The role of exercise right heart catheterization to guide pulmonary hypertension therapy in older adults.

The spectrum of patients referred for suspected pulmonary arterial hypertension (PAH) includes a population with clinical features suggestive of pulmonary hypertension due to left heart disease (PH-LHD). Even after right heart catheterization (RHC) performed at rest, it can be a challenge to identify patients who will clearly benefit from PAH drug therapy. Therefore, the objective of this study was to evaluate the role of exercise RHC to influence decisions regarding prescription of PAH drug therapy in this population. A retrospective cohort study was conducted of older adults with risk factors for PH-LHD and suspected PH referred for exercise RHC. One year follow-up was conducted to record clinical outcomes, all changes in PAH drug therapy, and changes in patient-reported quality of life. The final cohort included 61 patients, mean age of 69 ± 10; 44% and 34% had a history of coronary artery disease and atrial fibrillation respectively. Exercise changed the proportional breakdown of hemodynamic diagnoses from 36% No PH, 44% PAH, and 20% PH-LHD at rest to 15% No PH, 36% PAH, and 49% PH-LHD. Although a significant proportion of patients were reclassified as PH-LHD, there was an overall increase in the proportion of patients receiving PAH drug therapy, particularly for those with PAH confirmed by exercise RHC. A total of 11 PAH drug prescriptions were employed before exercise RHC increasing to 24 after (p = 0.002). Patients receiving PAH therapy demonstrated significant improvement in self-reported quality of life. Exercise RHC appeared to influence selection of PAH drug therapy.

Central venoarterial extracorporeal membrane oxygenation as a bridge to recovery after pulmonary endarterectomy in patients with decompensated right heart failure.

INTRODUCTION: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) and decompensated right heart failure (DRHF) have worse outcomes after pulmonary endarterectomy (PEA). We reviewed the role of central veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to recovery after PEA in these patients. METHODS: Of 388 consecutive patients undergoing PEA, 40 (10.3%) were admitted with DRHF before PEA. This group was compared to the remaining 348 patients undergoing PEA (elective group). We also compared 2 periods: 2005-2013 (n = 120) and 2014-2019 (n = 268) after which early central VA-ECMO was introduced as a strategy to manage difficulty weaning from cardiopulmonary bypass (CPB). RESULTS: The proportion of patients with DRHF remained similar between the first and second period (13% vs 9%, p = .2). The number of VA-ECMO bridge to recovery increased from 0.8% in 2005-2013 to 6.3% in 2014-2019 (p = .02). In the second period, 29% of DRHF patients were transitioned intraoperatively from CPB to central VA-ECMO for a median duration of 3 (2-7) days. After the introduction of central VA-ECMO as a bridge to recovery, the hospital mortality in patients with DRHF dropped from 31% in 2005-2013 to 4% in 2014-2019 (p = .03). In the long-term, the functional recovery and survival after discharged from hospital was similar between the DRHF group and the elective group. However, at 5 years, DRHF patients more frequently required PH targeted medical therapy (45% vs 20% in the elective group, p = .002). CONCLUSIONS: Central VA-ECMO as a bridge to recovery is an important treatment strategy that can decrease hospital mortality in patients with DRHF and lead to excellent long-term outcome.

Outcome after pulmonary endarterectomy for segmental chronic thromboembolic pulmonary hypertension.

OBJECTIVE: Determine the long-term outcome and need for additional therapy after pulmonary endarterectomy (PEA) for segmental chronic thromboembolic pulmonary hypertension. METHODS: Retrospective analysis of a prospective cohort of 401 consecutive Canadian patients undergoing PEA between August 2005 and March 2020 in Toronto. The outcome of segmental disease defined as Jamieson type 3 was compared with 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 durig 2016-2020 compared with 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 or 2 disease (P = .07). Mortality after PEA was similar between type 3 and type 1 and 2 disease at 30-days (2.8% vs 2.3%; P = .8) and at 1 year (7.7% vs 5.5%; P = .4). At 5 years, the survival was lower in type 3 disease (80% vs 91% in type 1 or 2 disease; P = .002). Type 3 disease was an independent predictor for the initiation of pulmonary hypertension-targeted medical therapy after PEA with a cumulative incidence of 38% at 10 years compared with 20% in type 1 and 2 disease (P < .0001). Post-PEA balloon pulmonary angioplasty was predominantly performed in type 3 disease (8% vs 1% in more type 1 or 2 disease; P = .0002). CONCLUSIONS: PEA achieved excellent early and long-term results in segmental chronic thromboembolic pulmonary hypertension. However, patients with segmental disease are at increased risk of requiring additional therapy after PEA and should be carefully monitored.

