|Year : 2020 | Volume
| Issue : 3 | Page : 216-225
Left Ventricle Can't Stay Alone – A Review of Right Ventricular Failure Post-Left Ventricular Assist Device Implantation
Manoj Kumar Sahu1, Prateek Vaswani2
1 Intensive Care for CTVS, CT Centre, New Delhi, India
2 Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||09-Jun-2020|
|Date of Decision||13-Aug-2020|
|Date of Acceptance||15-Sep-2020|
|Date of Web Publication||23-Dec-2020|
Dr. Manoj Kumar Sahu
Intensive care for CTVS, CT Centre, AIIMS, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Background: Increasing incidence of heart failure with end-stage heart disease and limited availability of donor heart for transplantation made mechanical assist devices a lucrative option. Left ventricular assist device (LVAD) is used increasingly in recent years as a bridge to transplant and also as destination therapy with significantly improved outcomes. Implantation of LVAD improves the left heart systolic dysfunction, but its reliance on adequate right ventricular (RV) function with proposed risk of aggravating RV dysfunction may result in dismal outcomes if not intervened timely. Methodology: MeSH database was searched for LVAD, RV failure (RVF), RV anatomy and physiology, assessment for RV functions from 1990 till current year and was included in the narrative review. Results: The above searched English Medical Literature revealed that RVF contributed to dismal outcomes post-LVAD implantation. The absence of consistent defining criteria makes it hard to determine RVF. RVF leads to impaired LVAD flows, difficulty in weaning from cardio-pulmonary bypass, decreased tissue perfusion, and multi-organ failure, increasing the morbidity and mortality. Ideal durable mechanical assist devices to support the RV are still not available. Conclusion: This review highlights the details about perioperative assessment for RV dysfunction, criteria for RVF, investigational modalities to assess RV function, and management of RVF following LVAD implantation. Early identification, treatment, and prevention of RVF are of paramount importance and understanding this is a pivotal first step in successfully managing RVF post-LVAD implantation. The development of durable right-sided mechanical support would improve the scope of care of LVAD patients developing persistent RVF.
Keywords: End-stage heart disease, heart failure, left ventricular assist device, right ventricular failure
|How to cite this article:|
Sahu MK, Vaswani P. Left Ventricle Can't Stay Alone – A Review of Right Ventricular Failure Post-Left Ventricular Assist Device Implantation. J Pract Cardiovasc Sci 2020;6:216-25
|How to cite this URL:|
Sahu MK, Vaswani P. Left Ventricle Can't Stay Alone – A Review of Right Ventricular Failure Post-Left Ventricular Assist Device Implantation. J Pract Cardiovasc Sci [serial online] 2020 [cited 2021 Jan 18];6:216-25. Available from: https://www.j-pcs.org/text.asp?2020/6/3/216/304528
| Introduction with Magnitude of Problem|| |
According to a survey conducted in India, heart failure affects 1.2/1000 with more than half requiring repeat hospitalizations, thereby adding to the economic burden. In advanced stages, heart failure may not be manageable by drugs wherein mechanical circulatory assist devices providing as a bridge to transplant come into play. To formulate a management plan for advanced heart failure, it is prudent to appropriately assess the right ventricular (RV) function, as the success of left ventricular assist device (LVAD) implantation would require adequate RV function and contractility.,, RV dysfunction will lead to significantly dismal outcome and reduced survival in LVAD recipients.
The lacunae of a consistent definition for RV failure (RVF) post-LVAD and quest for ideal RVAD device will be highlighted. This narrative review would focus on the importance of RV function (perioperative assessment, monitoring, and management) on successful long-term outcome and quality of life post-LVAD implantation.
| Methodology|| |
Pubmed MeSH database search for keywords including “heart failure,” “LVAD,” “RVF,” “RV anatomy and physiology,” “assessment for RV function,” “Management of RVF,” and “RV Mechanical Support” was done. The search was filtered to “humans” and literature in the English language without restriction to study type. The resultant searches were scrutinized before inclusion in this narrative review.
