO. The presence of high RAP attenuates the gradient for forward blood flow across the capillary network of the renal vasculature, ultimately resulting in glomerular dysfunction with consequent decreased renal performance and urinary output (ie, cardiorenal syndrome type 1).¹⁶ Furthermore, the reduced CO causes inadequate renal perfusion, prompting renin release from the juxtaglomerular cells, which in turn leads to a vicious circle of additional sodium/fluid retention. In addition, as the RV dilates, it may induce pericardial constraint, leading to interventricular competition for space and altering LV filling and output. Loss of normal interventricular septal curvature from RV dilation and RV pressure/volume overload can further compromise RV function, as the septum contributes substantially to overall RV performance.¹⁷ RV dilatation also increases myocardial oxygen demand while potentially reducing supply, particularly affecting coronary artery flow, thereby exacerbating ischemia and further diminishing RV contractility and CO.

Clinical Presentation and Diagnosis of ARVF

Early diagnosis of ARVF is crucial for promptly treat this condition and its underlying cause. The initial clinical presentation of RV failure can be subtle, with vague symptoms like fatigue and abdominal discomfort/distention that are often misinterpreted, leading to a late diagnosis. Subsequently, the overt clinical syndrome is typically characterized by signs of systemic congestion, which may also be accompanied by signs of hypoperfusion in cases of low CO³ (Figure 2).

Figure 2.

Different causes and management of acute right ventricular failure. This figure depicts the causes and management of acute right ventricular failure (ARVF), resulting from acute or chronic stressors that affect preload, contractility, and afterload. Clinical manifestations include ascites, gastrointestinal congestion, peripheral edema, dyspnea, and jugular vein distension. Management strategies involve fluid control, addressing the underlying condition, and possible tricuspid valve repair. Hemodynamically unstable patients may require inotropes, vasopressors, or mechanical circulatory support (MCS), while stable patients undergo clinical follow-up and medical optimization. AMI indicates acute myocardial infarction; MAP, mean arterial pressure; PE, pulmonary embolism; PH, pulmonary hypertension; and TV, tricuspid valve.

Initial Diagnostic Tools

ECG and echocardiography are the most accessible diagnostic tools to support the diagnosis of ARVF. While there are numerous ECG manifestations of acute and chronic RV disease (eg, S1-Q3-T3 pattern or RV hypertrophy), they lack sensitivity and specificity.

Echocardiography is essential to exclude possible reversible extrinsic causes of RV impairment and to assess RV size and function, pulmonary pressures, and TVR severity. The most important echocardiographic feature in ARVF is acute RV enlargement compared with the usual size (RV basal diameter <41 mm),³ while supportive information in the discrimination between acutely and chronically dilated RV is the ventricular free wall thickness, as a value above 5 mm suggests a chronic RV overload.¹⁸ Several echocardiographic parameters are used to assess RV function (Table 1), but these measures are often influenced by preload/afterload conditions and the RV’s complex geometry. Advanced Doppler hemodynamic assessments enhance the utility of echocardiography by estimating RV-pulmonary artery (PA) coupling, mainly by normalizing longitudinal indices of RV function such as tricuspid annular plane systolic excursion and RV free wall longitudinal strain for systolic PA pressure. Both the ratio of tricuspid annular plane systolic excursion/systolic PA pressure and RV free wall longitudinal strain/systolic PA pressure appeared as important prognostic determinants in PH and patients with heart failure.^19,20

Table 1.

Multimodality Parameters Currently Adopted to Assess Right Ventricular Function

Echocardiography is also useful in determining hemodynamic and fluid status. RAP is mostly estimated by inferior vena cava diameter and collapsibility, but this is a useful insight only for high and low RAPs, while for intermediate values (5–12 mm Hg) the inferior vena cava assessment might be inaccurate.²¹ A further insight comes from the ratio between systolic vein flow/(diastolic+systolic vein flow) in the hepatic vein, with a value >55% suggestive of increased RAP.²² Systolic PAP can be estimated from the TVR velocity, assuming an adequate Doppler envelope.²³ This can be underestimated in cases of poor ultrasound alignment or severe TVR, and PAPs are flow-dependent, meaning that high-output states can lead to elevated PAPs, while low-output states can result in lower PAPs for a given PVR.

