Right Ventricular Afterload Indices in Lung Surgery

The investigators hypothesise that a transient, acute rise in right ventricular (RV) afterload occurring during lung resection surgery triggers a sterile inflammatory RV injury resulting in persistent RV dysfunction - even in the absence of sustained postoperative pulmonary vascular resistance - which contributes to disabling postoperative dyspnoea and exercise limitation.

Therapeutic pulmonary vasodilation is a mainstay of treatment to reduce RV afterload and improve V/Q matching in complex conditions such as pulmonary hypertension, thoracic organ transplant, respiratory distress syndromes and congenital cardiac disease, with well-established safety and feasibility profiles. Anti-inflammatory and cytoprotective properties have also been demonstrated. The inhaled route provides systemic and renovascular stability, ease of administration, selective targeting of the pulmonary vasculature, with high bioavailability and a short half-life. Unlike traditional approaches focussing on PH management, the application of IPVs for postoperative RV dysfunction may simultaneously address both contractility and afterload reduction.

Perioperative inhaled pulmonary vasodilator (IPV) therapy may prove to protect the RV from the relatively homogenous insult occurring in controlled clinical conditions as described above. Prior to clinical trials of IPVs, it is necessary to first demonstrate the feasibility of continuous RV / pulmonary vascular haemodynamic perioperative monitoring in lung resection, understand the time course of the perioperative afterload insult and characterise pulmonary vasoreactivity. This study seeks to characterise intraoperative haemodynamics, demonstrating feasibility and inform power calculation for a future early phase IPV trial in lung resection patients.

Aims

Perform a pragmatic single-centre, prospective study of adults undergoing elective lung resection by VATS and RATS to:

• Assess the feasibility and quality of continuous pressure-derived right ventricular afterload measurement using right heart catheterisation in contemporary elective thoracic surgical patient pathway.
• Characterise perioperative RV and PA haemodynamics (PVR/time area under curve relationship) throughout the perioperative lung resection pathway.
• Quantify perioperative pulmonary vasoreactivity.

Methods

• RHC and continuous cardiac output (CCO) monitoring with novel "RVCO" (right ventricular cardiac output) algorithm to permit continuous perioperative RV/pulmonary haemodynamic measures.
• Contrast CMR to quantify cardiopulmonary blood flow, as the gold standard measure against which other measures (RHC) are compared.
• Interval cardiac biomarker (HsTn & BNP) measurement to provide standard for measurement of perioperative RV injury.
• Characterise perioperative pulmonary vasoreactivity using oxygen and iNO.
• Conduct validated patient-reported quality of recovery questionnaires.

Primary objective

• Assess the feasibility of collecting perioperative RHC-derived CCO RV/pulmonary haemodynamic data in 15 adult patients undergoing elective lung resection.

Secondary objectives

• Obtain perioperative (esp. intraoperative) PVR vs time area under the curve (AUC).
• Characterise scale, chronology and predictability of intraoperative pulmonary vasoreactivity.
• Quantify the cardiac bio-inflammatory response to lung resection.
• Clinical and patient-reported outcome measures.
• Assess the precision of RHC-measured, RVP waveform-derived PA flow waveform against CMR (gold standard for flow volumes).

Inclusion criteria

• Age ≥18
• Presumed or confirmed non-small cell lung cancer
• Planned (elective) minimally invasive (VATS/RATS) lobectomy using OLV
• Able to provide informed consent

Exclusion criteria

• Pulmonary / RV physiological: Severe right sided valvular (tricuspid, pulmonary) disease, Preoperative atrial fibrillation / flutter / non-controlled tachydysrhythmia, Severe RA/RV dilatation, Severe PH (mPAP >55mmHg).
• Awake RHC contraindicated: Severe coagulopathy (PTr >1.5, PTTr >1.5), Thrombocytopenia (<50x109/L), Abnormal vasculature, Unable to lie supine and head down, Endocarditis or intra-cardiac tumour or thrombus, Right-sided valve prosthesis or other implanted cardiac device (e.g. pacing wire), Skin/soft tissue infection overlying insertion point.
• CMR contraindicated: Severe claustrophobia/unable to lie supine, Class III obesity (BMI >40), Presence of non-MRI compatible foreign body or implanted device.
• Gadolinium contrast contraindicated: CMR contraindicated (as above) and/or: Intravenous (IV) contrast (Gadolinium) allergy, Acute or chronic renal failure (eGFR <59ml/min).
• Surgical / medical: Planned sub-lobar resection / wedge resection / isolated middle lobectomy / segmentectomy / pneumonectomy, Planned secondary procedure (e.g. mediastinal/cardiac), Pregnancy.
• Research: Ongoing participation in other investigational research which would undermine the scientific basis of this study.