The challenges in the management of right ventricular infarction

Abstract

In recent years, right ventricular (RV) infarction seems to be underdiagnosed in most cases of acute myocardial ischaemia despite its frequent association with inferior-wall and, occasionally, anterior-wall myocardial infarction (MI). However, its initial management is drastically different from that of left ventricular MI, and studies have indicated that RV infarction remains associated with significant morbidity and mortality, even in the mechanical reperfusion era. The pathophysiology of RV infarction involves the interaction between the right and left ventricle (LV), and the mechanism has been clarified with the advent of diagnostic non-invasive modalities, such as echocardiography and cardiac magnetic resonance. In recent years, considerable progress has been made in the treatment of RV infarction; early revascularization remains the cornerstone of the management, and fluid resuscitation, with appropriate target selection, is necessary to maintain appropriate preload. Early recognition in intensive care with clear understanding of the pathophysiology is essential to improve its prognosis. In terms of management, the support strategy for RV dysfunction is different from that for LV dysfunction since the former may often be temporary. Along with early reperfusion, maintenance of an adequate heart rate and atrioventricular synchrony are essential to sustain a sufficient cardiac output in patients with RV infarction. In refractory cases, more intensive mechanical support is required, and new therapeutic options, such as Tandem-Heart or percutaneous cardiopulmonary support systems, are being developed.

Introduction

Right ventricular (RV) infarction rarely occurs in isolation,¹ with approximately between one-third and half of the patients with inferior-wall myocardial infarction (IWMI) having some RV involvement. The reported incidence of RV infarction varies widely, depending on the criteria and methodology of the study in question. RV infarction can be defined pathologically, haemodynamically, echocardiographically, electrocardiographically, or by cardiac magnetic resonance (CMR). In this manuscript, we first discuss the incidence and diagnosis of RV infarction, with focus on the non-invasive modalities, such as CMR. Then, we aim to provide an overview of its prognosis with respect to changes between the fibrinolytic and mechanical reperfusion era. Finally, we discuss the management of RV infarction focusing on biventricular interdependence, which is expected to promote the understanding of optimal volume replacement, early revascularization, and utilization of newly developing treatment modalities.

Incidence and diagnosis

Physical examination

The clinical triad of hypotension, clear lung fields, and elevated jugular venous pressure has been traditionally considered as a maker of RV infarction in patients with IWMI. However, this triad has high specificity (96%) but very low sensitivity (25%).² Kussmaul’s venous sign (distension of the jugular vein on inspiration), a feature of constrictive pericarditis, may also occur with RV infarction.³ Electrocardiography and other non-invasive imaging modalities continue to be the cornerstones of the diagnosis of RV infarction because of the high specificity but low sensitivity associated with physical examination.

Electrocardiography

In clinical practice, RV infarction is frequently diagnosed electrocardiographically. An ST-segment elevation of >1 mm in lead V₄R is considered significant and correlates closely with other noninvasive evidences of RV dysfunction.^4–7 This electrocardiographic finding is also a strong independent predictor of major complications and in-hospital mortality.⁸ This ST-segment elevation is thought to represent an ischaemic injury of the posterobasal septum, since this area of contiguous myocardium is invariably damaged in patients who have pathological evidence of IWMI involving the RV.⁹

Notably, most of the so-called RV ‘infarctions,’ indicated by right-sided ST-segment changes or pathological Q waves, do not progress to an actual infarction (e.g. myocardial necrosis and scar formation); these electrocardiographic findings usually represent an early, transient phenomenon.¹⁰ This has been demonstrated recently in a study with sequential CMR imaging.¹¹ Several unique anatomic and physiological characteristics of the right ventricle contribute to recovery from RV infarction. First, pulmonary circulation is approximately one-tenth the length of systemic circulation, and a 5-mmHg perfusion gradient is sufficient to propel blood across the pulmonary circuit.¹² Second, unlike diastolic flow in the left ventricle (LV), the thin RV free wall allows the biphasic perfusion of coronary blood, with approximately equal contributions during systole and diastole.¹² Third, the right ventricle has rich collaterals from the left anterior descending artery in addition to right coronary artery (RCA) blood flow. Thus, RV infarcts may be clinically suspected in many patients with a stunned or hibernating RV free wall.

