Right Ventricular Failure

Authors, Journal, Affiliations, Type, DOI

• Brian A. Houston MD, Evan L. Brittain MD, Ryan J. Tedford MD
• New England Journal of Medicine, 2023;388:1111–1125
• Medical University of South Carolina (Houston, Tedford); Vanderbilt University Medical Center (Brittain)
• Review article (NEJM Review)
• DOI: 10.1056/NEJMra2207410

Overview

This NEJM review provides a comprehensive, mechanistic framework for understanding right ventricular (RV) failure across its multiple aetiologies. The right ventricle — long underestimated — plays a critical pathophysiological and prognostic role in left heart failure, pulmonary arterial hypertension (PAH), acute pulmonary embolism, and COVID-19. The authors organise RV failure by underlying mechanism: disorders of excessive preload (tricuspid regurgitation, intracardiac shunts, arteriovenous fistulas), disorders of excessive afterload (acute PE, chronic pulmonary hypertension), and disorders of contractility (RV MI, post-surgical dysfunction, cardiomyopathy, ARVC, sarcoidosis). Treatment strategy depends on identifying the primary pathophysiological insult and optimising preload, reducing afterload, and augmenting contractility — with caution that many of these interventions are disease-specific and some (e.g., pulmonary vasodilators in LHD) are contraindicated in other subgroups.

Keywords

Right ventricular failure, pulmonary arterial hypertension, RV–PA coupling, preload, afterload, contractility, echocardiography, cardiac MRI, right heart catheterization, tricuspid regurgitation, pulmonary embolism, ARVC

Key Takeaways

Anatomy and Physiology

• The RV is a thin-walled crescent-shaped structure derived from the secondary heart field; it sits anteriorly and depends on the interventricular septum for ~25–30% of its contractile function (ventricular interdependence)
• The helical septal myofibrils produce primarily longitudinal contraction; RV free wall contributes transverse shortening (less prominent normally)
• The Fontan procedure (effectively removing the RV) reduces exercise capacity by 40%, confirming the RV is essential even in the absence of overt failure

Pathophysiology — Cellular and Molecular Mechanisms

• Key pathological processes: myocyte hypertrophy, fibrosis, ischaemia, neurohormonal activation, inflammation, metabolic substrate shifts
• Adaptive phase (homeometric adaptation): Concentric RV hypertrophy with maintained stroke volume via increased adrenergic tone; neurohormonal activation is initially compensatory
• Maladaptive phase (heterometric adaptation): Neurohormonal activation leads to reduced β₁-adrenergic receptor density, depleted adrenergic effectors, failure of adenylate cyclase stimulation; RV dilates to maintain stroke volume → ventriculoarterial uncoupling → RV failure
• RV ischaemia: Mismatch of O₂ demand (increased wall stress, hypertrophy) and reduced supply (capillary rarefaction, reduced right coronary artery flow); right coronary flow impairment is proportional to RV mass and RVEDP
• Fibrosis: Cardiac fibroblast collagen production stimulated by mechanical stress, ischaemia, neurohormonal activation; initially protective against dilatation; later impairs diastolic function and excitation–contraction coupling; most prominent at septal insertion points; highest in systemic sclerosis–associated PAH, lowest in CHD-related PH
• Metabolic shifts: Normal RV derives 60–90% ATP from fatty acid oxidation (FAO); progressive hypertrophy activates hypoxia-inducible factor-1 → glycolytic enzyme upregulation and FAO suppression; glucose uptake correlates inversely with RV function; partially reversed by pulmonary vasodilator therapy; adaptive vs maladaptive nature of this shift is unresolved
• Obesity and diabetes: Modifiable risk factors; diabetes worsens RV systolic and diastolic function via fibrosis, inflammation, microvascular ischaemia, lipotoxicity; obesity contributes via increased preload, afterload, pericardial constraint, sleep-disordered breathing

Diagnosis and Evaluation

Clinical Assessment

• History: dyspnoea, lower-extremity oedema, early satiety, abdominal fullness, fatigue, right-upper-quadrant tenderness
• Risk factors to elicit: CAD, left heart failure, valvular disease, chronic lung disease, VTE, connective tissue disease, HIV, anorexigen use, family history PAH (20% hereditary mutation in "idiopathic" PAH)
• Physical signs: elevated JVP, RV heave, loud P₂, TR murmur, pulsatile liver, hepatojugular reflux, ascites, lower-extremity oedema
• ECG: right atrial dilatation, right axis deviation, RVH; ST-segment and T-wave changes in inferior leads (RV MI)
• BNP/NT-proBNP: diagnostically sensitive but not specific; valuable in the absence of left heart failure