Advanced Cardiovascular Imaging and PAC

Cardiac magnetic resonance has emerged as the gold standard for RV evaluation, due to its capability to provide an accurate and reproducible evaluation of function and tissue characterization.²⁴ However, the exam is time-consuming, patients need to be stabilized, and must cooperate during the execution so that cardiac magnetic resonance does not find application in the hyper-acute setting, while it can be extremely useful in stabilized patients.

A computed tomography angiogram is commonly utilized in the acute setting, especially to rule out specific aetiologies. Indeed, a simple computed tomography pulmonary angiogram can be used to rapidly exclude acute PE, while a complete gated cardiac computed tomography can provide data on RV morphology and dimensions, giving useful tools for the identification of other RV pathologies (ie, PH, congenital heart disease, chronic obstructive pulmonary disease.^25,26

Invasive hemodynamic assessment using a PA catheter (PAC) provides important diagnostic information regarding ARVF. A key PAC finding suggesting ARVF is an elevated RAP, but distinguishing primary RV failure (low PA pressures) from RV failure due to increased afterload (elevated PA pressures) is fundamental as the treatment strategy can profoundly differ. Accordingly, an increase in PA pressures during treatment may reflect a favorable response (ie, increased CO due to inotropic support) or an unfavorable response (ie, increased afterload due to rising PVR).

Several hemodynamic parameters are used to identify the presence of RV failure, and they can be helpful to possibly discriminate primary RV failure from biventricular failure. The ratio between RAP and pulmonary capillary wedge pressure (PCWP) provides insight into the balance of right and left heart-filling pressures. A ratio of RAP/PCWP >0.86 was associated with evidence of RV infarction at necropsy, while other experiences showed that even lower values of RAP to PCWP were demonstrated to be associated with poor outcomes in patients implanted with LVAD.^13,27 PA pulsatility index is the ratio between PA pulse pressure and RAP, providing an estimate of RV pulsatile load and contractility strength which carries important prognostic value, particularly in ARVF and CS due to primary RV myocardial dysfunction. A value of PA pulsatility index <1.85 was shown as a strong negative predictor in LVAD recipients.²⁸ RV stroke work index is another hemodynamic parameter that provides specific insights on RV work to eject blood in the pulmonary circulation. Higher values of RV stroke work index suggest high RV afterload, and it was also demonstrated to be a negative prognosticator in LVAD recipients.²⁹ PAC is also particularly useful for the optimization of fluid balance and gives a precise characterization of the pathophysiology underlying ARVF. Indeed, apart from giving overall information on the pressures in different heart chambers, various formulas can be used to identify RV pressure and volume overload, including estimation of PVR, PA compliance and impedance.⁸

Treatment of ARVF

General Principles

Medical management of ARVF is profoundly influenced by the underlying etiology and it is firstly aimed to identify and treat any reversible underlying condition, including invasive treatments such as coronary revascularization for acute coronary syndrome or thrombolytic therapy/catheter-based therapy for acute PE.⁴

Volume Optimization

RV function is sensitive to loading conditions and medical treatment is addressed to achieve optimal volume balance. Excessive volume loading can cause RV overdistension, leading to augmented wall stress, impaired contractility and increased interventricular dependence, which ultimately reduces CO. Conversely, patients with ARVF have obligate RV diastolic dysfunction and require higher than normal RAP to provide optimal CO; these patients can seem preload dependent and cautious volume loading could be adopted in cases of low filling pressures. Previously normal patients with ARVF (eg, RV myocardial infarction or PE) are more likely to require volume loading than those with acute-on-chronic RV failure (eg, PH), who often have subtle but significant volume overload. Utilization of PAC or central venous pressure (CVP) monitoring can be useful to guide fluid management: a target of CVP between 9 mm Hg and 12 mm Hg (up to 15 mm Hg in selected patients) should be pursued, with fluid loading for patients who are hypotensive or have low CO in the setting of a low CVP, and diuresis stimulation for those with elevated filling pressures.² Severely elevated CVP >18 to 20 mm Hg will result in RV overdistention and systemic congestion and is important to lower acutely. Crucially, diuresis can dramatically improve RV performance and is central in the management of acute-on-chronic RVF.

