Association Between the Pulmonary Artery Pulsatility Index and Prognosis in Pulmonary Arterial Hypertension: A Multicentre Study.

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.

Contexte: La stratification des risques est fondamentale dans la prise en charge de l'hypertension artérielle pulmonaire (HTAP). L'indice de pulsatilité des artères pulmonaires (iPAP), défini comme la pression différentielle dans les artères pulmonaires divisée par la pression auriculaire droite (PAD), est un indice hémodynamique qui s'est révélé prédictif d'une dysfonction ventriculaire droite (VD) aiguë dans plusieurs situations. Notre objectif était d'évaluer l'utilité pronostique de l'iPAP dans une cohorte multicentrique diversifiée de patients atteints d'HTAP. Méthodologie: Une étude de cohorte multicentrique rétrospective de patients adultes consécutifs atteints d'une HTAP nouvellement diagnostiquée par cathétérisme cardiaque droit entre janvier 2016 et décembre 2020 a été effectuée dans quatre grands centres au Canada. Les données hémodynamiques, les données cliniques et les résultats ont été recueillis. La corrélation de l'iPAP et d'autres va-riables hémodynamiques avec la mortalité a été évaluée par les courbes caractéristiques opérationnelles du receveur et des modèles à risques proportionnels de Cox. Résultats: Nous avons recensé 590 patients dont l'âge moyen était de 61,4 ± 15,5 ans; la proportion de femmes était de 66,3 %. Un faible iPAP (défini comme une valeur < 5,3) a été associé à une hausse de la mortalité à 1 an : 10,2 % contre 5,2 % (p= 0,02). Dans un modèle multivarié comprenant l'âge, le sexe, l'indice de masse corporelle et la classe fonctionnelle, un faible iPAP a été associé à la mortalité à 1 an (aire sous la courbe de 0,64 [intervalle de confiance à 95 %; de 0,55 à 0,74]). Cependant, une PAD élevée (> 8 mmHg) a aussi été un facteur prédictif de mortalité, l'aire sous la courbe étant de 0,65. Conclusions: L'iPAP a été associé à la mortalité dans une vaste cohorte de patients atteints d'une HTAP. Toutefois, la valeur discriminante de l'iPAP n'a pas été supérieure à celle de la PAD seule.

Optimizing COPD Acute Care Patient Outcomes Using a Standardized Transition Bundle and Care Coordinator: A Randomized Clinical Trial.

BACKGROUND: Acute exacerbations of COPD (AECOPD) are associated with high morbidity and mortality and frequent readmissions. RESEARCH QUESTION: What is the effectiveness of a COPD transition bundle, with and without a care coordinator, on rehospitalizations and ED revisits? STUDY DESIGN AND METHODS: Two patient cohorts were selected: (1) the group exposed to the transition bundle and (2) the group not exposed to the transition bundle (usual care group). Patients exposed subsequently were randomized to a care coordinator. An AECOPD transition bundle was implemented in the hospital; patients randomized to the care coordinator were contacted ≤ 72 h after discharge. Six hundred four patients (320 to the care coordinator and 284 to routine care) who met eligibility criteria from five hospitals across three cities in Alberta, Canada, were exposed to the transition bundle, whereas 3,106 patients discharged from the same hospitals received the usual care. Primary outcomes were 7-day, 30-day, and 90-day readmissions, median length of stay (LOS), and 30-day ED revisits. RESULTS: The transition bundle cohort were 83% (relative risk [RR], 0.17; 95% CI, 0.07-0.35) less likely to be readmitted within 7 days and 26% (RR, 0.74; 95% CI, 0.60-0.91) less likely to be readmitted within 30 days of discharge. Ninety-day readmissions were unchanged (RR, 1.05; 95% CI, 0.93-1.18). The transition bundle was associated with a 7.3% (RR, 1.07; 95% CI, 1.0-1.15) relative increase in LOS and a 76% (RR, 1.76; 95% CI, 1.53-2.02) greater risk of a 30-day ED revisit. The care coordinator did not influence readmission or ED revisits. INTERPRETATION: The COPD transition bundle reduced 7- and 30-day hospital readmissions while increasing LOS and ED revisits. The care coordinator did not improve outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03358771; URL: www. CLINICALTRIALS: gov.

Upfront riociguat and ambrisentan combination therapy for newly diagnosed pulmonary arterial hypertension: A prospective open-label trial.

