Perioperative Right Ventricular Dysfunction: Analysis of Outcomes

Published:January 20, 2021DOI:https://doi.org/10.1053/j.jvca.2021.01.032
      Right ventricular dysfunction (RVD) is a well-known prognostic factor for adverse outcomes in cardiovascular medicine. The right ventricle (RV) in medically managed heart failure patients and in surgical patients perioperatively generally is overshadowed by left ventricular disease. However, with advancement of various diagnostic tools and better understanding of its functional anatomy, the role of the RV is emerging in many clinical conditions. The failure of one ventricle has significant effect on the function of the other ventricle and it is predominantly due to ventricular interdependence.
      • Santamore WP
      • Dell'Italia LJ
      Ventricular interdependence: Significant left ventricular contributions to right ventricular systolic function.
      The etiology of RVD is multifactorial and irrespective of etiology. RVD has been associated with significant increases in morbidity and mortality in various clinical scenarios.
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      American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia. Evaluation and management of right-sided heart failure: A scientific statement from the.
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      Right ventricular function and failure: Report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure.
      The primary objective of this comprehensive review is to analyze various etiology-related outcomes of RVD in the perioperative population.

      Key Words

      Clinical Predictors and Etiology of RV Dysfunction in Medically Treated Patients

      RIGHT VENTRICULAR DYSFUNCTION (RVD) develops due to increased right ventricle (RV) afterload, decreased RV contractility, or RV volume overload (Table 1). The prevalence of left ventricular (LV) dysfunction and pulmonary hypertension (PH) in patients with RV failure is particularly high, which corroborates the fact that the majority of RV failure is secondary to left-sided cardiac or pulmonary vascular diseases.
      • Voelkel NF
      • Quaife RA
      • Leinwand LA
      • et al.
      Right ventricular function and failure: Report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure.
      Similar findings were observed in a recently published single-center retrospective analysis of 1,299 nonsurgical patients with severe RVD diagnosed by echocardiography. The most common causes of severe RVD were left-sided heart disease (46%), pulmonary thromboembolic disease (18%), chronic lung disease (17%), and pulmonary arterial hypertension (PAH) (11%) (Fig 1, A). Intrinsic RV pathology (related to RV infarct, myocarditis, or RV myopathy) was the cause of severe RVD in only 5% of cases.
      • Padang R
      • Chandrashekar N
      • Indrabhinduwat M
      • et al.
      Aetiology and outcomes of severe right ventricular dysfunction.
      Table 1Etiologies of RVD
      • 1
        Pressure overload
      • a
        Increased pulmonary venous pressure
      • i
        LV dysfunction, including HFrEF and HFpEF
      • i
        Left-sided valvular disease
      • i
        Mitral regurgitation or stenosis
      • i
        Pulmonary veno-occlusive disease
      • a
        Increased pulmonary artery pressure
      • i
        Chronic lung disease
      • i
        Chronic pulmonary arterial hypertension
      • i
        Chronic pulmonary thromboembolic disease
      • i
        Acute pulmonary vasoconstriction due to hypoxia or hypercarbia
      • i
        Mechanical ventilation (related to elevated PEEP and plateau airway pressure)
      • i
        ALI and ARDS (including postsurgical ALI due to post-CPB or lung transplantation)
      • i
        Extensive lung resection
      • i
        Acute pulmonary embolism (thromboembolic, air, bone cement, tumor, or amniotic fluid)
      • i
        Acute chest syndrome in sickle cell disease
      • i
        Congenital cardiac disease with pulmonary outflow obstruction
      • i
        Drugs (eg, protamine)
      • a
        RV outflow tract obstruction
      • i
        Congenital cardiac disease
      • i
        Postcardiac surgery
      • 1
        Decrease in contractile function
      • a
        RV ischemia or infarction
      • a
        Arrhythmogenic RV cardiomyopathy
      • a
        Relative RV ischemia (inadequate coronary perfusion related to oxygen consumption in overload conditions)
      • a
        LV dysfunction (through ventricular interdependence)
      • a
        Cardiomyopathy
      • a
        Myocarditis (viral, bacterial)
      • a
        Post-CPB LVAD-related change in RV geometry
      • a
        Chest trauma with cardiac contusion
      • a
        Arrhythmias
      • 1
        Volume overload
      • a
        Valvular disease
      • i
        Severe tricuspid regurgitation
      • i
        Severe pulmonary regurgitation
      • a
        Hypervolemia (in susceptible patients)
      • a
        Intracardiac shunts
      Abbreviations: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; CPB, cardiopulmonary bypass; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; LVAD, left ventricular assist device; PEEP, positive end-expiratory pressure; RV, right ventricular; RVD, right ventricular dysfunction.
      Fig 1
      Fig 1Etiologies of severe RVD and their effect on survival. (A) Pie chart summarizing the common etiologies of severe RVD and (B) Kaplan–Meier survival curves of patients with severe RVD based on the top four most common etiologies. ARVC/RV, arrhythmogenic right ventricular cardiomyopathy/right ventricle; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; RV, right ventricle; RVD, right ventricular dysfunction. Reproduced with permission from Padang et al.
      • Padang R
      • Chandrashekar N
      • Indrabhinduwat M
      • et al.
      Aetiology and outcomes of severe right ventricular dysfunction.

      Pulmonary Hypertension

      Historically, mitral valve disease probably has been the most common cause of PH complicated by some degree of RVD in the majority of patients.
      • Alexopoulos D
      • Lazzam C
      • Borrico S
      • et al.
      Isolated chronic mitral regurgitation with preserved systolic left ventricular function and severe pulmonary hypertension.
      Although heart failure with preserved ejection fraction (HFpEF) is recognized as the predominant cause of elevated LV filling pressures resulting in PH,
      • Hoeper MM
      • Barberà JA
      • Channick RN
      • et al.
      Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension.
      RVD is more common among patients with heart failure with reduced left ventricular ejection fraction (HFrEF), compared with those with preserved ejection fraction (approximately 50% v 35%).
      • Konstam MA
      • Kiernan MS
      • Bernstein D
      • et al.
      American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia. Evaluation and management of right-sided heart failure: A scientific statement from the.
      High resistance in the pulmonary arteries (PA) can be a result of long-standing elevation of left-sided pressures, poor regulation of vascular smooth muscle vessel tone, or pulmonary vascular remodeling. Initially, the RV becomes hypertrophic in response to high pulmonary artery pressure (PAP) and can generate much higher pressures than in the normal low-afterload state. With time, RV hypertrophy may not be sufficient, and the RV dilates, with a subsequent decrease in contractile function and symptoms of right-sided heart failure.