| Structural and Functional Differences between Left Ventricular and Right Ventricular|| |
The RV is structurally primitive compared to the left ventricle. RV has two layers of muscles with approximately about one-fifths of muscle mass of LV owing to its exposure to low pressure pulmonary circulation. In contrast, LV is thicker and has additional oblique muscle layer and contracts against higher systemic pressures. RV receives blood throughout the cardiac cycle compared to LV which receives during diastole; hence, RV is more tolerant to ischemia. Thinner wall of RV makes it to conveniently adopt to higher degrees of volume overload; however, sudden rise in pressure is poorly borne. The twist of interventricular septum significantly contributes to RV contraction; hence, LV failure (LVF) would lead to reduced RV function by ventricular interdependence. Therefore, LV failure begets RVF. Furthermore, LV failure increases end diastolic pressure which leads to raised left atrial pressures and subsequently elevated pulmonary venous pressures. The reflex arteriolar vasoconstriction, passive retrograde transmission of venous pressures, and irreversible effects to pulmonary parenchyma in long-standing raised pressures lead to pulmonary artery hypertension which increases RV afterload and RV dilatation and failure subsequently.,
RV compensates physiologically by dilating in response to excess volume and hypertrophy in response to chronic excess in pressure. However, the thin wall does not protect against acute afterload increase. This increased RV afterload from hypertensive pulmonary circuit results most commonly from LV failure or regurgitant and stenotic mitral valvar pathologies and associated atrial arrhythmias. The other causes of pulmonary artery hypertension being idiopathic pulmonary hypertension, sequelae of lung parenchyma disorder, pulmonary thrombo-embolism, or various combinations of these. There is reduced RV output which translates into low LV input, and hence, further decreasing LV output and compromised systemic circulation.
| The Right Ventricular Failure post-Left Ventricular Assist Device – The Definition, Severity Gradation, and Incidence (Early and Late Right Ventricular Failure)|| |
RVF post LVAD is defined as:,,
- Central venous pressure (CVP) ≥16 mm Hg
- Cardiac index <2 L/min/m2
- ≥2 weeks of persisting inotropic support
- ≥48 h of dependence on inhaled or intravenous pulmonary vasodilators
- Need for mechanical circulatory support or RV assist device (RVAD).
Interagency registry for mechanically assisted circulatory support categorized RVF as the following grades according to severity:,
- Mild: ≤7 days requirement of inotropes
- Moderate: 8–14 days' requirement of inotropes
- Severe: ≥14 days requirement of inotropes and mechanical ventilation.
Incidence of RVF post-LVAD implantation was observed to be 60.7% according to the above-mentioned criteria. Early-onset RVF has an incidence of 9%–44%. There has been proposed two hit theory with one hit being before surgery and the other is surgery with LVAD affecting RV function. Vasoplegia has also been postulated as a causal factor in the early postoperative period.
Late-onset RVF has been observed in 11% cases, weeks to months after LVAD implantation and has been thought to be either extension of early RVF or a separate pathophysiological phenomenon. It manifests with increased hospital admissions, intolerance/resistance to diuresis/diuretics, kidney and liver dysfunction, requirement of inotropes, and failure to thrive. low dose digoxin, judicious use of diuretics, and pulmonary vasodilators may manage this type of RVF.
| Assessment of Right Ventricular Contractility and Dimensions|| |
This is cumbersome and affected by:
- RV geometry affected by different interrogating planes
- Less muscle mass, hence, less prominent walls compared with LV,
- No specified landmarks anatomically
- Retrosternal in location.
Various imaging modalities being used are magnetic resonance imaging (MRI), computerized tomography (CT) scan, trans-thoracic and trans-esophageal echocardiography, and catheter angiography. The latter two are invasive while the former two are the noninvasive ones.
Magnetic resonance imaging, computerized tomography scan, and right heart catheterization
MRI precision in defining RV accurately is well-documented; however, lack of portability and availability at various centers and interference or incompatibility with LVAD device prohibit its use., CT scan although provides excellent anatomic detail is limited by artifacts from the device and lack of availability at various centers with radiation risk. Therefore, although being invasive in assessment, catheter-based regime is considered the gold standard for profiling RV and both preload and afterload measurements. The precision in pressure measurements in both systemic and pulmonary circuits helps in accurate calculation of pulmonary artery pulsatility index (PAPI), and this parameter is being used in various scores for RVF risk prediction post-LVAD implantation.,
RV functional assessment with two-dimensional TTE is based on parameters including dimensions, volume, Doppler, and speckle track images according to criteria laid out by the American Society of Echocardiography [Table 1].,
|Table 1: American Society of Echocardiography for assessment of right ventricle function as adapted from Lang et al|
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Since the introduction of strain by imaging the deform in myocardium, RV functional parameters are better defined and criteria resulting from strain have been added to the latest guidelines. This strain imaging can be accessed through speckle tracking and Doppler tissue imaging but the former relies less on angle of view, hence preferred., This speckle analysis for LV function is based on the addition of longitudinal strain of LV in 17 segments in multiplane assessment., These criteria for RV profiling are inconsistent in literature; however, three-dimensional echo calculated ejection fraction approximates the one calculated by MRI and is reliable.
