Left ventricular heart failure and pulmonary hypertension

Abstract

In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65-80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a 'left ventricular phenotype' to a 'right ventricular phenotype' across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context.

Keywords: Heart failure; Post-capillary; Pre-capillary; Pulmonary hypertension.

Figure 1

Cardiopulmonary interaction and pathobiology of pulmonary hypertension (PH) in left ventricular heart failure. Shown is (i) the backward transmission of elevated left ventricular filling pressures into the pulmonary circulation (post-capillary haemodynamic profile), (ii) potential superimposed components contributing to the extent of PH (leading to a pre-capillary component), which may be associated with (iii) pulmonary vascular remodelling in some patients, thus leading to (iv) right ventricular strain and dysfunction over time. Right ventricular (RV) dilation and increase in wall stress/tension (internal RV afterload) result in elevated myocardial oxygen consumption, which with concomitant reduction in coronary perfusion gradient leads to RV ischaemia and progressive RV failure.

Figure 2

Left atrial (LA) remodelling and dysfunction in heart failure. (A) Phases of LA function. PEV, passive empting volume = V_max – V_p; CV, conduit volume = LV stroke volume – (V_max– V_min); AEV, active emptying volume = V_p – V_min (modified from Rossi et al.). (B) Left atrial pressure–volume loops in normal LA function (left) and LA dysfunction (right). (C) Left atrial imaging by cardiac magnetic resonance imaging (cMRI) in a patient with pulmonary arterial hypertension and normal LA function (left) vs. LA enlargement and dysfunction in a patient with left heart disease (right) (cMRI movies may be downloaded from the Supplementary material online).

Figure 3

Sequence of pathophysiological factors contributing to pulmonary hypertension in left ventricular heart failure. Backward transmission of left- to right-sided pathological features at the level of the ventricles, atrioventricular valves, and atria. Data derived from Tedford et al. showing that in left heart failure related pulmonary hypertension with increased wedge pressure the RC time is constant, but slightly decreased (leftward shift) (images containing video loops may be downloaded from the Supplementary material online).

Figure 4

‘Left ventricular phenotype’ vs. ‘right ventricular phenotype’ in pulmonary hypertension associated with left heart disease. Shown is the spectrum of right ventricular dysfunction and presentation, the impact on mortality, therapeutic implications, and resting pulmonary haemodynamics.

Figure 5

Pulmonary arterial wedge pressure (PAWP). (A) Potential misclassifications between pre- and post-capillary pulmonary hypertension depending on the method of PAWP reading.^, (B) Example of a patient with pulmonary hypertension-heart failure with preserved ejection fraction before (left) and after (right) treatment with diuretics, illustrating the impact of volume load on pulmonary haemodynamics (modified from Dumitrescu et al.).

Figure 6

Differential diagnosis between pulmonary arterial hypertension (PAH, Nice Group 1) and pulmonary hypertension associated with left heart disease (PH-LHD Nice Group 2). Shown is a diagnostic algorithm, integrating non-invasive tests, and haemodynamic variables assessed by cardiac catheterization. For interpretation of non-invasive tests, see corresponding Table 2. *Limitations and uncertainties of pulmonary arterial wedge pressure/left ventricular end-diastolic pressure measurement are depicted in Table 1. Ipc-PH, isolated post-capillary PH; Cpc-PH, combined post- and pre-capillary PH.