Vasoactive Agents and Inotropes

Vasopressors and inotropes can be used to maintain organ perfusion and improve myocardial contractility. Catecholamine vasopressors, primarily targeting α-1 receptors, increase systemic MAP, which can not only improve coronary and other organ perfusion but also improve RV performance by reversing pathological septal flattening.³⁰ However, catecholamine vasopressors can also increase PVR by causing α-1-mediated pulmonary vasoconstriction, potentially increasing RV afterload. Norepinephrine is the most commonly adopted vasopressor in intensive care units, and it was demonstrated to restore MAP organ perfusion with minor changes in PVR and an improvement in RA-PA coupling.^31,32 Vasopressin is another vasopressor agent that binds to V1 receptors on vascular smooth cells.³³ At lower doses, it causes pulmonary vasodilatation through the stimulation of endothelial nitric oxide (NO), and it can potentially be combined with catecholamine vasopressors due to this positive hemodynamic effect on the pulmonary vascular bed.³⁴Any β1-adrenergic receptor agonist (eg, dobutamine, dopamine, epinephrine) can be used to further improve CO by stimulating myocardial contractility and increasing heart rate, although these agents can provoke tachyarrhythmias that compromise RV function.^31,35,36 In addition, levosimendan or phosphodiesterase-3 inhibitors (eg, milrinone) can increase myocardial contractility and induce pulmonary vasodilation, reducing RV afterload at the potential risk of systemic hypotension.²

The use of vasoactive drugs and inotropes should be tailored to the patient’s hemodynamic profile. Ideally, vasopressors are recommended in the presence of low MAP and low to normal PVR. Conversely, when low MAP is primarily due to reduced CO and high vascular resistance are documented, inotropes and inodilators should be prioritized as first-line agents, since vasopressors in these cases can exacerbate RV afterload. In certain situations, a combination of multiple drugs may be necessary to fully restore organ perfusion and achieve optimal hemodynamic conditions. Although noninvasive hemodynamic assessment using echocardiography and CVP monitoring can guide therapeutic decisions, in cases of CS or ambiguous noninvasive findings, the use of a PAC should be considered to refine therapeutic strategies and optimize patient management.

Pulmonary Vasodilators

For patients with precapillary PH and no evidence of an elevated PCWP, pulmonary vasodilators can be considered. The most easily accessible of these agents are inhaled pulmonary vasodilators such as NO or alprostadil/epoprostenol which are often given via continuous inhalation for intubated patients with ARVF. These agents have the advantage of rapid onset, improved ventilation/perfusion matching, and lack of systemic effects.^37–40 For patients with WHO group 1 PAH and chronic thromboembolic PH in the absence of parenchymal lung disease, systemic drugs such as phosphodiesterase 5 inhibitors, endothelin receptor antagonists, soluble guanylate cyclase stimulators, and oral or parenteral prostanoids can be used under expert guidance.^6,14 These drugs can cause severe toxicity even when used appropriately, especially for patients with lung disease (by inducing ventilation/perfusion mismatch and hypoxemia via intrapulmonary shunting) or LV failure (by causing pulmonary congestion or edema) in whom they are best avoided.

Oxygenation and Ventilation

Maintenance of adequate oxygenation is essential, and inhalation of 100% FiO2 can transiently lower PA pressures in acute settings. However, the potential benefits of supporting oxygenation must be balanced with the potentially harmful effects of excessive positive airway pressure on RV preload/afterload. Accordingly, the use of a nonrebreather mask or, preferably, high-flow nasal cannula oxygen is typically preferred in the absence of biventricular failure with pulmonary edema. Alternatively, noninvasive positive-pressure ventilation may be beneficial when pulmonary edema or hypercarbia are central drivers of ARVF.⁶ The swings in intrathoracic pressure induced by intubation and mechanical ventilation can be risky in patients with severe isolated ARVF (particularly with PAH), and in selected cases, escalation to extracorporeal membrane oxygenation (ECMO) may be considered for the treatment of severe hypoxemia even before intubation.⁶

Treatment of Specific Causes of ARVF

The treatment of ARVF is profoundly affected by the etiology, and the management of the single patient should be tailored based on hemodynamic principles and the clinical scenario. Although the 3 main determinants of ARVF (reduced contractility, increased afterload and increased preload) can be specific to certain etiologies, they often coexist, and the resulting clinical setting is usually a complex interplay between them.