Echocardiography

Since the late 1980s, considerable progress has been achieved in echocardiography and radionuclide techniques; these modalities revealed that RV involvement may be present in as much as 59% of the patients with IWMI at the initial presentation.^13–15 In particular, echocardiography is a widely available and inexpensive tool for the comprehensive evaluation of the size and function of the right ventricle. However, echocardiographic imaging of the RV has technical challenges due to the chamber’s complex shape; the RV cannot be completely visualized in any single two-dimensional (2D) echocardiographic view. Furthermore, although RV infarction inherently complicates the initial management in cases of acute infarction, echocardiographic abnormalities can be temporary and resolve within a few hours.^16,17 Therefore, information from all available acoustic windows is necessary for the complete assessment of the RV. Although not validated in acute situations, three-dimensional (3D) echocardiographic RV volumes are comparable to those derived by CMR and are probably more accurate than 2D echocardiographic volumes.¹⁸

Cardiac magnetic resonance

CMR using late gadolinium enhancement imaging enables the accurate characterization of ischaemic myocardial injury (Figure 1). CMR studies have indicated that RV infarction occurs in a high number of cases in patients with IWMI (47–57%) and that some patients with anterior MI (11–65%) also have RV involvement to some extent.^11,19,20 Indeed, two observational reports comparing the frequency of RV involvement between different modalities in patients with acute MI indicated that RV involvement was detected significantly more frequently with CMR than with electrocardiography or echocardiography.^19,20 Although the recent advances in CMR may contribute to understanding the pathology as well as providing a more accurate diagnosis of RV infarction, further investigations are essential to establish the usefulness of the CMR technique, since the numbers of patients included in these observational studies were limited.

Figure 1.

Contrast-enhanced cardiovascular magnetic resonance image of right ventricular myocardial infarction (a) and cine angiogram before (b) and after (c, d) percutaneous angioplasty in the corresponding case.

Enlarged short-axis view with infarction of the right ventricular wall (red arrows) and the inferior left ventricle. The occluded proximal right coronary artery was recanalized with percutaneous angioplasty, and the major right ventricular branch (white arrows) was recognized.

Prognosis

Short-term prognosis

Patients with acute IWMI have a substantially increased risk of death during hospitalization if RV involvement is present. In a meta-analysis from the fibrinolytic era, the mortality rate was noted to be higher in the presence of RV infarction (17%) than in its absence (6.3%), thereby corresponding to an overall pooled relative risk mortality increase of 2.6 (95% confidence interval, 2.0–3.3).²¹ The worse outcome is mainly attributable to the high incidence of refractory cardiogenic shock. In a typical scenario, infarcted RV tissue fails to offer a sufficient preload, which is essential for adequate LV performance, and consequently, a low cardiac output will lead to systemic hypoperfusion.

The revascularization strategy has improved the overall short-term mortality rate of acute MI (7 vs. 9%) compared with that associated with the fibrinolytic strategy.²² However, although the number of patients with RV infarction is small, these patients seem to have a higher risk of in-hospital mortality in the mechanical reperfusion era than during the fibrinolytic era. Figure 2 shows the changes in the in-hospital mortality rate and relative risk of RV infarction for in-hospital mortality between the fibrinolytic and mechanical reperfusion era;^8,23–36 An increase in the relative risk of RV infarction from 2.29 (95% CI 1.67–3.14) to 2.98 (95% CI 1.41–6.31) also occurred during this period. The precise explanation for the paradox remains unknown. Despite the advances in therapeutic strategy, including mechanical reperfusion for acute MI, improvement in the in-hospital mortality could not be achieved even by mechanical reperfusion in patients with fatal RV infarction, and therefore, the relative risk of in-hospital mortality in such a population might have been highlighted.

Figure 2.

Changes of in-hospital mortality rate and relative risk of RV infarction for in-hospital mortality between the fibrinolytic and mechanical reperfusion era.