BACKGROUND: Initial combination therapy with an endothelin receptor antagonist (ERA) and riociguat in pulmonary arterial hypertension (PAH) has limited supporting data. METHODS: We performed a prospective, single-arm, open-label trial of riociguat, and ambrisentan for incident PAH patients in functional class III. The primary endpoint was pulmonary vascular resistance (PVR) at 4-months. RESULTS: Twenty patients (59 ± 13 years old, 85% female) enrolled and 1 died before their 4-month follow-up. Fifteen patients completed a 4-month and 13 completed the 12-month follow-up. At 4-months PVR decreased 54% with an absolute change of -5.8 Wood units (95% CI -4.0; -7.5, p < 0.001). Other hemodynamic variables and risk scores also improved. Six patients discontinued riociguat and 8 discontinued ambrisentan, with 5 (25%) discontinuing both. CONCLUSIONS: These results do not support the routine use of riociguat plus ambrisentan in initial regimens. Future studies are needed to compare this strategy with phosphodiesterase-5 inhibitors and an ERA with respect to tolerability and long-term outcomes.

Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Canadian Cardiovascular Society/Canadian Thoracic Society Position Statement on Pulmonary Hypertension.

The landscape of pulmonary hypertension (PH) has changed significantly since the last Canadian Cardiovascular Society/Canadian Thoracic Society position statement in 2005. Since then, advances in our understanding of the pathophysiology of PH and improvements in diagnostic and therapeutic options have transformed the care of patients with PH. Globally, PH has an estimated prevalence of 1%, increasing to 10% in those aged 65 years and older, most commonly due to left heart or lung disease. Although pulmonary arterial hypertension (PAH) is less common, the morbidity and mortality is significant and early diagnosis and treatment are essential. This document is targeted at clinicians and describes a framework for screening and diagnosis of PH, with recommendations for performance and interpretation of echocardiography, cardiac magnetic resonance imaging, and right heart catheterization. In addition, the current approach to PAH management in Canada including risk stratification and pharmacologic therapy aimed at achieving a low-risk profile is discussed. The rationale to avoid specific PAH therapy in patients with left heart disease and lung disease-related PH is emphasized, along with special considerations for the diagnosis and management of chronic thromboembolic PH. Future advancements in the identification of novel pathways and therapies, personalized approaches to direct therapy, as well as interventional approaches such as balloon pulmonary angioplasty for chronic thromboembolic PH promise to continue the rapid evolution of this field.

Dasatinib-Induced Pulmonary Arterial Hypertension.

A 73-year-old woman with chronic myeloid leukemia developed severe pulmonary arterial hypertension (PAH) and pleural effusions after treatment with dasatinib. During workup, partial anomalous pulmonary venous connection and a sinus venosus atrial septal defect were found; these anomalies may have predisposed her to developing this rare and life-threatening condition. Fortunately, her PAH was completely reversible by discontinuation of dasatinib. This case highlights dasatinib's ability to cause PAH in patients predisposed to pulmonary vascular disease.

A Prospective Evaluation of the Diagnostic Accuracy of the Physical Examination for Pulmonary Hypertension.

BACKGROUND: The usefulness of physical examination findings for pulmonary hypertension (PH) is not well established. The purpose of this study was to evaluate prospectively the diagnostic performance of the physical examination for detecting PH. METHODS: Consecutive patients undergoing right-sided heart catheterization (n = 116) were examined by an attending physician, medical resident, and medical student in a blinded fashion. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for each physical finding. Jugular venous pulsation (JVP) height was compared with right atrial pressure (RAP) by using linear regression. The association between physical findings and PH was assessed using univariate and multivariate logistic regression. RESULTS: The prevalence of PH was 87%. Only a JVP > 3 cm (positive LR, 2.5; 95% CI, 1.2-5.4) and pulmonic regurgitation murmur (specificity, 100%; 95% CI, 79%-100%) helped rule in PH. The absence of JVP > 3 cm (negative LR, 0.4; 95% CI, 0.3-0.6) and absence of loud pulmonic component of the second heart sound (negative LR, 0.5; 95% CI, 0.3-0.9) had modest usefulness in excluding PH. JVP correlated with RAP (r = 0.59; P < .001) but tended to lead to underestimation of RAP (mean bias, -3.4 cm H2O; 95% limits of agreement, -14.0 to 7.2). The presence of JVP > 3 cm and a parasternal heave discriminated PH (area under the curve [AUC] = 0.75). The combination of JVP > 3 cm, heave, and peripheral edema discriminated severe PH (mean pulmonary arterial pressure ≥ 45 mm Hg; AUC = 0.82). CONCLUSIONS: Individual physical examination findings have inadequate diagnostic usefulness for PH. No combination of findings can be used to exclude PH, but the presence of high JVP, peripheral edema, and parasternal heave suggests severe PH.

Characterization of Right Ventricular Deformation in Pulmonary Arterial Hypertension Using Three-Dimensional Principal Strain Analysis.