Echocardiography

• TAPSE: ≥17 mm normal; easy, reproducible, prognostic
• Tissue Doppler velocity (lateral tricuspid annulus): RV systolic function surrogate
• Fractional area change: RV systolic function
• TAPSE/PASP ratio: Noninvasive surrogate for RV–PA coupling; at least moderately correlated with gold standard Ees/Ea ratio
• RV free-wall longitudinal strain: Sensitive measure of RV dysfunction; prognostic across a broad spectrum of cardiovascular diseases
• Eccentricity index >1 (anteroposterior/septolateral ratio): RV overload; septal flattening in diastole = volume overload; in systole = pressure overload
• Dilated IVC without inspiratory collapse: elevated right atrial pressure

Cardiac MRI

• Reference standard for RV size, RVEF, and mass
• RVEF, stroke volume index, RV end-systolic volume index: Prognostic and for risk stratification
• Stroke volume/end-systolic volume ratio: Simplified RV–PA coupling surrogate; larger physiologic range than RVEF, more sensitive to change when RVEF mildly–moderately reduced
• LGE and extracellular volume (ECV): Quantify replacement fibrosis (permanent scar, typically at septal insertion points) vs interstitial fibrosis (dynamic, modifiable)
• Aids diagnosis of ARVC (fibrofatty RV free wall changes)

Right Heart Catheterisation

• Direct measurement of intracardiac pressures, CO, preload (RAP, RVEDP), and afterload (PVR, PA compliance, PA elastance)
• Surrogate RV function measures: stroke volume index, RAP/PAWP ratio, RV stroke work index, pulmonary artery pulsatility index (PAPi)
• PAPi was most strongly correlated with maximal RV myocyte force generation (Aslam 2021)
• Limitations: pressure alone does not reflect intravascular volume; preload estimates based on pressure have important limitations

Pressure–Volume Loops (Gold Standard Research Tool)

• Ees (end-systolic elastance, slope of ESPs during preload reduction) = load-independent contractility
• Ea (effective arterial elastance = end-systolic pressure/stroke volume) = afterload
• Ees/Ea ratio 1.5–2.0: Optimal coupling (maximal energy transfer from ventricle to circulation)
• Ees/Ea <0.6–0.8: RV–PA uncoupling → worse outcomes
• Complex, invasive, costly; single-beat methods and combined RHC + CMR/3D echo methods under development

Disorders of Excessive Preload

• Tricuspid regurgitation: Acute severe TR initially well-tolerated if RV afterload normal; chronic TR leads to RV volume overload, dilatation, reduced systolic function
• Intracardiac left-to-right shunts: Detected by bubble contrast echo or oximetric run during RHC (shunt quantitation)
• Arteriovenous fistulas (e.g., HD access): AV fistula flow rate correlates with RV dilatation and reduced RV systolic function; chronic high-output state

Disorders of Excessive Afterload

• Acute pulmonary embolism: Classic example of poorly-tolerated acute afterload increase; McConnell's sign (midwall akinesis + apical hypercontractility) on echo; CT-PA preferred diagnostic test
• Acute lung injury + PPV: Positive pressure ventilation can further increase RV afterload
• Chronic PH: See concepts/Pulmonary-Hypertension-Classification and concepts/PAH-Risk-Stratification

Disorders of Contractility

• RV MI: Right coronary artery occlusion (proximal) compromises RV; clinical triad: hypotension, elevated JVP, clear lungs; inferior ST changes + right-sided leads for diagnosis; urgent reperfusion
• Myocarditis: Isolated RV myocarditis reported but more common with bilateral involvement
• Post-surgical RV dysfunction: Common after cardiac surgery and LVAD implant (altered septal geometry, loss of LV contribution to RV contractility, free wall anchoring)
• Left heart failure: Most common cause of RV failure; both chronic preload increase AND the same myopathic process affect RV; RV involvement worsens prognosis
• ARVC: Fibrofatty dysplasia → RV contractile failure; 2010 Task Force Criteria; sarcoidosis can mimic ARVC
• Systemic sclerosis–associated PAH: Depressed sarcomere function (unique among PAH causes), explaining worse outcomes than idiopathic PAH
• Atrial fibrillation: Commonly co-exists with RV failure; reduces right atrial emptying fraction and reservoir function → exacerbates RV failure pathophysiology

