The role of the left ventricle in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and aggravates many common critical diseases (acute respiratory distress syndrome, pulmonary embolism, acute myocardial infarction, and postoperative cardiac surgery). Several supportive therapies, including mechanical ventilation and fluid management, can make RV dysfunction worse, potentially exacerbating shock. We briefly review the epidemiology, pathophysiology, diagnosis, and recommendations to guide management of acute RV dysfunction in ICU patients. Our aim is to clarify the complex effects of mechanical ventilation, fluid therapy, vasoactive drug infusions, and other therapies to resuscitate the critical patient optimally.
The role of the left ventricle (LV) in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and exacerbates many common critical illnesses (e.g., acute respiratory distress syndrome (ARDS), pulmonary embolism (PE), inferior acute myocardial infarction, and postoperative cardiac surgery).
There is a variety of definitions for acute RV dysfunction (RVD), RV failure (RVF), and right heart failure (RHF) in the literature that must be clarified and not used interchangeably.
Acute occurrence of RV systolic dysfunction by measuring the longitudinal systolic displacement and dilation [ Unexplained increase of natriuretic peptides in the absence of LV or renal disease Electrocardiographic (ECG) RV strain patterns which are strong markers of moderate-to-severe RV strain. While specific, they are limited by a lack of sensitivity.
Acute right ventricular dysfunction definition
Echo parameters | ECG signs | Biomarkers | |
---|---|---|---|
RV systolic function | RV dilation | ||
TAPSE < 16 mm | ED RVD/LVD ratio > 0.9 | Complete RBBB | BNP > 100 pg/mL |
S < 10 cm/sec | ED RVA/LVA ratio > 0.6 | Incomplete RBBB | NT-proBNP > 900 pg/mL |
RV fractional area change < 35% | ED RVD > 42 mm (at the base) | Anteroseptal ST elevation | |
RV ejection fraction < 45% | ED RVD > 33 mm (at the middle third of RV) | Anteroseptal ST depression | |
Septal dyskinesia in the RV focused view | Anteroseptal T-wave inversion |
BNP: B-type natriuretic peptide; ED RVD/LVD ratio: end-diastolic RV diameter/LV diameter ratio; ED RVA/LVA ratio: end-diastolic RV area/LV area ratio; ED RVD: end-diastole RV diameter; NT-proBNP: N-terminal pro-BNP; S: pulsed Doppler S wave; TAPSE: tricuspid annular plane systolic excursion.
Evidence of cardiomyocyte death (elevation of troponin
Mechanisms of acute right ventricular dysfunction/failure (RVD/RVF). RV dysfunction begins with excessive increases in preload or afterload or injury that results in decreased contractility. RV ischemia and LV function impairment ensue a vicious cycle worsening hemodynamics and precipitate the transition to RVF. ARDS: acute respiratory distress syndrome; A-V: atrioventricular; CO: cardiac output; CVP: central venous pressure; MI: myocardial infarction; PE: pulmonary embolism; PFO: patent foramen oval; POCS: postoperative cardiac surgery; RAP: right atrial pressure; R → L: right-to-left; SV: stroke volume.
In the present work, we will focus on the epidemiology, pathophysiology, diagnosis, and treatment of acute RVD/RVF.