      Cardiomyopathy

      Essentially all myocardial diseases involving the left heart may affect the RV. These include myocardial ischemia or infarction, myocarditis or septic cardiomyopathy, Takotsubo cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy. However, patients with nonischemic cardiomyopathy have a higher proportion of RVD than those with ischemic cardiomyopathy.
      • Konstam MA
      • Kiernan MS
      • Bernstein D
      • et al.
      American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia. Evaluation and management of right-sided heart failure: A scientific statement from the.
      In a separate series by La Vecchia, patients with nonischemic dilated cardiomyopathy had a higher proportion of RVD than those with an ischemic cause: 65% versus 16%.
      • La Vecchia L
      • Paccanaro M
      • Bonanno C
      • et al.
      Left ventricular versus biventricular dysfunction in idiopathic dilated cardiomyopathy.
      Cardiomyopathies with primary involvement of the RV include arrhythmogenic RV cardiomyopathy,
      • Corrado D
      • van Tintelen PJ
      • McKenna WJ
      • et al.
      Arrhythmogenic right ventricular cardiomyopathy: Evaluation of the current diagnostic criteria and differential diagnosis.
      Uhl's anomaly (aplasia or hypoplasia of most of the RV myocardium),
      • Aguiar Rosa S
      • Agapito AF
      • António M
      • et al.
      Uhl's disease: An uncommon presentation of a rare disease.
      and Ebstein's anomaly,
      • Rydman R
      • Shiina Y
      • Diller G
      • et al.
      Major adverse events and atrial tachycardia in Ebstein's anomaly predicted by cardiovascular magnetic resonance.
      although the latter two are extremely rare in the adult population.
      RVD may occur with more advanced left heart failure, and this may be secondary to increased RV afterload from postcapillary PH, volume overload, arrhythmias, or the underlying myocardial disease process affecting the LV. The overall prevalence of RVD in HFrEF varies widely, but it is universally associated with increased mortality.
      • Iglesias-Garriz I
      • Olalla-Gomez C
      • Garrote C
      • et al.
      Contribution of right ventricular dysfunction to heart failure mortality: A meta-analysis.
      The prevalence of RVD in a meta-analysis of patients with HFrEF was 48%.
      • Guazzi M
      • Borlaug BA.
      Pulmonary hypertension due to left heart disease.
      In patients with preserved left ventricular ejection fraction (LVEF), however, it is difficult to distinguish primary RVD from that resulting from secondary PH, given the afterload-dependency of RV function.
      • Gorter TM
      • Hoendermis ES
      • van Veldhuisen DJ
      • et al.
      Right ventricular dysfunction in heart failure with preserved ejection fraction: A systematic review and meta-analysis.
      In a study by Melenovsky et al., 33% of patients with HFpEF had RVD defined as RV fractional area change <35%.
      • Melenovsky V
      • Hwang SJ
      • Lin G
      • et al.
      Right heart dysfunction in heart failure with preserved ejection fraction.
      In a separate study of 51 patients by Puwanant, depending on the criteria used, RVD was present in 33% to 50% of patients with HFpEF, in contrast to 63% to 76% of those with HFrEF.
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      • Priester TC
      • Mookadam F
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      Right ventricular function in patients with preserved and reduced ejection fraction heart failure.

      RVD in the Acute Care Setting

      In the acute care setting, the incidence of acute RVD is 14% to 50% in patients with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation.
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      Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.
      However, this incidence can be higher depending on the severity of lung injury and the chosen ventilator strategy.
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      • Schmidt GA.
      Acute right ventricular dysfunction: Real-time management with echocardiography.
      In a study of 700 patients with moderate-to-severe ARDS, the presence of pneumonia, a PaO2/FIO2 ratio <150 mmHg, PaCO2 >48, and driving pressure >18 were associated with the occurrence of acute RVD.
      • Mekontso-Dessap A
      • Boissier F
      • Charron C
      • et al.
      Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact.
      The prevalence of acute RVD in the setting of acute pulmonary embolism ranges from 25% to 60%.
      • Konstam MA
      • Kiernan MS
      • Bernstein D
      • et al.
      American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia. Evaluation and management of right-sided heart failure: A scientific statement from the.
      Occlusion of more than 30% to 50% of the total cross-sectional area of the pulmonary arterial bed by thromboemboli increases PA pressure significantly, leading to RVD. Echocardiographic evidence of RVD is present in between 30% and 56% of normotensive patients with PE.
      • Grignola JC
      • Domingo E.
      Acute right ventricular dysfunction in intensive care unit.
      Acute RV myocardial infarction (RVMI) complicates up to 50% of inferior myocardial infarctions, and isolated RVMI is extremely rare.
      • Kakouros N
      • Cokkinos DV.
      Right ventricular myocardial infarction: Pathophysiology, diagnosis, and management.
      Since contraction of the interventricular septum plays a significant part in RV stroke work, a functionally relevant acute RVMI generally requires disruption of blood flow to both the RV free wall and the interventricular septum.

      RVD in Chronic Lung Disorders

      RV alterations detected in chronic lung disorders have been attributed to increased pulmonary vascular resistance (PVR). Chronic alveolar hypoxia potentially causes pulmonary vasoconstriction and alterations or remodeling of pulmonary vasculature. In addition, hypoxemia also contributes to increase in PVR through the induction of polycythemia and release of inflammatory mediators. Mechanical factors, such as the loss of vascular bed in patients presenting with emphysema, thrombosis, and hyperinflation, also contribute to increased PAP. Recent results suggest that alterations in RV systolic pressure in patients with chronic obstructive pulmonary disease (COPD) may occur due to genetic influence.
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      • Rabahi MF.
      State of the art review of the right ventricle in COPD patients: It is time to look closer.

      Outcomes of RV Dysfunction in Medically Treated Patients

      Several studies demonstrated poor outcomes after RVD, although survival rate varied with underlying etiology. Common hemodynamic and echocardiographic markers of RVD associated with increased mortality include RA and RV dilation, elevated right atrial pressure (RAP), RV systolic dysfunction, the presence of a pericardial effusion, decreased PA capacitance, and reduced cardiac output (CO).
      • Mahapatra S
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      • Sorajja P
      • et al.
      Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension.
      Other variables associated with reduced survival include lower functional class, lower blood pressure, higher heart rate, increased B-type natriuretic peptide, reduced diffusion capacity of the lung for carbon monoxide, and reduced six-minute walk distance.
      • Benza RL
      • Miller DP
      • Gomberg-Maitland M
      • et al.
      Predicting survival in pulmonary arterial hypertension: Insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL).
      Overall RVD is associated with decreased exercise capacity measured by peak oxygen consumption and worse New York Heart Association functional class.
      • Baker BJ
      • Wilen MM
      • Boyd CM
      • et al.
      Relation of right ventricular ejection fraction to exercise capacity in chronic left ventricular failure.
      Irrespective of etiology of RVD, the presence of PH in patients with elevated LV filling pressure predicts worse outcomes and higher mortality.
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      • Lewis GD.
      What is the prognostic significance of pulmonary hypertension in heart failure?.
      ,
      • Ben-Dor I
      • Goldstein SA
      • Pichard AD
      • et al.
      Clinical profile, prognostic implication, and response to treatment of pulmonary hypertension in patients with severe aortic stenosis.
      The presence of RVD in patients with pulmonary arterial hypertension (PAH) is a strong predictor of adverse outcomes and more closely associated with clinical outcomes than the PAPs.
      • Chin KM
      • Kim NH
      • Rubin LJ.
      The right ventricle in pulmonary hypertension.
      In a United States cohort of patients in the REVEAL registry (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management), one- and five-year survival rates were 85% and 57%, respectively.
      • Benza RL
      • Miller DP
      • Barst RJ
      • et al.
      An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry.
      Similar outcomes observed in the recent retrospective study, with survival at one and five years were 76% and 50%, respectively, and authors attributed that to availability of effective PAH-specific therapies over the past two decades.
      • Padang R
      • Chandrashekar N
      • Indrabhinduwat M
      • et al.
      Aetiology and outcomes of severe right ventricular dysfunction.
      PAH secondary to portopulmonary hypertension is associated with a particularly bad <40% one-year survival.
      • Robalino BD
      • Moodey DS.
      Association between primary pulmonary hypertension and portal hypertension: Analysis of its pathophysiology and clinical, laboratory, and hemodynamic manifestations.
      However, Le Pavec et al. demonstrated better survival in portopulmonary hypertension with overall survival rates at one, three, and five years of 88%, 75%, and 68%, respectively.
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      • Souza R
      • Herve P
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      Portopulmonary hypertension: Survival and prognostic factors.
      Overall, five-year morality in portopulmonary hypertension was higher in the no-treatment group (85%) compared with medical therapy or liver transplantation, 65% and 33%, respectively.
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      • Wiesner R
      • Nyberg S
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      Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups.
      In a small cohort of patients with dilated cardiomyopathy, RVD was seen in ≈ 60% of patients and was associated with greater mitral regurgitation and tricuspid regurgitation (TR), more rapid progression of clinical heart failure, and decreased survival.
      • Lewis JF
      • Webber JD
      • Sutton LL
      • et al.
      Discordance in degree of right and left ventricular dilation in patients with dilated cardiomyopathy: Recognition and clinical implications.
      From a Multi-Ethnic Study of Atherosclerosis, presence of RV hypertrophy was associated with a more-than-twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio [HR] = 2.52; 95% confidence interval [CI], 1.55-4.10, p < 0.001).
      • Kawut SM
      • Barr RG
      • Lima JA
      • et al.
      Right ventricular structure is associated with the risk of heart failure and cardiovascular death: The Multi-Ethnic Study of Atherosclerosis (MESA)–right ventricle study.
      Patients with RV systolic dysfunction in hypertrophic obstructive cardiomyopathy, have a higher risk for cardiovascular mortality (p = 0.026), but no significant difference in all-cause mortality (p = 0.118) and heart failure-related rehospitalization (p = 0.485).
      • Shah JP
      • Yang Y
      • Chen S
      • et al.
      Prevalence and prognostic significance of right ventricular dysfunction in patients with hypertrophic cardiomyopathy.