Post-acute myocardial infarction ARVF

Reduced contractility is the primary mechanism of ARVF in the context of inferior acute myocardial infarction due to right coronary artery occlusion.⁴¹ Nevertheless, during ischemic insult, the RV becomes stiff, reducing peak systolic pressure and augmenting end-diastolic volume, consequently end-diastolic pressure. This combined systolic and diastolic dysfunction leads to underfilling of the left side of the heart and low-output syndrome.⁴² Besides revascularization of the culprit vessel, medical management of ARVF post-acute myocardial infarction is targeted to maintain organ perfusion with adequate volume status, which is usually higher than normal to produce effective CO (CVP target between 12 and 15 mm Hg), and agents that compromise RV preload such as nitrates or diuretics, might be deleterious in this setting. In the case of CS, treatment with vasopressors and inotropes could be necessary to restore organ perfusion. However, the arrhythmic effect of β1-adrenergic receptor agonists can be even more pronounced in the presence of ongoing ischemia, so the utilization of this agent should be minimized. Fluid loading works in only about half of patients, and either dobutamine or inhaled NO has been shown to increase CO in fluid-unresponsive patients.^43,44 If refractory ARVF following an RV acute myocardial infarction persists despite medical management, temporary MCS with a percutaneous RVAD or ECMO may be indicated.

Arrhythmogenic RV Cardiomyopathy

The occurrence of ARVF in patients with arrhythmogenic RV cardiomyopathy typically arises in the later stages of the disease, often due to pronounced RV dilation and decreased myocardial contractility, and is primarily exacerbated by arrhythmic events.⁴⁵ Although β-blockers and antiarrhythmic drugs are the cornerstones of treatment for this condition, when symptoms of low output and significant congestion are present, short-term management with inotropes and inodilators can be considered (better avoiding pure β1-adrenergic receptor agonists in the presence of a high arrhythmic burden). In cases of refractory arrhythmias and lack of response to medical therapy, venoarterial (VA)-ECMO is recommended.⁴⁵ Heart transplant (HT) represents the gold standard in the end stages of the disease, but implantation of an off-label long-term right ventricular assist device (RVAD) has been successfully documented in small case series with significant RV decompensation in cases of lack of donors or HT contraindications.^46,47

Acute Cor Pulmonale

ARVF due to acutely increased afterload is typically seen in patients with acute pulmonary diseases such as acute PE, ARDS, and pneumonia. In ARVF due to acute PE, thrombolysis, catheter-based treatment, or surgical embolectomy are the first treatment choices.¹ Typically, pulmonary pressures are not elevated in the acute setting, because PVR needs more time to be augmented. In this phase, cautious volume loading can be done, guided by CVP assessment in the presence of significant hypotension. In ARDS, PVR is usually augmented by the combination of persistent hypoxic/hypercapnic vasoconstriction and microthrombi formation, aggravated by the adverse effects of positive-pressure ventilation on RV afterload.⁴⁸ Oxygen and ventilation support is often needed in both etiologies, and peak/plateau airway pressures should be limited as they can elevate PVR and intrathoracic pressures, further reducing RV preload.⁴⁹ Prone positioning is extremely effective in unloading the RV in ARDS; indeed, it extends lung recruitment and aeration, leading to improved ventilation homogeneity, decreased ventilation/perfusion mismatch, enhanced oxygenation, reduced hypercapnia, diminished PVR, and lower driving pressures.⁵⁰ Ultimately, for eligible patients with ARDS who require high airway pressures causing cor pulmonale, venovenous ECMO may be needed to allow unloading of the RV by reducing the aggressive ventilator support.⁵¹