Symptoms Are More Useful Than Echocardiography in Patient Selection for Pulmonary Endarterectomy.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is still largely underdiagnosed in the general population. Although transthoracic echocardiogram (TTE) is recommended to screen for CTEPH, it may not detect patients with chronic thromboembolic disease (CTED) and mild or exercise-induced pulmonary hypertension (PH) who could also benefit from pulmonary endarterectomy (PEA). METHODS: All patients referred to our CTEPH program with persistent mismatched perfusion defects on ventilation-perfusion (VQ) scan between January 2005 and June 2015 were divided into three groups according to TTE and right heart catheterization (RHC) as follows: (1) typical CTEPH group (PH on RHC and TTE), (2) TTE-negative (neg) CTEPH group (PH on RHC, but not TTE), or (3) CTED group (no PH on RHC and TTE). RESULTS: Of 225 patients with abnormal VQ scans, 188 (84%) had typical CTEPH, 15 had TTE-neg CTEPH, and 22 had CTED. PEA was performed in 179 patients (80%). Reasons for exclusion in CTEPH patients included primarily distal disease (n = 11) and comorbidities (n = 10). In contrast, the absence of functional limitation was the main cause of exclusion in CTED patients (75% versus 3% in CTEPH patients, p < 0.0001). The 90-day mortality rate after PEA was 4% in the typical CTEPH group and 0% in the TTE-neg CTEPH and CTED groups. Pulmonary arterial pressures and functional class significantly improved after PEA in all three groups. CONCLUSIONS: Patients with mild CTEPH can benefit from PEA, but may not be detected by TTE. Symptomatic patients with functional limitation and persistent mismatched perfusion defects on VQ scan should undergo further investigations with pulmonary angiogram and RHC.

Sex disparities in systemic sclerosis-associated pulmonary arterial hypertension: a cohort study.

BACKGROUND: The impact of male sex as a determinant of health outcomes in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is controversial. The primary objective of this study was to evaluate the effect of sex on survival in patients with SSc-PAH. The secondary objectives were to evaluate the effect of sex on age of PAH diagnosis, time from SSc diagnosis to PAH diagnosis, and SSc disease manifestations. METHODS: Sex-based disparities were evaluated in a cohort of SSc-PAH patients with a primary outcome of time from PAH diagnosis to all-cause mortality. Secondary outcomes were differences in age of diagnosis, disease duration, and SSc manifestations. Survival differences were evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: We identified 378 SSc-PAH (58 males, 320 females) patients, with a female:male ratio of 5.5:1. Males had a shorter mean ± standard deviation time from SSc diagnosis to PAH diagnosis (1.7 ± 14 versus 5.5 ± 14.2 years); shorter PAH duration (3.5 ± 3.1 versus 4.7 ± 4.2 years), increased frequency of renal crisis (19 % versus 8 %, relative risk (RR) 2.33, 95 %CI 1.22, 4.46), interstitial lung disease (67 % versus 48 %, RR 1.41, 95 %CI 1.14, 1.74), and diffuse subtype (40 % versus 22 %, RR 1.84, 95 %CI 1.26, 2.69). Males appeared to have decreased 1-, 2-, 3-, and 5-year survival (83.2 %, 68.7 %, 53.2 %, 45.6 %) compared to females (85.7 %, 75.7 %, 66.4 %, 57.4 %). However, there was no difference in mortality between sexes (HR 1.43 (95 %CI 0.97, 2.13). CONCLUSIONS: Sex disparities appear to exist in the frequency of PAH, time to PAH diagnosis, PAH disease duration and SSc disease burden. However, male sex does not independently impact SSc-PAH survival.

