Pathophysiology and management of right ventricular failure in critically ill patients: A narrative review

Abstract

Right ventricular (RV) failure accounts for significant morbidity and mortality in critically ill patients. The RV is particularly vulnerable in conditions characterized by elevated pulmonary vascular afterload, which are commonly encountered in the intensive care unit (ICU). Conditions such as acute respiratory distress syndrome, pulmonary embolism, and decompensated pulmonary arterial hypertension are associated with acute and acute-on-chronic RV failure. In the ICU, RV failure may develop or worsen in patients with parenchymal pulmonary disease who acutely experience fluctuations in preload, excessive afterload, and/or insufficient myocardial contractility, often in addition to mechanical ventilation and circulatory compromise. This dynamic clinical scenario demands early recognition and intervention tailored to an individual patient’s physiology. Distinguishing between acute and chronic RV failure in critical illness informs diagnostic workup, hemodynamic monitoring, and resuscitative efforts. This narrative review will provide an overview of common conditions associated with RV failure in critical illness, highlighting a practical, physiology-oriented approach to diagnosis and optimization of ventilator support, fluid resuscitation, vasopressor and inotrope use, and mechanical circulatory support. RV failure due to RV infarction or severe LV failure and decompensated congenital heart disease are distinct pathophysiologic entities. These conditions require distinct treatment approaches and are beyond the scope of this review.

Key Words: Right ventricular failure; Pulmonary hypertension; Shock; Mechanical circulatory support; Pulmonary embolism; Cardiac tamponade

Core Tip: Right ventricular (RV) failure is a common and complex problem among critically ill patients. The management of RV failure is highly dependent on its underlying etiology, chronicity, and resource availability. General principles of RV failure include maintenance of adequate systemic blood pressure, reduction of RV afterload, provision of inotropic support, correction of acidosis and hypoxemia, and management of the underlying precipitating condition. This review provides a comprehensive and practical approach to RV failure in critical illness, highlighting common scenarios and summarizing the available evidence.

INTRODUCTION

Right ventricular (RV) failure is a significant driver of morbidity and mortality of critically ill patients[1]. The RV is more sensitive to acute changes in afterload than the left ventricle (LV), making it particularly vulnerable in conditions characterized by elevated pulmonary vascular afterload, which are commonly encountered in the intensive care unit (ICU). Conditions such as acute respiratory distress syndrome (ARDS), high-risk pulmonary embolism (PE), and decompensated pulmonary arterial hypertension (PAH) are associated with acute and acute-on-chronic RV failure[2,3]. In the ICU, RV failure may develop or worsen in patients with parenchymal pulmonary disease who acutely experience fluctuations in preload, excessive afterload, and/or insufficient myocardial contractility, often in addition to mechanical ventilation and circulatory compromise[4]. This creates a challenging and dynamic clinical scenario which demands early recognition and intervention tailored to an individual patient’s physiology.

Distinguishing between acute and chronic RV failure in critical illness is essential, as it informs diagnostic workup, hemodynamic monitoring, and resuscitative efforts[5]. This narrative review will provide an overview of common conditions associated with RV failure in critical illness, highlighting a practical, physiology-oriented approach to diagnosis and optimization of ventilator support, fluid resuscitation, vasopressor and inotrope use, and mechanical circulatory support (MCS). RV failure due to RV infarction or severe LV failure and decompensated congenital heart disease are distinct pathophysiologic entities. These conditions require distinct treatment approaches and are beyond the scope of this review.

DEFINITIONS AND PATHOPHYSIOLOGY

RV failure in critical illness is characterized by the inability of the RV to generate enough pressure to compensate for an acute change in preload or increase in afterload. Importantly, RV dysfunction refers to impaired RV systolic or diastolic performance on imaging or hemodynamics, whereas RV failure is a clinical syndrome characterized by systemic congestion and/or low cardiac output due to inadequate RV contractility[1]. RV preload refers to right heart filling pressure, whereas RV afterload refers to the resistance to flow in the pulmonary vasculature. Contractility refers to the ability of the RV to eject a certain amount of stroke volume into the pulmonary circulation. The term acute pulmonale, which refers to acute increase in RV afterload due to a primary pulmonary pathology (e.g., ARDS, PE, pneumonia, etc.)[2] will not be used in this review as it is not specific and, in clinical practice, the chronicity of RV failure is not always clear in critical illness. This review will focus instead on RV failure as a pathophysiologic continuum and provide diagnostic and treatment suggestions on the basis of clinical findings.

RV contractility is driven by a combination of free wall contraction (a ‘bellows’ effect), longitudinal contraction, and tension on RV myocardial fibers by LV contraction. The naïve RV, anatomically characterized by a thin wall and crescentic shape, is adapted to pump against a low-resistance, high-compliance pulmonary vascular bed. Consequently, it is ill-suited to tolerate abrupt increases in afterload[3,4].

The normal pulmonary vascular bed is designed to allow for distention and recruitment in response to increases in cardiac output; thus, the pulmonary vascular resistance (PVR) normally remains constant. Pulmonary arteriopathy, such as that seen in PAH, reduces pulmonary artery compliance and ultimately leads to RV remodeling. RV hypertrophy may allow for greater tolerance in RV pressure changes[5]; however, RV hypertrophy is often accompanied by myocardial fibrosis, which can impair augmentation of inotropy[6], as can the change in the RV sarcomere length-pressure relationship seen in RV dilation[7]. Compensatory RV changes, or lack thereof, in response to pulmonary arteriopathy are a particular problem in some subtypes of PAH, such as systemic sclerosis[8,9].

RV failure can arise through distinct mechanisms depending on the underlying pathology. In PAH, chronic remodeling of the pulmonary vasculature leads to a progressive rise in PVR, which increases RV afterload and ultimately negatively affects RV function. In contrast, ARDS may not cause a significant elevation in PVR early in the disease course. However, factors such as hypoxic pulmonary vasoconstriction, microvascular injury, and positive-pressure ventilation can transiently increase pulmonary artery pressure and increase RV afterload, particularly in severe prolonged cases[10]. PE represents a different pathophysiologic insult: Acute mechanical obstruction of the pulmonary vasculature leads to a sudden increase in RV afterload, which can cause abrupt RV dilation, septal displacement, and impaired LV filling. This results in decreased cardiac output and systemic hypotension.