These data were derived from previously published meta-analyses,²¹ which included many prospective or retrospective studies, assessing the impact of RV infarction in patients with acute MI up to June 2007,^{8,23–30,33–36} and two additional observational studies that met the same inclusion criteria up to June 2012.^31,32

Long-term prognosis

The prognosis associated with RV infarction is worse in the short term, but those patients who survive hospitalization have a relatively good long-term prognosis.³⁷ This is in concordance with the findings in patients with LV cardiogenic shock; in the SHOCK study, 1 year after revascularization, the survival curves remained relatively stable with an annual mortality rate of 8–10 deaths per 100 patient-years. This annual mortality rate is comparable to that reported in a broad cohort of post-percutaneous coronary intervention patients.³⁸

Therapy

The management of RV infarction should be started with volume replacement, and recent studies have highlighted the adverse effect of excessive volume loading. Early revascularization is also applied to RV infarction, in which the complete revascularization of the affected vessels, including the major RV branch, plays an important role in the recovery of RV function. Electrical stabilization, including adequate heart rate and the maintenance of atrioventricular synchrony, is another key factor for preserving cardiac output in RV infarction. Furthermore, various extracorporeal support devices have been used to support RV failure secondary to RV infarction and contributed to the improvement of RV shock.

Volume replacement

When RV infarction is complicated by acute MI, it is widely recognized that adequate therapy can be achieved only by expanding the plasma volume, ideally with the aid of invasive monitoring. However, fluid replacement can be challenging in some patients with RV infarction, particularly in the presence of severe RV dysfunction.³⁹ The concept of fluid replacement was first described as a treatment option approximately 25 years ago with the development of pulmonary artery catheterization. Since then, several studies have validated the usefulness of volume loading for ischaemic RV dysfunction.^40–43 Therefore, the initial therapy for hypotension in patients with RV infarction without pulmonary congestion has traditionally been volume expansion, particularly if the estimated central venous pressure was <15 mmHg.⁴⁴

In previous studies, maintenance of the RV preload with volume loading and normal saline alone was thought to resolve the accompanying hypotension and improve the cardiac output.⁴⁵ The typical regimen consisted of normal saline (40 ml/min, up to total of 2 l, intravenously), while maintaining the right atrial pressure (RAP) at <18 mmHg to prevent volume overload.⁴⁶ However, later clinical studies reported variable responses to aggressive fluid therapy with a target pulmonary wedge pressure (PWP) of 18–24 mmHg (Figure 3).^47–51 Some studies, including two prospective ones, showed that volume loading further elevates the right-sided filling pressure without improving cardiac output.^47,50,51 Berisha and associates,⁵² in a study of 41 patients who fulfilled the diagnostic electrocardiographic and haemodynamic criteria for RV infarction, reported that the maximal RV stroke work index occurred when the filling pressure was 10–14 mmHg, and a mean RAP of >14 mmHg was almost always associated with a reduced RV stroke work index (Figure 3). Although the haemodynamic characteristics of RV infarction may be extremely variable, depending on the patient’s state of hydration and the degree of concomitant LV involvement, this study indicated that the mean optimal PWP, which corresponded to the maximum LV stroke work index in each patient, was 16 mmHg.

Figure 3.

Responses before and after volume replacement therapy in patients with right ventricular myocardial infarction.

The association between mean right atrial pressure (mRAP) and the right ventricular systolic work index (RVSWI) is shown by a blue line. An mRAP of 10–15 mmHg seems to be an optimal target for right-sided filling pressure.⁵² Changes of pulmonary wedge pressure (PWP) and cardiac index from smaller studies are shown by a red line. There is a wide variation in its response, but no clear linear association was noted between PWP and cardiac index with a higher right-sided filling pressure target.^47–51

Clinical implications of biventricular interdependence

Two physiological concepts explain the detrimental effect of excessive volume loading in patients with RV infarction (Figure 4). First, data from animal studies suggest that excessive RV dilatation can further compromise LV output because of pericardial restraining effects.⁵³ Biventricular interdependence is mediated by the shared interventricular septum and the surrounding pericardium. The disproportionate elevation of RV filling pressure because of surplus volume loading can lead to marked RV dilatation, elevation of intrapericardial pressure, and subsequent equalization of RV and LV diastolic pressures. By compromising LV filling, this situation will precipitate a low-output state. The resultant impairment of interventricular septal motion can further aggravate this condition.^54,55

Figure 4.