      RVD in Reduced (HFrEF) and Preserved (HFpEF) LVEF

      Analogous to outcomes in HFrEF populations, RVD is associated with increased morbidity and mortality in HFpEF populations.
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      • Gailani M
      • Vaz Pérez A
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      Right ventricular myocardial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction.
      Two-year mortality in the study by Melenovsky was ≈45% for patients with RVD in HFpEF, compared with 7% in those without RVD.
      • Melenovsky V
      • Hwang SJ
      • Lin G
      • et al.
      Right heart dysfunction in heart failure with preserved ejection fraction.
      A systemic review and meta-analysis from 38 included studies, showed tricuspid annular plane systolic excursion (TAPSE) (HR 1.26/5 mm decrease; p < 0.0001), fractional area change (FAC) (HR 1.15/5% decrease; p < 0.0001), mean pulmonary artery pressure (HR 1.26/5 mmHg increase; p < 0.0001), and pulmonary artery systolic pressure (PASP) (1.16/5 mmHg increase; p < 0.0001) were all uinvariably associated with mortality.
      • Gorter TM
      • Hoendermis ES
      • van Veldhuisen DJ
      • et al.
      Right ventricular dysfunction in heart failure with preserved ejection fraction: A systematic review and meta-analysis.
      A population-based cohort study (n = 637) from Asian ethnicity, demonstrated decreased ratio of TAPSE/PASP and right ventricle longitudinal strain (RVLS)/PASP were associated with all-cause mortality or heart failure hospitalization without any differences between HFrEF and HFpEF.
      • Bosch L
      • Lam CSP
      • Gong L
      • et al.
      Right ventricular dysfunction in left-sided heart failure with preserved versus reduced ejection fraction.
      A prospective study by Santas et al. focused on HFpEF, proposed progressive staging of RVD from 1 to 4, based on combination of TAPSE/PASP and status of functional TR. After multivariate adjustment, stages 3 and 4 compared with stage 1, were independently associated with high mortality (HR 1.8219; 95% CI, 1.308-2.538; p < 0.001 and HR = 2.2632; 95% CI, 1.540-3.325; p < 0.001, respectively) (Fig 2).
      • Santas E
      • De la Espriella R
      • Chorro FJ
      • et al.
      Right ventricular dysfunction staging system for mortality risk stratification in heart failure with preserved ejection fraction.
      From four community hospital databases (n = 1,004) with mean age of 76 years, patients free of heart failure at baseline but with lower right ventricle ejection fraction (RVEF) and worse RV-PA coupling were associated with heart failure or death, independent of LVEF and pro B-type natriuretic peptide (HR 1.20; 95% CI, 1.02-1.42 per 5% decrease in RVEF; p = 0.03; HR 1.65; 95% CI, 1.15-2.37 per 0.5 unit decrease in RVEF/PASP ratio; p = 0.007).
      • Nochioka K
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      Right ventricular function, right ventricular-pulmonary artery coupling, and heart failure risk in 4 US communities: The Atherosclerosis Risk in Communities (ARIC) Study.
      Fig 2
      Fig 2Cumulative event rates of all-cause mortality according to the stage of right ventricular dysfunction. Reproduced with permission from Santas et al.
      • Santas E
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      • Chorro FJ
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      Right ventricular dysfunction staging system for mortality risk stratification in heart failure with preserved ejection fraction.
      RVMI is associated with hemodynamic compromise in 25%-to-50% of patients presenting with infarct pattern.
      • Ondrus T
      • Kanovsky J
      • Novotny T
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      Right ventricular myocardial infarction: From pathophysiology to prognosis.
      One-year mortality after RVMI was reported to be 18% in patients with isolated right coronary lesions, compared with 27% in the presence of combined right and left coronary artery disease. In long-term follow-up, mortality beyond the first year remained at an additional 2%/year-to-3%/year through year ten.
      • Gumina RJ
      • Murphy JG
      • Rihal CS
      • et al.
      Long-term survival after right ventricular infarction.
      Similarly, among 666 patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention, excluding those with cardiogenic shock on admission, electrocardiographic and echocardiographic evidence of RVMI was associated with higher in-hospital and one- and six-month mortality compared with patients with either anterior or inferior MI without evidence of RVMI.
      • Assali AR
      • Teplitsky I
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      Prognostic importance of right ventricular infarction in an acute myocardial infarction cohort referred for contemporary percutaneous reperfusion therapy.

      RVD in Aortic Stenosis

      RVD is an important and independent predictor of mortality in aortic stenosis (AS). Bohbot et al. observed higher mortality in asymptomatic patients with severe AS and preserved ejection fraction with TAPSE <17 mm (HR 2.14; 95% CI, 1.31-3.51). Aortic valve replacement (AVR) was associated with a pronounced reduction in mortality independent of TAPSE, suggesting that AVR should be discussed before right ventricular dysfunction occurs in severe AS.
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      • Guignant P
      • Rusinaru D
      • et al.
      Impact of right ventricular systolic dysfunction on outcome in aortic stenosis.
      Gille et al., in data from more than 200 patients with a mean age of 79 years, showed biventricular dysfunction (TAPSE ≤17 mm and LVEF ≤50%) as the strongest predictor of prognosis (HR 4.08; 95% CI,1.36-12.22; p = 0.012) in severe AS.
      • Galli E
      • Guirette Y
      • Feneon D
      • et al.
      Prevalence and prognostic value of right ventricular dysfunction in severe aortic stenosis.
      In a retrospective analysis from low-flow low gradient in severe AS, RVD (HR 2.86; 95% CI, 1.21-6.75; p = 0.02) was an independent risk factor for all-cause mortality after adjustments for potential clinical and echocardiographic confounders such as aortic valve replacement, Society of Thoracic Surgeons Mortality score, severity of tricuspid regurgitation, and LV global longitudinal strain.
      • Cavalcante JL
      • Rijal S
      • Althouse AD
      • et al.
      Right ventricular function and prognosis in patients with low-flow, low-gradient severe aortic stenosis.
      Supraventricular arrhythmias, such as atrial fibrillation or multifocal atrial tachycardia, commonly are present in RVD secondary to pressure overload and have been associated with poor long-term outcomes.
      • Haddad F
      • Doyle R
      • Murphy DJ
      • et al.
      Right ventricular function in cardiovascular disease, part II: Pathophysiology, clinical importance, and management of right ventricular failure.
      Ventricular tachyarrhythmias originating from the RV in moderate-to-severe RVD potentially can lead to sudden cardiac death in patients with LVEF >35% without or with implantable cardioverter-defibrillator (ICD) (HR 4.12; p = 0.003 and HR 5.04; p < 0.001, respectively).
      • Naksuk N
      • Tan N
      • Padmanabhan D
      • et al.
      Right ventricular dysfunction and long-term risk of sudden cardiac death in patients with and without severe left ventricular dysfunction.
      Several observational studies have demonstrated significant improvement in RV function in RVD after cardiac resynchronization therapy (CRT).
      • Ricci F
      • Mele D
      • Bianco F
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      Right heart-pulmonary circulation unit and cardiac resynchronization therapy.
      ,
      • Campbell P
      • Takeuchi M
      • Bourgoun M
      • et al.
      Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) Investigators. Right ventricular function, pulmonary pressure estimation, and clinical outcomes in cardiac resynchronization therapy.
      Current guidelines do not recommend ICD for primary prevention in RVD except for arrhythmogenic RVD with significant risk factors for sudden cardiac death.
      • Priori SG
      • Blomström-Lundqvist C
      • Mazzanti A
      ESC Scientific Document Group
      2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).
      From a Danish trial, Elming et al. showed significant survival benefits of implanting ICD in biventricular failure.
      • Elming MB
      • Hammer-Hansen S
      • Voges I
      • et al.
      Right ventricular dysfunction and the effect of defibrillator implantation in patients with nonischemic systolic heart failure.
      Although RV remodeling and hypertrophy are relatively common in chronic lung disease, RVD generally is not progressive and overall outcomes are affected by underlying chronic lung disease severity. Modest increases in MPAP (>20 mmHg) have been associated with shorter life span in COPD.
      • Weitzenblum E
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      Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease.
      A five-year follow-up study in patients with COPD showed that only 36% survived with MPAP >25 mmHg compared with 65% with MPAP <25 mmHg.
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      • Quoix E
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      Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure.
      Similarly, in patients with interstitial lung disorders, one-year mortality was 28% with PH versus 5.5% in those without PH.
      • Lettieri CJ
      • Nathan SD
      • Barnett SD
      • et al.
      Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis.
      In the idiopathic pulmonary fibrosis population, the presence of PH influences long-term survival (16.7% v 62.2%, with and without PH, respectively).
      • Hamada K
      • Nagai S
      • Tanaka S
      • et al.
      Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis.
      In sarcoidosis, PH increases mortality with adjusted HR of 10.4 compared with patients without PH, and presence of interstitial lung disease (ILD) further increase mortality by five-fold.
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      • Engel PJ
      • Taylor L
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      Survival in sarcoidosis-associated pulmonary hypertension: The importance of hemodynamic evaluation.
      ,
      • Mathai SC
      • Hummers LK
      • Champion HC
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      Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: Impact of interstitial lung disease.