The dynamic interaction between RV contractility and RV afterload is called RV-PA coupling. Early in PA pressure elevation, the RV augments its contractility to match PA pressure. As RV afterload continues to rise, the RV, unable to increase inotropy further, begins to dilate, which leads to an inefficient pressure-length relationship of myocardial fibers and impingement of the RV into the LV[2]. In fact, a 20 mmHg increase in afterload can lead to an almost 30% decline in RV stroke volume[11]. Echocardiographically, this may manifest as RV dilation and septal flattening, development of a D-shaped appearance of the LV in short axis view, and RV free wall hypokinesis with preservation of apical contractility (also known as McConnell’s sign) (Figure 1). In critically ill patients, a combination of multiple factors, including hypoxia, acidosis, and inflammation with increased oxygen consumption results in reduction of contractility and, thus, impairment of the ability of the RV to compensate for increased afterload. Furthermore, these relationships are different between patients with naïve, thin-walled RVs and those with PAH and chronically hypertrophied and fibrotic RVs[12,13].

Figure 1 Echocardiographic appearance of right ventricle failure showing RV dilation and compression of the left ventricle, septal flattening, and D-shaping of left ventricle. A: Apical 4-chamber view; B: Parasternal short-axis view. RV: Right ventricle; LV: Left ventricle; RA: Right atrium; LA: Left atrium; S: Interventricular septum.

A pivotal and clinically devastating progression in this context is the so-called “RV Death Spiral”. This is a self-perpetuating cycle of a relatively acute increase in PA pressure leading to RV dilation and systolic dysfunction, which in turn increases RV wall tension and myocardial oxygen demand while simultaneously impairing coronary perfusion[14] (Figure 2). Dilation of the RV stretches the tricuspid annulus, worsening tricuspid regurgitation, increasing RV preload, and further augmenting RV dilation[14,15]. This regurgitant flow increases right atrial (RA) pressure, leading to RA dilation and exacerbating systemic venous congestion. The structural and functional changes in the RV impair efficient transfer of energy from the contracting myocardium to the pulmonary circulation, termed RV-PA uncoupling, which further compromises forward flow[15]. The LV and RV exist in a state of ventricular interdependence; thus, as progressive RV dilation causes the interventricular septum to adopt a convex curvature and bulge into the LV, the LV preload and diastolic filling are reduced and cardiac output falls[16].

Figure 2 The right ventricle “death spiral”, a self-perpetuating process of progressive RV dilation, hypoperfusion, and ultimate failure. PA: Pulmonary artery; RV: Right ventricle; RA: Right atrium; LV: Left ventricle.

This multifaceted cascade leads to systemic hypotension which then further impairs RV coronary perfusion, completing the vicious cycle[17]. Because of this, end-stage RV failure may manifest with a decline in PA pressure (as measured by PA catheterization or estimated from the tricuspid regurgitant velocity on echocardiography) due to a drop in RV cardiac output[18]; thus, clinicians should interpret these values in the context of the patient’s clinical picture and the visualized appearance of RV function by echocardiography.

COMMON CAUSES OF ACUTE RV FAILURE IN THE ICU

PE

PE is a classic example of acutely increased RV afterload. Obstruction of ≥ 30%-50% of the total cross-sectional area of the pulmonary arterial bed, often seen in high or intermediate-high risk PE, leads to increases in PA pressure[19]. However, the increase in PA pressure is not directly proportional to the degree of vascular obstruction; PA pressure is further increased by vasoconstriction mediated by the release of hormones (e.g. serotonin), inflammatory mediators (e.g. thromboxane A2), and hypoxemia[20]. RV failure is the major driver of mortality in patients with PE who are in shock (also termed high-risk PE), with an estimated 30-day all-cause mortality of around 30%, most of whom die during hospitalization[21]. Furthermore, among all patients with PE, even those who are hemodynamically stable, RV dysfunction is a known independent negative prognostic marker of mortality[22-24].

The management of PE-specific RV dysfunction hinges on resolution of thrombosis. All patients with PE should be treated with systemic anticoagulation, and contemporary guidelines recommend that patients with shock due to PE (i.e., those with RV failure) be additionally treated with systemic thrombolysis[25]. Treatment of patients who have RV dysfunction but are not in shock (also termed intermediate-risk PE) is more controversial; large-scale randomized controlled trial data has suggested that systemic thrombolysis may improve PE-related hemodynamic decompensation and death, but at the cost of significant bleeding risk[26]. Increased interest and a growing body of literature suggests that catheter-directed (percutaneous) thrombectomy and thrombolysis have a role in patients with intermediate- or high-risk PE, particularly among those at high risk of hemorrhage[27]. To date, studies have suggested improvement in RV function among patients with PE treated with catheter-directed thrombolysis[28-30] and thrombectomy[31-33]. More recent data has compared the two catheter-directed modalities, favoring catheter-directed thrombectomy[34]. However, trials directly comparing intervention with anticoagulation monotherapy for intermediate-risk PE are ongoing. Surgical embolectomy, once a mainstay of therapy but accompanied by significant procedural morbidity and mortality[35], is falling out of favor for the majority of patients with acute PE as catheter-directed procedures become more commonly available.

Decompensated PAH

PAH is characterized by a progressive pulmonary arteriopathy, characterized by increasing PVR. Initially, patients may remain asymptomatic as progressive remodeling of the pulmonary vasculature occurs, but ultimately the RV undergoes compensatory concentric hypertrophy to maintain cardiac output against increased afterload[5]. This is accomplished through multiple unique pathways, which differ from those that enable concentric hypertrophy of the LV, in an effort to maintain RV stroke volume while simultaneously minimizing wall stress[36]. Over time, however, the RV begins to undergo eccentric hypertrophy and dilation to accommodate escalating afterload[37]. This signifies a shift from the adaptive modifications in the RV shape and function to a series of maladaptive and dysfunctional changes including impaired angiogenesis leading to reduced coronary blood flow, oxidative stress leading to chronic inflammation and RV fibrosis, altered RV myocardial metabolism, inhibition of autophagy of myocardial waste products, apoptosis of RV cardiomyocytes, and downregulation of adrenoreceptors[36]. The end result of these maladaptive changes is overt RV failure[37].