Transesophageal echo assessment
Transesophageal echo (TEE) is widely used in the intra-operative and post-operative periods for monitoring and as a guide for RV assessment. The absence of defined criteria and the alterations played by anesthetic drugs on vascular physiology and myocardium makes TEE-based assessment unreliable. In addition, RV in its entirety is difficult to evaluate in traditional views, hence, focused RV view visualizing the entire cardiac cycle determines RV size reliably. Accuracy in determination based on Doppler or motion mode in TEE is limited by the challenges faced in alignment of these structures. RV longitudinal strain assessed during TEE was found variable; hence, multi-planar imaging is required for appropriate characterization. In a study, this value if ≤9.2% most closely heralded RVF.
| Systemic Effects of Right Ventricular Failure and Blood Biochemistry|| |
Pulmonary artery hypertension as a result of LV failure increases RV afterload. Increased pressure overload on RV leads to RV hypertrophy (RVH), increasing the RV mass, and altering its geometry. Now RV becomes spherical, dilated with increased wall stress which leads to increased systemic venous pressure (CVP) resulting in interstitial congestion which promotes the release of local pro-inflammatory cytokines (interleukin-6, tumor necrosis factor alpha, endothelin-1, and vascular cell adhesion molecule-1). These cytokines lead to chronic inflammation and progressive organ damage which is depicted in the flow diagram [Figure 1].
|Figure 1: Pathological changes in Liver, Kidney and Gut in RV Failure. IVC: Inferior vena cava, HV: Hepatic vein, RV: Renal vein, TAMO: Trimethylamine N-oxide, SIRS: Systemic inflammatory response syndrome|
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- Hepatic and renal failure may contraindicate LVAD placement and heart transplant in the patient
- Trimethylamine N-oxide elevation is also associated with decreased actin-myosin activity and progressive myocardial fibrosis which aggravates ventricular dysfunction further progressing heart failure
- Multivariate analysis in various studies have confirmed serum level of bilirubin ≥2 mg/dl, blood urea nitrogen ≥39 mg/dl, serum creatinine ≥2.3 mg/dl, systemic BP ≤96 mm Hg, aspartate aminotransferase levels ≥80 U/L, use of inotropes or circulatory support devices before surgery, history of cardiothoracic surgery, and preoperative mechanical ventilation have been found to correlate well with risk of RVF post-LVAD support.,,,
| Risk Factor Scores for Diagnosing Right Failure Post-Left Ventricular Assist Device|| |
There has been a paradigm shift from pulsatile flow to continuous flow ventricular assist devices from 2010, increasing survival from 56% in 2008 to 80% in 2011. Continuous flow devices have demonstrated significantly improved LV profile and reduction in pulmonary vascular resistance.,,, There have been many risk factor score models designed for the prediction of RVF; however, they have been limited by:,
- Retrospective single center-based studies
- Pulsatile flow device entries were based for calculating these scores, not correlating well with recent data
- Therapeutic goal shift from predominantly bridge to transplant to equally divided between bridge to transplant and destination therapy (DT)
- Absence of uniformity in defining RVF.
Kalogeropoulos et al. in their study attempted validation of RVF prediction models in 116 patients with continuous flow LVADs. They found 32% incidence of RVF which could not be accurately predicted by any of the six most commonly used models.
Bellavia et al. in their meta-analysis of RVF in LVAD evaluated 4428 patients finding RVF in 35% cases concluded that none of the parameters either individually or in combination could predict RVF accurately.
The latest risk predictor ALMA score, efficient in predicting RVF with sensitivity and specificity of >82% is based on the following five parameters with defined score of 1 for each:
- Used for DT
- PAPI <2
- RV/LV ratio (right to left ventricular end-diastolic ratio) >0.75
- RV Stroke Work Index <300 mm Hg/ml/m2
- Model for end-stage liver disease excluding International Normalized Ratio XI score >17.
However, this is yet to substantiated by other studies.
| Left Ventricular Assist Device Success Based on Proper Assessment and Management of Right Ventricular|| |
Since LVAD is reliant on provision of adequate preload by a good functioning RV, pump velocity of LVAD is slowly raised striking a balance between LV afterload and RV preload. Multidisciplinary team is required for the selection of LVAD patients based on institutional protocols, laboratory samples, adequate profiling of RV function, and dimensions. Optimal medical management with proper diuresis and inotropic support if required should always be instituted.