Acute RVD is both common and potentially lethal in critically ill patients. Different clinical entities can produce acute RVF in ICU as a consequence of alterations in one or more of the determinants of RV performance (preload, afterload, and contractility). We will discuss the clinically most important etiologies of acute RVD/RVF: Acute PE is a common cause of acute RVD/RVF due to an excessive increase in afterload secondary to obstruction by clots, vasoconstriction in nonobstructed areas, and intracardiac hemolysis (resulting from the turbulent flow across the pulmonary value). Echocardiographic RVD is present between 30 and 56% of normotensive patients with PE. All-cause mortality rate at 30 days in the patients with confirmed PE was 5.4 to 10%, and in-hospital mortality rate directly attributed to PE was 1.1 to 3.3%, depending on whether it is in-patients versus out-patients registry and the degree of illness [ ARDS is one of the most common entities to challenge the RV. The incidence of acute RVD in ARDS varies from 30 to 56%, depending on the definition criteria of RVD, the severity of lung injury, and ventilatory strategy which is associated with increased 28-day mortality even in the lung-protective mechanical ventilation era and Berlin definition of ARDS [ RV myocardial infarction (RVMI) can be complicated by acute RVD in 30–50% of patients with inferior wall ST-elevation MI. Meanwhile, severe hypotension and low CO are present in 10% on admission in the reperfusion era [ Acute RVF is a serious problem after cardiothoracic surgery. It occurs in 0.1% of patients after cardiotomy, in 2-3% of patients undergoing heart transplantation, and in 10–20% of patients needing LV assist device insertion [ The extent of pulmonary parenchymal resection (loss of pulmonary tissue) and the preexisting PVD/RVD predict the risk and severity of postoperative RVD in patients undergoing lung resection. Hypoxia, atelectasis, and hypercarbia may precipitate acute RVD [
The anatomy and physiology of the RV are both unique and complex and quite different from LV. In contrast to the ellipsoidal shape of the LV, the RV appears triangular and crescent-shaped. Anatomically, RV can be described regarding three components: (
Regarding the myofiber architecture of the heart and according to Torrent-Guasp and other authors, the ventricular myocardium is constituted by a continuous band of muscle that extends from the pulmonary artery root to the aortic root, forming a helical structure with two spirals and delimiting the two ventricular cavities. This myocardial band would be composed of the “basal loop” and the “apical loop.” The basal loop is predominantly horizontal and comprises the right and left segments; the apical loop is predominantly vertical and consists of the descending segment (“left septum”) and the ascending segment (“right septum”) [
Under normal afterload, RV contraction begins at the sinus (inlet chamber) and progresses toward the conus or infundibulum (outlet chamber) (approximately 25 to 50 ms apart), indicating a peristaltic/asynchronous bellows-like pattern of contraction from apex to base. In contrast, LV contracts in a squeezing/synchronous pattern by twisting and rotational movements from apex to base (likened to wringing a towel) [
The low impedance and the high capacitance of the normal pulmonary circulation are reflected in the triangular shape of the RV pressure-volume loop, without distinct periods of isovolumic contraction and relaxation [
RV mechanics and function can be altered in the setting of either pressure/volume overload and primary reduction of contractility owing to myocardial ischemia (Figure
The heart has intrinsic mechanisms to maintain CO to beat-to-beat changes in preload and afterload by a heterometric dimension adaptation described by Starling’s law of the heart. Myocardial stretch elicits a rapid increase in developed force, which is mainly caused by an increase in myofilament calcium sensitivity (Frank-Starling mechanism). In the next 10–15 min, a second gradual increase in force takes place (slow force response), increasing the calcium transient amplitude secondary to a cardiac autocrine-paracrine nongenomic mechanism and named homeometric autoregulation described by Von Anrep more than 100 years ago [
Acute adaptation of the RV to PH depends on both the stationary (pulmonary vascular resistance) and the pulsatile (PA stiffness, total pulmonary capacitance, and reflected wave) components of afterload [
RV systolic impairment and dilation emerge once both myocardial intrinsic adapting mechanisms are exhausted. Several molecular and cellular mechanisms have been proposed in the development of acute RVD secondary to PH. RV wall tension increase leads to the cardiomyocyte stress and injury secondary to ischemia, substrate depletion, and mitochondrial energy metabolism impairment [
The biochemical and mechanical changes accounting for the transition from acute RVD to failure remain a subject of intense study. Some authors have proposed that acute RV failure begins when the coronary vasodilator reserve is exhausted as a consequence of RV ischemia although it is not possible to discard the concomitant existence of a primary RV failure, related to an overdistension of the ventricle [
Finally, RV cardiomyocyte ischemia produces another vicious cycle of increased oxygen demand in the setting of decreased oxygen delivery, leading to circulatory collapse and multiorgan failure (Figure
The clinical presentation of acute RVF varies depending on the underlying cause, the presence of comorbidities, and the cardiovascular reserve of the right ventricle-arterial unit. It can occur suddenly or catastrophic in a previously “healthy heart” or in a hidden way, worsening of compensated RVD in the setting of a chronic heart and lung disease. The diagnosis of acute RVF in ICU patients can become very difficult due to the presence of comorbid conditions that may cause organ hypoperfusion even in the absence of RVD (e.g., sepsis, LV dysfunction, and hypovolemia).