The stepwise progression of PAH can occur acutely, often described as a decompensation. Triggers such as infection, arrhythmias, volume overload, hypoxemia, pregnancy, surgery, methamphetamine use, or nonadherence to therapy can precipitate a rapid decline in RV function, but a trigger for decompensation is only identified in 20%-40% of cases of acute RV failure in PAH[38]. Irrespective of the inciting event, depending on the extent of baseline dysfunction, the RV may not be easily able to compensate for acute changes in hemodynamics or contractility.

Management is focused on aggressive reduction of RV afterload using pulmonary vasodilators, optimization of preload, treatment of the underlying precipitant, and early consideration of MCS and transplantation, as discussed later.

RV dysfunction complicating septic shock

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection[39]. A significant number of patients who present to an emergency room with sepsis progress to septic shock within 48 hours[40], a process manifesting as profound hypotension leading to organ dysfunction due to diffuse vasodilation as a result of nitric oxide and prostacyclin overproduction, reduction in vasopressin, and catecholamine resistance, among others[41]. This vasodilatory state requires compensation by increasing chronotropy and inotropy to maintain adequate cardiac output for end-organ perfusion. A subset of patients with septic shock develop septic cardiomyopathy[42], and the increased myocardial demand of distributive shock leads to worse outcomes in patients who have underlying PAH[43].

The 2021 Surviving Sepsis Campaign guidelines recommend prompt resuscitation with at least 30 mL/kg of intravenous crystalloid fluid for patients with sepsis and hypotension within the first three hours that sepsis is identified[44]. However, this aggressive fluid loading can be detrimental to the RV, which is particularly vulnerable to both the effects of septic cardiomyopathy and the frequent increases in PA pressure seen in septic patients[45], especially those with concurrent ARDS. Administering a large fluid bolus to an already strained and afterload-mismatched RV can cause acute over-distension, progressive RV failure, and impaired LV filling, which may compound the shock state. The key to management of the septic patient with RV dysfunction is with a patient-oriented, bedside approach to fluids and vasopressors, as described later.

ARDS

ARDS is an inflammatory condition of the pulmonary parenchyma which results acute hypoxemic respiratory failure. The resulting imbalance of mediators of pulmonary vascular tone, such as nitric oxide, endothelins, and prostanoids, causes hypoxic pulmonary vasoconstriction, ultimately resulting in an increase in RV afterload[46]. Additionally, vascular lesions and microthrombosis, which have been identified in postmortem histopathological studies of patients with ARDS, lead to microvascular obstruction in pulmonary vasculature, further increasing RV afterload[46]. In addition to hypoxemia, ARDS often leads to hypercapnia, which further increases PA pressure and RV afterload[47].

These gas exchange abnormalities often necessitate the use of invasive mechanical ventilation (IMV), which can further exacerbate the increase in RV afterload due to lung overdistension caused by high airway pressures and large tidal volumes (i.e., barotrauma and volutrauma); the principles of lung protective ventilation, with use of higher positive end-expiratory pressure (PEEP) and permissive hypercapnia, can further contribute to an increase in RV afterload[47]. As described above, the RV is uniquely sensitive to changes in pressure and volume status, and the increased intrathoracic pressure caused by mechanical ventilation can lead to a significant reduction in RV preload[48]. Through a combination of these mechanisms, acute RV dysfunction develops in approximately 20% of ARDS patients and is independently associated with higher mortality in ARDS[49]. This patient population may be uniquely responsive to inhaled pulmonary vasodilators (such as inhaled nitric oxide), and specific management of mechanical ventilation in the context of ARDS-associated RV dysfunction is described below.

A summary of conditions common in critical illness and associated with RV failure, and their associations with preload, afterload, and contractility, can be seen in Table 1.

Table 1 Selected conditions and their associated impact on preload, afterload, and contractility.

Factor	Pre-load (↑ or ↓)	Afterload (↑ or ↓)	Contractility (↑ or ↓)
Pulmonary embolism	↓ (In RV failure and venous return impairment)	↑↑ (Vascular obstruction with vasoconstriction)	↓ (In RV ischemia from pressure overload and failure)
Decompensated PAH	Variable (however, often ↑ due to volume overload)	↑↑ (Chronic ↑ PVR + inciting event)	↓ (RV dysfunction with progression)
Septic shock (w/RV dysfunction)	↑ (Aggressive fluid resuscitation → RV over-distension)	↑ (Microvascular changes, ARDS-related ↑ PA pressures)	↓ (Septic cardiomyopathy)
ARDS (and mechanical ventilatory support)	↓ (↑ Intrathoracic pressure → ↓ venous return)	↑ (Hypoxic vasoconstriction, microthrombi, high airway pressure)	↓ (Secondary to RV strain/failure)
Mechanical ventilation (High PEEP or tidal volume)	↓ (↑ Intrathoracic pressure → ↓ venous return)	↑ (Overdistension → ↑ PVR)	↓ (If RV ischemia/strain occurs)
Hypoxemia/hypercapnia		↑ (Vasoconstriction→ ↑ PVR)	↓ (If prolonged → RV dysfunction)
Arrhythmia (in PAH)	↓ (Ineffective filling)	-	↓ (Loss of coordinated contraction)
Fluid loading in sepsis	↑ (Aggressive fluids → RV over-distension)

PA: Pulmonary artery; PVR: Pulmonary vascular resistance; RV: Right ventricle; PAH: Pulmonary arterial hypertension; PEEP: Positive end-expiratory pressure; ARDS: Acute respiratory distress syndrome.

CLINICAL MANIFESTATIONS AND DIAGNOSIS OF RV FAILURE

Clinical features

Diagnostic evaluation of RV failure centers around recognizing systemic congestion and low cardiac output. The patient’s history is critically important, highlighting any known underlying disease (e.g., PAH or conditions associated with PAH, such as systemic sclerosis or methamphetamine use) and the temporal pattern of symptoms (e.g., the progressive systemic congestion associated with slowly worsening RV failure in PAH, vs the acute dyspnea and chest pain associated with PE). Patients with RV failure present with symptoms attributable to subacute systemic congestion including weight gain due to edema, fatigue, right upper quadrant and/or epigastric pain or discomfort, dizziness, syncope/presyncope and dyspnea on exertion; unlike patients with progressive PAH who are often volume overloaded, patients with acute failure of the naïve RV (e.g., due to PE) are often hypovolemic or euvolemic, and may have chest pain, dyspnea, and syncope/presyncope beginning days to hours prior to presentation.