Pericardiotomy leads to dilated RV and affects pressure volume loops with reduced RV contractility; hence, minimally invasive LVAD placement preserves integrity of pericardium around RV, thereby, preserving its function. The continuous flow Heartware LVAD is shown in [Figure 2] and [Figure 3] with description of parts and blood flow, whereas Heartmate II is shown in [Figure 4] and [Figure 5]. The LVAD placement has been achieved using anterior thoracotomy or upper mini sternotomy or left thoracotomy., These are, however, limited by intraoperative one lung ventilation requirements for aiding a successful exposure of LV apex for cannula placement, hence, pulmonary parenchymal diseases, and co-existing cardiac lesions requiring median sternotomy have to be excluded. The adoption of a surgical technique which aids in reducing bypass time, meticulous hemostasis, and careful de-airing is a pre-requisite for comprehensive RV protection. The surgeon should insist on maintaining a low tidal volume ventilation even during cardiopulmonary bypass.
|Figure 2: Heartware left ventricular assist device as seen outside with part description|
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|Figure 3: Heartware left ventricular assist device internal device parts and blood flow direction|
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|Figure 4: Heartmate II left ventricular assist device as seen outside with part description|
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|Figure 5: Heartmate II left ventricular assist device internal device parts and blood flow direction|
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There have been no set guidelines for tricuspid valve (TV) management for tricuspid regurgitation during LVAD placement. In a study by Han et al., TV repair or replacement, although reduced regurgitation late postoperatively but did not offer a survival benefit. The addition of these procedures led to longer bypass duration, increased rate of re-exploration due to surgical hemorrhage, and multiple blood product transfusions with increased incidence of kidney dysfunction and prolonged intensive care unit and hospital stays.,, The surgical strategy and concerns are mentioned in [Table 2].
The labile hemodynamic parameters should be comprehensively managed. This is achieved by titrating sedative and paralytic agents while maintaining a close balance between the two. The inotropic support started before surgery is extended intra-operatively for continued systemic perfusion, ensured coronary perfusion, and for optimization of systemic venous return to RV. The hemodynamic support is summarized in [Table 3]. Intra-operative TEE for exclusion of thrombus or mass, assessment of valves, and atrial septal defect should be ensured for successful LVAD placement., There should be emphasis on prevention against transfusion-related lung injury. The intraoperative TEE assessment is mentioned in [Table 4].
Left ventricular assist device and intra-operative concerns
There should be close communication between surgical and anesthesia team. The decompression of LV should be observed with TEE for ensuring adequate preload to RV as well as prevention of rapid and excessive LV decompression. Rapid LV decompression leads to shifting to septum toward LV cavity; therefore, only RV free wall contributing to RV contractility and function. There is also increased venous return causing increased RV preload. The absence of septal RV contribution leads to decreased forward flow, and therefore, compromised systemic perfusion and LVAD function. The other contributory factors of poor RV contractility would be poor myocardial protection, dysfunction post cardioplegic arrest, air emboli in coronaries, and ischemic reperfusion injury. Postoperative TEE after LVAD placement should compare RV hemodynamics (including contractility and regurgitant TV jet), visualization of LVAD circuit (directing the inflow cannula toward the mitral valve and orienting away from the septum), flowing mechanics of device, preload to LV and deviation of interventricular septum.,
Vasoplegia manifests with worsening hemodynamics while coming off from cardiopulmonary bypass. The underlying mechanism can be explained by desensitization of smooth muscle receptors, altered pathway of second messengers, critical illness associated reduced intrinsic steroids, and raised levels of nitric oxide (NO). This is efficiently managed with adequate intra-vascular volume augmentation and vasopressor support. Nor-adrenaline is usually considered first followed by vasopressin. Methylene blue and hydroxycobalamin have been tried in most resistant cases, however, without much substantial evidence and improperly understood mechanism of action., Low dose steroids have been added as last resort in conjunction with the former agents.
Immediate postoperative mechanical ventilation can be challenging in these patients with chronic heart failure before surgery with a history of repeated episodes of pulmonary edema and resultant reduced pulmonary compliance. Raised pulmonary pressures also add to the difficulties in the immediate postoperative ventilation weaning. Lung protective ventilation strategy with low tidal volume and higher frequency with optimal positive end expiratory pressure while keeping a close watch on plateau pressure, striking close balance between permissible hypercapnia and hypoxia, mild hypothermia with marginal acidosis should be strived in this period. The above measures in conjunction with appropriate pharmacological management and judicious diuresis results in an effective cardiac index with LVAD, improved lung function which facilitates weaning from mechanical ventilation aiding in quick pulmonary rehabilitation post-LVAD placement.