Decompensated PAH

Patients with PAH can develop overt ARVF mainly due to precipitating factors such as infections and arrhythmias.⁵² Compared with patients with acutely increased afterload, these patients usually present signs of congestion, and diuretics and oxygen supply to maintain arterial oxygen saturation >90% are the first-line treatment options. Pulmonary vasodilators are frequently used to decrease RV afterload, although care must be taken to avoid systemic hypotension or worsening hypoxemia.⁵² For patients with ARVF due to WHO group 1 PAH who are not already on systemic prostanoids, intravenous prostacyclin is generally considered the first-line therapy, and inhaled NO can be useful initially. Notably, compared with WHO group 1 PAH, patients with systemic sclerosis and PH show less benefit from vasodilators due to the intrinsic inability of the RV to handle the same level of afterload.⁵³ Inotropes and vasopressors may be needed but can be ineffective in the setting of extremely high PVR. VA-ECMO is generally more appropriate if MCS is needed, as percutaneous RVADs can dramatically increase PA pressures, leading to hemorrhage or rupture.⁶

Post-LVAD ARVF

The main etiology of ARVF after LVAD is maladaptation of the RV to the increased venous return from the unloaded LV due to the lack of adequate RV contractile reserve, particularly in those with preexisting RV dysfunction. If there is excessive venous return, the intraventricular septum may be shifted toward the LV, altering the RV performance. In this case, the LVAD speed should be decreased, aiming for a midline septum to balance LV unloading and optimal venous return.⁵⁴ In the perioperative and postoperative setting, supporting RV contractility with β1-adrenergic receptor agonists or phosphodiesterase-3 inhibitors may be necessary to maintain adequate RV output, and weaning from these agents should be guided by serial echocardiographic evaluation and PAC data.⁵⁵ At the same time, RV dysfunction can also be due to insufficient unloading of the LV during LVAD support, so when high filling pressures are documented, diuretic therapy, vasodilators, or raising LVAD pump speed can be useful maneuvers to decrease RV afterload, always guided by assessing the septal position initially and during LVAD speed change. Furthermore, a substantial number of patients who undergo LVAD implantation have preoperative PH with significantly raised PVR.⁵⁶ Although LVAD support is capable of significantly reducing pulmonary pressures, the initial presence of high PVR increases RV afterload, and the utilization of pulmonary vasodilators such as NO has been demonstrated to help reduce RV stress and overdistension.⁵⁷ Post-LVAD ARVF is one of the most common indications for temporary RVADs, although VA-ECMO is commonly used.⁵⁵

Postcardiotomy ARVF

Postcardiotomy ARVF occurs in up to 10% to 20% of high-risk surgical populations, and it is accompanied by high mortality in the severe forms.⁵⁸ It results from a complex interplay of pathophysiological mechanisms, and key contributing factors include ischemia-reperfusion injury to the RV, acute pressure overload from residual PH, and volume overload secondary to fluid shifts during cardiopulmonary bypass. The management includes optimization of RV preload and afterload, mostly guided by PAC, with cautious diuresis and pulmonary vasodilators (especially inhaled NO) as the most commonly adopted agents to avoid RV pressure and volume overload. Also, inotropic agents like epinephrine, dobutamine, or milrinone are often needed to improve RV contractility when signs of low CO are evident. MCS devices like centrifugal-flow pumps or ECMO can be necessary for patients with refractory shock.

Congenital Heart Disease

As a result of a broad spectrum of diseases, the management of ARVF in congenital heart disease can be extremely challenging. RV volume overload (typically in the presence of left-to-right atrial shunts or significant TVR) or RV pressure overload (mainly seen in RV outflow obstruction and pulmonary stenosis) are the main determinants of ARVF in these patients.^59,60 Treatment options should be tailored according to the clinical phenotype and may include surgical/percutaneous correction of the structural abnormalities. Mechanical support is also feasible in these patients as a bridge to HT, although higher mortality has been reported.⁵⁹

Temporary MCS for ARVF Complicated by CS

Current guidelines recommend the utilization of short-term MCS in cases of CS and persistent hemodynamic instability despite pharmacological measures as a bridge to decision, bridge to recovery, or bridge to bridge.^61,62 Most of the data on MCS come from studies and clinical trials addressed to CS predominantly due to LV failure, while the utilization of MCS in the setting of CS due to biventricular failure and isolated ARVF has been less explored, and the actual data come from small nonrandomized studies.^63–66