Classic physical exam findings of acute RV failure are caused by systemic hypoperfusion, hypotension, and congestion and include diaphoresis, cyanosis, cool extremities, tachycardia, elevated jugular venous pressure, hepatomegaly, a prominent pulmonic component of the S2 heart sound, holosystolic murmur of tricuspid regurgitation, and peripheral edema (particularly if superimposed on chronic RV failure). As RV failure progresses, end-organ dysfunction develops, including acute kidney injury, transaminase elevation, and encephalopathy. Kussmaul Sign (increased jugular venous pressure with inspiration) and hepatojugular reflux (a sustained elevation in jugular venous pressure for ≥ 15 seconds with gentle pressure applied to the right upper quadrant of the abdomen) are additional exam findings that are suggestive of right heart dysfunction

Diagnostic testing

Electrocardiogram (ECG) can aid in the diagnosis of RV failure. In chronic RV failure, ECG often demonstrates right axis deviation and markers of RV or RA hypertrophy. In acute RV failure, ECG may demonstrate sinus tachycardia or supraventricular tachyarrhythmias such as atrial fibrillation or flutter or new-onset right bundle branch block[50]. The ECG pattern that includes an initial S deflection in lead I, Q deflection in lead III, and T-wave inversions in lead III (the so-called S1Q3T3 pattern) is classically seen in high-risk PE and has been shown to have high specificity, albeit with low sensitivity, for RV strain[51].

Serum markers that are often used in the assessment of RV function include troponin, B-type natriuretic peptide (BNP), metabolic panels, and hepatic function tests. Acute RV failure due to acute coronary syndromes presents with elevated troponin, however troponin may also be elevated in other causes of RV failure due to demand ischemia or myocardial stress[52]. BNP is a marker released by ventricles in response to increased stretch, and can be elevated in acute RV failure due to venous congestion with increased RV preload or in cases of acute RV failure due to increased RV pressure afterload[53,54]. Hepatic transaminases and bilirubin may be elevated in acute RV failure due to hepatic congestion[55]. In severe cases of RV failure, systemic hypoperfusion and venous congestion can combine to cause the cardiorenal syndrome, which may lead to renal insufficiency and elevation in blood urea nitrogen and creatinine; importantly, acute kidney injury due to a reduction in renal perfusion pressure is due to a smaller gradient between central venous pressure and mean arterial pressure-that is, an elevation in central venous pressure and a reduction in mean arterial pressure both significantly contribute to renal congestion[56].

Computed tomography (CT) angiography can be a useful tool in evaluation of the pulmonary parenchyma (i.e., in evaluating for interstitial lung disease, emphysema, etc.), the pulmonary vasculature (in evaluating pulmonary thromboembolic burden), the shape and size of the RV relative to the LV, and reflux of contrast into the inferior vena cava (IVC). Prior work has demonstrated the utility of RV to LV ratio > 1.0 on CT angiography as a predictor of reduced cardiac index[57] and worse prognosis in acute PE[58]. Additional measurements of PA thrombus burden in acute PE, such as the PA obstruction index, the Qanadli or the Miller indices, have been also associated with higher PA pressure and worse prognosis[59,60].

Echocardiography is the primary diagnostic imaging tool for evaluating RV function. It is important to note that due to the retrosternal position of the RV and its complex geometry, there may be significant operator and observer variability in echocardiography of the RV, particular with point-of-care ultrasound (POCUS)[61]. In patients with significant parenchymal lung disease, such as ARDS or interstitial lung disease, visualization of the RV and tricuspid valve for estimation of PA pressure can be challenging[62]. Although certain limitations exist, the inherent advantages of POCUS transthoracic echocardiography (POCUS TTE)-including its ease of use, speed, non-invasiveness, and lack of radiation-are contributing to its growing adoption in critical care, and is often significantly faster to obtain to get basic views of RV function than formal TTE[63].

A full review of echocardiographic guidelines can be found elsewhere[64], but common TTE measurements that are often used to diagnose RV systolic dysfunction include tricuspid annular plane systolic excursion (TAPSE) < 17 mm, RV fractional area change (FAC) < 35%, and tricuspid annular systolic S’ tissue doppler velocity < 10 cm/second[64] (Table 2). TAPSE refers to the movement of the lateral tricuspid annulus on the apical 4-chamber view. RV FAC refers to the percentage change between end-diastole and end-systole as measured in the apical 4-chamber view. The S’ tissue doppler velocity of the tricuspid annulus is the speed of motion of the tricuspid annulus during systole. The RV outflow tract velocity time integral (RVOT VTI) can be assessed by measuring the area under the curve of Doppler flow immediately adjacent to the pulmonic valve during systole in the parasternal short axis view. Low RVOT VTI has been associated with PE-related mortality[65]. Additional findings on TTE that can suggest acute RV failure include RV dilation (demonstrated by the ratio of RV end diastolic diameter to LV end diastolic diameter > 1.0), IVC dilation (> 21 mm) with inspiratory collapse < 50%, McConnell’s sign (RV free wall akinesis with apical hyperkinesis), and the so-called “D Sign” that is suggestive of exaggerated ventricular interdependence (septal bowing into the LV during systole is suggestive of RV pressure overload, while bowing during diastole is suggestive of RV volume overload)[18,64]. Lastly, the tricuspid regurgitant jet velocity can be used to estimate the PA systolic pressure (or RV systolic pressure), with values > 2.8 m/second considered pathologic[64]. LV function should be assessed as well as left- or right-sided valvular disease and the presence of pericardial effusion. As mentioned earlier, in end-stage RV failure with RV-PA uncoupling, estimated PA pressure may be low because of the RV’s inability to generate an inadequate contractile force, and a fall in PA systolic pressure in the context of severe RV failure should not be reassuring. A thorough review of RV evaluation in critical care echocardiography can be found elsewhere[66].

Table 2 Echocardiographic findings suggestive of right ventricular failure, as compared with normal parameters.

