Pulmonary Hypertension in Heart Failure Contexts

Pulmonary hypertension (PH) arising in the context of heart failure represents a frequent and formidable complication that significantly worsens prognosis. In left heart disease, elevated left atrial pressure transmits to the pulmonary vasculature, leading initially to isolated post-capillary PH and, in a subset of patients, to a further pre-capillary component characterised by pulmonary vascular remodelling and increased pulmonary vascular resistance. This combined pre- and post-capillary PH accelerates right ventricular dysfunction, undermining exercise capacity and increasing mortality. Advances in imaging, haemodynamic monitoring and molecular profiling have refined diagnostic algorithms, enabling precise phenotyping and stratification of risk. A growing body of work has explored the mechanisms linking myocardial dysfunction, endothelial injury and altered vasomotor control, while therapeutic efforts target both cardiac filling pressures and pulmonary vascular tone. Improved understanding of these interrelated processes is pivotal to developing tailored interventions that mitigate right heart strain, enhance quality of life and reduce hospitalisation burden across diverse healthcare settings.

Research from Nature Portfolio

Pre-clinical validation of non-invasive echocardiographic indices in a murine model of heart failure with reduced ejection fraction has established a reliable threshold of left ventricular wall-motion score index to predict elevated right ventricular systolic pressure and right ventricular hypertrophy. This platform accelerates translational studies by enabling longitudinal assessment of pulmonary vascular disease and therapeutic modulation without repeated invasive measurements. In parallel, transcriptome-wide analysis in patients with preserved ejection fraction heart failure has uncovered upregulation of the transcription regulator ID2 in those who develop combined pre- and post-capillary PH. Replication in an animal model confirmed that pathways associated with cell proliferation and mitochondrial function are implicated in the transition from isolated post-capillary to combined haemodynamic phenotypes, suggesting novel targets for pharmacological intervention.

Pulmonary Hypertension in Heart Failure Contexts publication trend

The graph below shows the total number of articles in pulmonary hypertension in heart failure contexts across all publications each year (not limited to Nature Index journals).

Technical terms

Pulmonary hypertension (PH): Elevation of mean pulmonary artery pressure above normal, leading to increased right ventricular afterload.

Heart failure with preserved ejection fraction (HFpEF): A form of heart failure characterised by symptoms of congestion despite a normal or near-normal left ventricular ejection fraction.

Combined pre- and post-capillary PH (CpcPH): A subtype of PH due to left heart disease in which additional pulmonary vascular remodelling produces raised pulmonary vascular resistance alongside elevated left atrial pressure.

Echocardiography: Ultrasound imaging of the heart and great vessels used to assess chamber sizes, pressures and function non-invasively.

Transcriptome-wide analysis: High-throughput sequencing of RNA transcripts to profile gene expression patterns across the genome.

References

1. Clinical phenotypes and outcomes of pulmonary hypertension due to left heart disease: Role of the pre-capillary component. PLOS ONE (2018).
2. Phosphodiesterase 5 inhibitor sildenafil in patients with heart failure with preserved ejection fraction and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study. BMC Cardiovascular Disorders (2020).
3. Reduction of Pulmonary Hypertension After Transition to Sacubitril/Valsartan in Patients With Heart Failure With Preserved Ejection Fraction. Frontiers in Cardiovascular Medicine (2021).
4. Echocardiographic validation of pulmonary hypertension due to heart failure with reduced ejection fraction in mice. Scientific Reports (2018).
5. Transcriptome-wide analysis associates ID2 expression with combined pre- and post-capillary pulmonary hypertension. Scientific Reports (2019).
6. Pathophysiology and Diagnosis of Pulmonary Hypertension Due to Left Heart Disease. Frontiers in Medicine (2018).