Phenotyping CS Due to ARVF

Predominant RV failure is observed in 5% to 10% of patients with CS with a mixed etiology, carrying a similar prognosis to CS due to preponderant LV failure.^67,68 Adequate phenotyping of CS is fundamental to guide clinicians in tailoring the patient’s treatment and in the choice of the proper MCS device. High RAP with concomitant signs of low CO are hallmark features of CS due to RV failure, especially when normal LV function is noninvasively documented. However, the proper definition of CS due to predominant ARVF should rely on a complete hemodynamic assessment. A ratio of RAP/PCWP >0.6 and a PA pulsatility index <1.85 are the major criteria to define predominant RV CS, but the concomitant presence of high PCWP, even in patients with normal LV systolic function identifies biventricular involvement, which may include isolated LV diastolic dysfunction. MCS that primarily targets the RV can be inadequate in this case due to the potential higher pulmonary flow. At the same time, mere echocardiographic evidence of RV dysfunction in the presence of high LV filling pressure (ie, PCW >15 mm Hg) and low RAP (ie, <12 mm Hg) might identify candidates who would only benefit from LV unloading, even without the need for RV support.

Temporary MCS for ARVF

Several surgical and percutaneous devices specifically designed to support the RV are available, and their utilization in intensive care units has substantially increased, although the selection of the optimal candidate and specific device choice remains under debate.⁸

Percutaneous RVADs (ie, the Impella RP and Tandem Heart RV assist devices [TH-RVAD]), and VA-ECMO are the currently most used temporary percutaneous ARVF-MCS devices utilized. RVADs are more appropriate when RAP is elevated in the presence of low PA pressures and PVR (primary RV involvement), while VA-ECMO is more appropriate in the setting of severe PH and biventricular involvement. These devices have different implant techniques and hemodynamic effects, and they could be categorized according to their mechanism of either direct or indirect RV bypass system (Figure 3).

Figure 3.

Temporary mechanical support devices for the treatment of acute right ventricular failure. The figure summarizes the characteristics, implantation techniques, and hemodynamic effects of the currently most adopted mechanical cardiac support devices for the treatment of acute right ventricular failure. LV indicates left ventricular; PA, pulmonary artery; RA, right atrium; RV, right ventricular; TH-RVAD, Tandem Heart right ventricular assist device; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.

Impella RP

Impella RP (Abiomed) is a 22F 3-dimensional catheter-based microaxial flow pump delivered percutaneously under fluoroscopy guidance, mostly from the femoral vein. It delivers blood from the inferior cava vein-RA to the PA, directly unloading the RV. It can provide a forward flow in the range of 3.5 to 4 L/min, and its utilization is intended for up to 14 days. The RECOVER RIGHT trial evaluated the utilization of Impella RP in 30 patients with medically refractory ARVF, showing immediate improvement in hemodynamics and rapid weaning from inotropes and vasopressors.⁶⁶ The survival rate at 30 days was 73%, and all discharged patients were alive at 6 months. Bleeding complications were seen in 60% of patients and hemolysis in <20%. Since the aforementioned trial, several nonrandomized small-sized studies assessed the use of Impella RP in ARVF of different etiologies^66,69–72 (Table 2).

Table 2.

Clinical Studies Evaluating Mechanical Support Devices for Treatment of Acute Right Ventricular Failure

While all studies confirmed the positive hemodynamic effects, the mortality rate was usually higher than in the RECOVER RIGHT trial, and morbidity remained poor due to frequent vascular, bleeding, and hemolysis complications. Due to these results, the FDA issued an official recall for excess mortality in Impella RP recipients.

Recently, Impella RP Flex with SmartAssist (Abiomed), which is an 11-F cannula inserted through the internal jugular vein with a 22F peel-away sheath, has been approved by the FDA for the treatment of ARVF for up to 14 days. Although this configuration allows early mobilization, consistent data are still not available, and this device was recently recalled by the FDA for the reported high frequency of blood clots, especially with ACT levels below 160 seconds.