Clinical clues and ECG signs of acute RVD are varied and limited by a low sensitivity and specificity. Therefore, diagnosis typically relies on echocardiography. The ascendance of intensivist-conducted echocardiography has become important not only for early detecting acute RVD in ICU patients but also for monitoring and guiding a rational therapy preventing RVF from occurring.
Measurements by two-dimensional echocardiography (2DE) are challenging because of the complex three-dimensional geometry of the RV and sonographic interference from the lungs. While transthoracic echocardiography (TTE) provides adequate imaging in 99% of critically ill patients for diagnosing acute RVD and cardiac cause of shock [
Multiple views are required to an accurate assessment of RV structure and function. We can resume the following views to be used in ICU patients: the parasternal long and short axis, apical four-chamber, and subcostal four-chamber views on TTE and mid-esophageal four-chamber, RV inflow-outflow, and transgastric short axis views on TEE [
It is advisable to gather three groups of parameters (Table RV structural parameters: linear and areas measurements to assess RV dilation (absolute and relative to LV) predominantly at inlet chamber RV functional parameters: predominantly global longitudinal systolic function (since shortening of the RV is greater longitudinally than radially, drawing the tricuspid annulus toward the apex) RV afterload assessment.
Cut-off values of RV structural and functional parameters and RV afterload assessment.
RV structural parameters | RV functional parameters | RV afterload assessment |
---|---|---|
Basal RV diameter |
RV fractional area change ≥ 35% | AccT < 100 msec |
RV mid-diameter |
MPI§ > 0.43 (pulsed Doppler); >0.54 (tissue Doppler) | Shape of doppler RV outflow tract envelope |
RV EDD/LV EDD |
TAPSE |
(i) No notch |
RV/LV EDA |
S wave° < 10 cm/s | (ii) Late notch |
LV eccentricity index |
Peak RV free wall 2D strain |
(iii) Midsystolic notch |
McConnell’s sign |
||
RV wall thickness > 5 mm |
AccT: acceleration time of RV outflow tract flow; EDD: end-diastolic diameter; EDA: end-diastolic area; LV: left ventricle; RV: right ventricle; MPI: myocardial performance index (the ratio of the sum of isovolumic contraction plus relaxation time and ejection time intervals); S wave: peak velocity of systolic excursion at the lateral tricuspid annulus; TAPSE: tricuspid annular plane systolic excursion.
Given the potential risks of placing a PAC and the availability of bedside echocardiography, the use of PAC is much less common nowadays. In general, invasive monitoring should be reserved for those patients with echocardiographic evidence of severe RVD at risk of acute RVF or patients with established RVF, since we can perform repeated measurements rapidly [
The usual PAC findings suggestive of acute RVD include an elevated CVP (greater than 20 mmHg), an inverse pressure gradient (CVP > PAWP), and a low cardiac index (<2 L/min/m2), stroke volume index (<30 mL/m2), and mixed-venous oxygen saturation (SvO2 < 55%) [
One of the challenges of using PAC is the accuracy and precision of PAWP assessment due to the influence of respirophasic effects of mechanical ventilation, end-expiratory versus mean digital measurements, the volume of balloon inflation, and increase extension of zones 1 and 2 (West) [
In summary, combining the use of real-time echocardiographic evaluation bedside with the knowledge of RV physiology is the desirable way to diagnose acute RVD/RVF in ICU patients. PAC might contribute to the monitoring and adjustment of the treatment.
Effective treatment of acute RVF requires a skilled multidisciplinary team to rapidly assess and triage the patient. The treatment of acute RVD can be divided into the following bundles: (a) general measures including avoiding increasing RV afterload, decreasing RV contractility and optimization of RV preload, applying an “RV-protective” ventilation strategy, and maintaining sinus rhythm and atrioventricular synchrony; (b) pharmacological treatment with a guided inotropic and vasoactive supports; (c) mechanical circulatory support devices. Real-time monitor with bedside echocardiography assessment and the invasive hemodynamic monitoring remain the most valuable methods to guide a rational therapy of acute RVD/RVF in critically ill patients.
The prevention of acute RVF in ICU begins with the identification of high-risk patients, for example, patients with severe ARDS and inferior AMI and patients undergoing cardiac surgery with long cardiopulmonary bypass times and receiving cardiac allografts with either long ischemic time or mismatched in size. Once the severe RVD or RVF is recognized, we have to identify and treat any underlying reversible conditions that are either primarily responsible for (triggering factors) or contributing to the progressive impairment of RV function.