BACKGROUND: Pulmonary arterial hypertension (PAH) can cause maladaptive right ventricular (RV) functional changes associated with adverse prognosis that are challenging to accurately quantify noninvasively. The aim of this study was to explore principal strain (PS) with contraction angle analysis using three-dimensional echocardiography to characterize RV deformation changes in patients with PAH. METHODS: Three-dimensional echocardiography was performed in 37 patients with PAH and 20 healthy control subjects with two-component (primary and secondary) PS and principal contraction angle analysis. Patients were stratified according to World Health Organization (WHO) functional class. RESULTS: Primary PS differed significantly between patients with PAH and healthy control subjects (-20.2 ± 3.3% vs -26.8 ± 3.3%, P = .01), while secondary PS was not significantly different (3.6 ± 5.1% vs -2.5 ± 4.7%, P = .12). Principal contraction angle was significantly lower in patients with PAH (63 ± 22° vs 71 ± 7°, P = .01), with the greatest reduction for the RV free wall. Primary PS and principal contraction angle differed significantly between WHO class I and II and class III and IV patients (-23.9 ± 4.7% vs -18.1 ± 4.8% [P = .03] and 69 ± 9° vs 58 ± 14° [P = .03], respectively), while secondary PS was not significantly different between groups (P = .13). Compared with healthy control subjects, septal principal contraction angle was not different in patients with WHO class I and II PAH (P = .62), but it was significantly reduced in those with WHO class III and IV PAH (P < .01). The area under the curve for primary PS to differentiate patients with PAH by WHO functional class was 0.81 (95% CI, 0.77-0.89; P = .01). Primary PS intraclass correlation coefficients for intraobserver and interobserver variability were 0.91 (95% CI, 0.88-0.93) and 0.86 (95% CI, 0.81-0.88), respectively. CONCLUSIONS: PS analysis using three-dimensional echocardiography provides comprehensive quantification of RV deformation and characterizes alterations occurring in PAH that are associated with WHO functional class.

Effectiveness of a standardized electronic admission order set for acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Variation in hospital management of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may prolong length of stay, increasing the risk of hospital-acquired complications and worsening quality of life. We sought to determine whether an evidence-based computerized AECOPD admission order set could improve quality and reduce length of stay. METHODS: The order set was designed by a provincial COPD working group and implemented voluntarily among three physician groups in a Canadian tertiary-care teaching hospital. The primary outcome was length of stay for patients admitted during order set implementation period, compared to the previous 12 months. Secondary outcomes included length of stay of patients admitted with and without order set after implementation, all-cause readmissions, and emergency department visits. RESULTS: There were 556 admissions prior to and 857 admissions after order set implementation, for which the order set was used in 47%. There was no difference in overall length of stay after implementation (median 6.37 days (95% confidence interval 5.94, 6.81) pre-implementation vs. 6.02 days (95% confidence interval 5.59, 6.46) post-implementation, p = 0.26). In the post-implementation period, order set use was associated with a 1.15-day reduction in length of stay (95% confidence interval - 0.5, - 1.81, p = 0.001) compared to patients admitted without the order set. There was no difference in readmissions. CONCLUSIONS: Use of a computerized guidelines-based admission order set for COPD exacerbations reduced hospital length of stay without increasing readmissions. Interventions to increase order set use could lead to greater improvements in length of stay and quality of care.

Reduction of pulmonary complications and hospital length of stay with a clinical care pathway after head and neck reconstruction.

BACKGROUND: Pulmonary complications are common after major head and neck oncologic surgery with microsurgical reconstruction and are associated with increased mortality and morbidity. Clinical care pathways are evidence-based tools that reduce unnecessary practice variation and ultimately improve patient outcomes. In this study, the authors evaluate the effectiveness of a comprehensive care pathway on reducing postoperative pulmonary complications and hospital length of stay in patients undergoing major head and neck carcinoma resection with free flap reconstruction. METHODS: Fifty-five consecutive patients treated according to a prescribed postoperative clinical care pathway were compared to a historical cohort of patients treated before the implementation of the pathway. The incidence of pulmonary complications, hospital length of stay, and free flap survival were compared between the control and intervention groups. RESULTS: Patients on the clinical care pathway had 32.5 percent fewer pulmonary complications (p < 0.0001) and 7.4 days' shorter hospital length of stay (p = 0.0007) than patients not on the postoperative pathway. There was no significant difference in the rate of flap reoperation. CONCLUSIONS: A multidisciplinary, comprehensive, clinical care pathway for patients undergoing major head and neck surgery with microsurgical reconstruction is effective in reducing postoperative pulmonary complications and hospital length of stay. The postoperative pathway is safe in this patient population and should be considered for adoption into clinical practice. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Delayed mobilization after microsurgical reconstruction: an independent risk factor for pneumonia.