TH-RVAD and Protek Duo Dual-Lumen Cannula

The TH-RVAD (LivaNova) system utilizes an extracorporeal centrifugal-flow pump (TH or Centrimag) with 2 21F venous cannulas to deliver blood from the RA to the PA. The inflow cannula is inserted in the RA through the left femoral vein, and the outflow cannula in the PA through the right femoral vein. This approach was recently substituted in most centers by the Protek Duo dual-lumen cannula (LivaNova), which contains 2 lumens: the proximal one with a 29F or 31F cannula and the distal one with a 16F or 18F cannula. It is inserted through the jugular vein, allowing single vascular cannulation and patient mobilization.⁷³ TH-RVAD and Protek Duo Cannula were tested in small studies including ARVF from different etiologies, consistently showing hemodynamic benefits and significant improvement in mean arterial pressure.^{63,64,73–77} Both devices appeared although aggravated by several vascular and bleeding complications, and mortality remained high in CS.⁶³ Compared with the single-access intravascular Impella RP, the dual-catheter TH-RVAD and dual-lumen catheter Protek Duo have the advantage of improving systemic oxygenation by splicing an oxygenator in the circuit, known as an oxy-RVAD.⁷⁸

Venoarterial-ECMO

The utilization of VA-ECMO in CS increased markedly in the past years, as a system to provide biventricular support and improvement in systemic oxygenation.⁷⁹ Different VA-ECMO implantation techniques (ie, percutaneous versus surgical; central versus peripheral) have been adopted, displacing blood from the RA into the arterial circulation through an extracorporeal centrifugal pump. VA-ECMO provides indirect support to the RV by effectively bypassing and unloading it, removing venous blood and returning it to the systemic circulation. Clinical data supporting the use of VA-ECMO in isolated ARVF are limited to some case reports and small case series⁸⁰ and further studies are needed to clarify its real clinical contribution in this setting. However, in the presence of biventricular failure, VA-ECMO is the most adopted MCS, as the utilization of specific RV-MCS such as Impella RP or Protek Duo in the presence of LV dysfunction can lead to pulmonary edema due to excess LV preload that cannot be managed by the failing LV.⁸¹

The combination of an LVAD and RVAD (BIVAD) can be used in patients with biventricular failure, most often starting with the LVAD, which can improve RV performance by lowering PA pressures, with the RVAD being added as needed. In situations where ARDS or severe hypoxia is the sole cause of ARVF, the use of venovenous ECMO has proven to be effective, leading to significant improvements in precapillary oxygenation and effectively reducing pulmonary vasoconstriction caused by hypoxia and high airway pressures.⁸²

CentriMag

CentriMag is an extracorporeal centrifugal pump that can be utilized as a part of a TH and VA-ECMO circuit or implanted surgically (as is common in post-LVAD ARVF).⁸³ Nevertheless, its use has been approved as an isolated RVAD for up to 30 days in patients with CS.⁸⁴ The inflow cannula is positioned in the RA through direct insertion via the superior or inferior cava vein, and the outflow is typically anastomosed to the PA and, for patients with concomitant respiratory failure, an oxygenator may be added to the configuration. A meta-analysis of almost 1000 patients supported with CentriMag found that it was used as a ventricular assist device configuration in 72% of cases, with isolated RVAD in 42% of cases.⁸³ The survival rate at discharge varied depending on the indications, but it reached 83% in RVAD support for ARVF post-LVAD placement.

Durable MCS for ARVF

A substantial number of patients with ARVF cannot be weaned from temporary MCS. Indeed, up to 50% of patients who receive RV MCS after LVAD placement do not see a recovery of RV and several strategies of biventricular support have been used.⁸⁵ Furthermore, patients with irreversible causes of RV failure may require long-term RV support since HT, which is considered the gold standard, is limited by a lack of donors.⁴⁶ Isolated pulsatile RVADs, surgically deployed rotary-flow RVADs, and Total Artificial Hearts (SynCardia or Aeson) have been used in cases of persistent RV failure, mostly as a bridge to HT.⁸⁶ However, these devices require close in-hospital monitoring and strongly limit the patient’s quality of life, so clinicians have started to use off-label LVADs to support the RV. According to the Interagency Registry for Mechanically Assisted Circulatory Support, >600 patients have been supported worldwide with continuous-flow BiVADs.⁸⁵ Off-label isolated RV support with HeartMate 3 as destination therapy has also been reported in some patients suffering from arrhythmogenic RV cardiomyopathy and right heart failure unresponsive to medical treatment.^46,47