Proper management of
We should be aware of the limitation of the dynamic fluid responsiveness predictors in fluid management whenever RV dysfunction is present. It is well known that the presence of RV failure should be suspected when a patient has significant variations of stroke volume or pulse pressure but does not respond to fluids [
Besides, RV preload requirements differ substantially based on whether afterload is normal or increased. When acute RVD occurs in the setting of increased RV afterload, we should be restrictive with volume management. Increasing blood volume to an already overloaded RV (e.g., PE, ARDS) will not only improve perfusion but also impair CO, aggravating RV dilatation, increasing tricuspid regurgitation and right-sided venous congestion and subsequent underfilling of the LV (ventricular interdependence and serial effect), all of which will lead to hypoperfusion and multiorgan dysfunction. On the contrary, when acute RVD occurs in the setting of normal pulmonary vascular resistance (e.g., RV myocardial infarction), we can be more liberal with fluid reposition to maintain CO. Some authors have proposed a mini-fluid challenge (100 mL of colloid or crystalloid fluid over 1 minute) as a safer and rational approach in some clinical scenarios (e.g., ARDS) [
The dominant RV effects of
Right atrial contraction contributes up to 40% of RV filling and is more important when the RV compliance is impaired (e.g., RV dilatation). Appropriate sinus heart rate and rhythm, and the maintenance of atrioventricular synchrony and atrial kick, can be among the simplest methods of maintaining and avoiding RV contractility impairment. Electrical or pharmacological cardioversion for the restoration of sinus rhythm and the placement of a temporary pacemaker if heart block is present should be considered [
The pharmacological treatment will be focused on reducing the RV afterload and preserving an appropriate systemic pressure (vasoactive support) and increasing the RV contractility (inotropes drug therapy). The ideal cardiovascular drug for use in acute RVF would be an agent that enhances systemic arterial pressure and RV contractility without raising pulmonary vascular resistance (PVR). In summary, the pharmacological treatment should provide the following properties: (
Regarding the
Cardiovascular drugs for the management of acute RVF.
Agent | Receptors agonism | Cardiovascular properties | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
|
|
|
D | V1 | CI | PVR | SVR | PVR/SVR |
|
|
Vasopressors | ||||||||||
|
++ | + | + | + | ++ | −/+ | + | |||
Phenylephrine | ++ | − | ++ | + | + | − | ||||
|
+ | + | +/− | +/− | ++ | − | − | |||
|
||||||||||
Inotropes | ||||||||||
Epinephrine | ++ | ++ | + | ++ | − | ++ | − | ++ | ||
Dopamine | ||||||||||
<5 |
+ | ++ | + | − | − | − | + | |||
5–10 |
+ | ++ | ++ | + | + | + | +/− | + | ||
>10 |
++ | ++ | ++ | + | + | ++ | + | + | ||
|
++ | + | ++ | − | − | − | + | |||
|
||||||||||
Inodilators | ||||||||||
|
++ | − | − | − | +/− | |||||
|
++ | − | − | − | + |
The next major goal is to improve RV myocardial contractility by using
Both dopamine and epinephrine are not recommended for tachycardia, arrhythmic events, and an increase in the myocardial oxygen consumption. At moderate-high doses of dopamine, PVR/SVR ratio increases [
Among
Pulmonary vasodilators drugs, pathways, and mechanisms of action. AC: adenylate cyclase; sGC: soluble guanylate cyclase; ATP and GTP: adenosine and guanosine triphosphate, respectively; cAMP and cGMP: cyclic adenosine and guanosine monophosphate, respectively; inh: inhaled; i.v.: intravenous; NO: nitric oxide; −PDE: phosphodiesterase inhibitor; PK: protein kinase;
Specific
Inhaled NO (iNO) is a potent pulmonary vasodilator at concentrations from 5 to 40 parts per million with a rapid onset of action and very short half-life, making it an ideal agent for management of PH and/or hypoxemia in critically ill patients in whom lowering PAP and improving RV function is paramount (e.g., ARDS, POCS, and heart transplantation) [
The use of other currently available pulmonary vasodilators, such as the endothelin receptor antagonists (ERA) and the recently approved soluble guanylate cyclase stimulator, riociguat, should probably be avoided in acute RVF due to concerns about unreliable oral absorption. ERA use in the ICU is limited by the potential hepatotoxicity and riociguat may have significant systemic vasodilator effects, especially under conditions such as sepsis. However, oral pulmonary vasodilators can be useful when patients have become hemodynamically stable, and the medical team is planning to withdraw parenteral or inhalation agents, avoiding the rebound of PH [
Despite optimal medical management, some patients fail to improve and require implantation of a mechanical circulatory support device. The RV may exhibit a greater capacity for rapid recovery compared with the LV. Recent literature suggests that 42% to 75% of patients with acute RVF recover hemodynamic and functional status enabling device explantation [
Two types of mechanical circulatory assistance have been described in the setting of RVF: (a) RV assist devices (RVAD) and (b) extracorporeal membrane oxygenation (ECMO) [
Differences between venoarterial and venovenous extracorporeal membrane oxygenation (ECMO).