OBJECTIVES/HYPOTHESIS: Large defects secondary to oral cancer resection are reconstructed with microsurgical free flaps. Pulmonary complications in these patients are common. Postoperative mobilization is recommended to decrease respiratory complications; however, many microsurgeons are reluctant to adopt early mobilization protocols due to the perceived risk of flap compromise. The purpose of this study was to determine the incidence of pneumonia among patients undergoing oral cancer resection and immediate free flap reconstruction and to compare the incidence of this complication between patients mobilized early (<4 days postoperative) versus later. A secondary goal was to determine whether early postoperative mobilization affected microvascular flap outcome. STUDY DESIGN: Retrospective cohort study. METHODS: Sixty-two consecutive patients treated between 2005 and 2009 with oral carcinoma resection and free flap reconstruction were studied. Information pertaining to comorbidities, postoperative care, and complications were collected. Risk factors for development of pulmonary and flap complications were analyzed. RESULTS: The incidence of pneumonia was 30.6%. Longer intensive care unit stay (P = 0.01), tracheostomy decannulation later than 10 days (P = 0.04), and longer operative times (P = 0.04) were significantly associated with pneumonia. Delayed mobilization (after day 4 postoperative) was an independent risk factor for pneumonia (OR = 4.2, 95% CI: 1.1, 17.1). Early mobilization (before day 4 postoperative) was not associated with an increased incidence of secondary flap procedures or flap failure. CONCLUSION: Late mobilization of free flap patients is an independent risk factor for developing postoperative pneumonia. Earlier mobilization does not increase flap failure rates, is safe, and should be strongly considered in all free flap patients to reduce pulmonary complications.

Diagnostic evaluation and management of chronic thromboembolic pulmonary hypertension: a clinical practice guideline.

BACKGROUND: Pulmonary embolism is a common condition. Some patients subsequently develop chronic thromboembolic pulmonary hypertension (CTEPH). Many care gaps exist in the diagnosis and management of CTEPH patients including lack of awareness, incomplete diagnostic assessment, and inconsistent use of surgical and medical therapies. METHODS: A representative interdisciplinary panel of medical experts undertook a formal clinical practice guideline development process. A total of 20 key clinical issues were defined according to the patient population, intervention, comparator, outcome (PICO) approach. The panel performed an evidence-based, systematic, literature review, assessed and graded the relevant evidence, and made 26 recommendations. RESULTS: Asymptomatic patients postpulmonary embolism should not be screened for CTEPH. In patients with pulmonary hypertension, the possibility of CTEPH should be routinely evaluated with initial ventilation/perfusion lung scanning, not computed tomography angiography. Pulmonary endarterectomy surgery is the treatment of choice in patients with surgically accessible CTEPH, and may also be effective in CTEPH patients with disease in more 'distal' pulmonary arteries. The anatomical extent of CTEPH for surgical pulmonary endarterectomy is best assessed by contrast pulmonary angiography, although positive computed tomography angiography may be acceptable. Novel medications indicated for the treatment of pulmonary hypertension may be effective for selected CTEPH patients. CONCLUSIONS: The present guideline requires formal dissemination to relevant target user groups, the development of tools for implementation into routine clinical practice and formal evaluation of the impact of the guideline on the quality of care of CTEPH patients. Moreover, the guideline will be updated periodically to reflect new evidence or clinical approaches.

Clinically active serologically quiescent systemic lupus erythematosus.

OBJECTIVE: To identify the frequency and characteristics of clinical activity with serological quiescence (CASQ) in a large cohort of patients with systemic lupus erythematosus (SLE) followed prospectively at a single center. METHODS: Patients followed at the Lupus Clinic between 1991 and 1995 who on at least 3 consecutive visits had clinical activity in the absence of a low complement and elevated DNA binding were identified. Demographics, disease characteristics, and therapy for the CASQ periods, as well as prior and subsequent disease course until April 2002 were analyzed. RESULTS: Of 514 patients followed at the Lupus Clinic according to a standard protocol, 62 patients had at least one episode of CASQ lasting a 9.8 +/- 6.4 months. During these periods, patients showed evidence of clinical disease activity with a SLEDAI-2K of 8.9 +/- 5.3. Major organ involvement (central nervous system, renal, vasculitis) occurred in 43 patients. Forty-four patients were treated with prednisone 16.7 +/- 11.4 mg/day, 21 were on immunosuppressive medication and 30 on antimalarials. Of the 58 patients who had followup after their last CASQ defining visit, 9 remained CASQ for 39 +/- 23 months. Of the remaining 49 patients, 23 became inactive, 21 became clinically and serologically active, and 5 were serologically active but clinically quiescent (SACQ). CONCLUSION: Clinical laboratory correlation in SLE is a heterogeneous relationship. The majority of patients have clinical-serological concordance. The minority have discordance between clinical and serological status, and are either SACQ or CASQ. Therefore, monitoring both clinical and serological features in patients with SLE is important.