Two physiological concepts explaining the detrimental effects of excessive volume loading. (a) Normal ventricle: at end-systole (ES), the right ventricular (RV) free wall moves toward the septum. (b) Pericardial restraining effects (above, before volume loading; below, after excessive volume loading): RV dilatation, as a result of excessive volume loading, can lead to the elevation of intrapericardial pressure, increase in pericardial constraint (red arrow), and change of geometry due to interventricular septum shift. These changes contribute to the low-output state by decreasing left ventricular (LV) distensibility, preload, and ventricular elastance. (c, d) Role of the interventricular septum (c, pure RV infarction; d, RV infarction with septal ischaemia). (c) At ES, the RV free wall moves toward the septum. At end-diastole (ED), the RV dilates during diastole and the septum reverse curves toward the volume-reduced LV. At ES, the septum thickens but moves paradoxically into the RV, displacing the RV volume despite RV free wall dyskinesis. (d) Septal ischaemia depresses septal contraction and global LV function, resulting in LV dilatation. The septum stops thickening and there is increased systolic septal displacement into the RV. Pansystolic septal thinning and more extensive paradoxical displacement are associated with further depression of RV performance.

In addition, in isolated RV infarction, RV performance can be largely attributed to a force generated by the interventricular septum.⁵⁶ Patients with intact LV-septal contraction would be expected to manifest a pattern of paradoxical septal motion with preserved septal thickening,⁵⁷ portending a better prognosis. Damage to the interventricular septum significantly impairs RV emptying and exacerbates diastolic dysfunction, with an increase in the filling pressure. In RV infarction associated with septal dysfunction, compensation from LV-septal contraction transmitted through systolic ventricular interaction is lacking, and these patients usually present with hypotension and low cardiac output that are refractory to initial volume loading. Under these circumstances, inotropic stimulation of contractility, usually with dobutamine, has consistently improved RV performance by enhancing global LV contraction and increasing paradoxical septal displacement into the right ventricle.⁵⁸ These important impacts of the interventricular septum on RV performance after acute MI were observed in a study using echocardiography, in which the recovery of RV function was best correlated with the improvement of the interventricular septum wall.⁵⁹

In earlier studies, RV infarction was defined by haemodynamic criteria, such as an elevated RAP or PWP. At present, in most coronary units, physicians are able to identify RV infarction more precisely using non-invasive imaging techniques (e.g. echocardiography, radionuclide imaging, cardiac magnetic resonance), as discussed earlier. With these non-invasive modalities, the extent of interventricular involvement is essential for the precise assessment of fluid balance, early risk stratification, and prognostic evaluation.

Early revascularization

In the typical situation of a haemodynamically significant RV infarction, RCA occlusion compromises right atrial and RV branch perfusion, resulting in RV ischaemic dysfunction related to the loss of the critical compensatory contribution of augmented right atrial contraction. Patients with proximal RCA culprit lesions have worse baseline characteristics, less spontaneous recanalization, and a greater clot burden than those without.⁶⁰

Although the relative prognostic impact of RV infarction has been more prominent, successful mechanical reperfusion has improved the absolute clinical outcome as a whole, in relation to RV infarction (Figure 2). Because of the higher reperfusion rate achieved with primary angioplasty, the mortality among patients treated with this method has been relatively low. In addition, the clinical outcomes have been acceptable in patients with proximal RCA culprit lesions, despite their worse baseline characteristics; these outcomes have been similar to those of patients with nonproximal RCA culprit lesions.⁶⁰ Technically, a shorter time taken to reperfusion and complete revascularization of the affected vessels, including the major RV branch, play an important role in the recovery of RV function. Early revascularization leads to an immediate recovery of RV function; conversely, late revascularization is associated with higher RV dysfunction and complications.^61,62 Asalli and colleagues³⁰ reported that complete revascularization of the RCA, including the major RV branch, was more closely associated with a higher recovery rate of RV function by echocardiography and better 30-day mortality than incomplete revascularization in patients with RV infarction. Further, in cases of complication with ventricular arrhythmia, reperfusion results in a better prognosis.⁶³ Thus, prompt, successful, complete revascularization seems to benefit all patients with RV infarction.

