Ali Kapasi’s research while affiliated with University of British Columbia and other places

Background: Risk stratification is fundamental in the management of pulmonary arterial hypertension (PAH). Pulmonary artery pulsatility index (PAPi), defined as pulmonary arterial pulse pressure divided by right atrial pressure (RAP), is a hemodynamic index shown to predict acute right ventricular (RV) dysfunction in several settings. Our objective was to test the prognostic utility of PAPi in a diverse multicentre cohort of patients with PAH. Methods: A multicentre retrospective cohort study of consecutive adult patients with a new diagnosis of PAH on right heart catheterization between January 2016 and December 2020 was undertaken across 4 major centres in Canada. Hemodynamic data, clinical data, and outcomes were collected. The association of PAPi and other hemodynamic variables with mortality was assessed by receiver-operating characteristic curves and Cox proportional hazards modeling. Results: We identified 590 patients with a mean age of 61.4 ± 15.5 years, with 66.3% being female. A low PAPi (defined as < 5.3) was associated with higher mortality at 1 year: 10.2% vs 5.2% (P = 0.02). In a multivariable model including age, sex, body mass index, and functional class, a low PAPi was associated with mortality at 1 year (area under the curveof 0.64 (95% confidence interval 0.55-0.74). However, high RAP (> 8 mm Hg) was similarly predictive of mortality, with an area under the curve of 0.65. Conclusion: PAPi was associated with mortality in a large incident PAH cohort. However, the discriminative value of PAPi was not higher than that of RAP alone.

Introduction Alemtuzumab is a potent immunosuppressive that has been used for treatment of refractory acute lung allograft dysfunction (ALAD); however, its use in combination with plasmapheresis (PP) after lung transplantation has not been described. Case Report A 35 year old female underwent bilateral lung transplantation for WHO group 1 pulmonary arterial hypertension secondary to limited scleroderma. Induction consisted of basiliximab and steroids, initial maintenance included steroids, mycophenolate and tacrolimus. Post operative day (POD) 5 she developed progressive respiratory failure requiring VV-ECMO support. Infectious and HLA DSA workup were negative; however, CT and bronchoscopic findings were suggestive of antibody mediated rejection (AMR). A presumptive diagnosis of non-HLA AMR was made. Treatment consisted of PP, ATG, IVIg and rituximab. After transient improvement, on POD 47 a second course of ATG and steroid pulse with taper was required due to progressive ALAD. By POD 66 there was further deterioration of graft function. Alemtuzumab rescue was administered with PP for elimination of effector immune cells and treatment of presumed persistent non-HLA AMR. In the absence of PP alemtuzumab is known to exceed concentrations that inhibit reconstitution (>0.7 ug/mL) for several weeks. To ensure PP did not impair prolonged cytoreduction, or alemtuzumab-induced tolerogenicity, plasma monitoring of alemtuzumab was used to allow for redosing if the level fell below 0.7 ug/mL after PP. Elimination was not significantly altered after redosing (figure 1). Her ALAD stabilized although she developed severe restrictive CLAD. There were no infectious complications. 153 days following alemtuzumab administration, after completing inpatient prehabilitation, she was successfully retransplanted. Summary Therapeutic drug monitoring can be used to safely readminister alemtuzumab when used in combination with PP for rescue of refractory ALAD.