Survival in rheumatoid arthritis-associated pulmonary arterial hypertension compared with idiopathic pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: In this study, we evaluated survival in rheumatoid arthritis-associated pulmonary arterial hypertension (RA-PAH) compared with idiopathic pulmonary arterial hypertension (IPAH) patients, and evaluate differences in disease severity and treatment. METHODS: We conducted a retrospective cohort study of RA-PAH and IPAH at the University Health Network Pulmonary Hypertension Programme, Toronto, Canada. The primary outcome was time to all-cause mortality. We evaluated survival using Kaplan-Meier curves. Using a propensity score-matched cohort, we used Cox proportional hazards models to estimate survival. RESULTS: Screening 1385 patients identified 18 RA-PAH and 155 IPAH patients. RA-PAH patients had an older median age of onset (64.0 vs 53.7 years) and lower baseline mean pulmonary arterial pressure (mPAP) (41 vs 50 mm Hg, P = 0.02). RA-PAH patients tended to have a higher proportion of females (83% vs 70%, relative risk 0.55, 95% confidence interval (CI): 0.19-1.57), lower proportion with baseline World Health Organization functional class III/IV (39% vs 52%), lower median baseline brain natriuretic peptide (58.4 vs 95.0 pg/mL) and longer baseline 6-min walk distance (440 vs 397 m). There were 35 deaths, 2/18 (11%) RA-PAH patients and 33/155 (21%) IPAH patients. The unadjusted 1-year survival was 93% for RA-PAH and 94% for IPAH. In the matched cohort, there were seven deaths: 2/18 (11%) RA-PAH and 5/18 (28%) IPAH patients, hazard ratio 1.53 (95% CI: 0.15-2.84). Separation of survival curves did not achieve statistical significance, log-rank 0.56. CONCLUSIONS: Compared with IPAH patients, RA-PAH patients have an older age of onset and lower baseline mPAP. RA-PAH patients have comparable survival to IPAH patients.

Pulmonary endarterectomy in severe chronic thromboembolic pulmonary hypertension.

BACKGROUND: The outcome of patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) after urgent hospitalization for decompensated right heart failure (DRHF) remains unclear. METHODS: Among 120 consecutive patients undergoing PEA, 16 (13%) presented with a history of urgent hospitalization for DRHF (severe RHF group). This group was compared with the remaining 104 patients presenting with total peripheral vascular resistance (TPR) < 1,200 dynes · sec · cm(-5) (n = 78, control group) and >1,200 dynes · sec · cm(-5) (n = 26, high TPR group). RESULTS: DRHF occurred predominantly in patients with TPR > 1,200 dynes · sec · cm(-5) (prevalence of 32% vs 5% in patients with TPR < 1,200 dynes · sec · cm(-5), p < 0.0001). The overall in-hospital mortality after PEA was 4% (n = 5). All deaths occurred in patients with TPR > 1,200 dynes · sec · cm(-5) and DRHF. The proportion of patients with residual PH immediately after surgery was higher in the high TPR group (50%) and severe RHF group (56%) compared with the control group (29%; p = 0.04). In multivariate analysis, risk factors for residual PH after surgery were TPR > 1,200 dynes · sec · cm(-5), Jamieson disease Type III-IV, and female gender. A history of DRHF by itself was not a risk factor for residual PH after PEA. The overall 5-year survival was 87%. After a median follow-up of 20 months, the proportion of patients receiving medical therapy for residual PH was higher in patients with post-operative mean pulmonary artery pressure ≥35 mm Hg (61% vs 9%, p = 0.0007). CONCLUSIONS: DRHF occurs more frequently in patients with TPR > 1,200 dynes · sec · cm(-5), increasing the operative risk in these patients. The outcome of patients with high TPR in the absence of DRHF is excellent. However, patients with residual mean pulmonary artery pressure ≥35 mm Hg frequently receive pulmonary hypertension therapy after PEA.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: the Toronto experience.