      Clinical Predictors and Etiology of RV Dysfunction After Cardiothoracic Surgery

      In cardiac surgery, impaired LV function has been recognized as a well-known independent risk factor for morbidity and mortality. However, limited data exist on predictors of RVD and impact of RV function on mortality in cardiac surgery. The majority of the data were from limited-to-small-sample-sized studies, performed in patient populations selected for well-known hemodynamic features already associated with RV failure.
      • Haddad F
      • Doyle R
      • Murphy DJ
      • et al.
      Right ventricular function in cardiovascular disease, part II: Pathophysiology, clinical importance, and management of right ventricular failure.
      ,
      • Wencker D
      • Borer JS
      • Hochreiter C
      • et al.
      Preoperative predictors of late postoperative outcome among patients with nonischemic mitral regurgitation with ׳high risk׳ descriptors and comparison with unoperated patients.
      ,
      • Maslow AD
      • Regan MM
      • Panzica P
      • et al.
      Precardiopulmonary bypass right ventricular function is associated with poor outcome after coronary artery bypass grafting in patients with severe left ventricular systolic dysfunction.
      Advanced age, body weight, New York Heart Association class, COPD, poor LVEF, and higher risk scores (Acute Physiology and Chronic Health Evaluation and European System for Cardiac Operative Risk Evaluation) were considered as potential risk factors for RVD after cardiac surgery.
      • Bootsma IT
      • de Lange F
      • Koopmans M
      • et al.
      Right ventricular function after cardiac surgery is a strong independent predictor for long-term mortality.
      Similar to medically treated RVD patients, the presence of pulmonary hypertension has been recognized as a risk factor with significant prognostic value. Overall, the prognostic impact of RV dysfunction on mortality in a large cardiac surgery population remains unclear.
      During cardiac surgery, acute RV failure can be caused by hypoxia or myocardial ischemia, microemboli, air emboli leading to MI, arrhythmias, and excessive volume loading.
      • Haddad F
      • Couture P
      • Tousignant C
      • et al.
      The right ventricle in cardiac surgery, a perioperative perspective, I: Anatomy, physiology, and assessment.
      Although overall RV function remains preserved, the combination of cardiopulmonary bypass and pericardiotomy leads to a reduction in RV longitudinal contraction and an increase in transverse shortening.
      • Raina A
      • Vaidya A
      • Gertz ZM
      • et al.
      Marked changes in right ventricular contractile pattern after cardiothoracic surgery: Implications for post-surgical assessment of right ventricular function.
      RVD frequently is seen within five days of cardiac surgery and may persist despite improvements in LV function.
      • Diller GP
      • Wasan BS
      • Kyriacou A
      • et al.
      Effect of coronary artery bypass surgery on myocardial function as assessed by tissue Doppler echocardiography.
      Studies have shown decreased RV function, especially longitudinal strain after AVR primarily due to cardioplegia, induced myocardial injury even in patients with normal preoperative RV function.
      • Duncan AE
      • Sarwar S
      • Kateby Kashy B
      • et al.
      Early left and right ventricular response to aortic valve replacement.
      The minimally invasive AVR has the slight advantage of preserving RV function compared with conventional AVR.
      • Hashemi N
      • Johnson J
      • Brodin LÅ
      • et al.
      Right ventricular mechanics and contractility after aortic valve replacement surgery: A randomised study comparing minimally invasive versus conventional approach.
      Analysis from the PARTNER 2a trial showed an 8.3% RVD incidence in TAVR as compared with 24.7% with SAVR (p < 0.0001). In a multivariate model, SAVR (odds ratio [OR] –4.05; 95% CI, 2.55-6.44), a dilated RV (OR 2.38; 95% CI, 1.37-4.14), and more-than-mild TR (OR 2.58; 95% CI, 1.25-5.33) were associated with worsening RV function in the aortic valve stenosis population.
      • Cremer PC
      • Zhang Y
      • Alu M
      • et al.
      The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: Insights from PARTNER IIA.
      From a prospective registry trial in the TAVR only group, one-third of patients developed new-onset RV dysfunction.
      • Asami M
      • Stortecky S
      • Praz F
      • et al.
      Prognostic value of right ventricular dysfunction on clinical outcomes after transcatheter aortic valve replacement.
      From a meta-analysis of more than 3,000 patients, RV dilation and severe TR were identified as independent predictors for RVD in TAVR patients.
      • Grevious SN
      • Fernandes MF
      • Annor AK
      • et al.
      Prognostic assessment of right ventricular systolic dysfunction on post-transcatheter aortic valve replacement short-term outcomes: Systematic review and meta-analysis.
      Many studies have shown transient and persistent RVD even years after mitral valve repair or replacement. The PREPARE-MVR study (PRediction of Early PostoperAtive Right vEntricular failure in Mitral Valve Replacement/Repair patients) demonstrated changes in RV mechanics, primarily reduction in longitudinal fraction in the immediate and delayed postoperative period causing RVD, compared to radial motion (OR = 1.33; 95% CI, 1.08-1.77; p < 0.05).
      • Tokodi M
      • Németh E
      • Lakatos BK
      • et al.
      Right ventricular mechanical pattern in patients undergoing mitral valve surgery: A predictor of post-operative dysfunction?.
      Grapsa et al., in their prospective study of degenerative mitral valve disease in patients, showed favorable results in reverse RV remodeling with mitral valve repair compared with valve replacement by reduction of RV end-diastolic volume, p < 0.01; reduction of RV mass, p < 0.01; and reduction of tricuspid regurgitant velocity, p = 0.019.
      • Grapsa J
      • Dawson D
      • Pandis D
      • et al.
      Mitral valve repair results in better right ventricular remodelling than valve replacement for degenerative mitral regurgitation: A three-dimensional echocardiographic study.
      Although bypass time was higher in the minimally invasive MVr compared with open mitral valve repair (MVr) (80 min ± 22 v 40 min ± 20, p < 0.0001), deterioration in RV contraction is less pronounced in minimally invasive MVr and was associated with enhanced RV functional recovery at one year.
      • Orde SR
      • Chung SY
      • Pulido JN
      • et al.
      Changes in right ventricle function after mitral valve repair surgery.
      Concomitant tricuspid valve (TV) repair along with MVr more markedly reduces RV dimensions and does not have a negative impact on RV systolic function in comparison to an isolated MV repair.
      • Ordienė R
      • Orda P
      • Vaškelytė JJ
      • et al.
      Changes in right ventricular longitudinal function: Primary mitral and concomitant tricuspid valve repair.
      TR is a common echocardiographic finding, and mild TR is present in 80%-to-90% of individuals with RVD. Although less common, moderate-to-severe TR affects >one million people in the United States. The severity of TR affects prognosis even when controlling for LV dysfunction or PH.
      • Taramasso M
      • Vanermen H
      • Maisano F
      • et al.
      The growing clinical importance of secondary tricuspid regurgitation.
      Isolated TV repair or replacement is relatively uncommon compared with MVR/AVR and there are data to suggest a significant difference in the residual RVD between TV repair and replacement, 14.3% versus 5.9% (p = 0.57), respectively.
      • Ejiofor JI
      • Neely RC
      • Yammine M
      • et al.
      Surgical outcomes of isolated tricuspid valve procedures: Repair versus replacement.

