Review
Pulmonary hypertension in left heart disease: A review

https://doi.org/10.1016/j.ijcard.2011.06.013Get rights and content

Abstract

Pulmonary hypertension (PH) occurs commonly in patients with left heart disease, and is associated with increased morbidity and mortality. The pathophysiologic mechanisms of PH in left heart disease are complex, and are thought to be a composite of both passive and active components. PH that is disproportionate to the underlying left heart disease may be attributable to reactive pulmonary vascular remodelling. Management of these patients is focused upon treatment of the underlying left heart disease and its associated comorbidities. There is no supporting evidence for the routine use of specific PH therapies in these patients at present. However, there is some suggestion that PDE-5 inhibitors may be useful, but their safety and efficacy needs to be formally evaluated in controlled trials before further recommendations are made.

Introduction

PH is common in patients with left heart disease, and is associated with increased morbidity and mortality [1], [2], [3], [4], [5]. Pathophysiologic mechanisms are complex, comprised of both passive and active components. PH disproportionate to the underlying left heart disease may be attributable to reactive pulmonary vascular remodelling. Left ventricular diastolic dysfunction may be difficult to diagnose, but is best assessed with echocardiography and right heart catheter (RHC). Management of PH in these patients is focused upon treatment of the underlying left heart disease and its associated comorbidities. There is no supporting evidence for the use of specific PH therapies in these patients at present [1], [6]. However, there is some suggestion that PDE-5 inhibitors may be useful, but their safety and efficacy needs to be formally evaluated in controlled trials before further recommendations are made [7].

Section snippets

Definition and classification

PH is defined haemodynamically by an increase in mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg at rest, as assessed by right heart catheterisation (RHC) [8]. Previously, the definition of PH included those with exercise-induced PH (mPAP ≥ 30 mm Hg on exercise) [9]. However, the data for exercise-induced PH is limited, and the recent reclassification of PH does not include exercise-PH in its definition.

PH is a severe, progressive disorder, which may be idiopathic, or related to a spectrum of

Prevalence and prognostic implications

The prevalence of PH in left heart disease increases with the severity of functional impairment. 40–70% of patients with isolated diastolic dysfunction, and up to 60% of those with left ventricular systolic dysfunction have PH at presentation [1], [2]. In patients with valvular heart disease, the prevalence of PH increases with the severity of the valvular defect, and is reported in up to 100% of cases with severe left-heart valvular disease [3].

In general when PH develops in association with

Histopathology

The histopathology of PH associated with left heart disease is characterised by pulmonary venous distension and thickening, pulmonary capillary and lymphatic dilatation, as well as interstitial oedema and alveolar haemorrhage. Over time, pulmonary vascular remodelling occurs, but the classic changes of the distal pulmonary vasculature, including the formation of plexiform lesions seen in pulmonary arterial hypertension (PAH), are rarely seen in PH associated with left heart disease [10], [11].

Pathophysiology

The pathophysiology of PH related to left heart disease is complex, and may be best considered as a combination of passive and active mechanisms. Passive pulmonary venous stretch resulting from backward transmission of elevated left heart pressures is important (Table 2). Purely passive PH is usually reversible with acute vasodilator testing, and may be more responsive to chronic heart failure treatment [12].

However, in some cases there is an additional active component, leading to PH ‘out of

Diagnosis

Recognition of PH may be delayed, as it is often masked by the clinical picture of the underlying left heart disease. Symptoms including dyspnoea and fatigue are common to both PH and left heart disease. Physical signs reflective of PH (such as a loud pulmonary component of the second heart sound) are often difficult to hear. Signs of right heart failure (including peripheral oedema) are generally late findings.

It may be difficult to distinguish between PH associated with diastolic dysfunction

General principles

Management of PH related to left heart disease centres on the treatment of the underlying disorder with medications such as diuretics, angiotensin converting enzyme inhibitors, ß-adrenoreceptor blockers, or other interventions [12]. Corrective valve surgery is recommended, and is usually associated with clinical improvement, and resolution of the PH [3], [32]. This improvement may take several weeks to months, and may be incomplete, due to the fixed obstructive changes of pulmonary vascular

Conclusion

PH is common in patients with left heart disease, and is associated with increased morbidity and mortality. Pathophysiologic mechanisms are complex, comprised of both passive and active components. PH disproportionate to the underlying left heart disease may be attributable to reactive pulmonary vascular remodelling. Left ventricular diastolic dysfunction may be difficult to diagnose, but is best assessed with echocardiography and RHC. Management of PH in these patients is focused upon the

Conflict of interest statement

TC has received compensation from Pfizer UK, Actelion UK, Pfizer and GSK for travel to conferences, and has received an educational grant from Actelion UK. SW has received compensation from Pfizer UK, Actelion UK and GSK for travel to conferences, and speaking engagements, and has received educational grants from Actelion UK. TM has no conflict of interest to declare.

Acknowledgments

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [62].