BACKGROUND: Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH). However, this surgery remains performed in few experienced centres only. The goal of the study is to review our overall experience since the implementation of our program in August 2005. METHODS: Review all patients referred to our program between August 2005 and July 2011. RESULTS: Among 84 consecutive patients referred to our program, 52 patients underwent elective PEA and 6 emergency PEA. After PEA, 74% patients were extubated within 2 days, 71% were discharged from the intensive care unit within 4 days and 64% were discharged from hospital within 15 days. One patient undergoing elective surgery and 2 patients undergoing emergency surgery died within 30 days of surgery for an operative mortality of 1.9% after elective pulmonary endarterectomy and an overall operative mortality of 5.2%, when the 6 emergency operative cases were included. The total pulmonary vascular resistance decreased from 965±445 to 383±162 dynes per second per cm(-5) and was associated with significant improvement in World Health Organization/New York Heart Association (WHO/NYHA) functional class, 6 minutes walk distance, echocardiographic findings, and brain natriuretic peptide level at 6 months after PEA. After a median follow-up of 23 months (1-65 months), 3 patients had to be started on targeted PH therapy for deterioration of their (WHO/NYHA) functional class. CONCLUSIONS: Elective PEA can be performed with limited risk, and results in excellent early and long-term outcome. All patients diagnosed with chronic thromboembolic PH should be referred for consideration of PEA in a specialized centre.

Early postoperative pulmonary vascular compliance predicts outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

BACKGROUND: Despite a major reduction in pulmonary vascular resistance (PVR), patients with chronic thromboembolic pulmonary hypertension (CTEPH) do not always return to functional New York Heart Association (NYHA) class I after pulmonary endarterectomy (PEA). We hypothesized that residual abnormal compliance (Cp) after PEA is associated with incomplete functional recovery despite major improvement in PVR. METHODS: The Cp of 34 consecutive patients with CTEPH was assessed before and after PEA. Cp was defined as stroke volume over pulse pressure and was divided into three groups: < 2.0 mL/mm Hg, 2.0 to 3.9 mL/mm Hg, and ≥ 4 mL/mm Hg. To establish predicted Cp after PEA, we collected an age- and gender-matched control group. RESULTS: Before PEA, Cp was < 2.0 mL/mm Hg in 82% (n = 28) of the patients. After PEA, Cp improved to 2.0 to 3.9 mL/mm Hg in 11 patients and to ≥ 4.0 mL/mm Hg in 14 patients. Residual Cp < 2.0 mL/mm Hg was associated with delayed extubation and prolonged hospital stay. At 3 months' follow-up, 13 patients (93%) with postoperative Cp ≥ 4.0 mL/mm Hg returned to NYHA class I, whereas 45% with Cp of 2.0 to 3.9 mL/mm Hg and 25% with Cp < 2.0 mL/mm Hg returned to NYHA class I. In multivariate analysis, postoperative Cp ≥ 4.0 mL/mm Hg was the only predictor of functional recovery to NYHA class I. The group of patients with postoperative Cp ≥ 4.0 mL/mm Hg was also the only group to achieve hemodynamic parameters similar to those of their matched control subjects. CONCLUSIONS: Postoperative Cp is an important predictor of recovery after PEA. Residual vascular stiffness after PEA can be associated with persistent functional limitation and lack of complete remodeling of the right ventricle.

Pulmonary vasodilators--treating the right ventricle.

Pulmonary hypertension remains a significant complication of several systemic and cardiothoracic diseases. It is important to emphasize that the hemodynamic relevance relates to the effect of pulmonary hypertension on right ventricular function and right-left ventricular interaction. The goal of pulmonary vasodilation should focus on optimizing right ventricular function and improving systemic perfusion. The properties of an optimum vasodilator include selective pulmonary vasodilation (avoiding systemic vasodilation), rapid onset of action, short half-life, and ease of administration. Inhaled nitric oxide or nebulization of traditional systemically administered agents offers the greatest clinical promise. An additional merit of selective pulmonary vasodilation consists of augmenting oxygenation by improving ventilation perfusion matching.

Identifying motivations and barriers to patient participation in clinical trials.

BACKGROUND: This study assessed cancer patients' knowledge and attitudes towards clinical trials (CTs). METHODS: A survey was administered to 100/141 cancer outpatients. RESULTS: 82% respondents had heard of CTs, but many could only provide limited definitions and perceived them as high risk. About half had previously been approached to participate in a trial, and 67% had agreed to participate. Factors influencing participation in trials, barriers to recruitment, and suggestions for increased recruitment in clinical trials were identified. CONCLUSIONS: The findings suggest general support of CTs. Education programs are needed to raise awareness, reduce fears, and dispel myths about CT participation.