      RVD in Left Ventricular Assist Device Implantation

      Twenty percent or more of patients undergoing isolated left ventricular assist device (LVAD) implantation experience RVD, which is a leading cause of premature morbidity and mortality.
      • Soliman OI
      • Akin S
      • Muslem R
      EUROMACS Investigators
      Derivation and validation of a novel right-sided heart failure model after implantation of continuous flow left ventricular assist devices: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) Right-Sided Heart Failure Risk Score.
      Patients with a history of chemotherapy-associated cardiomyopathy, female gender, destination therapy compared with bridging for transplant, preexisting circulatory failure, presence of mechanical LV assist devices such as an intra-aortic balloon pump, pulmonary hypertension, moderate-to-severe TR, and redo surgery are the potential risk factors for RVD after LVAD.
      • Argiriou M
      • Kolokotron SM
      • Sakellaridis T
      • et al.
      Right heart failure post left ventricular assist device implantation.
      In a multicenter study, multiregression analysis revealed that a central venous pressure/pulmonary capillary wedge pressure (PCWP) >0.63 (OR 2.3; 95% CI, 1.2-4.3; p = 0.009), need for preoperative ventilator support (OR 5.5; 95% CI, 2.3-13.2; p < 0.001), and blood urea nitrogen >39 mg/dL (OR 2.1; 95% CI, 1.1-4.1; p = 0.02) were independent predictors of right ventricular failure after LVAD.
      • Kormos RL
      • Teuteberg JJ
      • Pagani FD
      • et al.
      Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: Incidence, risk factors, and effect on outcomes.
      From a prospective LVAD database, Mathews et al. observed vasopressor requirement, aspartate aminotransferase >80 IU/L, bilirubin >2.0 mg/dL and creatinine >2.3 mg/dL were independent predictors of RV failure.
      • Matthews JC
      • Koelling TM
      • Pagani FD
      • et al.
      The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates.
      The pathophysiology of RVD is complex. From a hemodynamic perspective, activation of an LVAD increases venous return, potentially overwhelming a functionally impaired RV, leading to RV dilatation, TR, leftward shift of the interventricular septum, and decline in RV stroke volume. The RV is dependent on the LV for a significant portion of its contractile function, and leftward septal shift resulting from LV unloading can have a direct, detrimental effect on RV contraction.
      • Farrar DJ
      • Compton PG
      • Hershon JJ
      • et al.
      Right heart interaction with the mechanically assisted left heart.
      Furthermore, anchoring of the LVAD to the LV apex may alter the normal twisting contractile pattern of the heart. Whether the direction of apical deformation (ie, apical pull versus push, depending on device configuration and placement) alters the risk of RVD remains uncertain. A single-center analysis of patients implanted with the HeartMate I pulsatile-flow LVAD compared with the HeartMate II continuous-flow LVAD revealed similar rates of RV dysfunction—35% versus 41%, respectively, although fewer patients ultimately required an RV assist device in the latter group.
      • Patel ND
      • Weiss ES
      • Schaffer J.
      Right heart dysfunction after left ventricular assist device implantation: A comparison of the pulsatile HeartMate I and axial-flow HeartMate II devices.
      Late RVD in the LVAD recipients, after initial hospital discharge, occurs in ≈10% of patients and is associated with reduced survival and lower quality of life and functional capacity.
      • Takeda K
      • Takayama H
      • Colombo PC
      • et al.
      Incidence and clinical significance of late right heart failure during continuous-flow left ventricular assist device support.
      The development of ventricular and atrial tachyarrhythmias may be a significant factor contributing to the development of late right heart failure (RHF).

      RVD After Heart Transplantation

      Acute RVD remains a common and difficult problem to manage after heart transplantation (HT). Primary graft dysfunction affects 7% or more of patients after cardiac transplantation and is the leading cause of early mortality. Diagnosis of primary graft dysfunction of the RV alone requires, at minimum, the following three criteria: (1) RAP >15 mmHg, PCWP <15 mmHg, and cardiac index <2.0 L/min/m2; (2) transpulmonary gradient <15 mmHg and PASP <50 mmHg; or (3) the need for an RV assist device.
      • Kobashigawa J
      • Zuckermann A
      • Macdonald P
      • et al.
      Report from a consensus conference on primary graft dysfunction after cardiac transplantation.
      Contributing causes consist of donor (donor-recipient mismatch >20%), procedural (longer ischemia time, marginal organ preservation), and recipient-level factors, including inflammatory mediators resulting from brain death, elevated PVR, and ischemia/reperfusion injury associated with preservation issues and acute allograft rejection.
      • Chen EP
      • Bittner HB
      • Davis RD
      • et al.
      Right ventricular adaptation to increased afterload after orthotopic cardiac transplantation in the setting of recipient chronic pulmonary hypertension.
      Increased levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate, or creatinine in the early postoperative period have been associated with right heart failure after HT. Increased preoperative pulmonary capillary wedge (p = 0.005) and mean pulmonary artery pressure (p = 0.006) were identified as significant risk factors for severe RHF from a single-center study.
      • Klima U
      • Ringes-Lichtenberg S
      • Warnecke G
      • et al.
      Severe right heart failure after heart transplantation. A single-center experience.