Treatment

Preload Management

• Acute RV failure (elevated afterload or reduced contractility): Volume loading may augment stroke volume IF patient has relative volume depletion; otherwise volume loading can worsen output (increased pericardial constraint, reduced LV transmural filling pressure)
• Acute PE: Volume expansion did not increase LV stroke work in animal models beyond a single embolism; furosemide single dose outperformed placebo in intermediate-risk PE (LHPEITHO-type study)
• RV MI: Variable response — benefit only in relative volume depletion; invasive haemodynamic monitoring guides therapy
• Chronic RV failure: Volume removal (IV diuretics, ultrafiltration); reduces TR annular dilatation, RV wall stress, and septal deformation; normalises preload

Afterload Reduction

• PAH (Group 1): Endothelin receptor antagonists, PDE5i, prostacyclin pathway agents; upfront combination therapy is standard of care; sotatercept emerging
• Pulmonary hypertension from lung disease: Inhaled treprostinil improved exercise capacity (RCT)
• Chronic thromboembolic PH (Group 4): Surgical pulmonary endarterectomy first-line; balloon pulmonary angioplasty for inoperable; anticoagulation; adjunctive pharmacotherapy
• LHD-associated PH (Group 2): Direct pulmonary vasodilators have not proved beneficial and may be harmful; SIOVAC trial — sildenafil worsened outcomes in persistent PH after correction of left-sided valvular disease; treatment is optimisation of GDMT and reduction of left atrial pressure
• Inhaled pulmonary vasodilators (NO, epoprostenol): Immediate benefit in acute RV failure with chronic precapillary afterload elevation

Contractility Augmentation

• Urgent reperfusion for acute RV MI
• Immunosuppression for inflammatory RV failure (myocarditis, sarcoidosis)
• Dobutamine: Increases CO and stroke volume in RV MI and PH
• Milrinone: Useful; avoid systemic hypotension → RV ischaemia
• Digoxin: Mixed evidence
• Temporary MCS devices: Growing role in cardiogenic shock from RV failure (studied predominantly with concomitant left heart failure); isolated RVAD contraindicated in severe PAH (risk of pulmonary haemorrhage); VA-ECMO for severe cases
• Palliative care early and in parallel for intractable RV failure

Future Directions

• Better noninvasive surrogates for RV–PA coupling needed
• Better identification of the "at-risk" RV
• Direct RV inotropic/lusitropic therapies (most current therapies are load-based)
• RV should be included in clinical trial design (inclusion criteria, endpoints, response stratification)

Limitations of the Document

• Review article based on existing literature; most molecular/cellular data derive from animal models or PAH-specific studies; applicability to other RV failure causes unclear
• Pressure–volume loop methods (gold standard) remain primarily research tools; clinical applicability limited by complexity, cost, and invasive nature
• Most evidence for sleep-disordered breathing treatment in PH is observational
• PAPi correlation with myocyte function is based on a single study

Key Concepts Mentioned

• concepts/RV-PA-Coupling — central mechanistic concept; Ees/Ea thresholds for coupling/uncoupling
• concepts/Right-Ventricular-Failure — main subject; mechanisms, diagnosis, treatment
• concepts/Pulmonary-Hypertension — major afterload cause of RV failure
• concepts/Pulmonary-Hypertension-Classification — Group 1–5 aetiological context
• concepts/Right-Heart-Catheterization — key diagnostic tool including RV function surrogates

Key Entities Mentioned

• entities/Pulmonary-Hypertension — leading cause of chronic RV afterload elevation
• entities/Pulmonary-Embolism — classic acute afterload excess cause
• entities/ARVC — RV contractility disorder; fibrofatty dysplasia
• entities/Heart-Failure — LHF as most common RV failure cause

Wiki Pages Updated

• Created wiki/sources/rvfailure-nejm-2023.md (this file)
• Created wiki/concepts/Right-Ventricular-Failure.md
• Updated wiki/concepts/RV-PA-Coupling.md — added NEJM 2023 source and expanded clinical content
• Updated wiki/concepts/Pulmonary-Hypertension.md — added RV failure context from NEJM review
• Updated wiki/sourceindex.md
• Updated wiki/wikiindex.md