References (62)

  • A.M. Groves et al.

    Semi-quantitative assessment of tricuspid regurgitation on contrast-enhanced multidetector ct

    Clin Radiol

    (2004)
  • D.H. Roberts et al.

    Oxygen therapy improves cardiac index and pulmonary vascular resistance in patients with pulmonary hypertension

    Chest

    (2001)
  • S. Fojon et al.

    Inhaled nitric oxide through a noninvasive ventilation device to assess reversibility of pulmonary hypertension in selecting recipients for heart transplant

    Transplant Proc

    (2005)
  • A. Haraldsson et al.

    Comparison of inhaled nitric oxide and inhaled aerosolized prostacyclin in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance

    Chest

    (1998)
  • R.M. Califf et al.

    A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST)

    Am Heart J

    (1997)
  • W. Kiowski et al.

    Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure

    Lancet

    (1995)
  • L.E. Spieker et al.

    Acute hemodynamic and neurohumoral effects of selective et(a) receptor blockade in patients with congestive heart failure. Et 003 investigators

    J Am Coll Cardiol

    (2000)
  • P.J. Cowburn et al.

    Short-term haemodynamic effects of bq-123, a selective endothelin et(a)-receptor antagonist, in chronic heart failure

    Lancet

    (1998)
  • G. Torre-Amione et al.

    Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure

    J Am Coll Cardiol

    (2003)
  • J.R. Teerlink

    Recent heart failure trials of neurohormonal modulation (overture and enable): approaching the asymptote of efficacy?

    J Card Fail

    (2002)
  • I. Anand et al.

    Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the endothelina receptor antagonist trial in heart failure (earth): randomised, double-blind, placebo-controlled trial

    Lancet

    (2004)
  • J.J. Lepore et al.

    Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide

    Chest

    (2005)
  • M. Guazzi et al.

    The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure

    J Am Coll Cardiol

    (2004)
  • S.D. Katz et al.

    Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure

    J Am Coll Cardiol

    (2000)
  • M. Guazzi et al.

    Long-term use of sildenafil in the therapeutic management of heart failure

    J Am Coll Cardiol

    (2007)
  • L.G. Shewan et al.

    Ethics in the authorship and publishing of scientific articles

    Int J Cardiol

    (2010)
  • N. Galie et al.

    Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT)

    Eur Heart J

    (2009)
  • A. Vahanian et al.

    Guidelines on the management of valvular heart disease: the task force on the management of valvular heart disease of the European Society of Cardiology

    Eur Heart J

    (2007)
  • S.V. Abramson et al.

    Pulmonary hypertension predicts mortality and morbidity in patients with dilated cardiomyopathy

    Ann Intern Med

    (1992)
  • L.J. Addonizio et al.

    Elevated pulmonary vascular resistance and cardiac transplantation

    Circulation

    (1987)
  • S. Gibbs

    Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland

    Thorax

    (2008)
  • Cited by (8)

    • Soluble guanylate cyclase stimulator riociguat and phosphodiesterase 5 inhibitor sildenafil ameliorate pulmonary hypertension due to left heart disease in mice

      2016, International Journal of Cardiology
      Citation Excerpt :

      The PH due to left heart disease (LHD) is classified as a group 2 PH and is one of the most common forms of PH [1]. Though the true prevalence of PH in chronic heart failure (CHF) is not known, it is estimated that about 60% to 70% of patients with left ventricular (LV) dysfunction have PH [2]. Presence of PH and right ventricular (RV) dysfunction worsens prognosis in patients with CHF [3–5].

    • Pressure reflection in the pulmonary circulation by echocardiography in patients with left heart disease indicates reactive pulmonary hypertension

      2013, International Journal of Cardiology
      Citation Excerpt :

      Chronic heart failure is a major global health issue and its prevalence continues to increase [1]. Pulmonary hypertension (PH) is a well-known complication of chronic heart failure with prognostic [2–5] and therapeutic implications [6–10]. Pulmonary hypertension in patients with left heart disease (LHD) can be due to increased pulmonary venous pressure (passive PH), increased pulmonary vascular resistance (reactive PH) or a combination.

    • The Imaging of Pulmonary Hypertension

      2012, Seminars in Ultrasound, CT and MRI
      Citation Excerpt :

      The prevalence of PH is 40%-70% in isolated diastolic dysfunction, 60% in left ventricular systolic dysfunction, and up to 100% in severe left-sided valvular disease. Treatment is targeted to the underlying cardiac condition, most often identified at TTE or CT.4,5,41,93 CT evidence of pulmonary venous dilatation and smoothly thickened septal lines are clues to pulmonary venous congestion and a left-sided cardiac etiology for PH. CT findings of underlying mitral valve disease include leaflet thickening, calcifications, and left atrial chamber dilatation.

    • Pulmonary hypertension in left heart disease

      2019, Archives of Medical Science
    View all citing articles on Scopus
    View full text