Management of Right Ventricular Failure in the postoperative period
This is achieved with:
- Ionotropic support – increasing RV contractility as well as decreasing afterload with Milrinone and/or dobutamine. Adrenaline can be added to the combination if milrinone is not tolerated due to systemic hypotension
- Pulmonary vasodilators – Decrease pulmonary vascular resistance reducing RV afterload e.g., Epoprostenol, inhaled NO, phosphodiesterase 5 inhibitors (sildenafil) and endothelin receptor antagonist e.g., Bosentan,
- Newer agent such as Riociguat has been used with variable success in reducing pulmonary vascular resistance. It acts through soluble guanylate cyclase (sGC) stimulation. There are two proposed mechanisms, one is by sensitization of sGC to endogenous NO and the other is by stimulation of sGC independent of intrinsic NO. It also induces vasodilation and there have been observed effects against fibrosis, inflammation, and cellular proliferation in certain animal studies
- Milrinone acts through both pathways, however, due to its effect on systemic circulation, hypotension is expected which limits the use in cases with lower SVR. Inhaled Milrinone has been put to use in view of lower doses, shorter half-life causing early elimination, and targeted effect on pulmonary circulation
- Use of sildenafil in oral or intravenous forms effectively reduces pulmonary vascular resistance and improves RV contractility,,
- Levosimendan, a calcium ion sensitizer, acts as an iono-dilator without increasing myocardial oxygen demand can be tried in the certain scenarios of advanced RVF, however, unpredictable effects on systemic vascular resistance with resultant systemic hypotension preclude its use as a first-line management agent,
- Pimobendan, first used by Imamura et al., increases sensitivity for calcium and selectively inhibits phosphodiesterase 3. This has been approved for use in RVF in Japan.,
Mechanical support devices
- Intra-aortic Balloon Pump reduces LV afterload and augments diastolic blood pressure, hence, used as first line of therapy, however, has not substantiated for use in RVF in various researches,
- Veno-arterial ECMO – Provides optimal relief to RV and prevents end organ ischemia; however, interference with LVAD device circuit and provision of increased resistance to LVAD, potentially limits its usage. There have been reports of thrombus formation due to reduced flow rates in LVAD owing to non-physiologic retrograde aortic flows and pulmonary shunting
- RVAD – Previously used LVAD devices for RV support were limited by the differences between the two ventricles both anatomically and physiologically. The longer outflow cannula of LVAD interfered with pulmonary circulation, creating resistance and the length of inflow cannula restricted apically displaced TV with risk of inter-ventricular septal injury. Inflow circuits used in RA as a modification were also limited by thinness of RA wall and the tip's proximity to interatrial septum with potential for iatrogenic ASD creation., Ideal RVAD shall have the following characteristics as proposed by Ranganath et al.:,
- Hemodynamic characteristics:
- Nominal flow = 2–6 L/min (excludes transient pulsations)
- Nominal pump pressure difference of 20–60 mm Hg
- Availability of pulsatile modes
- Normal power versus flows above range of operability (ensuring automaticity).
- Optimal size with light weighted circuit
- Versatile cannula placement (right atrium or ventricle)
- Reduced length of inflow circuit
- Sewing ring with felt spacers and height adjustability
- Provision of placement without bypass and bloodless insertion reducing blood transfusion in postoperative period
- Allows minimal access placement
- Anatomic single controller for configuring to biventricular mode.
Recent developments have been observed with dual lumen cannula device (ProTek Duo) with one tip placed in right internal jugular vein draining right atrium and one in pulmonary artery., Percutaneous RVADs, for example, Impella with microaxial pump placed through femoral vein have been introduced., These are short-term assist devices approved for use upto 14 days only. The quest for an ideal device, however, still continues.
| Conclusion|| |
The anatomical and physiological differences among the two ventricles with interventricular dependence for the functioning of both play a pivotal role in understanding the heart failure. RVF predicts dismal outcome in LVAD recipients acting as an Achilles heel. Absence of conclusive definition of RVF and lack of evidence-based RVF prediction risk scores limits the process further. The limited RV visualisation due to anatomic limitations, MRI incompatibility, server based variation in TTE, and lack of evidence-based guidelines for use of TEE assessment further add road blocks to RV assessment. Multidisciplinary evaluation preoperatively with cardiologist being the lead physician, intra-operative close communication between the surgeon, and the anesthesiologist and vigilant early postoperative care may prevent and effectively antagonise RVF. Further advances are required in developing durable long term RVADs for successful LVAD functioning and optimising overall outcome.
We acknowledge Mr Ramchandra B. Pokale, Chief Artist, Center for Community Medicine, AIIMS, New Delhi, India, for contributing the artwork for this review.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]