      RVD in Congenital Heart Diseases

      Survival into adulthood has improved dramatically in adult congenital heart diseases, primarily due to advances in both medical and surgical management. However, at the same time, RV failure has become a major concern in this population.
      • Davlouros PA
      • Niwa K
      • Webb G
      • et al.
      The right ventricle in congenital heart disease.
      RV outflow tract obstruction after total correction of tetralogy of Fallot (TOF), pulmonary stenosis, atrial switch surgery for transposition of the great arteries (TGA), congenitally corrected TGA, and systemic RV failure after Fontan surgery are the key causes of pressure-overload right ventricle failure (RVF). Atrial septal defect repair, residual pulmonary regurgitation, and tricuspid regurgitation are associated with volume-overload RVF.
      • Voelkel NF
      • Quaife RA
      • Leinwand LA
      • et al.
      Right ventricular function and failure: Report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure.
      Schuuring described a multivariate logistic regression analysis of congenital cardiac disease surgery in adults, showing that preoperative dysfunction of the RV, supraventricular tachycardia, and a cardiopulmonary bypass time >150 minutes were the key determinants for RVF.
      • Schuuring MJ
      • van Gulik EC
      • Koolbergen DR
      • et al.
      Determinants of clinical right ventricular failure after congenital heart surgery in adults.
      Severe pulmonary regurgitation is the most common cause of progressive RV dilatation and dysfunction in patients with repaired TOF. In Ebstein's anomaly, ≥ one leaflet of the TV is adherent to the RV wall, leading to atrialization of a portion of the RV chamber with varying degrees of TR. The degree of long-term RHF depends on the degree of RV hypoplasia or the success of TV reparative surgery.
      • Pradat P
      • Francannet C
      • Harris JA
      • et al.
      The epidemiology of cardiovascular defects, part I: A study based on data from three large registries of congenital malformations.
      Transposition of the Great Arteries presents a notable challenge. The majority of patients with L-TGA (L-looped transposition) have other significant cardiac defects, most commonly including ventricular septal defect, pulmonic stenosis, and TR. RHF occurs in up to 50% of patients with L-TGA by middle age, with the risk increased by the presence of associated lesions such as TV disease.
      • Graham Jr, TP
      • Bernard YD
      • Mellen BG
      • et al.
      Long-term outcome in congenitally corrected transposition of the great arteries: A multi-institutional study.
      Analogous to patients with L-TGA, the RV in D-TGA (Right-looped transposition) patients is at increased risk of dilatation and failure. Moons et al. observed moderate RV dysfunction in 10% of their patients and severe dysfunction in 2%, which correlated with severity of tricuspid valve regurgitation after Senning or Mustard repair.
      • Moons P
      • Gewillig M
      • Sluysmans T
      • et al.
      Long term outcome up to 30 years after the Mustard or Senning operation: A nationwide multicenter study in Belgium.
      There are various forms of single-ventricle morphology; hypoplasia or total absence of the LV (ie, hypoplastic left heart syndrome) is the most severe form of congenital heart diseases. In these patients, pulmonary blood flow is achieved by connecting the vena cavae directly to the pulmonary arteries (Glenn and Fontan operations). Systemic RV dilatation, TR, and RHF become increasingly common as patients enter their third and fourth decades. Patients with a systemic RV are at greater risk of developing heart failure than patients with a systemic LV.
      • Julsrud PR
      • Weigel TJ
      • Van Son JA
      • et al.
      Influence of ventricular morphology on outcome after the Fontan procedure.
      Fibrosis is present in >25% of patients with a Fontan surgery.
      • Rathod RH
      • Prakash A
      • Powell AJ
      • et al.
      Myocardial fibrosis identified by cardiac magnetic resonance late gadolinium enhancement is associated with adverse ventricular mechanics and ventricular tachycardia late after Fontan operation.