	Normal	Suggestive of RV failure
Tricuspid annular plane systolic excursion	≥ 17 mm	< 17 mm
RV fractional area change	≥ 35%	< 35%
Tricuspid annular systolic S’ tissue doppler velocity	≥ 10 cm/second	< 10 cm/second
RV: LV end-diastolic diameter ratio	≤ 1.0	> 1.0
IVC measurement	≤ 2.1 cm diameter, > 50% inspiratory collapse	> 2.1 cm diameter, < 50 % inspiratory collapse
Tricuspid regurgitant jet velocity	≤ 2.8 m/second	> 2.8 m/second
McConnell’s sign	Absent	Present
“D Sign”	Absent	Present

RV: Right ventricle; LV: Left ventricle; IVC: Inferior vena cava.

Although the diagnosis of acute RV failure can typically be made with the findings described above, hemodynamic monitoring via a Swan-Ganz PA catheter can provide definitive diagnosis, with a mean PA pressure > 20 mmHg. Findings in isolated right heart failure include elevations in RV systolic pressure (> 25 mmHg) and RA pressure (or central venous pressure; > 15 mmHg) and can be distinguished from biventricular failure by elevations of the pulmonary capillary wedge pressure (PCWP; > 15 mmHg) and PA diastolic pressure (> 15 mmHg). Cardiac output should be determined by the thermodilution method or, if available, direct Fick. Features that suggest LV failure vs primary right heart failure include measures that suggest discordant right-to-left filling pressures such as the RA pressure to PCWP ratio (≥ 0.8 is suggestive of primary RV failure) and the transpulmonary gradient (mean PA pressure-PCWP; > 12 mmHg is suggestive of primary right heart failure)[2]. A full review of best practices for PA catheter placement and troubleshooting is available elsewhere[67].

Overall, the diagnosis of acute RV failure requires synthesizing suggestive elements from the patient’s history, clinical exam, laboratory findings, and imaging (especially echocardiography). If the diagnosis is still unclear or if additional questions remain, invasive hemodynamics can provide useful information in selected patients.

MANAGEMENT

The management of acute RV failure is multifaceted and must be rapidly initiated. Key principles are to: (1) Address the underlying cause; (2) Optimize RV preload; (3) Reduce RV afterload; and (4) Support RV contractility and systemic perfusion. Below we outline major treatment strategies, emphasizing critical care interventions.

Addressing the underlying cause and contributing factors

The first step is to correct any obvious precipitant. Patients who have a shock with RV failure due to PE should be immediately initiated on therapeutic anticoagulation and undergo urgent reperfusion with systemic thrombolysis or, as discussed earlier, catheter-directed therapies. Although sinus tachycardia is common, supraventricular arrhythmias (such as rapid atrial fibrillation) will further worsen LV filling and should be quickly controlled with cardioversion. Intravenous amiodarone is preferred to calcium channel blockers or beta blockers as these can exacerbate hypotension and have potent negative inotropic effect[68]. Consideration can be made for digoxin as adjunctive therapy[68].

If acute decompensation is triggered by infection, sepsis must be treated with appropriate antimicrobials and source control. A particular nuance in patients with RV failure who present with sepsis of occult source is the possibility of bacteremia and endotoxemia from bowel, caused by venous congestion and reduction in cardiac output[69]. Patients who require emergent surgery in the context of RV failure should be optimized as much as is possible in the clinical scenario; a detailed description of this approach can be found elsewhere[70].

Patients with PAH who have decompensation due to abrupt discontinuation of PAH therapy should be immediately reinitiated on medication, often with parenteral prostacyclins, described in greater detail below. Decompensation triggered by anemia requires transfusion to restore the blood’s oxygen carrying capacity. Hypoxemia must be addressed immediately, ideally using high-flow nasal cannula (HFNC). If mechanical ventilation is required, strategies to minimize the impact of positive pressure ventilation on RV function should be employed and are described below.

Monitoring tools

Although there is scant data on the value of monitoring tools in RV failure in critical illness, general recommendations are to use methods commonly used for shock resuscitation[68]. Patients should have central venous access, ideally terminating in the superior vena cava proximal to the RA, to allow for secure and consistent administration of vasoactive agents and measurement of central venous oxygen saturation. A PA catheter can be considered but is not necessary in every case and should only be utilized by a clinician experienced in its placement and interpretation of the data obtained. Most patients should have arterial monitoring, which facilitates accurate titration of vasoactive agents and frequent blood gas measurement. These tools of invasive hemodynamic monitoring should be appropriately leveled and calibrated.

Accurate, granular markers of end-organ perfusion should be assessed repeatedly. Urine output should be measured with an indwelling urinary catheter. Hepatic function, serum lactate, and electrolytes, as well as blood gases, should be checked frequently. Serial repeating of cardiac troponin levels is probably unnecessary unless acute coronary syndrome is suspected. BNP levels can be helpful as a general trend over time if checked every few days but do not reflect immediate actions to correct the shock state. All patients should be on continuous telemetry monitoring with continuous pulse oximetry.

Volume management

Volume management is of paramount importance in the treatment of acute RV failure, particularly in PAH[71]. The classic teaching of patients with acute RV failure being “preload dependent” is overly simplistic, and a more accurate term is that these patients are “euvolemia dependent”. Volume status must be managed cautiously, as hypovolemia can cause RV collapse and worsen cardiac output, while hypervolemia leads to congestion and exaggerated interventricular dependence, which similarly worsens cardiac output. In essence, the goal is to relieve congestion without underfilling the RV.

A key component of volume management is to understand that pressure and volume are not synonymous, and that patients may be pressure-overloaded while euvolemic or even hypovolemic. Unfortunately, clinical tools commonly used to determine volume status in critical illness fundamentally look at pressure-including CVP and IVC collapse. Thus, determining volume status in patients with RV dysfunction can be very challenging. A stiff, dilated RV can be associated with IVC non-collapsibility, even in hypovolemic states. As RV failure progresses, the severity of tricuspid regurgitation can decrease, leading to a drop in RA pressure and a paradoxical increase in IVC collapse[72]. To determine true volume status, therefore, the bedside clinician should evaluate the patient’s history and physical exam in the context of available imaging. Patients with longstanding PAH, for example, are often volume overloaded on presentation and should undergo volume removal with either loop diuretics (with or without thiazide addition) or renal replacement therapy – even if hypotensive or with acute kidney injury[18,73]. In fact, diuresis has been shown to reduce mortality in patients with decompensated heart failure, even in the setting of reduced kidney function[74]. Patients with de novo RV failure due to PE often require cautious volume administration as they may have high insensible losses from hyperventilation.