Objective Determine the long-term outcome and need for additional therapy after pulmonary endarterectomy (PEA) for segmental chronic thromboembolic pulmonary hypertension (CTEPH). Methods Retrospective analysis of a prospective cohort of 401 consecutive Canadian patients undergoing PEA between 08/2005 and 03/2020 in Toronto. The outcome of segmental disease defined as Jamieson type 3 was compared to more proximal disease defined as Jamieson type 1 and 2. The cohort was divided into 3 intervals to analyze the trend over time, 2005-2010, 2011-2015, and 2016-2020. Results Type 3 disease accounted for 41% of patients undergoing PEA in 2016-2020 compared to 7% in 2006-2010. Total pulmonary vascular resistance improved by 505±485 dynes.s.cm⁻⁵ in type 3 disease and by 593±452 dynes.s.cm⁻⁵ in type 1-2 disease (p=0.07). Mortality after PEA was similar between type 3 and type 1-2 disease at 30-day (2.8% vs 2.3%, p=0.8) and at 1-year (7.7% vs 5.5%, p=0.4). At 5-year, the survival was lower in type 3 disease (80% vs 91% in type 1-2 disease, p=0.002). Type 3 disease was an independent predictor for the initiation of PH targeted medical therapy after PEA with a cumulative incidence of 38% at 10-year compared to 20% in type 1-2 disease (p<0.0001). Post-PEA balloon pulmonary angioplasty (BPA) was predominantly performed in type 3 disease (8% vs 1% in more type 1-2 disease, p=0.0002). Conclusions PEA achieved excellent early and long-term results in segmental CTEPH. However, patients with segmental disease are at increased risk of requiring additional therapy after PEA and should be carefully monitored.

Background Primary graft dysfunction (PGD) after lung transplantation has previously been associated with increased risk of death and chronic lung allograft dysfunction (CLAD), but the relationship to baseline lung allograft dysfunction (BLAD), where graft function fails to normalize, is not known. Methods We reviewed all double lung transplant recipients transplanted in our program 2004 - 2016. We defined PGD and CLAD as per recent consensus definitions and BLAD as failure to achieve both FEV1 and FVC ≥80% predicted on 2 consecutive tests ≥3 weeks apart. We used logistic and proportional hazards regression to test the association between severe high-grade PGD (PGD3) with BLAD and CLAD respectively, adjusting for known and identified confounders. Results 446 patients met inclusion criteria and 76 (17%) developed PGD3 at 48- or 72-hours post-transplant. PGD3 occurred more frequently in patients with interstitial lung disease or pulmonary vascular disease, those with higher BMIs and recipients of older donors. PGD3 was associated with more frequent (58% vs. 36%; p=0.0008) and more severe BLAD (p<0.0001) and increased BLAD risk in an adjusted model (OR 2.00 [95% CI 1.13-3.60]; p = 0.0182). PGD3 was not associated with CLAD frequency, severity or time to CLAD onset in an adjusted model (HR 1.10 (95% CI 0.64-1.78), p=0.7226). Conclusion Severe PGD was associated with increased risk and severity of BLAD but not CLAD. The mechanisms via which PGD may mediate baseline function warrant further investigation.

Background Primary graft dysfunction (PGD) is an important contributor to early mortality in lung transplant recipients and is associated with impaired lung function. The radiographic sequelae of PGD on computed tomography (CT) have not been characterized. Methods We studied adult double lung transplant recipients from 2010‐2016 for whom protocol 3‐month post‐transplant CT scans were available. We assessed CTs for changes including pleural effusions, ground glass opacification, atelectasis, centrilobular nodularity, consolidation, interlobular septal thickening, air trapping and fibrosis, and their relationship to prior post‐transplant PGD, future lung function, post‐transplant baseline lung allograft dysfunction (BLAD) and chronic lung allograft dysfunction (CLAD). Results Of 237 patients studied, 50 (21%) developed grade 3 PGD (PGD3) at 48 or 72h. PGD3 was associated with increased interlobular septal thickening (p=0.0389) and atelectasis (p=0.0001) at 3 months, but only atelectasis remained associated after correction for multiple testing. Atelectasis severity was associated with lower peak forced expiratory volume in 1 second (FEV1) and increased risk of BLAD (p=0.0014) but not with future CLAD onset (p=0.7789). Conclusions Severe PGD was associated with atelectasis on 3‐month post‐transplant CT in our cohort. Atelectasis on routine CT may be an intermediary identifiable stage between PGD and future poor lung function.