      Outcomes After RVD in Cardiac Surgery

      Patients with preexisting RVD with right ventricle fractional area change (RV-FAC) <45% before coronary artery bypass grafting were associated with prolonged duration of mechanical ventilation (12 v one days; p < 0.01), longer intensive care unit (ICU) stay (14 v two days; p < 0.01) longer hospital stays (14 v seven days; p = 0.02) and also had more frequent and severe LV diastolic dysfunction in a severe LV dysfunction compared to RV-FAC >45%.
      • Maslow AD
      • Regan MM
      • Panzica P
      • et al.
      Precardiopulmonary bypass right ventricular function is associated with poor outcome after coronary artery bypass grafting in patients with severe left ventricular systolic dysfunction.
      In combined coronary artery bypass grafting and valve surgery, patients with reduced RVEF had a greater incidence of long-term cardiac repeat hospitalization versus patients with normal RVEF (31% v 13%, p < 0.05). Moreover, abnormal RVEF was a predictor for long-term cardiac repeat hospitalization (HR 3.01; CI, 1.5-7.9, p < 0.03) irrespective of LV functional status.
      • Lella LK
      • Sales VL
      • Goldsmith Y
      • et al.
      Reduced right ventricular function predicts long-term cardiac re-hospitalization after cardiac surgery.
      Comparing transcatheter versus surgical AVR patients with worsening RV function, after adjusting for clinical and echocardiographic variables, had higher all-cause mortality (HR 1.98; 95% CI, 1.40-2.79) (Fig 3). Moreover, there was no difference in mortality between TAVR and SAVR (HR 1.16; 95% CI, 0.61-2.18) in patients with RVD. However, worsening RV function from baseline normal RV function conferred the worst prognosis (HR 2.87; 95% CI, 1.40-5.89).
      • Cremer PC
      • Zhang Y
      • Alu M
      • et al.
      The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: Insights from PARTNER IIA.
      Data from the SWISS TAVR registry demonstrated more than two-fold increased risk of cardiovascular death at one year in patients with RVD (20.1% v 7.1%; HR 2.94; 95% CI, 2.02-4.27). Although two-thirds of patients recovered from RVD, 30 days after TAVR there was a gradient of increasing risk of cardiovascular death among recovering patients with RVD (HR adj: 2.16; 95% CI, 1.16-4.02), new RVD (HR adj: 3.93; 95% CI, 2.09-7.39), and maintained RVD (HR adj: 8.74; 95% CI, 5.33-14.3), respectively (Fig 4).
      • Asami M
      • Stortecky S
      • Praz F
      • et al.
      Prognostic value of right ventricular dysfunction on clinical outcomes after transcatheter aortic valve replacement.
      In data from meta-analysis in TAVR patients, RVD was found to be a predictor of adverse procedural outcome (HR 1.31; 95% CI, 1.1-1.55; p = 0.002) and had significant influences on one-year survival.
      • Grevious SN
      • Fernandes MF
      • Annor AK
      • et al.
      Prognostic assessment of right ventricular systolic dysfunction on post-transcatheter aortic valve replacement short-term outcomes: Systematic review and meta-analysis.
      In another meta-analysis comparing SAVR and TAVR, RV systolic dysfunction was associated with a significant 78% relative risk increase (risk ratio [95% CI] = 1.78 [1.37, 2.31], p < 0.01), albeit significant heterogeneity (I2 = 64%, p < 0.01). RV function remained unchanged up to one year, whereas deterioration of RVF was observed in the SAVR group.
      • Ren B
      • Spitzer E
      • Geleijnse ML
      • et al.
      Right ventricular systolic function in patients undergoing transcatheter aortic valve implantation: A systematic review and meta-analysis.
      Fig 3
      Fig 3All-cause mortality in patients with and without worsening right ventricular function in TAVR and SAVR. RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, trans catheter aortic valve replacement. Reproduced with permission from Cremar et al.
      • Cremer PC
      • Zhang Y
      • Alu M
      • et al.
      The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: Insights from PARTNER IIA.
      Fig 4
      Fig 4Cumulative incidence of (A) all-cause death, (B) cardiovascular death, and (C) MACCE up to one year according to presence or absence of RV dysfunction. CI, confidence interval; HR, hazard ratio; MACCE, major adverse cardiovascular and cerebrovascular event; RV, right ventricle; TAVR, trans Catheter Aortic Valve Replacement. Reproduced with permission from Asami et al.
      • Asami M
      • Stortecky S
      • Praz F
      • et al.
      Prognostic value of right ventricular dysfunction on clinical outcomes after transcatheter aortic valve replacement.
      Similar to AVR, the degree of RV function was found to be a strong predictor of long-term postoperative survival in a small preselected population undergoing mitral valve repair.
      • Wencker D
      • Borer JS
      • Hochreiter C
      • et al.
      Preoperative predictors of late postoperative outcome among patients with nonischemic mitral regurgitation with 'high risk' descriptors and comparison with unoperated patients.
      In a study of 5,223 patients by Nath, one-year survival rates were 92%, 90%, 79%, and 64% in patient groups with no, mild, moderate, or severe TR, respectively. Moderate or greater TR was associated with increased mortality regardless of PASP or LVEF. Severe TR, older age, lower LVEF, inferior vena cava dilation, and moderate or greater RV enlargement were associated with worse survival.
      • Nath J
      • Foster E
      • Heidenreich PA.
      Impact of tricuspid regurgitation on long-term survival.
      Bootsma et al. published single-center retrospective data that included more than 1,000 patients after heterogeneous cardiac surgeries and found that RVD after surgery increased overall short- and long-term mortality. Two-year mortality was significantly different based on RVEF, 4.1% with RVEF >30%, 8.2% with RVEF 20% to 30%, and 16.7% with RVEF <20%, p < 0.001, as shown in Figure 5.
      • Bootsma IT
      • de Lange F
      • Koopmans M
      • et al.
      Right ventricular function after cardiac surgery is a strong independent predictor for long-term mortality.
      In a multivariate analysis from single-center data over four years, RVD was shown to be significantly associated with increased ICU length of stay (OR 0.934; CI, 0.908-0.961, p < 0.001), along with prolonged duration of mechanical ventilation (OR 0.969; CI, 0.942-0.998, p = 0.033), usage of inotropic drugs (OR 0.944; CI, 0.917-0.971, p < 0.001), and increase in creatinine (OR 0.962; CI, 0.934-0.991, p = 0.011).
      • Bootsma IT
      • Scheeren TWL
      • de Lange F
      • et al.
      Impaired right ventricular ejection fraction after cardiac surgery is associated with a complicated ICU stay.
      Fig 5
      Fig 5All-cause mortality based on RVEF, right ventricle ejection fraction. Reproduced with permission from Bootsma et al.
      • Bootsma IT
      • de Lange F
      • Koopmans M
      • et al.
      Right ventricular function after cardiac surgery is a strong independent predictor for long-term mortality.
      Multiple studies have demonstrated reduced short-term and long-term survival rates in LVAD patients with RVD. Drakos et al., in their single-center study over 15 years, showed significantly higher mortality at 30, 180, and 365 days in patients with RVD compared with those without RVD.
      • Drakos SG
      • Janicki L
      • Horne BD
      • et al.
      Risk factors predictive of right ventricular failure after left ventricular assist device implantation.
      Patients with RV failure after LVAD implantation experienced worse outcomes, with only 71% surviving to transplantation, recovery, or with ongoing device support at 180 days compared with 89% among patients without RV failure.
      • Kormos RL
      • Teuteberg JJ
      • Pagani FD
      • et al.
      Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: Incidence, risk factors, and effect on outcomes.
      Before LVADimplantation, an increase in RV failure risk score <3, 4-to-5, >5.5, calculated based on preclinical data, was associated with shorter survival at 180 days, 90 ± 3%, 80 ± 8%, and 66 ± 9%, respectively.
      • Matthews JC
      • Koelling TM
      • Pagani FD
      • et al.
      The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates.
      Multiple other studies also have noted higher postoperative mortality, longer length of hospital stay, higher redo operation rates for bleeding, worsened end-organ function, and lower likelihood of successful bridging to transplantation among patients with RV failure.
      • Dang NC
      • Topkara VK
      • Mercando M.
      Right heart failure after left ventricular assist device implantation in patients with chronic congestive heart failure.
      ,
      • Morgan JA
      • John R
      • Lee BJ
      • et al.
      Is severe right ventricular failure in left ventricular assist device recipients a risk factor for unsuccessful bridging to transplant and post-transplant mortality.
      In a single-center retrospective data of more than 200 patients supported with continuous-flow LVADs, severe RV dysfunction on an echocardiogram before LVAD implantation was associated with an increased risk of gastrointestinal bleeding after adjustment for age and ischemic cardiomyopathy (HR 1.799; 95% CI, 1.089-2.973, p = 0.022).
      • Sparrow CT
      • Nassif ME
      • Raymer DS
      • et al.
      Pre-operative right ventricular dysfunction is associated with gastrointestinal bleeding in patients supported with continuous-flow left ventricular assist devices.
      Acute RVD is a major contributing factor to overall morbidity and mortality after HT, accounting for 50% of all cardiac related complications and about 20% of early mortality. The poor prognosis is presumed to be related to the high venous pressures, which, in conjunction with low arterial pressure, reduce the already impaired oxygen supply in vital organs, resulting in multiorgan dysfunction or even failure. Acute RVF is the second leading cause of 30-day morbidity and mortality besides acute rejection.
      • Hosenpud JD
      • Benett LE
      • Keck BM
      • et al.
      The registry of the international society for heart and lung transplantation: Fifteenth official report 1998.
      Patients with early RVF were associated with prolonged length of ICU (9.5 ± 9.0 days v 2.3 ± 2.2 days; p < 0.001), as well as duration of mechanical ventilation (9.2 ± 8.9 days v 1.6 ± 1.5 days; p < 0.001). Thirty-two out of 35 patients who developed acute RVF died within 30 days after HT.
      • Klima U
      • Ringes-Lichtenberg S
      • Warnecke G
      • et al.
      Severe right heart failure after heart transplantation. A single-center experience.
      Despite implementation of assist devices, most patients with severe RHF died in the early postoperative course. The benefit of assist device implementation in right ventricular failure remains controversial in HT.
      • Bank AJ
      • Mir SH
      • Nguyen DQ
      • et al.
      Effects of left ventricular assist devices on outcomes in patients undergoing heart transplantation.
      ,
      • Tenderich G
      • Koerner MM
      • Stuettgen B
      • et al.
      Mechanical circulatory support after orthotopic heart transplantation.
      Although LVAD therapy before transplant reduces an elevated PVR in heart transplant recipients, there was no statistically significant difference in survival after transplant in patients with PH, with or without LVAD therapy irrespective of the severity of the PH.
      • Liden H
      • Haraldsson A
      • Ricksten SE
      • et al.
      Does pretransplant left ventricular assist device therapy improve results after heart transplantation in patients with elevated pulmonary vascular resistance?.
      Progressive pulmonary regurgitation after repair of TOF in childhood leads to RV dilatation and RVF in adulthood, and it has been associated with increased arrhythmias, decreased exercise tolerance, and sudden death.
      • Davlouros PA
      • Niwa K
      • Webb G
      • et al.
      The right ventricle in congenital heart disease.
      Moreover, “restrictive RV physiology”, characterized by the presence of forward and laminar late diastolic pulmonary flow throughout respiration, has been associated with worse outcome with low-output syndrome and prolonged length of ICU stay after repair of TOF.
      • Cullen S
      • Shore D
      • Redington A.
      Characterization of right ventricular diastolic performance after complete repair of tetralogy of Fallot. Restrictive physiology predicts slow postoperative recovery.
      In adult patients after atrial switch, clinical heart failure is a rare occurrence, although between 10% and 50% of patients have echocardiographic evidence of RV systolic dysfunction. In a prospective study of somewhat older Mustard patients by Roos-Hesselink et al., a progressive decline in RV function occurred, along with a progressive increase in tricuspid regurgitation and lengthening of QRS.
      • Roos-Hesselink JW
      • Meijboom FJ
      • Spitaels SE
      • et al.
      Decline in ventricular function and clinical condition after Mustard repair for transposition of the great arteries (a prospective study of 22-29 years).
      As part of a study examining heart failure in a variety of patients with a subaortic RV, Piran et al. found clinical symptoms of heart failure in 20 of 90 Mustard patients (median age, mid-30s), with four subsequently dying.
      • Piran S
      • Veldtman G
      • Siu S
      • et al.
      Heart failure and ventricular dysfunction in patients with single or systemic right ventricles.
      Prieto et al., studying 65 patients with congenitally corrected TGA, found that the frequency of heart failure was 32% with 16 of 65 subsequent deaths.
      • Prieto LR
      • Hordof AJ
      • Secic M
      • et al.
      Progressive tricuspid valve disease in patients with congenitally corrected transposition of the great arteries.
      In both groups, subaortic RV dysfunction usually preceded clinical heart failure and symptoms were a strong predictor of mortality.