A second key component of volume management is to understand the RV pressure-volume relationship differences between a normal RV, an acutely dysfunctional naïve RV, and an acute-on-chronically failing RV[37]. Because of its high compliance, a naïve RV is relatively adaptable to volume administration, without significant changes in RV pressure (explaining why patients with septic shock do not enter RV failure after fluid resuscitation). However, a hypertrophied RV is less compliant, often with high RV pressure at baseline, and RV pressure will increase significantly with even small increases in RV volume; this is particularly pronounced in patients with RV-PA uncoupling[37].

Thus, volume administration or removal decisions should be based on the individual patient’s pathophysiology, RV structure and function, and echocardiographic evidence of adequate LV filling and ventricular interdependence.

Optimizing oxygenation and ventilation

Hypoxemia and hypercapnia, which may be present either as precipitants of acute RV failure or as secondary manifestations of acute RV failure, lead to increases in PA pressure and RV afterload[10,47]. The effect on PA pressure is additive with hypoxemia and acidosis. For example, at a pH of 7.4, a drop in PaO₂ to < 50 mmHg may lead to an up to 100% increase in PVR; however, at a pH of 7.2 (commonly acceptable in ARDS management), the PVR is 100% higher even at PaO₂ of 100 mmHg, and a drop of PaO₂ to < 50 mmHg can lead to a PVR increase of almost 450%[75]. Therefore, in RV failure, the PaO₂ target should be > 60 mmHg (or SaO₂ > 90%-95%), the PaCO₂ target should be the patient’s baseline, and the pH target should be 7.4. Isolated hypoxemia can be treated with HFNC, which can be combined with inhaled pulmonary vasodilators, such as nitric oxide or inhaled epoprostenol, to improve ventilation-perfusion matching, reduce hypoxic pulmonary vasoconstriction, and directly reduce RV afterload[76,77].

Intubation and IMV with positive pressure ventilation is fraught with dangers and should be avoided unless necessary (Figure 3). The goals of IMV, including permissive hypercapnia, low tidal volumes, high PEEP, which have been extrapolated from ARDS care to IMV for most critically ill patients, compete with RV-specific pathologic derangements[78,79]. Intubation should be done by the most experienced available provider, with avoidance of hypotension before or during induction and minimizing apneic time. When possible, consider using awake, fiberoptic intubation using local anesthesia with lidocaine, ideally with established arterial and venous access[80]. For patients in whom it is practical, consider use of HFNC with inhaled pulmonary vasodilators as a bridge to intubation.

Figure 3 The impact of positive pressure ventilation on pulmonary and systemic hemodynamics. A: Overall hemodynamic impact of positive pressure ventilation; B: Differential impact of alveolar distention on extra-and intra-alveolar pulmonary vasculature. LV: Left ventricle.

Negative pressure ventilation (the way people naturally breathe) promotes RV filling from the venae cava. Positive pressure ventilation may decrease RV filling due to an increase in intrathoracic pressure, which reduces venous return. It also reduces LV preload, impairing LV filling and contributing to hypotension. A common misconception is that higher PEEP will always lead to worsening RV function. In fact, there is a U-shaped effect of alveolar distention on intra-alveolar and extra-alveolar vessels. Higher alveolar distention (i.e., with higher PEEP or higher tidal volumes) will lead to greater compression (and rise in PVR) of intra-alveolar vessels; however, lower alveolar distention will lead to a rise in PVR of extra-alveolar vessels[78]. Both interventions will increase PVR hyperbolically as lung volume approaches total lung capacity or residual volume, respectively; this is demonstrated graphically in Figure 3. Thus, the best PEEP is one where lung volume approaches functional residual capacity and should be individualized based on the patient’s RV function and lung compliance[81]. Clinicians should keep in mind that the RVs of patients with less compliant lungs (e.g., in patients with ARDS) will be more sensitive to changes in PEEP and tidal volume than those with greater or normal lung compliance. Where possible, consider using esophageal manometry in combination with PA-derived hemodynamics to optimally titrate PEEP[82].

Prone positioning (if feasible), which has been proven to reduce mortality in severe ARDS[83], may improve RV preload and afterload by recruiting alveoli, improving oxygenation, reducing V/Q mismatch, and improving intrapulmonary shunting[84]. It has been hypothesized that the relatively fewer cardiac events seen in the prone positioning arm of the PROSEVA trial may be partly explained by a protective effect on the RV[85].

A final consideration is that acute increases in RV afterload can lead to the development of right-to-left shunting through opening of patent foramen ovale and atrial septal defects, which can further worsen hypoxemia. TTE with bubble study can assess for this complication, and, when present, it can be a consideration to use inhaled pulmonary vasodilators in an attempt to reduce RV afterload and reduce the shunt fraction[86].

Vasopressor and inotropic support

Vasopressor and inotropic agents should be considered early to augment RV contractility. As mentioned earlier, systemic hypotension significantly worsens coronary artery perfusion; in fact, the right coronary artery perfusion during systole can be close to zero as PA pressures reach near-systemic levels[87]. The effects of hypotension can be even more pronounced in situations where an additional process causing shock (e.g., sepsis or hemorrhage) is superimposed on underlying chronic RV failure.

Norepinephrine, a combined α1/β1 agonist, is a first-line vasopressor because it can improve systemic hemodynamics without meaningfully altering the PA pressure or PVR and may improve RV myocardial oxygen delivery and RV-PA coupling[88,89]. Epinephrine, an α1 agonist with more potent β1 and β2 agonism properties than norepinephrine, may similarly reduce hypotension and improve RV contractility[90,91]. Vasopressin, which acts on V1 receptors, may be infused at low-doses to improve systemic perfusion while having a minimal effect on PVR[92]; however, some data suggests that at higher doses it can increase PA and coronary artery vasoconstriction[93]. Phenylephrine, a pure α1 agonist, is often avoided because of concerns that it can increase PA pressure and lead to reflex bradycardia[94,95]; however, it may be a reasonable choice in patients who are persistently hypotensive despite other vasopressors (particularly in distributive shock states) and in patients who are sensitive to tachyarrhythmias associated with norepinephrine, epinephrine, or inotropes.