Venoarterial ECMO | Venovenous ECMO |
---|---|
Higher PaO2 is achieved | Lower PaO2 is achieved |
Lower perfusion rates are needed | Higher perfusion rates are needed |
Bypasses pulmonary circulation | Maintains pulmonary blood flow |
Decreases pulmonary artery pressures | Elevates mixed venous PO2 |
Provides cardiac support to assist systemic circulation | Does not provide cardiac support to assist systemic circulation |
Requires arterial cannulation | Requires only venous cannulation |
Schematic algorithm for selecting the appropriate extracorporeal life support in patients with refractory right ventricular failure. RA-LA: right atrial-left atrial; RVAD: right ventricular assist device; V-A: venoarterial; V-V: venovenous; ECMO: extracorporeal membrane oxygenation.
There was a lack of large comparison groups of patients with RVF managed with medical treatment only, RVADs, or ECMO. A prospective study that includes a clear definition of refractory RVF, guidelines for device use, and appropriate control groups is required.
We have described general management considerations for critically ill patients with acute RVF. A key principle in the management of acute RVD focuses on determination and treatment of the underlying etiology [
Mechanisms and targeted management in specific clinical scenarios of acute RV failure.
Clinical scenario | Mechanism | Treatment |
---|---|---|
Right ventricular infarct | Decreased RV contractility | Early myocardial reperfusion (percutaneous coronary intervention, systemic thrombolysis) |
Pulmonary embolism | Increase RV afterload (mechanical obstruction & vasoconstriction) | Systemic anticoagulation, systemic or catheter-directed thrombolysis, embolectomy |
Decompensated PAH | Increase RV afterload | Parenteral prostanoids (with or without inhaled pulmonary vasodilators |
ARDS | Increasing RV afterload/decreasing RV contractility | Limiting VT and PEEP, avoiding hypoxia, hypercapnia, and acidosis |
Noncardiac surgery | Acute PH, decreasing RV contractility (RV infarct) | Pulmonary vasodilators, myocardial reperfusion, inotropic drugs |
Cardiac surgery | Volume overload, myocardial ischaemia, preexisting RVD, arrhythmias | Diuretics, inotropic drugs, cardioversion, antiarrhythmic drugs |
ARDS: acute respiratory distress syndrome; PAH: pulmonary arterial hypertension; RVD: right ventricular dysfunction.
Early myocardial reperfusion of patients with
RVF is the principal determinant of early mortality in the acute phase of
Patients with previously unknown
In
Acute RVD/RVF is seen with increasing frequency in the intensive care unit and causes or aggravates many common critical diseases.
Bedside echocardiography assessment and invasive hemodynamic monitoring remain the most valuable methods to diagnose and to guide a rationale therapy of acute RVD/RVF in critically ill patients.
General precautionary measures, early diagnosis of RVD, and etiology-specific therapy may reduce the appearance of RVF. Supportive therapies focused on improving RV function via optimization of preload, enhancing contractility, and reducing afterload are the key principles in the management of acute RVF.
Future research should focus on better understanding the cellular and molecular mechanisms of acute RV cardiac dysfunction to develop novel therapies that directly target the injured myocardium.
The authors declare that there are no conflicts of interest regarding the publication of this paper.