      Clinical Predictors and Etiology of RV Dysfunction After Noncardiac Surgery

      RV failure is a common but under recognized cause of perioperative morbidity and mortality after noncardiac surgery, and predominantly the result of the development of acute PH or intraoperative myocardial ischemia.
      • Harjola VP
      • Mebazaa A
      • Čelutkienė J
      • et al.
      Contemporary management of acute right ventricular failure: A statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.
      RVD is found in up to 25% of hemodynamically unstable postoperative patients and its diagnosis leads to a change in the management in 59% of cases.
      • Markin NW
      • Gmelch BS
      • Griffee MJ
      • et al.
      A review of 364 perioperative rescue echocardiograms: Findings of an anesthesiologist-staffed perioperative echocardiography service.
      Irrespective of the type of surgery, potential contributing factors for the development of PAH eventually leading to RVD are listed in Table 2. In the nonobstetric and noncardiac surgical population with underlying PAH, risk factors for major complications were an elevated right atrial pressure (OR 1.1; 95% CI, 1.0-1.3; p = 0.01), a reduced six-minute walking distance <399 m at the last preoperative assessment (OR 2.2; 95% CI, 1.1-3.7; p = 0.04), the perioperative use of vasopressors (OR 1.5; 95% CI, 1.2-2.7; p = 0.03), and the need for emergency surgery (OR 2.4; 95% CI, 1.4-3.6; p = 0.01).
      • Meyer S
      • McLaughlin VV
      • Seyfarth HJ
      • et al.
      Outcomes of noncardiac, nonobstetric surgery in patients with PAH: An international prospective survey.
      Table 2Perioperative Risk Factors for PAH That Can Predispose to RVD
      Patient-related Perioperative Risk Factors in PAHSurgery-related Perioperative Risk Factors
      • Functional class >II• Emergency surgery
      • Reduced 6-minute walk distance• Duration of anesthesia >3 h
      • Coronary heart disease• Intraoperative requirement for vasopressor
      • Previous pulmonary embolism
      • Chronic renal insufficiency
      • Advanced right ventricular strain
      Abbreviations: PAH, pulmonary arterial hypertension; RVD, right ventricular dysfunction.
      RV alterations detected in COPD patients have been attributed to increased PVR due to pulmonary vasoconstriction caused by acute hypoxemia and vascular structural changes or remodeling caused by chronic hypoxemia. Mechanical factors, such as the reduction in size of the pulmonary vascular bed in patients presenting with emphysema, thrombosis, and hyperinflation, also contribute to increased PAP. Recent results suggest that alterations in RVSP in COPD patients may occur because of genetic influences.
      • Tannus-Silva DG
      • Rabahi MF.
      State of the art review of the right ventricle in COPD patients: It is time to look closer.
      The loss of pulmonary tissue and the preexisting pulmonary vascular disorder (PVD)/RVD predict the risk and severity of postoperative RVD in patients undergoing lung resection and precipitated by hypoxia, atelectasis, and hypercarbia.
      • Grignola JC
      • Domingo E.
      Acute right ventricular dysfunction in intensive care unit.
      RVD is greater after pneumonectomy than lobectomy.
      • Elrakhawy HM
      • Alassal MA
      • Shaalan AM
      • et al.
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      There have been reports of dynamic RV outflow obstruction after lung transplantation, and although, transient with inotropic usage in the perioperative period, occasionally leads to delayed RV failure.
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      Delayed right heart failure following lung transplantation.
      The common predictors for the development of acute RVD in patients with acute respiratory failure are pneumonia-induced ARDS, PaO2/FIO2 <150, PaCO2 ≥48 mmHg, and driving pressure ≥18 cmH2O.
      • Grignola JC
      • Domingo E.
      Acute right ventricular dysfunction in intensive care unit.
      Patients with end-stage liver disease develop RVD after liver resection or liver transplantation predominantly from an acute increase in RV afterload. Potential mechanisms of RV failure are splanchnic vasodilatation, splanchnic collateral formation and increased blood flow, smooth muscle hypertrophy, re-modelling and in situ thrombosis of the pulmonary vasculature leading to portopulmonary hypertension, and cirrhotic cardiomyopathy secondary to LV systolic and diastolic dysfunction.
      • Couperus LE
      • Vliegen HW
      • Sorgdrager BJ
      • et al.
      Prognostic importance of increased right ventricular afterload in orthotopic liver transplantation recipients with endstage cirrhosis.
      Irrespective of the type of surgery, general anesthesia induces hemodynamically significant changes in the RV function predominantly because of mechanical ventilation, as well as direct negative effects of anesthetic agents on right ventricular myocardial function.
      • Magunia H
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      • Keller M
      • et al.
      The effects of anesthesia induction and positive pressure ventilation on right-ventricular function: An echocardiography-based prospective observational study.

      Outcomes of RV Dysfunction After Noncardiac Surgery

      Postoperative acute respiratory failure is associated with increased mortality, prolonged length of stay, and increased resource use.
      • Denault AY
      • Pearl RG
      • Michler RE
      • et al.
      Tezosentan and right ventricular failure in patients with pulmonary hypertension undergoing cardiac surgery: The TACTICS trial.
      Data over ten years from 1,276 patients showed history of pulmonary embolism (p = 0.04), right-axis deviation (p = 0.02), RV hypertrophy (p = 0.04), RV index of myocardial performance ≥0.75 (p = 0.03), and RVSP/systolic blood pressure ≥0.66 (p = 0.01) were each associated with postoperative mortality of 7%.
      • Ramakrishna G
      • Sprung J
      • Ravi BS
      • et al.
      Impact of pulmonary hypertension on the outcomes of noncardiac surgery: Predictors of perioperative morbidity and mortality.
      Analysis from a large administrative database of more than 17 million patients with PH demonstrated an incidence of 0.81% of pulmonary arterial hypertension with RV dysfunction. In this study, PH remained independently associated with MACCE (OR 1.43; 95% CI, 1.40-1.46) after adjusting for demographics, clinical covariates, and surgery type.
      • Smilowitz NR
      • Armanious A
      • Bangalore S
      • et al.
      Cardiovascular outcomes of patients with pulmonary hypertension undergoing noncardiac surgery.
      Data from nonobstetric and noncardiac surgery showed higher mortality rate of 15% (two out of 13) in emergency procedures, compared with 2% (two out of 101) in nonemergency procedures (p = 0.01) in patients with RVD.
      • Meyer S
      • McLaughlin VV
      • Seyfarth HJ
      • et al.
      Outcomes of noncardiac, nonobstetric surgery in patients with PAH: An international prospective survey.
      Even in mild-to-moderate PH patients for nonthoracic and nonobstetric surgeries, 7% of patients died in the early postoperative period, and PH-related complications occurred in 29% of patients with PAH-associated RVD.
      • Price LC
      • Montani D
      • Jaïs X
      • et al.
      Noncardiothoracic nonobstetric surgery in mild-to-moderate pulmonary hypertension.
      Patients having major orthopedic surgeries with severe PH developed perioperative complications such as bleeding, experienced infections in 37.5%, and showed a mortality rate of 6.5%. With significant improvement in the management of PAH with pulmonary vasodilators before or during surgery, overall survival rate has been improving significantly in this high-risk population.
      • Frost AE
      • Badesch DB
      • Miller DP
      • et al.
      Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: A REVEAL Registry Analysis.
      In the liver transplant population, increased RV afterload has been associated with higher incidences of postoperative hemodynamic complications (8%, 17%, and 29% for normal, high-normal, and mildly elevated RV afterload, respectively, p = 0.03) and worse survival (eight-year survival 74%, 41%, and 37%, respectively, p = 0.01). Preoperative RV function was not associated with worse outcomes after orthotopic liver transplantation (OLT).
      • Couperus LE
      • Vliegen HW
      • Sorgdrager BJ
      • et al.
      Prognostic importance of increased right ventricular afterload in orthotopic liver transplantation recipients with endstage cirrhosis.
      Cardiac evaluation before liver transplantation plays a key role in identifying modifiable risk factors, with the goal of optimizing patients before surgery.
      • Ripoll C
      • Yotti R
      • Bermejo J
      • et al.
      The heart in liver transplantation.
      Preoperative identification of variables contributing to RV failure, careful perioperative optimization, and focused intraoperative and postoperative care are key to reducing morbidity and mortality in patients with RVD.

      Acknowledgments

      Barbara Weisser, Mayo Clinic Academic Support Office, Scottsdale, Arizona, USA.

      Conflict of Interest

      The authors have no conflict of interest or financial involvement with this manuscript.

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