The inodilator subclass of inotropes, including dobutamine (a β1 agonist) and milrinone (a phosphodiesterase-3 inhibitor) can both increase myocardial contractility and reduce both pulmonary and systemic vascular resistance, which can lower both RV and LV afterload. Dobutamine in particular has been shown to improve RV/PA coupling at low doses[88,96]. Milrinone has shown to increase pulmonary vasodilation and improve RV inotropy[97]. However, both of these inodilator agents have the potential for side effects, including tachyarrhythmias that can worsen RV cardiac output, and peripheral vasodilation that can cause severe systemic hypotension[70]. Milrinone exists in aerosolized form which may attenuate some of the hypotension associated with systemic use[98].

Dopamine can be a useful but challenging agent in RV failure due to somewhat-unpredictable dose-dependent effects on systemic and pulmonary circulation and cardiac inotropy. At low doses, dopamine is predominantly a systemic vasodilator; as doses increase, the hemodynamic effect is predominantly stimulation of β1 receptors, and at higher doses, a vasopressor effect on α1 receptors starts to appear. Thus, it can be associated with the development of arrhythmias before any meaningful effect on hypotension develops, and its use should be considered carefully.

In general, a reasonable approach is to first resolve hypotension using either norepinephrine or epinephrine, add low-dose vasopressin early to minimize the arrhythmogenic effects of norepinephrine or epinephrine, and add low-dose dobutamine and milrinone once the patient’s blood pressure can tolerate it[78]. Importantly, these agents should be titrated to discrete and separate parameters; i.e., norepinephrine or epinephrine to mean arterial pressure, and dobutamine or milrinone to either cardiac output or mixed (or central) venous oxygen saturation > 60%.

It must be noted that there is a potential for a blunted response to inotropes in patients with RV failure due to decompensated PAH. This is due to the increased elastance of the RV and the downregulation of adrenoreceptors that occur as maladaptive responses to chronically elevated RV afterload, which limit the effect of exogenous inotropes in these patients[36].

Pulmonary vasodilators

Selective pulmonary vasodilators can acutely unload the RV by reducing PA pressure and therefore RV afterload. Inhaled nitric oxide (iNO) or inhaled prostacyclins (e.g. inhaled epoprostenol) cause pulmonary vasodilation without significant systemic hypotension. These agents improve oxygenation by directing flow to better-ventilated lung units, improving V/Q mismatch, and reducing intrapulmonary shunting[73]. Inhaled nitric oxide and inhaled epoprostenol can both be used in-line with HFNC and with an IMV circuit.

Systemic pulmonary hypertension therapy should be reserved for patients who are known or are highly suspected to have PAH and should only be done with confirmatory invasive hemodynamics (i.e., PA catheterization). Patients who present in PAH crisis should be initiated on intravenous prostacyclin agents (epoprostenol or treprostinil) and rapidly uptitrated. They can be started simultaneously with inhaled nitric oxide to more immediately reduce RV afterload. Intravenous epoprostenol may have particular utility in critically ill patients with PAH, since its short half-life allows for more rapid dose titration[99]. Other PAH therapies, such as phosphodiesterase-5 inhibitors, endothelin receptor antagonists, soluble guanylate cyclase stimulators, and activin signaling inhibitors, should be considered on a case-by-case basis, understanding that most data for these patients come from outpatients with PAH.

The reduction in PVR caused by pulmonary vasodilators, particularly systemic pulmonary hypertension therapy, can directly lead to an increase in RV ejection fraction, stroke volume, and cardiac output. These medications should be used with caution in patients with left heart disease (including mitral and aortic valvulopathy) and possible pulmonary veno-occlusive disease as they can precipitate peripheral edema. They should also be used thoughtfully in patients with normal or high cardiac output at baseline (e.g., in patients with portopulmonary hypertension or hereditary hemorrhagic telangiectasia), because in these scenarios their impact on cardiac output will be detrimental[100]. These concerns highlight the potential utility of PA catheterization in critically ill patients with RV failure.

Pericardial effusions in decompensated PAH

The management of pericardial effusion and cardiac tamponade in patients with PAH merits special discussion. Patients with PAH are often at high risk of pericardial effusion, either due to increases in right-sided pressures or to underlying connective tissue disease[101]. The presence of underlying RV hypertrophy and elevated pressure/volume in the RV can mask the classic diastolic collapse of the RV or RA associated with cardiac tamponade[101]. PA catheterization in these patients will often reveal equilibration of right heart pressures, a prominent x wave, and reduction or absence of the y wave, which explains the delicate pressure balance between the RV cavity and the pericardial space[67]. If true tamponade is present, rapid drainage of the pericardial effusion will quickly precipitate RV dilation and hypokinesis, as well as impingement into the LV and obliteration of the LV cavity[100,101]. Thus, if cardiac tamponade is felt to be contributing to decompensated RV failure in PAH, drainage should be gradual and done with continuous invasive hemodynamic monitoring.

This approach is different from that of patients who have cardiac tamponade as a primary cause of RV collapse. In that scenario, which is not primary RV failure but rather an impediment to RV filling, clinicians should perform large volume pericardiocentesis immediately to stabilize the patient; a more complete description of cardiac tamponade can be found elsewhere[102].

MCS

When medical therapy fails, MCS devices may be used to stabilize the patient in RV failure, where available[78]. In the context of decompensated RV failure, MCS is generally used as a bridge to recovery or a bridge to transplant. The selection of an appropriate MCS device relies on identification of the etiology of the acute RV failure. For patients with isolated RV failure, temporary RV assist devices (RVADs) such as the Impella RP^® and Tandem Heart^® can be placed percutaneously and can help to offload RV workload until the cause of the acute RV failure can be addressed[103-106]. However, data primarily supports the use of RVADs in cases of primary acute RV failure (e.g., due to RV infarction, LV assist device implantation, or after heart transplant or cardiac surgery). There is very little evidence to support the use of RVADs in conditions where RV failure is secondary to acutely increased afterload or in the context of septic cardiomyopathy. Concerns with RVAD use in patients with chronically elevated PA pressure (such as patients with PAH) include worsening the already elevated PA pressure leading to pulmonary edema (especially with concurrent left heart disease) or pulmonary hemorrhage[107,108]. Additionally, the RVAD may not be able to supply adequate flow through the pulmonary vasculature if the elevated PA pressure exceeds its capabilities[109].