Other treatment modalities

The current treatment of RVMI patients, other than the optimization of RV and LV preload with intravenous fluids, the administration of inotropic agents, and revascularization, includes the maintenance of atrioventricular synchrony, intra-aortic balloon pump counterpulsation, and more intensive mechanical support, including an emergent cardiopulmonary bypass and use of a ventricular assist device (VAD). In this section, we summarize the newly developing modalities for patients with RV shock as follows: (1) electrical stabilization device, including adequate heart rate and the maintenance of atrioventricular synchrony; (2) percutaneous implantable VAD (especially focused on Tandem-Heart); and (3) percutaneous cardiopulmonary support (PCPS).

An adequate heart rate and the maintenance of atrioventricular synchrony can play an important role in sustaining a sufficient cardiac output. Patients with RV infarction tend to have bradyarrhythmia. In addition, the ischaemic right ventricle and, consequently, the preload-deprived left ventricle have a relatively fixed stroke volume, and cardiac output strongly depends on the heart rate.^64,65 Therefore, an adequate heart rate with pacing is essential for patients with RV infarction, regardless of the presence or absence of bradyarrhythmia. Moreover, several investigators have shown that atrioventricular sequential pacing in patients with a complete atrioventricular block associated with RV infarction leads to a significant improvement in the cardiac output and recovery from shock when ventricular pacing alone has no benefit.⁶⁶ Unfortunately, transvenous pacing may prove problematic due to ventricular sensing failure from the ischaemic right ventricle and difficulties with lead positioning after right atrial enlargement.

Surgically implanted right VADs have been used mostly for the support of surgical or pre-transplant patients. They have been less commonly used in the management of shock or for the post-cardiopulmonary arrest syndrome. However, in recent years, very few papers have described the use of percutaneous VAD implantation using Tandem-Heart (Cardiac Assist, Pittsburgh, PA, USA) for RV infarction.^67–72 Tandem-Heart is a temporary, external, continuous-flow, centrifugal pump that is placed nonsurgically in the catheterization laboratory through the femoral vein; it was originally intended for stabilizing critically ill patients who require short-term left heart support. The cannulas can be placed in the right atrium and pulmonary artery to support the right ventricle, as indicated in case reports. Percutaneous VADs are expected to allow time for the recovery of RV function in acute conditions or to serve as a bridge to other interventions, such as surgical VAD implantation.

PCPS has also been used successfully to provide support for patients with refractory RV failure secondary to RV infarction.⁷³ A PCPS is a compact, portable heart-lung machine that can be quickly installed using a thin-walled cannula inserted via the femoral vessels. Cannulas are advanced in the right atrium and femoral artery, and oxygenated blood is transmitted from the femoral artery in a retrograde fashion. Although the installation of the Tandem Heart for left ventricular support requires a trans-septal puncture to place the blood removal cannula into the left atrium, such techniques are not required to install a PCPS, which has been used to apply shock or for cardiopulmonary arrest due to accessibility issues. Suguta and colleagues⁷⁴ reported the first case of cardiogenic shock caused by RV infarction treated with a PCPS, which is now recognized as one of the therapeutic options.

Conclusion

In patients with MI, especially those with IWMI, RV involvement is an important contributor to shock, which significantly increases the risk of mortality. The recent advances in non-invasive modalities, such as CMR, provide a more accurate diagnosis of RV infarction, which in turn helps elucidate the precise pathophysiology. Although volume loading has long been considered the cornerstone of management in these cases, we can apprehend the harmful aspects of this therapy by understanding its effect on the interventricular septum. Early successful reperfusion, especially using revascularization, contributes to the recovery from shock associated with RV infarctions, which thus results in an improved prognosis. On the other hand, the importance of RV infarction is highlighted in this mechanical reperfusion era. The maintenance of an adequate heart rate and atrioventricular synchrony is another key factor for sustaining a sufficient cardiac output in patients with RV infarction. In refractory cases, more intensive mechanical support, including Tandem-Heart or PCPS, has been applied and is recognized as new therapeutic options.