The main concern that emerged by using HeartMate 3 as RVAD was the occurrence of pump thrombosis in up to 20% of patients.⁸⁷ This is mostly due to the need of maintaining lower pump speeds to avoid excessive flow in a low-resistance vascular bed. Therefore, outflow cannula downsizing could be considered in cases where the demanding flow is below 4 L/min to potentially increase the pump speed.⁸⁷

Limitations and Future Directions of MCS for ARVF

Although the progress in the MCS for the treatment of ARVF has been accompanied by great optimism in the medical community, many questions remain unanswered. Indeed, the currently available data come from small series, and no randomized trials that directly compare MCS and medical treatment in ARVF have been performed. To date, there is no conclusive data favoring one device over another, and the selection of the most appropriate device is based on the etiology, patient characteristics, and clinician’s personal experience.

MCS is associated with a high rate of vascular and bleeding complications. In addition, patients usually need to remain confined to bed, which increases their susceptibility to infections, malnutrition, and loss of muscular tone. Therefore, the use of MCS should be restricted to cases where it is absolutely necessary, and efforts to early weaning should be initiated as soon as feasible (Figure 4). Furthermore, the selection of the optimal candidate to MCS is still under debate. The paucity of data that we have now available from the literature suggests that the survival on MCS for ARV profoundly varies depending on the underlying etiology, with the best survival in patients post-LVAD implantation and, in general, reversible causes of ARVF. This should lead to consider these devices for particular etiologies where MCS can be extremely useful for the really acute setting and can be rapidly weaned avoiding complications of longer-term support. On the opposite side, patients in overt CS or patients with longer disease of RV are possibly worse candidates, with high mortality rates and likely no benefits from these devices. The off-label utilization of LVAD for the long-term support of RV is currently not approved by FDA, and its application can be considered only in rare situations where urgent HT is not possible and weaning from temporary MCS is not feasible.

Figure 4.

Flowchart for the treatment of acute right ventricular failure. Hemodynamic instability=persistent hypotension (systolic blood pressure <90 mm Hg) requiring ≥1 inotrope/vasopressor to maintain with signs of organ hypoperfusion. ARVF indicates acute right ventricular failure; AV, atrioventricular; Bipella, simultaneous use of Impella RP/Impella RP flex with Impella CP; CVP, central venous pressure; HT, heart transplant; iNO, inhaled nitric oxide; MAP, mean arterial pressure; MCS, mechanical cardiac support; PAC, pulmonary artery catheterization; PAH, pulmonary arterial hypertension; PDE3, phosphodiesterase-3; PGI, prostacyclin; PVR, pulmonary vascular resistance; RV, right ventricular; RV-MCS, right ventricular mechanical cardiac support; TH-RVAD, Tandem Heart right ventricular assist device; and VA-ECMO, venoarterial extracorporeal membrane oxygenation.

Future directions are addressing the development of newer devices for the acute setting aimed at reducing complications and patient discomfort, while for long-term support the implementation of VADs specifically designed for the RV could reduce the actual hemodynamic limitations. The Cleveland Clinic Universal Ventricular Assist Device, is seen as a promising VAD that is able to cover the hemodynamic needs of both ventricular chambers. The Universal Ventricular Assist Device is a hybrid of magnetically and hydrodynamically levitated centrifugal pumps, and it has a wide operating range, so it can be used on both RV and LV side.⁸⁸

Conclusions

ARVF is a common clinical scenario in the intensive care unit and still confers high morbidity and mortality. The treatment of this condition showed significant changes in recent decades, thanks to the implementation of MCS devices that specifically target the RV and offer important tools both for the critical phase and long-term support. However, the absence of clinical trials and the awareness of complications related to these devices make their utilization still controversial, and the selection of optimal MCS candidates remains extremely difficult. Future research should focus on developing precise algorithms for patient selection, as well as on establishing comprehensive monitoring and weaning protocols.

ARTICLE INFORMATION

Acknowledgments

The figures were done with the help of Biorender.

Sources of Funding

This study is supported by the Italian Ministry of Health–Ricerca Corrente.

Disclosures

None.