Extracorporeal membrane oxygenation (ECMO) is a key modality in the treatment of acute RV failure. The selection of the appropriate ECMO modality in acute RV failure is dependent on the underlying etiology and the presence or absence of concomitant cardiogenic shock. For patients in whom acute RV failure is secondary to severe hypoxemic or hypercarbic respiratory failure, such as in ARDS, veno-venous (VV)-ECMO is the indicated therapy. The primary rationale for VV-ECMO in this setting is to correct severe gas exchange abnormalities, which in turn reduces hypoxic pulmonary vasoconstriction, allows for less injurious ventilator strategies, and thereby decreases RV afterload. The best data for VV-ECMO comes from the EOLIA trial of patients with severe ARDS[110], and did not focus specifically on RV function. The Extracorporeal Life Support Organization notes that the only absolute contraindication to the use of VV-ECMO is lack of expected recovery without a viable plan for decannulation[111]. Relative contraindications are often institution-specific and may include significant, uncontrollable hemorrhage, underlying terminal illness, and advanced age[111].

In cases of RV failure with resultant cardiogenic shock, veno-arterial (VA)-ECMO is required as it provides full cardiopulmonary support by draining deoxygenated blood from the venous system and returning oxygenated blood to the arterial system, thereby directly unloading the failed RV while providing end-organ perfusion. This makes VA-ECMO a powerful tool as a bridge to recovery or definitive therapy such as organ transplantation. VA-ECMO is indicated when medical management including mechanical ventilation, inotropes, fluids, and other types of MCS fail to provide adequate systemic perfusion[112] and is the default configuration in emergent situations of actual or impending cardiac arrest. An important use of VA-ECMO is as a temporary bridge for percutaneous or surgical thrombectomy in acute high-risk PE[113]. The most common method of cannulation, peripheral insertion through the femoral vein and artery, carries a risk of north-south syndrome, where an improvement in RV function despite persistent parenchymal disease leads to deoxygenated blood being delivered to the heart and brain from a normal LV[70].

In circumstances where the patient remains in RV failure despite initiation of VV-ECMO, the circuit can be reconfigured into veno-arterio-venous configuration, where deoxygenated blood is passed through the circuit and returned to the PA and the arterial cannula in a ratio that can be adjusted by the circuit flowmeter[70]. Contraindications to VA-configuration are similar to those in VV-ECMO, with the exception that anticoagulation is more rigorously required in VA-ECMO[112]. The Novalung^® pumpless device surgically inserted between the PA and left atrium, where available, may be an alternative to VA-ECMO[68]. Decisions for timing and configuration of MCS should be individualized depending on patient and institutional factors.

Organ transplant

Lung or dual heart-lung transplantation should be considered in appropriate candidates with RV failure who fail to recover despite maximal invasive efforts. The majority of these patients will require lung transplantation, generally bilateral[114]. In general, patients with PAH are considered appropriate candidates for lung transplant listing if they are high-risk, with persistent RV failure despite maximal therapy, or hospitalized and requiring inotropic/vasopressor and/or ECMO support[114]. Although historically evaluated for combined heart-lung transplantation, it is now known that RV function recovers well after bilateral lung transplant, and experts now advocate heart-lung transplant in PAH only in the setting of irreparable complex congenital heart disease or severe LV failure[114]. Patients with RV failure due to parenchymal lung disease (including fibrotic disease after ARDS or other severe fibrotic interstitial lung disease) are generally also considered for bilateral lung transplant, although some patients who have fairly minimal pulmonary hypertension with severe parenchymal lung disease may undergo single lung transplantation.

For patients presenting with acute, fulminant RV failure who are deteriorating rapidly, early consideration for expedited transplant evaluation while on MCS is critical. There is evolving increasingly robust data for VA-ECMO as a bridge to successful lung transplant[115], particularly as it allows patients to remain awake, often not intubated, and able to mobilize[104]. The success of this strategy hinges on timely, collaborative decision making at centers experienced in MCS, pulmonary hypertension, and transplantation[116].

Balloon atrial septostomy (BAS), in which a right-to-left interatrial shunt is created percutaneously, may also be considered as a bridge to lung transplantation in patients with PAH. BAS may improve RV function (by reducing RV end-diastolic volume), increase LA filling, and improve LV function[117,118].

Supportive and palliative care in critical illness with RV failure

Critical illness and RV failure, despite maximal medical therapy, continues to carry high morbidity and mortality. Five-year ECMO and transplant-free survival after an episode of decompensated PAH is overall approximately 20%, and significantly less among patients over 50 years of age[119]. The rate of survival after cardiac arrest in patients with PAH, at experienced centers, is around 20%, with survival to hospital discharge in the single digits[120]. The survival of patients with ARDS and acute PE is much higher, particularly if they are treated in accordance with contemporary guidelines. Patients who are hospitalized with acute respiratory failure who have fibrotic lung disease and coexisting pulmonary hypertension have very poor outcomes[121].

Ideally, discussions about patient wishes in the event of deterioration of severe underlying PAH or parenchymal lung disease should take place well before hospitalization; however, data suggests that even among expert centers, fewer than 6% of patients with PAH are referred to palliative care, and of those, 43% are referred at their last visit prior to death[122]. Thus, it is often the critical care clinician who must have difficult conversations with patients in RV failure who are at the end of life. Determination of eligibility for MCS and transplantation should be done very early in the hospitalization, and frank discussions about goals of care, however difficult, should take place with patients and their families who are facing the end of life without the prospect of effective additional therapies.

CONCLUSION

RV failure is a common yet often overlooked medical condition, particularly in acute and critical care settings, with a broad range of underlying etiologies. Clinically, RV failure frequently presents with signs of systemic venous congestion and low cardiac output. While diagnosis is often clinical, supportive lab findings and imaging including echocardiography can play a crucial role in early identification of RV dysfunction and its etiology, chronicity, and severity. Ideally, when possible, these patients should be treated at institutions with subspecialty expertise in RV failure, MCS, and transplantation. Management of these patients should be thoughtful and individualized, and based on bedside echocardiography, invasive hemodynamic measures, and a well-versed understanding of the pathophysiology.